Gynaecological tuberculosis, past, present and future. Until the introduction of the anti-tuberculosis drugs about 25 years ago, the treatment of tuberculosis of the female genital tract was generally unsatisfactory although many different forms of therapy were employed. Surgery was associated with a high incidence of post-operative complications, particularly of fistula, and an appreciable mortality rate. The position improved greatly after the introduction of the anti-tuberculosis drugs. Several drug programmes were employed by the writer, the best results being obtained with a combination of streptomycin, PAS and isoniazid for at least 18 months. Where drug treatment had failed, or where pelvic masses developed, surgery under drug cover was employed. No serious complications and no fatalities occurred in these patients. The question of possible transmission through sexual intercourse of male genitourinary tuberculosis is being investigated. A new drug programme is now being employed, the drugs used being streptomycin, ethambutol and isoniazid.


[Oocytes morphology of tertiary follicles in women with normal and disturbed ovarian function (author's transl)]. During gynecological operations 2 to 20 mm tertiary ovarian follicles were punctured in 65 women aged from 20 to 50 years. 205 eggcells were obtained. Histological examination of these eggcells revealed the following results: 1. Oocytes of small tertiary follicles are not increasing in size during maturation of the follicle. The average diameter of the ooplasma is 109 mu. The most impressive morphological criterium of imminent ovulation in oocytes from Graafian follicles is a loose cloud of granulosa cells. 2. The puncture of all visible tertiary follicles of both ovaries revealed an average of 6 eggcells in younger women (28 to 40 years), but only 3 eggcells in older women (41 to 53 years). In both groups signs of degeneration were observed in one out of 3 eggcells. In cases of anovulatory cycles and Stein-Leventhal-Syndrom, up to 16 eggcells could be obtained from both ovaries, most of them with signs of degeneration. 3. No differences in the number of eggcells and the number of degenerated oocytes could be found during the different phases of the menstrual cycle. The degeneration of the oocytes can begin at any phase of the cycle. Even in the follicles of the preovulatory phase measuring more then 1 cm in diameter eggcells with signs of degeneration could be found.


[Hydroxyproline concentration in normal and pathologic altered placentae of the second part of pregnancy (author's transl)]. By using microanalytic Hydroxyproline (HP)-determination method (Woessner and Stegemann) the content of collagen in 50 normal and pathologicaltered placentae of the second part of pregnancy was measured. A positive linear correlation is demonstrated between HP-concentration and age of pregnancy in normal placentae. Most of the pathologic altered placentae have a lower content of collagen. HP-content measured in main stem and terminal villi of further 35 placentae showed the essential influence of the main stem villi on total placental collagen concentration. In the second part of gestation the HP-concentrations of the main stem villi rise on a factor about 5-6, in the terminal villi they remain constant. The values measured within both groups of villi show a great dispersion. The quantitative results were compared with the histology of the placentae.


[Electron microscopical investigations on the so-called reserve cells in the cylindrical epithelium of the human cervix uteri (author's transl)]. By electron microscopical investigations on the cylindrical epithelium of the human cervix uteri there can be shown that the regeneration of the endocervical epithelium takes place from bipotent reserve cells, which are of fetal origin, lying in the basal layer of the epithelium. These cells are able for mitosis even in postnatal life. The reserve cells differentiate if necessary to squamous cells or secretory cells by forming typical cell organelles. There is a discussion about the question whether the reserve cells are persisting elements from fetal life or whether the numeral balance of the endocervical epithelium is kept by permanent mitosis.


[Immunochemical investigations on the protein of the "pregnancy zone". X. Demonstration of immunosuppressive activities of the pregnancy-associated alpha2-glycoprotein (pregnancy zone protein) by means of the macrophage electrophoretic mobility test (author's transl)]. By means of the macrophage electrophoretic mobility (MEM) test the supposed immunosuppressive activity of the pregnancy-associated alpha2-glycoprotein (pregnancy zone protein) could be demonstrated significantly. Pregnancy sera and sera of nonpregnant women with hormonal contraception containing this pregnancy protein showed an immunosuppresive activity, too. On the contrary, serum of male donors with the blood group AB and human serum albumin had no inhibitory effects. The results suggest that the pregnancy-associated alpha2-glycoprotein rather influences the afferent limb of the immune response and does not interfere with the activity of the mediator (migration inhibiting factor).


[Studies on placental blood flow under drug induced hypertension (animal experiments) (author's transl)]. Placental blood-flow rates in rabbits were measured by the indirect method of local apparent conductivity. In our experiments, hypertension was produced by injection or infusion of hypertensive drugs. As a result of hypertension we observed a marked decrease in placental blood flow. Vasoconstriction seems to be the pathophysiologic mechanism causing the reduced blood flow rate. Accordingly, the placenta may not be considered as a "priviledged organ" in circulatory regulations. In our experiments, placental ischemia subsequently to ligatures did not produce hypertension so that the production of a placental pressor-substance could not be demonstrated. If we assume a circulus vitiosus hypertension-placental ischemia-hypertension, the hypertension seems to be the primary cause.


[Contribution to the determination of thallium in human head hair in forensic cases with flameless atomic absorption spectrometry]. Among various procedures for the determination of thallium as a toxic element, micro-techniques by means of flameless AAS play an important role in hair analysis. Referring to two cases of T1-intoxication laboratory procedures, techniques and instrumentation are reported, which prove to be useful, sensitive, and fast. Considerations concerning sample preparation, contamination problems and compensation of spectral background effects by a duochannel spectrophotometer are discussed.


Experimental drug intoxication: treatment with charcoal haemoperfusion. Dogs were given large doses of barbiturates, glutethimide, ethanol, methaqualone, ethchlorvynol, meprobamate, chloral hydrate, paracetamol and aspirin. These were treated by haemoperfusion using a column packed with charcoal coated with an acrylic hydrogel. Clearances for most drugs were significantly higher than those reported for haemodialysis. Minimal clearances of common biochemical entities were observed and although leucocyte and platelet counts were diminished, no deleterious effects attributable to this were encountered. Careful histological examination of tissues derived from perfused dogs revealed no evidence of charcoal emboli.


Studies with activated charcoal in the treatment of drug overdosage using the pig as an animal model. Pigs were given large oral doses of paracetamol, amylobarbitone and amitriptyline. The effect of administering activated charcoal at varying intervals after dosing on the blood drug-level profiles of paracetamol and amylobarbitone was assessed by comparison with the profiles obtained when charcoal therapy was withheld. An appreciable effect on paracetamol absorption was demonstrated when charcoal was given up to 1 h after dosing. The amylobarbitone-dosed pigs exhibited delayed gastro-intestinal absorption of drug and this was substantially reduced by activated charcoal given 4 hrs after dosing. The pigs metabolised amitriptyline at too high a rate for meaningful studies to be undertaken with this drug.


[Detection and determination of parathion and p-nitrophenol in biological material by reverse-phase-high-power-liquid chromatography (author's transl)]. In 2 persons (female and male) who committed suicide reverse-phase-high-power-liquid chromatography (HPLC) was used to detect, in the first case, Parathion in the stomach and blood as well as p-Nitrophenol in the kidneys, and in the second case, p-Nitrophenol in the urine. The Parathion in the stomach was analyzed in quantity, directly and also after hydrolysis to p-Nitrophenol. The results were checked with gas-chromatographic and spectralphotometric methods.


Biliary excretion of 7Be and its distribution after intravenous administration of 7BeCl2 in rats. Wistar female rats were given two i.v. doses of 7BeCl2 (dose A = 0.025 mg Be2+/kg b.w.; dose B = 0.25 mg Be2+/kg b.w.). The rats were decapitated at 5, 24, and 48 hrs after administration. The kinetics of 7Be bile excretion during the 5 hrs after administration, as well as 7Be retention in selected organs and the urine and stool excretion of beryllium were investigated. Significant differences between the effect of both doses were found particularly in the shape of biliary excretion curves of 7Be. Unproportionally higher 7Be blood levels after a higher dose persisted for a longer period of time. The decrease of 7Be in blood after a higher dose between the 5th and 24th hr after the administration was accompanied by an increased content of 7Be in the liver and spleen as well as by an increased urine excretion. The results obtained tend to prove that the reticuloendothelial system mainly participated in beryllium retention. Urine represents the main excretion route of beryllium after a parenteral administration.


Heredity of hexobarbital sleeping time and efficiency of drug metabolism in Wistar and Sprague-Dawley rats. Nature of considerable variability of hexobarbital sleeping time and drug metabolism efficiency within a single strain of rats were investigated. Wistar or Sprague-Dawley rats with shorter than average hexobarbital sleeping time had also higher rates of in vitro hepatic microsomal metabolism of hexobarbital, aminopyrine, aniline and benzene, higher liver weight, microsomal protein content and P-450 level, and faster hexobarbital blood level decline (but similar volumes of distribution) after intraperitoneal hexobarbital sodium than those with relatively longer hexobarbital sleeping time, but awakened with the same hexobarbital blood level. The differences were maintained throughout the life of rats and inherited in their offspring. It indicated a possible genetic control of hexobarbital sleeping time and efficiency of drug metabolisms with apparent differences in selection response for Type I and Type II substrates (hexobarbital and aminopyrine vs aniline): it might indicate different heredity mechanism for these types of substrates. Stronger hexobarbital narcotic effect in females was associated with the rate of hexobarbital metabolism, but also with higher brain sensitivity. Hexobarbital sleeping time pattern indicated more general pattern of drug metabolism (better for Type I substrates) and success of selection of rats for different efficiency of drug metabolism (up to 8-fold differences in F5 generation) suggested considerable genetic non-homogeneity of two common strains of laboratory rats.


Two unusual barbiturate deaths.

Two unusual barbiturate deaths. The case histories and toxicological examination of two unusual fatal barbiturate poisonings are presented. One case involved the suicidal ingestion of a veterinarian euthanasia preparation containing pentobarbital which resulted in extremely high concentrations of the drug in the blood and liver. The second case involved the suicidal ingestion of vinbarbital, a drug no longer available on the american pharmaceutical market. The case exemplifies the necessity for definitive and analytical procedures for the identification of drugs in biological samples. Identification of pentobarbital and vinbarbital was by infrared spectrophotometry and thin layer chromatography. Quantitation of these drugs was by ultraviolet spectrophotometry.


The pattern of meniscus damage in the rheumatoid arthritis. Forty-seven knees with rheumatoid arthritis were synovectomized. The changes at the cartilage surface were always more grave when seen at the operation as was expected from the conventional X-rays. On the other hand degenerative changes of the menisci were more advanced than those in the cartilages. An important destructive factor was the almost constant pannus-filled erosion found at the upper corner of the tibia under the menisci. Thus, it is indicated to remove the menisci if they show a slightest degree of destruction.


The presence of alkaline phosphatase in the subchondral bone of the medial tibial condyle in the normal state and in osteoarthritis and rheumatoid arthritis. A study has been carried out on the alkaline phosphatase activity in trabecular bone in the normal state, rheumatoid arthritis and osteoarthritis. Samples were taken from the subchondral bone of the medial tibial condyle in all cases. The reason for this study was to investigate whether changes in rheumatoid bone like trabecular microfractures and healing reactions were parallelled by a mineralization process which could be demonstrated by an increased alkaline phosphatase activity and compared to that in osteoarthritic and normal bone. This investigation disclosed that the alkaline phosphatase activity in rheumatoid bone did not differ much from either osteoarthritis or normal bone.


In vitro morphological study of cochlear epithelium. 1. The mammalian cochlear epithelium was successfully kept alive in long-term tissue cultures. The Na and K concentration of the culture medium was similar to that of perilymph. 2. The most vulnerable cells in the culture epithelium were the outer and inner hair cells followed by the inner zones cells and the interdental cells of the spiral limbus. The difference in disintegration time between the outer and inner hair cells was about 48 hrs under the same culture conditions. The same phenomenon was noted between the rows of outer hair cells. 3. When the outer hair cells were not supported by Deiters' cells or when the cochlear epithelium was separated between Deiters' cells and Hensens cells, the outer hair cells degenerated quickly. 4. The interdental cells appeared to be relatively highly differentiated and showed much activity. No evidence of secretory function of interdental cells could be obtained. 5. The inner sulcus cells, Hensens cells, Claudius' cells and Reissners membrane cells were flattened and arranged like covering epithelium.


[Measurement of sound transmitted through the body while drilling and grinding isolated petrous temporal bone (author's transl)]. Measurements of the effect of rotating drills and grinders on isolated fresh temporal bone on the sound transmitted through the body have not previously been made known. In contrast to measurement of air-conducted sound, they include the portion of sound which effects the hearing apparatus of the patient through the bone during the process of drilling the temporal bobe. Measurements were made with a calibrated acceleration pick-up in conjunction with a precision sound level meter (test amplifier with sound frequency analyser). The recording was made continuously between 20 Hz and 20 000 Hz. The range between 250 Hz and 8000 Hz was examined mathematically. Above 8000 Hz the curves dropped markedly, apart from a few exceptions. The level of the sound depends largely on the size of the drill bit, and consequently on the breadth and depth of the rotating cutting edges. The smaller drill heads produce a considerably smaller quantity of sound. The highest level of sound comes from the burrs and wing-cutters. The diamond head lies lower in the scale, but almost equals the effect of the steel drills. The speed of rotation of the drill head plays only a subordinate role. Between 16 000 and 80 000 r.p.m. the values are the same. In the region of 10 000 r.p.m. the sound level is frequently reduced, even if a few loud peaks may still occur here. The type of drilling machine, the handpiece or transmission handpiece used have no effect. Altogether, the rotary drill produces less sound transmitted to the inner ear through the body than through the air.


[Ultrahistochemical demonstration of glucose-6-phosphatase in hair cells of the guinea pig organ of corti (author's transl)]. This study is concerned with the ultrahistochemical demonstration of glucose-6-phosphatase activity and its localization in inner and outer hair cells of the guinea pig organ of Corti. The enzyme activity has been demonstrated by a method according to Hugon et al. (1970). In hair cells of the organ of Corti a characteristic distribution pattern of reaction products has been registered. Subsurface cisterns and the Hensen's bodies of outer hair cells were heavily loaded with reaction products. In addition, the endoplasmic reticulum and the nuclear membrane as well as postsynaptic cisterns were rich in precipitates. With regard to their morphologic pecularities the inner hair cells show a more homogeneous distribution of enzyme activity. The findings corroborate the former assumption of a genetic relationship of either subsurface cisterns and Hensen's body to the endoplasmic reticulum of outer hair cells. Furthermore, the high glucose-6-phosphatase activity of both subsurface cisterns and Hensen's bodies are considered indicative of their participitation in the energy metabolism of outer hair cells. Referring to biochemical studies of Thalmann and associates (1973), the narrow spatial relationship of glucose-6-phosphatase positive ER membranes to mitochondria presumably represents a morphologic correlation of aerobic and anaerobic metabolic pathways in the guinea pig organ of Corti.


A study of neurone activity in the spiral ganglion of the cat's basal turn. A small region of the spiral ganglion in the cat was surgically exposed through the round window. Metal microelectrodes were used to record extracellularly the electrical activity of single spiral ganglion cells. The response characteristics of the cells seemed to be, in general, similar to those seen for auditory-nerve fibres recorded with micropipets in the internal auditory meatus. Data are presented on spontaneous activity, tuning curves, responses to clicks, continuous tones, tone bursts and noise bursts. The relation between frequency selectivity of units and location along the basilar membrane is discussed. -Some units differed in behaviour from auditory-nerve fibres with respect to dead times in interspike-interval histograms and shapes of poststimulus-time histograms of responses to tone bursts and noise bursts. The significance of these deviations is unknown.


[The influence on sound damages by an extract of ginkgo biloba (author's transl)]. A fraction of Ginkgo biloba, used in experiments with animals ensured significantly the diminution of sound damages caused by white noise or by a pure tone of 4.5 kHz. Higher amplitudes of the acoustic nerve potentials show the protective effect of this fraction of Ginkgo biloba at acute sound damages. It is moreover possible to hold physiologically the adaptation of excitation of the hair cells of the organ of Corti by the fraction of Ginkgo biloba before and after sound damage caused by white noise or during a pure tone of 4.5 kHz. The influence of the fraction of Ginkgo biloba can be seen by a significantly slower recovery of the noise damaged evoked potentials of the acoustic cortex. An efferent protective influence on the neurons of the acoustic cortex is discussed. The fraction of Ginkgo biloba in this form of solution has not been tested for clinical use but it seems to be rich in meaning.


[The minimal freezing temperature for a necrosis of the epidermis and the influence of cryoprotective agents (author's transl)]. The sensitiveness to cold of the epidermis (cold threshold) is determined on the auricular skin of 24 rabbits, using freezing temperatures of -10, -15, -20, -25, -30, and -40 degrees C and a freezing time of 30 sec. The experiments are performed with and without application of cryoprotective agents (DMSO, glycerol and aethanol in a 10% solution) before cryosurgery. Only at -20 degrees C a necrosis of the epidermis is seen whereas after application of cryoprotective agents before freezing a necrosis of the epidermis first appears at -30 degrees C. Following these experiments clinically it might be possible to protect the epidermis in the periphery of the freezing area up to a certain degree with the use of cryoprotective agents, so that a topographically more concentrated epidermis-necrosis and therefore a limitation of the cryoeffect to the epidermis to a certain degree could be possible.


Evaluation of total pharyngolaryngectomy for hypopharyngeal cancer. In 37 patients with hypopharyngeal cancer treated by total pharyngolaryngectomy and radical neck dissection, the 5 year cure rate was 30%. Among these patients, T-1 and T-2 tumors had a 57% and 47% 5 year cure rate respectively. Better results were obtained in those patients with tumor of the posterior pharyngeal wall and tumor of sinus pyriformis extending toward postcricoid region or toward the larynx. In 14 patients treated with various approaches of partial pharyngolaryngectomy, the 5 year cure was 53%. It is concluded that the conservation surgery is the operation of choice for the tumors of T-1 and T-2 in securing the total cure and preserving the laryngeal function.


Fetal lung and kidney maturation in abnormal pregnancies. A variety of gestational factors have been reported to increase or decrease the incidence of hyaline membrane disease in newborn infants. The purpose of the current study was to determine if some of these factors influence the rate at which fetal lung structures mature. Histologic measures of lung maturation were retarded in some infants with Rh erythroblastosis and in some whose mothers had diabetes mellitus. By contrast, such maturation was accelerated in offspring of some toxemic gestations and in those whose membranes had ruptured before the onset of labor. Congenital bacterial pneumonia with intact membranes did not accelerate maturation. None of the factors that altered lung maturity influenced renal maturation.


[Quantitative determination of cyclophosphamide, ifosfamide, and trofosfamide and their stable metabolites on TLC-plates with the aid of 4-pyridine-aldehyde-2-benzothiazolyl-hydrazone (PBH) (author's transl)]. Cyclophosphamide, ifosfamide, and trofosfamide can be analysed quantitatively together with their stable alkylating urine metabolites on TL-plates by means of the PBH-reagent (4-pyridine-aldehyde-2-benzothiazolyl-hydrazone). The method requires only 0.01 ml urine, but a careful standardisation is necessary by using reference substances. The minimum measurable amounts are between 0.25 and 0.5 mug. In the urines of rat and man the carboxy derivatives and the dechloroethyl derivatives, respectively, resulting from side chain oxidation, are predominant next to cyclophosphamide, ifosfamide, or trofosfamide, respectively. Side chain oxidation can be prevalent, as we have found in some patients treated with ifosfamide. The method described allows not only the calculation of time functions for the excretion of PBH-reactive substances but also in vitro investigations of the chemokinetic properties of cyclophosphamide derivatives under physiological conditions.


[Antimicrobial action of potential isothiocyanate forming substances 7th communication (author's transl)]. A number of (N-aryl-dithiocarbamino)-alkanecarbonic acids bearing halogen substituents and related compounds are described which may be considered potential isothicyanate forming substances. The in vitro fungistatic activity of these compounds was investigated and the results obtained compared with those of captan and thiram. It was demonstrated that the halogen substituted (N-aryl)-dithiocarbamino)-alkanecarbonic acids exert an intensive fungistatic effect with a wide spectrum of activity and that the most active of them are equal to captan and thiram.


[Relations between the physico-chemical properties, the chemical reactivity and the local-anesthetic activity/part 33: studies on the interactions of local-anesthetically active cinchocaine homologues with phospholipids (author's transl)]. The general part consists of a review on nerve stimulus mechanism as well as the nerve structure and the function of nerve membrane as the site of action of local anesthetics. Furthermore a possibility of interaction between local anesthetics and the membrane components especially phospholipids is discussed. These phospholipids show interesting properties with respect to ions as well as local-anesthetics, which allow us to suppose that they are important participants in nervous stimulus transmission. In the experimental part two methods are described. The first deals with the measurement of electrical resistance as function of time at cephalin and cholesterin impregnated filter membrane in solutions of cinchocain homologues. An increase in the resistance with the increase in concentration of test substances was observed. The same was the effect of increasing chain length in alkoxy group where after butoxy derivative, a deformation of membrane was observed. In the second method the drug binding capacity of cephalin dispersed in aqueous medium was measured. Here, too, the increase in the binding capacity with the increase in alkoxy chain was observed. The large difference in free binding energy between two subsequent homologues is explained as the effect of increase in van der Waals' forces and hydrophobic interactions on one hand, and a change in colloidal form of cephalin dispersion on the other hand.


[MASCA-model of the biochemical-pharmacological drug research. Part 3: Structure-activity relationships and KANORA (author's transl)]. The KANORA (multivariate regression and correlation analysis) leads to a combination with the multivariate structure-activity analysis which encloses the time-, dose-response and biological screening analysis. Drug-receptor interactions can be considered in connection with structure-action relationship. The importance of the analysis of "nonsense"-correlations (by using the partial correlation) and the model II of regression analysis is demonstrated.


[Predictability of the activity of drug combinations--yes or no (author's transl)]. The following experiments were carried out on the question of the "predictability" of the effect of drug combinations. A methanol extract from Viscum album causes a rise in coronary perfusion in isolated and perfused (Langendorff's method) guinea pig hearts. Administration of a methanol extract from Crataegus oxyacantha results not only in a rise in coronary perfusion, but also in a positive inotropic effect. Combined application of the drugs leads to a pure addition of effects, which are therefore "predictable". Extracts from Rhamnus frangula, Rheum sinens. and Senna lead to a dose-dependent reduction in the gastro-intestinal passage time. Combining the three extracts results in a pure addition of the effects. An extract from Potentilla anserina, which when given alone lengthens the gastrointestinal passage time, antagonises the laxative effect of extracts from Rheum sinens., Rhamnus frangula and Senna. All the effects we tested in the area of the gastro-intestinal tract behaved in a purely additive way and were therefore "predictable". When given separately the ethereal oils menthol, oleum juniperi, borneol and eugenol as well as dehydrocholic acid-Na-salt and alpha-naphthyl acetic acid-Na-salt cause, in rats, a dose-dependent increase in bile flow. Combining two or three of these substances results in a pure addition of the effects. The effects of all the test substances were therefore "predictable". When given separately valepotriate, morphine, scopolamine, ajmalicine, rescinnamine, reserpinine and reserpine, as depressants of the central nervous system (CNS), lead to a dose-dependent lengthening of hexobarbital-induced sleeping time in mice. However, when combined, these substances lead to a lengthening of hexobarbital sleeping time which is well above what was to be expected following application of the single substances. So, it can happen that the combination of the two single doses which, when taken separately produce no effect, leads to a lengthening of hexobarbital-induced sleeping time by more than 100 percent. In the case of CNS depressants, it is therefore true to say that their effect, when given in combination, was "unpredictable". It can be seen from these findings that, at least in the case of the tested extracts and single substances, which are all of plant origin, the "predictability" of the effect of the test substances in combination is the rule, and the "unpredictability" the exception. In addition the investigations may give further information concerning the methods as to how the question of "predictability" can be studied experimentally.


[Radiochromatography studies on the metabolism of 3H-cyclophosphamide in sheep]. Radiochromatic analyses were made in serum and urine sample fractions as well as in extracts of different organs of a ewe and a ram up to 5 and 14 days, resp., after a single oral dose of 30 mg 3H-cyclophosphamide/kg bodyweight. In a polar and an unpolar system cyclophosphamide (CPM) and up to 7 more hydrophilic and up to 5 more lipophilic metabolites could be characterized by their typical Rf-values. The following results were obtained: 1. At the maximum (1 h p.a.) CPM only showed 25 percent of the total serum concentration and a very short half-life (t 1/2) in the fall of concentration of about 1 h. It was to be analysed up to 48 h. The intensive metabolism was confirmed by a low renal excretion of about 1 percent of the dose. The lipophilic metabolites showed very low concentrations in serum except of 4-keto-CPM, which was analysed over a limited time with higher concentrations but a short half-life; 3 and 8 percent, resp., of dose were excreted in form of this metabolite with urine. 2. 1 or 2, resp., more hydrophilic metabolites with alkylating activity are the chief breakdown products of CPM in sheep. Their part of the total serum concentration falls from 50 percent at the maximum to 25 percent after 24 h. 40 percent of the oral dose were eliminated with urine in form of these metabolites. NH-mustard was found in very low concentration in serum and urine. The course of concentration of these alkylating substances (t 1/2 2 h) corresponds very well with the concentration of the total alkylating activity (NBP-test). 3 mainly hydrophilic metabolites were analysed in all serum and urine samples. 3. More than 90 percent of the residual concentrations found in the organs and tissues after killing the animals were due to alkylating reactions with biologically active metabolites. The analysed more lipophilic breakdown products in the extracts of organs seem to be metabolized to inactive, more hydrophilic substances. CPM was found in smallest concentrations (mug/kg) only in lungs and thymus of the ewe and in kidneys and muscle of the ram. The alkylating main metabolite was questionably analysed only in liver and lung of the ewe. The alkylating reactions reach their maximum at about 2 h p.a. and may be terminated by 48 h p.a.


[The effects of elevated calcium concentrations in artificial cerebrospinal fluid on pial arteries during perivascular microperfusion and the Ca++-antagonistic effect of bencyclane (author's transl)]. The influence of artificial cerebrospinal fluid (CSF) containing 6, 9 and 18 mEq/l Ca++, respectively, on 145 pial arteries of nine anesthetized cats was investigated by the perivascular microperfusion technique. The higher the concentration of Ca++ in the perivascular space and the longer these high Ca++ concentrations acted on the vascular wall, the more pronounced were the constrictions of the arteries. If N-[3-(1-benzyl-cycloheptyloxy)-propyl]-N,N-dimethyl-amine (bencyclane-hydrogenfumarate, Fludilat) (10 mg/100 ml) was added to the CSF, dilatations occurred, even if the concentrations of Ca++ were higher than in normal CSF (3 meq/l). The degree of dilatation, however, was dependent on the Ca++ concentration in the CSF. With high Ca++ in the CSF the dilatatory action of bencyclane was inhibited when K+ and H+ in the CSF were kept constant. The reaction can be described as Ca++ antagonism, the possible mechanisms of which are discussed.


[Coronary-angiographic demonstration of the dilating effect of dipyridamole on coronary arteries and its inhibition by caffeine (author's transl)]. Selective coronary cineangiographies are performed repeatedly in 13 mongrel dogs. The contrast medium itself has no demonstrable dilating effect upon the vessels. After the first injection of 0.2 mg/kg of dipyridamole the left anterior coronary artery is significantly (p less than 0.001) dilated, which is in contrast to some results described in literature. Immediately after an injection of high doses of caffeine (10 mg/kg) the previously enlarged coronary diameter decreases significantly (p less than 0.001). During the action of caffeine subsequent infections of dipyridamole result in a very small, or no change in coronary diameter. The coronary-dilating effect of dipyridamole can be inhibited by high doses of caffeine (10 mg/kg).


[Relationships between structure and the noradrenaline depleting effects of guanidine and amidine derivatives (author's transl)]. In guinea pigs we studied the noradrenaline (NA) depletion in the sympathetic nerve terminals of the heart exerted by 24 derivatives of guanidine and amidine; the effects of these substances being considerably similar in their chemical structure were compared to those of reserpine, guanethidine, guanoxan and cyclazenin. Substitution of the free guanidine group to give an imidazoline or imidazolidine ring diminished the activity of the compounds. If the benzodioxane ring of guanoxan was "opened" to give a diether of catechol, the activity of the substances was not altered. We also observed a NA depletion after injection of some guanidine derivatives substituted with piperazine. The elongation of the aliphatic chain between guanidine and the aromatic substituent considerably decreased the activity of the compounds.


Anticonvulsive properties of cinnarizine and flunarizine in rats and mice. The anticonvulsive properties of orally administered cinnarizine [(E)-1-(diphenylmethyl)-4-(3-phenyl-2-propenyl)-piperazine], its difluoro derivative flunarizine [(E)-1-(bis-(4-fluorophenyl)methyl)-4-(3-phenyl-2-propenyl)-piperazine], diphenylhydantoin and phenobarbital, were studied against maximal metrazol seizures (MMS) in rats and maximal electroshock seizures (MES) in mice. In rats (MMS), the lowest ED50 for protection against tonic extension of hindpaws was 4.10 mg/kg (1 h 35 min after treatment) with sodium phenobarbital, 6.04 mg/kg (5 h 45 min) with flunarizine dihydrochloride, 9.84 mg/kg (2 h 34 min) with cinnarizine and 19.30 mg/kg (3 h 38 min) with diphenylhydantoin. In mice (MES), protection against tonic extension of hindpaws was (2 h after treatment) 7.0 mg/kg with diphenylhydantoin, 13.2 mg/kg with sodium phenobarbital, 20.9 mg/kg with flunarizine kihydrochloride and 49.0 mg/kg with cinnarizine. Except at subtoxic doses no side effects were observed in rats and mice given cinnarizine, flunarizine kihydrochloride or kiphenylhydantoin. Phenobarbital induced ataxia in rats and mice at 22 mg/kg and 42.7 mg/kg, respectively, and loss of righting reflex at 112.8 mg/kg and 160 mg/kg, respectively. Flunarizine is the longest-acting drug and has the slowest onset. At a dose of twice the minimal ED50 flunarizine affords protection against tonic extension of hindpaws in rats (MMS) for 23 h 30 min dephenylhydantoin for 11 h 38 min, phenobarbital for 8 h 22 min and cinnarizine for 8 h 16 min. Peak effect was reached with flunarizine at 5 h 45 min, with diphenylhydantoin at 3 h 38 min, with cinnarizine at 2 h 34 min and with phenobarbital at 1 h 35 min. The anti-MMS profiles of cinnarizine and flunarizine resemble that of dephenylhydantoin as all three compounds are selective blockers of tonic extension of hindpaws. Phenobarbital antagonized the whole MMS-pattern, i.e., tremors, clonic convulsions and tonic extension of fore- and hindpaws. However, the effects of phenobarbital against tremors, clonic convulsions and tonic extension of forepaws may reflect more a general CNS-depressant effect than a specific anticonvulsive activity since neurotoxic effects (ataxia and loss of righting reflex) appear at the same doses.


[Studies on the pharmacokinetics of hexobendine in rats. I. Distribution following i.v. administration (author's transl)]. The distribution of 14C-labelled N,N'-dimethyl-N,N'-bis-[3-(3',4',5'-trimethoxy-benzoxy)-propyl]-ethylenediamine-hydrochloride (hexobendine, Ustimon, Reoxyl) in the organs of rats was studied after i.v. injections of 0.5 mg/kg. Up to the 81st min 70-90 percent of the 14C-activity in the lung, heart, skeletal muscle, spleen and brain were formed by unchanged hexobendine, identified by thin-layer chromatography in tissue extracts. In the kidneys and erythrocytes less than 70 percent, in serum and liver less than 50 percent of the measured radioactivity consisted of hexobendine. The serum concentration of hexobendine was 0.1 mug/ml 3 min after administration. This concentration declined with a half-life of 7 min distribution and a half-life of 45 min for elimination. In certain organs the hexobendine concentration rose above the serum level: After 3 min the tissue/serum ratio in the lung was 69, in the kidneys 20, in the heart 7, in the spleen 5, in the liver and skeletal muscle 4, in the erythrocytes 1.2 and in the brain 0.7. The time-dependent decrease in hexobendine concentrations in the various organs was only slightly slower than that in the serum. Only 1 percent of the infected 14C could be detected in the analysed material 12 h after hexobendine administration.


Effects of different drugs on the urinary excretion of nifurpipone (NP) and of nitrofurantoin (NTF) in the rat. A study was made on possible interferences of several drugs on the urinary excretion of nifurpipone and of nitrofurantoin orally administered to rats. Phenobarbital, a microsomial enzyme inducer, SKF 525 A, a microsomial enzyme inhibitor, probenecid, an inhibitor of the tubular acid secretory system, quanine, an inhibitor of the tubular alkaline secretory system, and hydrochlorothiazide, a diuretic, were studied. None of these treatments altered in an important way the urinary excretion of nifurpipone or of nitrofurantoin.


Effects of "essential" phospholipids (EPL) on experimental ethanol-induced cardiomyopathy. 15 percent ethanol alone and together with "essential" phospholipids (EPL) was applied orally (as the only source of drinking fluid) ad libitum to white rats over 8 months. The evaluation of effects of EPL was based on biochemical assays of the blood serum, including creatine phosphokinase (CPK), a-hydroxybutyrate dehydrogenase (HBD) and free fatty acids (FFA) as well as on histological and histochemical studies of lactic dehydrogenase (LDH) of the heart muscle. In rats treated with ethanol alone we found increased CPK and HBD activities, elevation of FFA and lowered activity of LDH. EPL seem to protect against the above mentioned changes.


[Phalloidin antagonists/3rd communication: effects of antamanide derivatives in isolated perfused rat livers (author's transl)]. The protective effects of antamanide, O-carboxy-methyl-Tyr5-antamanide and of Tyr6-antamanide-monosulfate against phalloidin were tested in perfused rat livers. None of the applied doses was able to inhibit swelling and potassium loss of poisoned livers completely. In the perfused liver antamanide preferentially inhibited swelling but not potassium loss. O-Carboxymethyl-Tyr5-antamanide protected isolated hepatocytes against phalloidin. The different effects of antamanide derivatives in perfused livers and in vivo are discussed.


Studies of biosynthesis of insulin by isolated perfused rat pancreas. Incorporation studies with 3H-leucine have demonstrated that proinsulin is formed as a precursor of insulin in the perfused pancreas. A dependency of the insulin synthesis on the glucose concentration was revealed, based on a direct stimulation of the proinsulin synthesis. The conversion of proinsulin into insulin was not accelerated by glucose stimulation. The conversion also occurred in the absence of glucose.


[On the method of injecting into the yolk-sac in teratological studies in rabbits (author's transl)]. A method is described by which the embryotoxic and teratogenic effects of substances can be examined through their application into the yolk-sac. On the ninth day of gestation rabbits (white New Zealand) were laparatomised and the uterus bicornis together with the blastoderms were treated in 3 different experiments. The results show that after application of physiological saline into the yolk-sac the high rate of malformations and resorptions are caused mainly by an avoidable venous obstruction and by postoperative inflammations and infections.


Dose size and dosing interval determination. Knowing the necessary minimum inhibitory or minimum effective concentration of a drug dose size and/or dosing interval for multiple dose therapy can be calculated under the assumption that the blood level-time curve of a drug can be described by an open one-compartment or an open two-compartment model, that the drug does not show dose dependent pharmacokinetics for the therapeutic dose range and that the distribution coefficient is applicable for a wide body weight range and age group, excluding severe edemas and obesity. The dose size and dosing interval equations are derived from the minimum blood-level concentration c'min equation in multiple dosing. Substituting c'min by MIC or MEC, cop by D - f/Vd and Vd by delta' - BW either the required dose size or dosing interval can be calculated. In the case of renal failure adjustment can be made by inclusion of a correction factor into the equations using either the observed creatinine clearance or the serum creatinine value.


[Studies on metabolism and pharmacokinetics of alpha-acetyldigitoxin in man (author's transl)]. 3H-alpha-Acetyl-digitoxin was administered to 5 patients i.v. and 3 patients p.o. The half-life of label in the plasma was 8.5 +/- 1 (i.v.) and 8.8 +/- 1 (p.o.) days. 20.9 +/- 3.6% (i.v.) and 21.3 +/- 2.9% (p.o.) of the radioactive dose were excreted into the urine in 6 days. Two patients excreted within 18 days 14.3 and 16.1% of the given dose with the stool. After oral administration 22.3% of the orally administered 3H-activity were eliminated into the feces by one patient. 63% (i.v.) and 53% (p.o.) of the chlorofrom-extracted 3H-activity in the urine could be attributed to digitoxin by means of thin-layer chromatography. The volatile content of plasma radioactivity was 4.07 +/- 0.1% (i.v.) and 6.78 +/- 0.2% (p.o.). The protein binding of a 4%. Albumin solution was 83 +/- 0.54%, for plasma 80.8 +/- 2%.


[Physical factors in animal experiments for testing antimasspsychotic drugs]. Lemmingson et al. have observed that the movement of masspsychotic lemmings (Lemmus lemmus) shows a distinct preference for the left direction. They suggested that this is due to the influence of the Coriolis force. According to this proposition the influence of the Coriolis force on a group of masspsychotic animals has been investigated quantitatively. The results suggest the following model: Normally the influence of the Coriolos force, which on the northern hemisphere acts to the right, is compensated by a neuromuscular feedback mechanism. The tendency towards the left under masspsychotic conditions corresponds to overcompensation. The tendency to the left should also be observed on the southern hemisphere, if the direction of this compensation is determined genetically. Therefore, the test proposed by Lemmingson et al. is not suited to distinguish between the influence of the Coriolis force and the influence of biologically active left-isomer molecules.


Accidental subarachnoid injection of gallamine. A case report. Accidental subarachnoid injection of gallamine and its management is reported. Methods of identification of the drug in the c.s.f. are described. Early treatment should be initiated, since the drug was still identifiable in the c.s.f. after 90 min. Removal of the c.s.f. and sedation may have prevented a fatal outcome in our patient.


Treatment of malignant meningitis in retinoblastoma. Six patients with meningitis due to retinoblastoma are described. The diagnosis may be suspected on clinical examination but is made by the demonstration of malignant cells in the CSF. These patients have been treated with cranial irradiation together with systemic and intrathecal cytotoxic drugs. There is one survivor. It is suggested that the CSF should be examined in all cases at risk so that the appropriate treatment can be started promptly and thus improve the prognosis.


Isolation of Chlamydia from women attending a clinic for sexually transmitted disease. Cervical swabs for Chlamydia culture were collected from 638 unselected women attending a sexually transmitted diseases clinic with a fresh complaint. Chlamydia were isolated from 76 (12 per cent.) of the women. When the results were related to the patients' diagnoses, Chlamydia were present in 44 per cent. of women with gonorrhoea and in 22 per cent. of women who were contacts of men with nonspecific urethritis (women who may be regarded as having non-specific genital infection). Chlamydia were uncommon in women with no evidence of genital infection. Significant correlations were found between the presence of Chlamydia and cervical erosion, cervical cytological inflammatory change, and absence of symptoms. Isolates were obtained more frequently from women with non-specific genital infection who were primary contacts than from women who were secondary contacts. These findings support the concept that Chlamydia are pathogens in the genital tract and are sexually transmitted.


Blood ethanol concentrations in patients attending special clinics in Glasgow. Blood samples for measurement of ethanol concentration were taken on a routine basis from 543 male and 158 female patients attending Special Clinics in Glasgow. Ethanol was detected in 56 (10-3 per cent.) of the men and eight (5-1 per cent.) of the women, and at concentrations in excess of 0-1 g./l. in 37 (6-8 per cent.) and three (1-9 per cent.) respectively. In nine men and one woman, the blood ethanol concentration was over 0-8 g./l. when they attended the clinic. The majority (84 per cent.) of positive findings were obtained in specimens collected after 2 p.m. and one-quarter on Tuesday afternoons, the local half-day. The other peak periods related to attendance at football matches on Wednesday evenings, and to receiving wages on Friday mornings. Male new patients attending a clinic for the first time had the highest incidence, 32 (11-6 per cent.) having detectable amounts of ethanol among whom 26 (9-4 per cent.) had levels in excess of 0-1 g./l., compared with only 4-1 per cent. among those either returning to the clinics with a fresh infection or on surveillance. Only 5 per cent. of female patients attending for the first time and 3 per cent. of those on surveillance had detectable amounts of ethanol in the blood, compared with 9 per cent. of those few returning with fresh infections. Levels in excess of 0-1 g./1. were only found in promiscuous women. Those with concentrations in excess of 0-8 g./1. were unreliable attenders. Only one, a known alcoholic, completed surveillance; one defaulted after his fourth visit, four after the second, and four after the first visit.


Antibody as carrier of 131I in cancer diagnosis and treatment. Cell-surface localizing heterologous antibodies against mouse EL4 lymphoma, Ehrlich ascites carcinoma, and several human malignant tumors could be bound to varying amounts of 131I without interfering with the reactivity of these antibodies with their respective tumor cells. Exposure of the mouse tumor cells to radio-iodinated antitumor antibodies in vitro, or the injection of radio-iodinated antitumor antibodies into mice preinoculated with tumor cells resulted in either partial or complete tumor inhibition depending upon the amount of 131I activity carried by the antibodies. Injection of comparable amounts of the immunoglobulin alone or of 131I bound to normal globulin did not cause any tumor inhibition. Intraperitoneally injected radio-iodinated anti-EL4 antibody was found to localize preferentially in the subcutaneous transplants of EL4 lymphoma. Similar localization of intravenously injected radio-iodinated antibodies was observed in the metastases of two cancer patients.


Dietary factors and esophageal cancer in the Caspian Littoral of Iran. A study was undertaken to attempt to relate the distribution of exogenous factors to the varying incidences of esophageal cancer in the Caspian Littoral of Iran. For the study, 38 villages were chosen by random sampling in 14 regions defined by their esophageal cancer incidence and environmental characteristics. Information was obtained on the dietary, social, and cultural features of each village. In addition, an extensive 5-day study of 6 randomly selected households in each of the 38 villages was conducted. The study consisted of measured dietary intake, a historical food consumption questionnaire, and clinical examinations of adult occupants. Preliminary results show no single factor responsible for the etiology of esophageal cancer. However, there were some major dietary differences between the regions of different esophageal cancer risk. Bread was the chief staple food in high-incidence areas; rice, in low-incidence areas. In high-incidence areas, there was a low intake of vitamins A and C, riboflavin, animal protein, and fresh vegetables and fruit, but a greater consumption of sheeps and goat's milk. Analyses of food samples for aflatoxins, polycylic aromatic hydrocarbons, and nitrosamines showed low levels of these carcinogens in areas of high and low incidences. The use of tobacco and alcohol was not found to be of significance.


[New serotype of Salmonella of sub-strain II isolated in Greece: Salmonella 3,10 : 1,z-28 : 1,5]. A new Salmonella serotype, of sub-genus II, Salmonella 3,10 : 1,z28 : 1.5, has been isolated in Greece from refrigerated minced meat imported from South America.


[Intestinal bilharziasis in Guadelupa].

[Intestinal bilharziasis in Guadelupa]. The author studies the significance of intestinal bilharziosis in Guadeloupe. Immunologic methods have been used because of their greater sensitivity: a complement fixation micromethod using a delipidated antigen is described. The study of about 8,500 sera taken in various areas showed the significance of bilharziosis: the mean level of positive sera was 35%, a figure much higher than those obtained with parasitologic methods. The percentage observed in the various regions showed sometimes very great differences, which may be explained by various factors, the most important ones being the population density, the disposition of the hydrographic network and its relationships with habitat. Such a study, if it could be carried out during the next years, should allow to appreciate the efficiency of the control measures of the endemia.


[Present-day aspects of leprosy in Martinique]. Altogether my observations agree with the facts reported by others authors. Two data however should be pointed out: -- in spite of the progresses for its demonstration, lepra remains frequent in La Martinique; -- with 47% lepromatous forms and 25% tuberculoid forms, lepra in the West Indies constitutes an intermediary level between African lepra (60% tuberculoid forms) and South-American lepra (60% lepromatous forms).


[Use of peroxidase markers in the research and diagnosis of paludism]. The indirect peroxidase labelled technic for the diagnosis and research in malaria rests on the same principle than immunofluorescence test (I. F.). Homologous or heterologous antigens are incubated with patient serum in the same conditions than for I. F., and then with peroxydase, labelled, conjugate diluted 1/200. The resulting complex is colored by the diaminobenzidine method of Graham and Karnovski. The coloration is observed in light microscopy. This technic as sensitive as immunofluorescence test can be done, with a cheaper microscopic material. The possibility of studying the conjugate fixation in electron microscopy opens new direction for research.


[Heminoglobinopathies of young adults migrating from the Antilles to the Metropolis (apropos of 1,000 cases of electrophoresis)]. The systematic research of abnormal haemoglobins has been done on 1,000 subjects of both sexes (mostly 18 to 35 years) from Guadeloupe (500) and Martinique (500), examined in Paris. The following were found without significent difference in both islands : 86,9% heterozygote AS, 4,5% heterozygote AC, 0,3% double heterozygote SC, one homozygote CC, 0,3% increase of the fraction A2 and one increase of haemoglobin F. Those results were comparable to the few anterior studies in French West Indies.


[Lipid constants in the young adult Senegalese]. The matter of the study is an investigation carried out in a healthy population, representative of every ethnies living in Senegal, population who was given a traditional, but improved senegalese feeding. This study completes and corroborates some previous proceedings carried out in Dakar about blood lipids in African people. We have noticed that since some fifteen years, neither the modifications in feeding, nor the economic and social progress, have yet a repercussion on lipemia and cholesterolemia in Senegal. Every analysed parameter is lower than those noticed in European population and the proposed lipidic constants will be used as basic date for further investigations.


[Histoenzymologic study of anticholinesterase activity of ciguatoxic extracts of Ceochetus striatus (Gunther) and Plectrompus leopardus]. The use of histo-enzymological techniques for visualizing the cholinesterasic spots on the motory plate is turned to account by the authors to point out the inhibition of the cholinesterasic processes, by some fractions of the ciguatoxins at the level of the neuro-mucular synapsis. The results obtained confirm, on one hand, the efficiency of the method to test the anti-cholinesterasic activity of some fractions of the ciguateric extracts, and, on the other hand, enable the establishment of the fact that even clinically non toxic individuals from fishspecies, dwelling in tropical coral biotops, can provoke a slightly marked but real inhibition of the cholinesterases, provided the contact between the fish extract and the neuro-motory plate is long enough in time. This observation reinforces the thesis of the ecological origin of the toxins along the alimentary chain of the reef biocoenosis.


Effect of continuous irradiation upon some biological properties of murine lymphosarcoma LS/BL. Mouse lymphosarcoma LS/BL cells passaged in syngeneic hosts were continuously irradiated with 60Co gamma rays at an exposure of 1R/hour. Long-term irradiation did not substantially alter the proliferative rate of leukaemic cells. Radiation exposure in the duration of 60 and 70 weeks led to an increase in the mean survival time of the hosts and in the generation time of the cells. When compared to the changes observed in the hosts of unirradiated leukaemic cells, the decrease in erythrocyte counts was greater during the first few days after inoculation of irradiated tumour cells, whereas the increase in leucocyte counts was slower.


[Clinical comments on poisoning caused by marine animals in the Marquesas]. Intoxications due to sea animals in the Marquesas seem to be relatively frequent in this archipelago. Fish consumption under rarely realized favorable conditions does not induce intoxications. Although statistics are hazardous in Polynesia, the phenomena seem to progress from East to West, and to be cyclic, with a regression phase at the end of 1973. Two complementary syndromes have been isolated: -- one is primary, neuro-sensory, and is prevalent in the case of toxic crustaceans, molluscs or echinoderms consumption. Hemorragic signs are sometimes observed in the case of consumption of fish provoking an unusual toxi-infection. The specificity of the toxic species has not been demonstrated. -- the other one is secondary and presents the characteristics of transistory myalgiae and the strange neuropathic picture of "la Contamine" of Ua-Pou.


Marker chromosome 14q+ in two non-Burkitt lymphomas. Marker chromosome 14q+, similar to the specific marker of the Burkitt lymphoma, was revealed in all malignant blood cells of a patient with generalized lymphosarcoma, in all lymph node cells, and in a part of the blood cells of a patient with chronic lymphocytic leukaemia. Possible causes of this similarity are discussed.


Reactions of proteins with ethyl vinyl sulfone. Ethly vinyl sulfone (EVS) alkylates xi-amino groups of lysine side chains and imidazole groups of histidine residues in proteins. Amino acid analysis of hydrolyzates of EVS-treated polylysine shows that lysine forms two derivatives, presumably xi-N-(ethylsulfonylethyl)lysine and xi, xi, N,N-bis(ethylsulfonylethyl)lysine that are eluted as well-resolved peaks on the (long basic) physiological column of our amino acid analyzer at about 118 and 60 min, respectively. Peaks with identical elution times were also observed after EVS-treatment of BSA and wool. The postulated histidine derivative, presumably N3-im-(ethylsulfonylethyl)histidine is also eluted as a well-resolved peak on the same column at about 90 min. A peak with an identical elution time was observed in a hydrolyzate of EVS-treated polyhistidine. The described alkylation has potential utility for modifying proteins.


Effect of maternal malnutrition on surface activity of fetal lungs in rats. The effects of maternal malnutrition on fetal lung growth and surface forces were studied in albino rats. Pregnant albino rats were subjected to one of the following diets: rat chow ad lib. (controls), partial food deprivation (intake one-half that of the controls), complete food deprivation for 4 days (on gestation day 3-7, 9-13, or 17-21), low protein (8%), and fat free. The fetal lungs were studied on the 21st day of gestation (delivered by cesarean section) or at birth (gestation day 22). Fetuses and neonates after maternal food deprivation (FD) on the 17-21 day of pregnancy, and after a low-protein (LP) diet during pregnancy, had significantly smaller body weight and lung wet or dry weight/body weight ratio (hypocellular lungs). The minimum surface tension (gamma min) of fetal lung extracts was significantly increased with FD and LP. This was associated with a reduction of about 35% in lung lecithin content, expressed per lung DNA. The earlier in pregnancy the rat was subjected to 4-day food deprivation the less the effect on the fetus. At birth the gamma min and the lung lecithin content reached control values. This recovery occurred after birth (at age 4-10 h) and prior to first feeding. However, the lungs remained small and hypocellular. The results indicate that the nutritional status of the pregnant rat influences the surface activity and the growth of the fetal lung.


The Food and Drug Administration and the vinyl chloride problem--an overview. Recent evidence has shown that chronic exposure to vinyl chloride by inhalation may cause cancer in laboratory animals and in man. Its possible oral effects are currently being investigated. The history of the significant events leading to the investigation of this chemical is presented. The current and future activities of the Food and Drug Administration in this area are also described.


Dosimetry of several DTPA radiopharmaceuticals in cisternography. Previously published biologic distribution and clearance data for 169Yb-DTPA in cisternography were utilized to obtain effective spinal segment clearance data for six other easily dhelated radionuclides: 99mTc, 113mIn, 111In, 67Ga, 51Cr, and 203Pb. Absorbed radiation doses to the spinal cord and nerve roots were calculated for each radioactive DTPA compound, employing appropriate cylindrical geometry and reduction coeffients for the dose contributions from the electrons of each radionuclide. Doses are maximal at the surface and decrease rapidly with distance from the surface. The relative useful photon flux from each DTPA radiopharmaceutical for approximately the same average absorbed radiation dose to the spinal cord was determined. The results indicate that 111In and 203Pb should be considered as possible radionuclide tags for DTPA cisternographic imaging.


The prediction of fetal lung maturity from the surface tension characteristics of amniotic fluid. In recent years fetal lung maturity has been assessed by chemical determination of lung surfactant components in the amniotic fluid. The variation in the results, however, limits the clinical usefulness of these methods. To establish reliable criteria for fetal lung maturity 98 specimens of amniotic fluid were obtained in the 23rd to 41st week of gestation and their surface properties measured in the surface balance (Fig 1). A continuous rise in surface activity of amniotic fluid was observed during this period (Fig. 2). In the evaluation of the surface activity of amniotic fluid y-min appears to be the most suitable parameter because it shows a considerable change during the course of pregnancy and has low variations (Fig. 3). In 64 prematures amniotic fluid was obtained during delivery and its surface properties measured. The correlation of clinical symptoms of the premature with y-min of the amniotic fluid makes it possible to predict the fetal lung maturity at a given y-min value (Fig. 4). When the results are arranged according to the incidence of RDS (lethal RDS, recovered from RDS and without RDS) three y-min-ranges can be clearly distinguished. When y-min of the amniotic fluid is over 27 dyn/cm the probability of lethal RDS is 100%, whereas when y-min is under 17 dyn/cm a mature lung can be expected. In the range between 27 to 17 dyn/cm any degree of lung maturity can be encountered. By division of this range in two additional ones a more accurate prediction of fetal lung maturity is possible: In the y-min-range 27-23 dyn/cm RDS-probability is approximately 70%, in the range 23-17 dyn/cm it is only 30% (Fig. 4). Measurements of surface activity of the amniotic fluid make it possible to predict fetal lung maturity and estimate RDS-probability.


Analysis of Duboisia myoporoides R. Br. and Duboisia leichhardtii F. Muell. Duboisia samples were analyzed for scopolamine and hyoscyamine using GLC, by a slope ratio method, and by methods employing homatropine, tetraphenylethylene, and phenylacetyltropine as internal standards. Limits of precision were determined by the inverse prediction method. Phenylacetyltropine was the preferred internal standard. The alkaloids were silanized with either hexamethyldisilazane or N,O-bis(trimethylsily)acetamide to prevent dehydration to the apo forms. Samples from a commercial bale of Duboisia myoporoides were assayed. The alkaloid content varied considerably, depending on the sample position within the bale.


[Renal localization of lymphosarcoma in the child (author's transl)]. Eight children with renal localization of a lymphosarcoma are presented. Intravenous pyelography is generally carried out in the systematic full check-up of a known case of lymphosarcoma, in order to determine the degree of extension of the disease and in order to adapt chemotherapy. The different radiological appearances are discussed. They more frequently lead to the diagnosis of more well known conditions when the diagnosis of lymphosarcoma has not yet been established.


Quantitative evaluation of autoradiographs by X-ray spectroscopy. Measurements of mass of developed silver in autoradiograms have been made using X-ray microanalysis. This procedure has been applied to a scanning electron microscopic study of protease-induced cell stimulation in 3H-thymidine-labelled bladder tissues in vitro. Differences in silver concentrations over individual nuclei were demonstrated by X-ray analysis and quantitative data was obtained showing an increased rate of 3H-thymidine incorporation in protease-treated cultures. The initial evidence indicates that X-ray microanalysis could provide a potentially useful quantitative procedure for autoradiography.


Adsorption of DNA molecules to different support films. Protein-free adsorption of the DNA of the Escherichia coli bacteriophage T7 to carbon, collodion, aluminium-beryllium and aluminium films was studied. It was found that the appearance of DNA strands depended greatly upon the kind of support film used. Direct adsorption of DNA to aluminium-beryllium or aluminium films yielded specimens with 'thin and long' and 'thick and short' regions along the strand. Well extended, uncoiled and unaggregated DNA molecules were obtained only when DNA was adsorbed to carbon, collodion or mica in the presence of intercalating dyes such as ethidium bromide. Adsorption properties of the different films are well correlated with their surface charge. Aluminium-beryllium films carry a strong positive surface charge, aluminium films a weak positive charge and carbon films a weak negative charge. It is suggested that for the preparation of specimens by spontaneous adsorption of well extended and unaggregated strands it is necessary that the DNA molecule is stiffened by a ligand such as an intercalating dye, and that the charge on the surface of the support film is opposite to the charge of the macromolecule.


The effects of hypobaric atmospheres on living cells in layers of thin media and implications for electron microscopy. At present, the only possibility for improved resolution of intracellular movement appears to be electron microscopy using a hydration chamber (EMC) at reduced gas pressures with thinned medium around the cells. The environmental constraints of examining cells under such conditions were examined in the absence of ionizing radiation by using an EMC-analogue fitted to a light microscope. White blood cells and baby hamster kidney cells were examined. A 50% survival pressure value, for hypobaric atmospheres, was determined for these cells. Morphological changes of the hypobarically-exposed cells are described.


A freeze-fracture replication apparatus for biological specimens. A freeze-fracture apparatus of original design has been constructed which can be fitted onto a standard vacuum evaporator unit. In it, cell suspensions and organized tissue may be processed by inserting a sample into a cylindrical holder. By leaving a small part of the tissue protruding from the holder, pre-selected and aligned portions of the specimen can subsequently be revealed by fracture under vacuum. After rapid freezing, the specimen remains firmly attached to the inner wall of the sample holder, preventing its possible loss during fracturing. A mechanism, in the form of a double-sided converging wedge, which is operated from outside the vacuum chamber, is used to produce a fracture in the specimen. The device gently induces a fracture in the desired part of the tissue and lifts the protruding part of the specimen out of the way. In this way, reasonably flat fracture faces are produced for subsequent replication. As the fracturing mechanism comes into contact only with the outer edges of the specimen, damage and contamination liable to occur when the entire specimen is traversed by a blade, is avoided. In addition the specimen stage is surrounded by a cold metal shroud which acts as an efficient trap for contaminants. In this way, favourable vacuum conditions are produced in the vicinity of the specimen. Such effective enclosing of the specimen also facilitates controlled sublimation of the sample.


A simple technique for examining frozen hydrated specimens in the scanning electron microscope. The use of a wide angle backscattered electron detector in a scanning electron microscope, which has the capability of the specimen chamber pressure being controlled independently of the column pressure, provides a simple technique for examining frozen hydrated specimens. Large specimens have been examined within 1 min of being placed on the stub and have been examined for many hours without charging artefacts or distortion due to dehydration.


Coating sections for electron microscopic autoradiography: a stripping technique using liquid emulsion. A coating technique for electron microscope autoradiography is described which combines the advantage of forming an emulsion film by a dipping method with the ease of coating sections already on grids. Sections are coated so that a formvar support film separates the section and the emulsion crystals. This intermediate layer of formvar ensures a random distribution of the emulsion crystals. Using light gold sections, Ilford L-4 emulsion and Microdol-X development, the resolution of this technique, as determined by the half distance method, was 150 nm. The additional layer of formvar slightly reduced the image quality with biological samples in the electron microscope. This technique has a minimal loss of resolution and image quality for moderate resolution electron microscope autoradiography.


Limitations of bone scanning in clinical oncology. Radioisotope bone scanning is frequently used as the major, and sometimes the only, diagnostic test for neoplasia in bone. While the evidence is convincing that bone scans are frequently more sensitive than roentgenographic bone surveys for detection of metastatic bone disease, there are false-negative results for a variety of reasons, and positive findings must be interpreted with caution. Scans also appear more limited than roentgenograms in their usefulness for evaluating changes in abnormal bone structure. Case histories and discussion are offered to indicate that usually both radioisotope bone scans and roentgenographic bone surveys should be obtained for initial screening and subsequent assessment of bone metastases.


Epilesional scarification. Preliminary report of a new approach to local immunotherapy with BCG. Because of the serious toxicity of intralesionally injected BCG, including high fever, local ulceration, chronic drainage, and disseminated BCG disease, 13 patients received local BCG immunotherapy by the new approach of epilesional scarification. Three patients had complete responses, four had partial responses, and six had no response. Toxic reactions were minimal compared to those reported for intralesionally given BCG.


Adverse drug reactions. A critical review. The data on adverse drug reactions (ADRs) are incomplete, unrepresentative, uncontrolled, and lacking in operational criteria for identifying ADRs. No quantitative conclusions can be drawn from the reported data in regard to morbidity, mortality, or the underlying causes of ADRs, and attempts to extrapolate the available data to the general population would be invalid and perhaps misleading. To evaluate the impact as well as the causes of ADRs, representative populations, including general hospital and ambulatory patients of all medical specialties, must be studied, and operationally defined criteria must be used to establish the presence of an ADR in a prospective study that incorporates appropriate control populations. Similar studies on the benefits of drug use are needed to provide perspective on the risk-benefit aspects of drug therapy. Until such studies are performed, estimates of the nature and scope of the ADR problem can be only guesses.


Presentation of atrial septal defect in infancy. Four patients with atrial septal defects and congestive heart failure in the first year of life had none of the classic auscultatory findings of atrial septal defect. Three of four had murmurs suggestive of innocent pulmonary-artery branch stenosis.


[Cycloplegia and residual accommodation (author's transl)]. The cycloplegic effect of 1% Atropine Sulphate, 2% Homatropine Hydrobromide and 1% Cyclopentholate (Cyclolat) were compared on 8 to 10 year-old children with hyperopic accommodation and partial accommodation squint. The objective refraction was measured by skiascopy and with Hartinger's refractometer, and these two values were compared. The distant-vision correction, and also the near-vision correction needed so that Table 2 of Pursch's Tables could be read, were measured. Atropine showed itself to be the most effective cycloplegic agent. With atropine cycloplegia was attained in 46.77% - shown by a necessary near-correction of +2 dioptres, or less. In 27.42% the correction was +1.5 dioptres. With homatropine a correction of +2 dioptres or less occurred in 82.14%, after Cyclogyl in 72.34%. Better cycloplegia could be reached, if before the test correcting spectacles are worn. Only with repeated refraction-tests to overcome accommodation spasm could one succeed in finding the complete hypermetropic state -- even with the help of a not very demanding cycloplegic agent like atropine. Cyclogyl was found to be the most suitable agent here.


Evaluation of unilateral exophthalmos with ultrasonography: analysis of 258 consecutive cases. Ultrasound examination has emerged as a valuable technique for defining soft tissue abnormalities of the eye and orbit. As high frequency sound waves (5 to 20 megahertz) are projected through soft tissues, echoes are produced at tissue interfaces. These echoes are displayed on oscilloscopes as either one-dimensional amplitude spikes (A-mode ultrasonography), or as dots integrated into a two-dimensional image representing a thin section through the entire orbit (B-scan ultrasonography). A-mode indicates tissue substance, while B-scan illustrates tissue morphology. With this technique, orbital tumors are clearly distinguished in terms of their location, size, and configuration, as well as the basic tissue type (cystic, solid, angiomatous or infiltrative). Other orbital processes are defined by ultrasonography also, including inflammatory conditions such as diffuse pseudotumor or cellulitis, congestive conditions such as dysthyroid exophthalmos, and orbital hemorrhage. Intracranial and vascular etiologies of exophthalmos have no specific ultrasound signs. In a series of 258 consecutive patients with unilateral exophthalmos examined with ultrasonography, diagnosis of tumor was made in 26 percent (66 cases). Overall accuracy of orbital tumor diagnosis by ultrasonography was 94 percent in this series. Tumor localization, configuration, and extent indicated by the test aided in selecting surgical approaches. Other patients in the series were diagnosed ultrasonically as a variety of other entities, mostly inflammatory and dysthyroid exophthalmos. Normal ultrasound studies were found in 19 percent. None of these patients had subsequent diagnosis of tumor. Diagnostic ultrasonography is capable of detecting orbital tumors and distinguishing them from inflammatory, congestive, and other causes of exophthalmos with a high degree of reliability. The test is painless, well tolerated, non-invasive, and non-toxic. It now has a prominent role in evaluation of any patient with exophthalmos.


Light and electron microscopy of mouse lymphosarcoma LS/BL cells during the first hour after irradiation with x-rays. Mouse lymphosarcoma LS/BL cells growing in tissue culture were irradiated with 100, 316 and 1000 R respectively and fixed 5, 15 or 60 minutes later. Semithin sections were studied under a light and ultrathin under an electron microscopes. Under the light microscope, differences between the morphology of individual nuclei were found in all groups, including controls; the rate of their occurrence was without any relation to the irradiation. They may reflect the differences in the state of LS/BL cells which were not completely adapted to cultivation in small glass tubes. On the other hand, the frequency of some ultrastructural changes seen under the electron microscope showed a relation to the irradiation. They were: undulation of the outer nuclear membrane and dilatation of the space between the outer and inner nuclear membranes, slots in karyosomes adjacent to the surface of the nuclei, enlargement of cisternae and vesicles of endoplasmic reticulum and Golgi apparatus. The importance of a careful examination of control groups in such experiments is stressed.


[Multiple intracranial mycotic aneurysm. Report of a case (author's transl)]. A case of intracranial mycotic aneurysm was reported, in whom repeated cerebral angiographies demonstrated the seccessive appearance of multiple aneurysms in a short term after the septic cerebral infection, and the importance of repeated angiography in the treatment of the intracranial mycotic aneurysm was stressed. A 44-year old male who had heart failure developed suddenly a left hemiparesis with irritable meningial signs on Nov. 3, 1973. The right carotid angiography carried out on Nov. 16 in an admitted hospital showed partial obliteration of cortical branches of the middle cerebral shift of the anterior cerebral artery due to the cerebral infarction. No aneurysm was demonstrated in the angiogram. The second angiography of the right carotid and vertebral artery was done on the admission of Dec. 18. The previously shown contralateral shift of the anterior cerebral artery was remarkably decreased, and an aneurysm of 3 mm in diameter was recognized at the cortical branch of the right middle cerebral artery on the parietal region. Any aneurysm was not revealed by the vertebral angiography. The third angiography of bilateral carotid and vertebral artery was performed on Dec. 25. The previously revealed aneurysm increased in size. Multiple aneurysms was demonstrated at the anterior branches of the insular artery. The vertebral angiography demonstrated multiple aneurysms at the peripheral portion of the bilateral posterior cerebral arteries. The patient was improved neurologically after the administration of antibiotics, and was discharged on Dec. 27 on the convenience of his family and would be followed in conservative cares.


[Isocount scanning of the brain (author's transl)]. It is well known that the gamma ray emitted by a radionuclide is a Poisson process, so its statistic nature should be taken in consideration when the scintiscanning is performed. But very few attempts have been done from this point of view. After examining in detail the imaging pulse charactristics, the authors introduced a mean for evaluating the fidelity of the collected data, and based on this criterion, pointed out some problems in the conventional scanning method and finally described a statistical way of improving the scintigram. In the present investigation, as a measure of the stochastic fidelity of the scanned data the relative deviation eplision(n) = sigma(n)/E(n) is introduced; sigma is the standard deviation and E(n) is the expectation value of the counting rate. In the conventional scanning in which the detector moves with a costant speed, the relative deviation varies from area to area according to the concentration of the radioisotope in the brain. In the so-called cold area of the brain scintigram, the relative deviation fluctuates remarkably because of a rather low density of radioisotope in this area.


[False aneurysm due to mycotic angitis-case report (author's transl)]. Cerebral mycotic angitis takes place as a secondary disease to inflammation which is precipitated on the arterial wall to the artery, most frequently the vasa vasorum, as a result of settlement of infectious embolus into there,  and it is usually seen in the patient with cardiac disease. The middle cerebral artery is a major region where the lesion takes place in multitude, and it is only rarely seen in the patient having infection in the brain or dura mater. We have recently experienced a very rare case in which false aneurysm was induced in the internal carotid artery by angitis due to Aspergillus, and this report deals with case. A 26-year-old office-man: He was attacked by loss of consciousness, aphesia, right hemiparesis during work in his office. As left CAG demonstrated evidence of arteriovenous malformation, redical operation was performed. He took a favorable course postoperatively, but developed meningitis on 10th day, when massive antibiotic therapy was started. During treatment, however, his consciousness rapidly decreased, and it was found on left CAG that there was false aneurysm in the cisternal segment of the left internal carotid artery which has previously been completely healthy. Operation was practiced once again to reinforce the wall of the left internal carotid artery, but the patient died of aggravated meningitis. Autopsy demonstrated a very fragile left internal carotidartery associated with perporation which was surrounded byprominent coagula. Histological examinations indicated that the perforation of the vascular wall had been caused by angitis due to Aspergillus infection.


Intolerance of eight ounces of milk in healthy lactose-intolerant teen-agers. The ability of lactose-intolerant individuals to tolerate 8 ounces of milk was determined in healthy teen-agers. Thirty-two blacks were studied with 50-gm lactose tolerance tests. Nineteen (59%) had a flat blood sugar curve and 13 (39%) also developed bloating, cramps, loose stools, or diarrhea with the test. These latter 13 were defined as lactose-intolerant. Seven of the 13 lactose-intolerant teen-agers (54%) developed abdominal bloating and/or cramps after drinking 8 ounces of milk (half-pint). None had diarrhea. Eight were symptomatic with the equivalent amount of lactose (12 gm) while only one had symptoms with the monosaccharide components of lactose, glucose and galactose. The symptoms with milk and 12 gm of lactose were less severe than with the 50-gm tolerance test. A history of a prior awareness of milk intolerance was obtained from 11 of the 13 lactose-intolerant subjects. At least one half of lactose intolerant teen-agers might be expected to be symptomatic after drinking 8 ounces of milk without other food. Milk intolerance should be considered in the nutritional planning for teen-agers with special attention to members of population groups with a high prevalence of lactose intolerance.


Radioimmunoassay for anileridine, meperidine and other N-substituted phenylpiperidine carboxylic acid esters. Antibodies that bind an 125I-tyramyl derivative of N-succinylanileridine have been produced in animals immunized with N-succinylanileridine-hemocyanin conjugate. Several congeners and metabolites have been tested as competitors of this antigen-antibody reaction. The concentrations (in picomoles) required for 50% inhibition have been found to be: anileridine (0.2), meperidine (3.5), piminodine (3.8), diphenoxylate (20.5), normeperidine (20.0), meperidine acid (45,000) and anileridine acid (3,400). Although ester hydrolysis results in changes in inhibiting capacities on the order of 10(4), major structural changes in the substituent on the nitrogen of the piperidine ring are not readily recognized by the antibody. This radioimmunoassay can be used to study a variety of N-substituted phenylpiperidine carboxylic acid esters by relating the results to the standard curve obtained for the drug under investigation. For all practical purposes, alphaprodine, morphine and methadone do not interfere with the assay.


[Identification of organic substances by means of spectral methods in forensic toxicological analysis. II. Nuclear magnetic resonance]. In opening the paper, the authors present a brief outline of the fundamentals of nuclear magnetic resonance. Using selected cases from practice, they demonstrate the use of nuclear magnetic resonance for the purpose of forensic toxicologic analysis. The method is particularly suitable for identifying unknown organic compounds and for analysing mixtures of substances.


A review of obesity and its management in 263 cases. Obesity is defined with reference to hte probable cellular differences in adolescent and maturity-onset obesity. The aetiology and pathogenesis of obesity are briefly discussed. A multifactorial approach was used to treat 263 patients for obesity. This regimen included strict diet, programmed exercise, psychotherapy and medication. D-Phendimetrazine bitartrate in the long-acting form proved an excellent anorexiant for routine use. Fenfluramine was a valuable adjuvant drug for refractory cases. A detailed analysis of the results shows an over-all classified mean weight loss of 14,3%. Interrelationships between degree of overweight, age, degree of weight loss, etc., are critically examined. The most important conclusion was the need for close medical supervision and encouragement both during and after the formal weight loss programme.


Hormonal therapy of breast cancer with special reference to Masteril therapy. From 1968 to 1972, a trial of a new agent, drostanolone propionate (Masteril), was conducted. This agent was tested against oophorectomy in a group of premenopausal patients, against nandrolone phenylpropionate (Durabolin) in a perimenopausal group, and against ethinyl oestradiol in a postmenopausal group. In the premenopausal group, 44% responded to Masteril and 22% to oophorectomy. In the perimenopausal group, 34,5% responded to Masteril and 39% to Durabolin. In the postmenopausal group, 57% responded to oestrogens and 38,5% to Masteril. The side-effects of Masteril are generally not serious and rarely contra-indicate its use. Masteril has been shown to be a useful and safe agent for all age groups, even though it may appear to be less effective than oestrogens in the postmenopausal patients.


[Concerning the toxicity of parbendazole (Helmatac 30) to horses and ponies (author's transl)]. The toxicity of parbendazole in different doses was investigated with 52 horses and 16 ponies, in twelve groups. Side effects observed with the anthelmintic were laxation (soft dung, diarrhoea), anorexia, and listlessness. The seriousness of these symptoms depended greatly on the dose used. Half the therapeutic dose of parbendazole (2.5 to 3.75 mg/kg) administered on two consecutive days led, as a rule, to only slight toxic symptoms and proved highly effective with regard to gastro-intestinal nematodes occurring in horses and ponies. The utilisation of "standard powders" (not commercially available as such) is recommended for simplified dosing (and thus preventing overdosing as far as possible). The laxative side effect of parbendazole was greater during the performing of work (movement). This investigation involved eight Shetland ponies in foal. The pregnancy varied between four and eleven months. No unfavourable effect on the gravidity or on the development of the foetus were observed. Neither clinical examination nor clinical chemical serum examination gave any indication of the occurrence of hyperlipaemia after treatment with parbendazole.


[General anesthesia in patients with toxic goiter]. A report of the author's personal experience with analtesia in 604 patients having toxic goiter is given. During the procedure the effect of various anesthetics on the pulse rate at the time of surgery was studied. It was found that the combined neuroleptanalgesia and a combination of local infiltrative novacain anesthesia with nitrogen monoxide-oxygen narcosis renders the most favourable effect in such cases.


[Use of guthimine for treatment of intestinal paresis in peritonitis under experimental and clinical conditions]. A new stimulator of intestinal peristalsis-guthymine (guanylthiourea) was used experimentally and clinically for treatment of the bowel paresis in peritonitis. Preliminary, in experiments on 53 rabbits with colibacillar peritonitis an efficacy of guthymine was compared with other stimulators of the gastrointestinal tract: proserine, a hypertonic solution of sodium chloride and sorbitol. Guthymine was found to be the most effective drug. Clinically, in 23 of 33 patients with intestinal paresis a drip administration of 15-50 mg/Kg of guthymine would provide for aborting the signs of paresis. In 8 patients a moderately pronounced effect was noted. In 2 cases the use of guthimine failed to produce any positive effects.


[Detection of H2O2 in uperized milk (author's transl)]. Qualitative determination of H2O2 in uperized milk by means of PERID-test-tablets and quantitative tests by means of lactoperoxidase showed that H2O2 is more or less decomposed depending on the original concentration in the uperized milk. The relationship between H2O2-content, time of storage and ascorbic-acid-content are discussed.


Laboratory diagnosis of the atopic condition: evaluation of a possible method based on human serum complement consumption. Purified house dust allergen has been employed for screening the susceptibility to inactivation of haemolytic complement in the blood serum of atopic individuals and control subjects. Though the atopic sera displayed a tendency to higher susceptibility, no practical distinction was possible from the sera of patients with various forms of chronic pulmonary disease, extrinsic allergic alveolitis, or urticaria. CH50 and C4 levels were unrelated to allergen-sensitivity of haemolytic complement, nor was there a correlation with the titers of naturally-occurring sheep red cell haemolysins. Although blood group  specificity within the ABO system was distributed over the patients as expected for the normal population, the titers of A- and B-type antibodies displayed a trend to correlate with the allergen-sensitivity of fluid phase complement.


Blood group activity of allergenic preparations. Haemagglutination-inhibition studies showed that several different allergenic preparations exhibit A and B blood group activity. Most products displayed A-specificity, less often B-specificity; the inhibition titers were usually low. No correlation was evident between isoagglutination-inhibition titers and the complement-consuming capacity or skin-reactivity of the allergens. Absorption of A- and B-isoagglutinins from human serum did not affect the complement consumption by house dust allergens. Hapten-inhibition studies confirmed the non-participation of blood group antibodies in allergen-induced complement consumption. The observed inhibition by D-glucosamine is attributed to a partial structural homology with the lysine-sugar site on house dust allergens.


[The importance of radio-allergo-sorbent-test in comparison with intracutaneous test in diagnosis of allergic diseases]. A comparison of clinical skin-tesing using the prick-test and the intracutaneous test with the radio-allergo-sorbent-test (RAST) in 167 patients with different immediate-type allergies showed concordant results in 75.7 per cent of the cases. In 20 per cent of the cases, the skin-test was positive while the simultaneous RAST was negative. Results in male and female patients did not show any important difference. The two test methods agreed well with selected antigens, e.g. grass-pollen, animal-epithelium, fungi and egg white; whereas, the two methods showed considerably different results using tree pollen and housedust as antigens.


Therapeutic index of steroid aerosols in asthma. A single-blind comparative trial of beclomethasone dipropionate vs dexamethasone isonicotinate. 1) A 4-week single-blind study is reported which compares the responses of 10 matched pairs of adult asthmatic patients to Beclomethasone Dipropionate and Dexamethasone Isonicotinate aerosols, each at 12 metered-doses per day. 2) Therapeutic efficacy was evaluated by measurement of pulmonary function (PEFR) and by a physician's "overall evaluation" scale. 3) Side-effects related to systemic absorption were evaluated by A.M. blood cortisol levels and total eosinophil counts. 4) At the doses studied, Beclomethasone Dipropionate produced both no side-effects and a significant favourable clinical response, while Dexamethasone Isonicotinate produced significant side-effects and a lesser clinical response.


Electrophysiologic effects of tolamolol on atrioventricular conduction in man. The electrophysiologic effects of tolamolol (UK-6558-01), a beta-adrenergic blocking agent, were studied in 13 patients by means of intracardiac electrograms and the extrastimulus method. Tolamolol (4 to 30 mg. intravenously) resulted in : (1) prolongation of sinus cycle length (SCL) in all patients (p less than 0.01); (2) prolongation of sinus escape time (SET) in 11 of 13 patients (p less than 0.001); (3) prolongation of A-V nodal conduction time during sinus rhythm in 1i of 13 patients (p less than 0.001); (4) onset of A-V nodal Wenckebach block at longer paced cycle lengths in 10 of 11 patients (p less than 0.001); (5) prolongation of the functional refractory period (FRP) of the A-V node in 11 of 11 patients (p less than 0.001); and (6) prolongation of the effective refractory period (ERP) of the A-V node in 10 of 10 patients (P less than 0.001). Tolamolol had no effect on His-Purkinje system (HPS) conduction time in any patient, including 3 patients with abnormal H-V intervals. Because of the marked increase in A-V nodal conduction time encountered by premature atrial depolarizations, the relative and effective refractory periods of the HPS could not be determined in any patient after tolamolol. Atropine (0.5 or 1.0 mg. intravenously) significantly reversed the effects of tolamolol on: sinus cycle length (4 of 5 patients); sinus escape time (3 of 3 patients); A-V nodal conduction time (4 of 5 patients); and A-V nodal refractioriness (5 of 5 patients).


Iatrogenic respiratory distress syndrome. An analysis of obstetric events preceding delivery of infants who develop respiratory distress syndrome. The obstetric events leading to the birth of infants who developed respiratory distress syndrome (RDS) were evaluated. In a retrospective study of 100 consecutive cases it was determined that untimely or unwarranted physician intervention in the pregnancy was responsible for 15 per cent of cases and possibly responsible for another 18 per cent. Recommendations for prevention of "iatrogenic" RDS are made.


A new contrast medium for cholangio-cholecystography: meglumine iodoxamete. A preliminary study of 18 patients following a single bolus intravenous injection of 10 to 30 cc. of meglumine iodoxamate (Cholovue), a new contrast medium for cholangio-cholecystography, showed no significant adverse clinical or laboratory effects with 10 to 20 cc., and only transient, minor changes with 30 cc. Early and persistent visucalization of the subsegmented and major bile ducts and the gallbladder was obtained. Good to excellent opacification was obtained in all cases with doses ranging between 0.11 cc./kg. (19.7 mg. iodine) to 0.59 cc./kg. (108 mg. iodine). Meglumine iodoxamate appears to be highly effective agent for cholangio-cholecystography.


Primary tumors of the small bowel.

Primary tumors of the small bowel. Primary tumors of the small bowel are uncommon, representing less than 6 per cent of all gastrointestinal tumors and less than 2 per cent of all malignant gastrointestinal tumors. This report concerns a twenty-five year survey of our clinical records from 1946 to 1971 which revealed 140 primary small bowel tumors, excluding periampullary tumors. Fifty-two of the neoplasms (37 per cent) were benign; eighty-eight (63 per cent) were malignant and included twenty-eight adenocarcinomas (31.8 per cent), twenty-four lymphosarcomas (27.3 per cent), nineteen carcinoids (21.6 per cent), and ten leiomyosarcomas (11.4 per cent). The average age at the time of diagnosis was 56.9 years for patients with benign tumors and 55.9 years for those with malignant tumors. The illusive and obscure nature of small bowel tumors is illustrated by the fact that 63.3 per cent of patients with benign lesions and 47.6 per cent of those with malignant lesions had symptoms for more than six months before the diagnosis was made. Bleeding was the most common present complaint in patients with benign neoplasms (52.9 per cent) whereas patients with malignant lesions more often had symptoms of obstruction (50.6 per cent). Most of the benign lesions were located proximally in the small bowel (duodenum, 34.6 per cent; ileum, 11.5 per cent), and most of the malignant lesions were located distally (duodenum, 17.0 per cent; ileum, 61.4 per cent). Treatment of patients with malignant lesions was radical excision whenever possible. Adjunctive radiation therapy was used for those with lymphoma. A second benign or malignant tumor occurred in 42.9 per cent of the patients with primary small bowel tumors. The average period of survival after diagnosis of a malignant small bowel tumor was 5.03 years: for patients with adenocarcinoma, 3.6 years; lymphosarcoma, 1.3 years; carcinoid, 6.8 years; and leiomyosarcoma, 8.3 years.


Medical education and practic in People's Republic of China. A dramatic adaptation of medical education to meet indigenous needs and circumstances has occurred in the People's Republic of China in the context of a highly structured health care delivery and medical referral system, entailing a reduction in curriculum length from 6 to 3 years. Although general directions and guidelines are set centrally by Peking, considerable autonomy and flexibility exist in individual schools. The innovative approaches used include training medical students in countryside and factories as well as medical schools, combining traditional Chinese and modern Western medicine, opening hospital-run medical schools, and using unconventional methods of producing medical doctors. On graduation the students generally return to the communities from which they came. Although the total number of medical graduates still falls short of national requirements, the problem of maldistribution of physicians has been alleviated in China. Medical care is now readily available in rural areas, where 80% of the population resides.


Influence of carbohydrate and nitrogen source on patulin production by Penicillium patulum. A strain of Penicillium patulum, isolated from cheddar cheese, produced patulin when grown on liquid media containing lactose and milk nitrogen sources. Patulin production was affected by the temperature of incubation, the type and amount of carbohydrate, and the type of nitrogen source present. Patulin levels generally were depressed by incubation at 5 C and low carbohydrate levels. Patulin was produced at low levels in the absence of sugars at 5 C when the mold was grown on milk nitrogen sources. No patulin was detected in cultures grown on 25% casein slurries or cheddar cheese, even though growth of the mold was extensive.