Molecular basis of Tn-polyagglutinability. Spectrophotometric and gas-liquid chromatographic analyses on the carbohydrate moiety of tryptic erythrocyte glycopeptides from persons with Tn-syndrome reveal a selective lowering of the galactose and sialic acid content, the degree being dependent on the percentage of polyagglutinable cells. Alkaline borohydride specifically releases N-acetylgalactosaminitol, and the amount is correlated to the percentage of pathological acetylgalactosaminitol, and the amount is correlated to the percentage of pathological erythrocytes. It is concluded that the alkali-labile carbohydrate chains of Tn-polyagglutinable red cells solely consist of N-acetylgalactosamine linked to serine or threonine. Experiments with heterophile agglutinins whose specificity is known are in line with the above-mentioned results. As judged from SDS-polyacrylamide gel electrophoresis the three major membrane glycoproteins are affected to a different extent by the defect.


Studies on anti-Mi-a and the MiIII complex. Some Ms/Ms MiIII red cells react weakly with rabbit anti-N but not with human anti-N sera. Specificities of different anti-Mi-a within the Miltenberger complex have been defined by absorbtion studies with different Mi classes.


Amyloidosis of the orbit and adnexae.

Amyloidosis of the orbit and adnexae. Five patients representing a spectrum of orbital and adnexal amyloidosis are presented. One patient with conjunctival amyloidosis did not have antecedent infection nor systemic disease (primary localized amyloidosis), while another patient with conjunctival amyloidosis had a long history of repeated attacks of bacterial conjunctivitis (secondary localized amyloidosis). The third patient presented with serial bilateral lacrimal gland amyloid without systemic disease (primary localized orbital amyloidosis). Another patient had intraorbital amyloid associated with metastatic deposits or immunoglobulin-producing lymphoma cells in the orbit (secondary systemic amyloidosis) and a fifth patient, with borderline Congo red staining for amyloid, was shown by electron microscopy to have macrophages with intracellular amyloid-like fibrils and extracellular crystalline material resembling immunoglobulin deposits. Amyloidosis has been clearly shown to be associated with immunoglobulins and plasma cells. Electron microscopic findings in our two cases of primary localized orbital amyloidosis leave unresolved the suggestion that mesenchymal cells, in addition to plasma cells, may be responsible for the production of amyloid. It should be emphasized for the clinician that amyloidosis of the conjunctiva and orbit is almost always a benign disease without systemic implications. On the other hand, amyloid of the skin of the eyelids, is a hallmark of generalized amyloidosis.


Further studies on the isolation of injured Salmonellae from foods. Two series of experiments with artificially contaminated milk powder were carried out. In the first series the influence of storage on the minimal resuscitation time was studied. In the second series the influence of ox bile versus taurocholate as inhibitive substances in tetrathionate bile brilliant green broth was studied. The results clearly indicate that in a given population cells may be present which are injured to various degrees, and that studies to determine minimal resuscitation times may be complicated by this fact.


Relationship of milk consumption to blood glucose rise in lactose intolerant individuals. Lactose intolerant populations are heterogeneous with respect to their milk-drinking habits. A gradation of lactase activity in the intolerant population may result in sufficient lactose hydrolysis to obviate symptoms and lead to continued milk consumption. This paper reports on differences in maximum blood sugar rise in lactose intolerant children who are observed to consume or reject milk. Of the 89 black elementary school children, 48 (54 per cent) evidenced a flat lactose tolerance curve. Twenty-eight of these 48 children (58 per cent) were defined as nonmilk drinkers. The maximum blood sugar rise was 12.3 mg/100 in the 20 lactose malabsorbers who were defined as milk drinkers. It appears that some lactose malabsorbing children may have sufficient, albeit lower, levels of lactase to hydrolyze moderate amounts of milk.


Effects of dietary lactose and lactase preparation on the intestinal absorption of calcium and magnesium in normal infants. Effects of dietary lactose and a lactase preparation on the intestinal absorption of calcium and magnesium were studied in 3 groups under 8 months of age; infants on a proprietary milk, infants on a lactose-free milk, and infants on a proprietary milk to which a lactase preparation was added. The intestinal absorption of both elements was reduced in infants on a lactose-free milk and enhanced in infants who were fed on a proprietary milk and given a lactase preparation.


Lactose hydrolyzed milk.

Lactose hydrolyzed milk. Lactose intolerance is being reported in many populations. Yet, milk is highly nutritious and methods are being explored to use milk while limiting the lactose content. Thirty-two blacks 13-19 years of age were studied to determine a blood sugar rise with 8 ounces of the following test milks: 1) untreated whole milk (12 g/lactose); 2) 90% lactose hydrolyzed milk (1.2 g/lactose); and 3) 50% lactose hydrolyzed milk (6 g/lactose). In the 22 lactose malabsorbers, the peak blood sugars were: 1) untreated whole milk--4.4 mg/100 ml, 2) 90% lactose hydrolyzed milk--14.5 mg/100 ml, and 3) 50% lactose hydrolyzed milk--8.8 mg/100 ml. The 10 blacks with normal lactose absorption had a comparably high peak blood sugar on all three test milks. Differences between the blood sugar in the lactose absorbing and malabsorbing subjects when drinking untreated whole milk are significant (P less than 0.001); so are differences in the lactose malabsorbing subjects consuming untreated whole milk and 90% lactose hydrolyzed milk (P less than 0.001) as well as 50 and 90% lactose hydrolyzed milk. Symptoms were reported by three lactose malabsorbing subjects with untreated whole milk with two of the three symptomatic with 90% lactose hydrolyzed milk and none with 50% lactose hydrolyzed milk. No symptoms were reported by the lactose absorbers. Significant improvement in absorption with 90% lactose hydrolyzed milk is seen in low lactase subjects. Lactose hydrolyzed milk may serve as an important alternative for food planners wanting to provide milk to high risk populations with low lactase levels.


Reed-Sternberg-like cells in nodular lymphoma involving the bone marrow. McKenna, Robert W., and Brunning, Richard D. Reed-Sternberg-like cells in nodular lymphoma involving the bone marrow. Am JClin Pathol 63: 779-785, 1975. Two patients with cells indistinguishable from Reed-Sternberg cells in bone marrow lesions of nodular poorly differentiated lymphocytic lymphoma are described. Both patients had lymph node biopsies showing nodular lymphoma. Bone marrow and blood involvement with the lymphoma was demonstrated at the time of initial diagnosis. Reed-Sternberg-like cells were not demonstrated in either case until later in the course of the disease, after the patients had been treated with numerous chemotherapeutic agents. Other similarities of bone marrow involvement with nodular lymphoma to Hodgkin's disease of the bone marrow are noted. The origin of the Reed-Sternberg-like cells in nodular lymphoma is not clear, but they could result from morphologicalteration of lymphoma cells by chemotherapy. The finding of Reed-Sternberg cells in bone marrow lesions should be interpreted with caution unless diagnostic biopsy material from other sites is available for study. (Key words: Bone marrow lymphoma' nodular lymphoma; Reed-Sternberg cells).


Radiologic evaluation of the premature newborn rabbit after pharyngeal deposition of surfactant. Premature rabbit fetuses were delivered by hysterotomy and, prior to the first breath, a concentrated homologous surfactant suspension was deposited in the pharynx. With repeated radiograms, the effect of this treatment was studied during the first two hours of extrauterine life. The lung aeration was quantitated with densitometry, and the chest expansion was assessed by measuring the inferior angle formed by the fourth ribs. In comparison with control animals, the treated animals demonstrated a greater chest expansion, and their lungs were significantly better aerated. Clinical application has to await further studies.


Response in mice to an erythropoietin-generating factor. The bioassay for erythropoietin-stimulating factor (ESF) was compared in 3 strains of mice. One strain was made polycythemic by hypertransfusion and the other 2 by hypoxia. An erythropoiesis-generating factor (EGF) measured in the 3 strains generated approximately the same amounts of ESF, determined with log dose-log response curves for the respective techniques, after incubation with normal rabbit serum (NRS). The amount of ESF generated by EGF without prior incubation with NRS was also approximately the same in the 3 strains of mice.


Coincidence of Sarcoidosis and Hashimoto's thyroiditis. A 59-year-old, female patient died of pulmonary embolus 16 days after an operation for a Moore prosthesis. At autopsy, previously unsuspected sarcoidosis and Hashimoto's thyroiditis were found. The sarcoidosis was noted in one focus in the lung and in all lymph nodes examined. In the thyroid gland, Hashimoto's thyroiditis was observed. In addition, structures that could not be differentiated morphologically from papillary Hurthle cell carcinoma were seen in the thyroid.


Azaribine therapy for psoriasis. Evaluation of potential effects on the liver and other organ systems. An open study of azaribine was carried out on 38 psoriatic patients for two years. Thirty-five patients had previously taken methotrexate. Thirty-four patients had liver biopsies performed before azaribine therapy and 14 had liver biopsies performed after azaribine therapy. Of these 14, five had grade 1 liver biopsies before and after therapy; one had grade III before and after therapy; and three had grade IV before and after therapy. Liver biopsy findings were slightly worse in two patients, and three patients showed improvement in liver biopsy findings.


Lymphosarcoma of the right atrium. Angiographic and hemodynamic documentation of response to chemotherapy. A patient had metastatic lymphosarcoma involving the right atrium and tricuspid valve in which functional tricuspid valve obstruction was relieved by chemotherapy. Patients with disseminated or mediastinal lymphoma in whom cardiopulmonary symptoms occur should be considered for catheterization of the right side of the heart and angiography. These procedures may be useful for determining the presence, location, and nature of cardiac disease and may aid in deciding the proper course of therapy.


Metabolism of trichloroethylene in man. III. Interaction of trichloroethylene and ethanol. Volunteers inhaled a constant concentration of 50 ppm trichloroethylene (Tri) for 6 hrs per day on 5 consecutive days. Simultaneous ethanol (EtOH) ingestion (blood level 0.6%) inhibits the metabolization of Tri to trichloroethanol (TCE) and trichloroacetic acid (TCA) by 40% on the average. Oxidation of Tri to TCA does not occur as long as EtOH is present. During this time period the blood Tri-concentration increases 2 1/2-fold, that in the expired air rising 4-fold, as compared to Tri inhalation without EtOH. TCE glucuronidation is not subject to inhibition. On concurrent inhalation of Tri, the EtOH and acetaldehyde levels are slightly increased over the control values without Tri. The mechanisms underlying the alternate inhibition of mixed-function oxygenases and aldehyde dehydrogenase on simultaneous intake of Tri and EtOH are discussed. The intolerance reaction occurring on combined exposure to Tri and EtOH can be interpreted as an accumulation of Tri in the CNS resulting from the complete depression of Tri oxidation.


[Embryotoxicity and teratogenicity of derivatives of 1,3-indandion (author's transl)]. The embryotoxicity and teratogenicity of 1,3-indandion and of 3 of its derivatives were proved. Pregnant SWS mice were given single i.p. injections on day 9 of gestation. A mixture of physiologic saline and TWEEN20 (3:1) was used as a solvent. The results refute the hypothesis of the action of thalidomide as an acylating agent responsible for the embryotoxic and teratogenic effect. The results favor instead the hypothesis of an intercalation of the flat purine-like molecule moieties of thalidomide and some of its analogues between base pairs of the DNA double helix.


In vivo cytogenetic investigations in bone marrow cells of rats, Chinese hamsters and mice treated with 6-mercaptopurine. The chromosome-damaging effect of 6-mercaptopurine (6-MP) was investigated in bone marrow cells of rats, Chinese hamsters, and mice after single intraperitoneal injections of doses from 3.125 to 250 mg/kg, and after multiple applications of 10, 25, 50, and 125 mg/kg. The optimal time of investigation after single administration in these studies was 48 hrs after treatment for all 3 species. A nearly linear dose-response relationship with a low quadratic component was observed. The "critical dose" for all 3 species was 12.5 mg 6-MP/kg. However, mice generally demonstrated the highest sensitivity to the "clastogenic" effect of 6-MP. In agreement with results of acute toxicity studies, Chinese hamsters generally were less (and rats least) sensitive than the mouse to chromosomal damage induced by higher doses of 6-MP. After repeated treatment with low doses, the chromosome-damaging effect of 6-MP was less pronounced than after one single administration of a large dose equaling the total amount of substance applied in chronic treatment.


[The inhalation toxicity of tertiary butylisonitril in rats and mice. Acute toxicity and evaluation of embryotoxic and mutagenic effects (author's transl)]. The inhalation toxicity of tertiary butylisonitril (TBIN) was evaluated in rats and mice. In addition, pregnant rats were exposed to TBIN aerosols to test its embryotoxic effects and male mice were exposed to TBIN aerosols to evaluate its mutagenic effects using the dominant lethal test. Inhalation of TBIN aerosols caused death in rats only at high concentrations. The following inhalation LC50 values were determined for rats and mice following inhalation of TBIN aerosols: 4-hr exposure: male rats 715, female rats 710, male mice 377; five 4-hr exposures: male and female rats between 356 and 583 mg/m-3 air. The animals were impaired for a long period of time, and death occurred up to 10 days after the exposure. Female rats were exposed to TBIN aerosols from the 6th to the 15th day of gestation daily for 4 hrs. The used concentrations were not toxic to the pregnant rats. It became evident that only the lowest concentration (14 mg/m-3) was not effective to the development of the fetus. A TBIN concentration of 36 mg/m-3 definetely increased the resorption in embryos, and with 71 mg/m-3 a complete loss of the fetus occurred due to resorption. A teratogenic effect could not be determined. A single 4-hr inhalation of 125 mg TBIN/m-3 air caused changes of the sperms of male mice. There was a decreased fertilization capability during the first week of mating after the exposure and a decreased implantation rate with a simultaneous increase of pre-implantation losses in the females. With respect to industrial hygiene it is important that concentrations of TBIN in the air show embryotoxic and anti-spermatogenic effects in animals, which they tolerated without symptoms of poisoning.


On the question of extracorporeal hemodialysis in diquat intoxication. Extracorporeal hemodialyses were carried out in a female patient with severe diquat intoxication. Diquat clearance was on average, 3.17 ml/min. Only 0.84 mg diquat could be eliminated from the blood serum by 11.5 hrs of dialysis. Hemodialysis is therefore not an efficient technique for removing amounts of diquat from the organism that are toxicologically relevant one day after ingestion.


Antidote effect of liquid paraffin in oral solvent intoxication. The antidote efficacy of liquid paraffin in oral solvent intoxications was investigated in dogs. Groups of 3 to 4 animals each received 1 ml/kg of methylchloroform, 0.3 ml/kg of benzene, or 3 ml/kg of a synthetic gasoline mixture (hexane/heptane/octane, ratio 30:50:20) by gastric intubation. After a prolonged interval the same animals were given 5 ml/kg of liquid paraffin by a separate tube in addition to one of the above solvents. The solvent concentrations in the blood were determined by gas chromatography at appropriate intervals. Administration of liquid paraffin in conjunction with methylchloroform does not significantly affect the absorption process. In the case of benzene and the synthetic gasoline mixture, however, liquid paraffin produces a distinct reduction in the rate of absorption. It is thus concluded that in the therapy of oral solvent-intoxication, liquid paraffin exhibits favorable antidote properties which may however differ from one solvent to the other. In clinically relevant situations involving coadministration of purgatives, the antidote effect must be assessed as being of a higher order than in our animal experiments in which purgatives had to be omitted for external reasons.


[Examinations of the thresholds of discomfort of the ears treated by stapedectomy (author's transl)]. Ears treated by stapedectomy often are extremely irritated by noise. To clear up this phenomenon were plotted the thresholds of discomfort by tone- and speechaudiograms in the operated ears as well as in the non-operated. All our patients being examined had the stapedius muscle tendons cut. There was no clinical otosclerosis in the non-operated ears and the audition was the same on either side. A significant increase of the discomfort threshold was seen in the operated ears (93.8% in the toneaudiograms and 78.1% in the speech audiograms). In the tone audiograms the frequencies of 500, 1000 and 2000 cps were the most concerned. We consider this increase of discomfort as a consecutive result of the stapedius tendon cutting. It verifies the protecting function of the stapedius muscle against low frequencies.


[The protein- and nucleic acid biosynthese in isolated human tonsilar cells and his dependence of age (author's transl)]. The aim of our investigations was to discriminate unspecific age-depending function of the tonsil. In an in-vitro system of tonsillar lymphocytes we could show, that there are differences in the DNA-, RNA- and Proteinbiosynthese between children and adults. The children organ is more active. It could be shown that the observed differences are only age depending and not influenced by the clinical state of the organ.


[About the influence of body posture on the result of acoustical examinations (author's transl)]. Effect of socalled tonic reflexes on central processing of acoustic stimuli was studied by stimulating the patterns of tonic reflexes in 18 adults with normal hearing abilities. The parameters were: hearing threshold level, acoustical stapedius reflex and slow auditory evoked potential. Only in three positions-corresponding to the symmetrical tonic neck reflex (STNR) and tonic labyrinthine reflex in supine and prone position a hearing threshold shift of 1 dB could be observed. The level of the stapedius reflex showed an increase of 5 dB in one of these three positions. In the acoustical evoked slow potential only the amplitude but not the latency was influenced. In some cases we found an increase of amplitude, in others a decrease or even a complete suppression. In using ERA to evaluate possible auditory disturbances in children with cerebral palsy it seems necessary to consider these possible influences on the evoked potential.


Aberrant carotid artery in the middle ear. A myringotomy performed on a 2-year-old girl, resulted in profuse aural hemorrhage which recurred when the patient cried. Carotid angiography revealed bilateral aberrant internal carotid arteries in the middle ears. In this case, and in previously reported cases as well, otalgia was one of the initial symptoms of the anomaly. So as to avoid faulty myringotomy, recognition of this entity is essential in cases presenting reddish swelling of the inferior quadrant of the tympanic membrane.


[ERA and dichotic test by Feldmann of dyslectic children (author's transl)]. Many elementary school-children (nearly 20%-for the West German Republic) have difficulties in reading and writing. In most cases these troubles will cease during the further school development, only very few must be classified as dyslectic. Dyslexia and its audiological problems was studied in over 100 children ranging from the age of 5-16 years. Hearing thresholds showed only in a few cases pathological results. The dichotic discrimination test by Feldmann revealed significant lower results compared with normal children and same age group. EEG audiometry (ERA) showed in over 30% of all dyslectic children a two phasic curve with two negative deflections. Most of these pathological curves could be separated into groups by superimposing them accordingly to the first and second negative deflection.


[Aromatic N-mustard compounds. 1. Derivatives of 3-N, N-bis-(2-chlorethyl)amino-4-methylbenzoid acid]. Twenty-seven new derivatives of the 3-N,N-bis-(2-chlorethyl)-amino-4-methyl-benzoic-acid were synthesized and pharmacologically examined. The compounds showed to be highly active in the in vitro-vivo screening models (Crocker sarcoma 180, Sa-180; Friend virus leukemia, FVL) but less active in the in vivo screening models (leukemia L-1210; L-1210; Nemeth-Kellner lympho-sarcoma, NKL). The in vivo tumor growth inhibitions show that this class of compounds has possibilities for further improvement.


Effect ofO-(beta-hydroxyethyl)rutoside on intestinal tract cells following partial body irradiation. In the present study the influence of O-(beta-hydroxyethyl)-rutoside (HR) on the intestinal cells of irradiated mice was investigated. The mitotic activity in the duodenum after irradiation of the abdomen with 800 and 1200 R was shown to be significantly increased during the recovery phase after application of HR. The number of irradiation induced stem cell pycnoses was markedly reduced by HR in the case of both radiation doses. The initially decreased incorporation rate of H3-thymidine was found to increase more rapidly during the first few hours after irradiation in animals pretreated with HR than in those untreated. Cytogenesis of goblet cells, in the duodenum proved to be favourably influenced by HR. During the recovery phase the values were found to be above those observed in the control group and in the untreated animals. The mitosis free interval in the rectal cells immediately after irradiation proved to be shortened in the pretreated animals and the re-increase of the mitotic activity was found to be accelerated. The number of cell pycnoses was also markedly reduced after application of HR, while the incorporation rate of H3-thymidine was accelerated. The radiosensitivity of the goblet cells was not influenced by HR. Disorders in differentiation of the muciferous cells were observed in both test groups.


[Comparative studies of oral "quick-release" and "slowrelease" iron preparations in the postabsorption serum iron concentration test]. In Heilmeyer's iron-loading test the iron preparation SA (Eryfer) proved greatly superior to a commercially available effervescent tablet (iron preparation SC), to an iron preparation in a sustained release from (iron preparation SD) and to an iron preparation in the form of enteric-coated pellets (iron preparation SE), in producing and maintaining an increased serum iron level. As compared to a sodium bicarbonate-free preparation (iron preparation SB) the iron preparation SA must be considered equivalent. The results of our investigations made with iron preparation SA are supported by experiences made by other authors with therapeutic application.


[Experiences with niflumic acid in inflammatory glomerulopathies]. Thirty patients with histologically ascertained blomerulonephritis and proteinuria were treated over an average period of 4 months with 750 mg/die 2-m-trigluoromethylanilino-nicotinic acid (niflumic acid, Actol). The following was shown: 1. In 73% of the cases the proteinuria diminished. 2. Kidney function remained unchanged, that is, it worsened only in such cases in which there was already limited functioning. 3. In case of initially increased values the secretion of fibrinogen degradation products diminished in 70% of the cases. 4. When the medication was stopped, its effects vanished. Niflumic acid shows to be an effective drug in the treatment of the nephrotic syndrome and the number of complications is smaller due to the improved condition of protein metabolism. Therefore, this form of treatment, in certain ways, influences the prognosis of the disease.


Therapy of depression by phenylalanine. Preliminary note. To 23 subjects with endogenous depression after a previous unsuccessful treatment with common antidepressive drugs (imipramine-like or MAO inhibitors) dl- or d-phenylalanine was given in dialy oral doses of 50 or 100 mg during 15 days. A complete euthymia was obtained in 17 subjects between one and 13 days of treatment. No important adverse reaction was observed.


[Relations between chemical structure, physico-chemical properties, chemical reactivity and effect of various positionally isomeric local anesthetics 31.2]. 1. In the introduction, a short survey on the effect of different structural isomers on the activity of drugs is giben. The inductive, resonance and steric effect of the ring substitution are discussed and probable mechanism of local-anesthetic action is dealth with. 2. As model substances in this work, the diethylamino-ethyl-ester-hydrochlorides of amino-, butylamino, butoxy- and butyl-benzoic acids are synthesized and their purity tests as well as the spectroscopic identifications are made. Further more the data on the pKa, ionisation degree, turbidity pH, water solubility of the bases, partition coefficient and the surface activity of these substances are given. 3. The electron density of the carbonyl groups (sigma-values and IR-frequencies), the hydrolysis constants and the protein-binding values are studied as the measure of the chemical reactivity of the model substances. 4. Although a fairly good correlation between different physico-chemical properties of these substances was found, a satisfactory correlation of the hydrolysis constants, the partition constants, the electronic densities as well as the sigma-constants to the local anesthetic activity of these substances is compared only in the p-substituted compounds. For the inconsistency in the o- and m-derivatives, the steric effect of the substituents could be called responsible.


Dissolution and polymorphism of metolazone. The solubility and dissolution rate of five different solid forms of 7-chloro-1,2,3,4-tetrahydro-2-methyl-4-oxo-o-tolyl-6-quinazoline-sulfonamide (metolazone) in n-butanol, water and 0.01 n HCl are investigated and thermodynamic values have been computed. The amorphous metolazone dissolves about 8 times faster than the stable modification I (mp. 267-270 degrees C) in 0.01 n HCl at 37 degrees C.


[Metabolism of retro-progesterone and 17-hydroxy-retro-progesterone]. In comparative studes, the metabolism of retro-progesterone (9 beta,10alpha-pregn-4-ene-3, 20-dinoe) and 17-hydrozy-retro-progesterone (17-hydroxy-9 beta, 10 alpha-prgn-4-ene-3, 20-dione) as well as of progesterone and 17-hydroxy progesterone was investigated. The microsomal fraction from rat tests served as enzmye preparation. Whereas progesterone was metablised to 17-hydroxy-progesterone, testosterone and androstendion, retno-progesterone did not yield the corresponding reaction products. 16 alpha-Hydroxy-retro progresterone was found to be the main metabolite of retro-progesterone and identified by gas-liquid chromatopgray/mass spectrometry. In contrast to 17-hydroxy-progesterone,  no transformation of 17-hudroxy-retro-progesterone to C19-steriods was observed. From these experiments, it can beconcluded that C21 -retro-steriods are not attacked by the 17alpha-hydrozylase and the C17-C20-desmolase of mammalian origin.


Pharmacological action of FD-008, a new dopamine beta-hydroxylase inhibitor. I. Effects on blood pressure in rats and dogs. Hypotensive action of a new dopamine beta-hydroxylase (DBH) inhibitor, 5-(4'-chlorobutyl)picolinic acid (FD-008) was investigated in dogs and rats. FD-008, which is one of the most potent inhibitors among fusaric acid derivatives, decreased blood pressure in spontaneously hypertensive rats relatively parallel to DBH inhibition in vitro. The effect of FD-008 on blood pressure was stronger in hypertensive rats than in normotensive rats. No cumulative effect was observed in rats by repeated administration, On the other hand, repeated administration was required to lower blood pressure in normotensive dogs. The acute effect of FD-008 on blood pressure of anesthetized dogs was somewhat different from that of its mother compound, fusaric acid.


[Modification of hematotoxic effects of cyclophosphamide by anabolid steroids]. Human malignant tumors have been shown to be highly resistant to the chemotherapeutic agents so far available. Since these have to be administered in high doses, hematotoxic effects occur frequently during such treatment. Androgens and anabolic steroids being potent stimulators of normal and of some forms of impaired erythropoiesis, studies were initiated in rats to assess the possibility of a protective role of these steroids against the toxicity of cyclophosphamide. The following results were obtained: 1. A single dose of cyclophosphamide (100 mg/kg) significantly lowered the erythrocyte, reticulocyte, hemoglobin, leucocyte and platelet counts. 2. An initial treatment with nandrolone phenylpropionate signifiantly reduced the decrease of both the erythrocyte and the hemoglobin counts. 3. An initial treatment with metenolone enanthate (Primobolan-Depot) completely prevented the reduction of erythrocytes in appropriate experimental conditions and significantly reduced the decrease of hemoglobins. 4. There was no effect of these steroids on the drop of granulocytes, lymphocytes and platelets. These observations suggest that combination of anabolic steroid therapy with cyclophosphamide therapy may be worthy of clinical trial in patients whose tumors are not subject to growth stimulation by androgenic steroids.


Biochemical effects of 2-aryl- and 2,3-diarylindoles on the biosynthesis of zoxazolamine hydroxylase in rats. In continuation of our pharmacological research on the in vivo induction or inhibition of the drug metabolizing enzymes system, a series of 32 derivatives of indole bearing aryl substituents in position 2 and 3 were investigated in regard to their effect on the in vivo synthesis of zoxazolamine hydroxylase in the young rat. Most fo the compounds examined proved to be inducers of this enzyme; however, as is the case with polycyclic carcinogens, the inducing activity was found to be significantly dependent on molecular structure.


[Stimulation of the acid secretion of the stomach in rats with and without antrectomy in the perfusion test with betazole]. In the perfusion test of the stomach of rats the stimulation of acid secretion by betazol (Histalog) after one or repeated injections was studied. The experiments yielded the following results: 1. The i.v. injection of 20 mg/kg b.w. betazol was followed by a maximun acid secretion. 2. Another infusion two hours later intensified this effect. The same acid secretion was seen after a small initial dose (5 mg/kg b.w.) half an hour before the infusion of betazol. 3. The i.v. infusion of 30 mg/kg b.w. betazol showed in the intact rat stomach a smaller acid dsecretion response than did the dose of 20 mg/kg b.w. In comparison there was a significant higher stimulation with 30 mg/kg b.w. betzaol in the rat after a distal gastrectomy (antrectomy). 4. One s.c. injection of 50 mg/kg b.w. betazol showed a significant acid response of the parietal cells with a duration of at least 7 h on a percentage comparison.


Chemistry and pharmacology of naproxen.

Chemistry and pharmacology of naproxen. The need for a nonsteroidal anti-inflammatory agent effective in rheumatoid arthritis, osteoarthritis, gout, ankylosing spondylitis and related diseases with reduced side effects when compared to existing drugs led us to develop naproxen: d-2-(6'-methoxy-2'-naphthyl)-propionic acid. This new agent is a highly effective anti-inflammatory, analgetic, and antipyretic agent in the rodent administered orally. In a rat paw edema test for anti-inflammatory activity naproxen was 55 times more active than aspirin. Analgetic activity was assessed by three different assay procedures. In the mouse phenylquinone writhing test naproxen was 7 times as effective as aspirin. In the rat yeast-induced paw edema and the rat carrageenin paw edema analgetic assays the test compound was 10 and 20 times more effective than aspirin, respectively. A yeast-induced pyresis model in the rat indicated that naproxen was 22 times more potent than the standard aspirin. The relative potency of naproxen to phenylbutazone and indometacin is presented.


[Effect of naproxen on the semiconservative DNA synthesis and DNA repair of various cell systems]. d-2-(6'Methoxy-2'-naphthyl)-propionic acid (naproxen) in different concentrations was investigated as to its influence on the semiconservative DNA synthesis and DNA repair of human lymphocytes and mouse speen cells. As could be shown, there was a slight diminuation of the DNA synthesis. In view of a desired antiproliferating effect in the treatment of rheumatic diseases this fact could certainly prove useful. Additionally, with a naproxen concentration of 30 ppm, a diminuation of the endonuclease activity in mouse spleen cells could be shown. With naproxen concentrations higher than 60 ppm a slight lowering of the exonuclease and polymerase activities in mouse spleen cells as well as in human lymphocytes were observed. With naproxen in a concentration of 120 ppm, all three enzymes of the excision repair investigated showed a distinct loss of activity. Results of investigations on ligase activity will be presented separately. Under the administration of naproxen, late effects on the genetic material are rather improbable, as long as the substance is not admininstered concomitantly with agents which have a direct effect on the DNA.


[Effect of naproxen on DNA synthesis and DNA repair of human lymphocytes in in vivo experiments]. This investigation was conducted in order to evaluate the possibility of late defects caused by drugs. After their base-line blood levels had been assessed, 3 patients with classical rheumatoid arthritis (according to ARA criteria; American Rheumatism Association) received 500 mg of d-2-(6'-methoxy-2'-naphthyl)-propionic acid (naproxen) daily (in capsules). At the peak of naproxen blood levels following the first naproxen dose, and once monthly for 7 months, thereafter, blood samples were drawn. After separating the lymphocytes from the whole blood, they were damaged by means of 60-Co. Hydroxyurea was added for the suppression of their semiconservative DNA-synthesis. The incorporation of 3-H-THYMIDINE INTO THE DNA of the cells was measured after radiation at different incubation periods. The results showed normal behaviour of the DNA-synthesis following naproxen administration in all three patients. The DNA-repair capacity was normal in one female patient, but slightly lowered in the remaining two.


[Naproxen, a 'specific" antirheumatic drug?]. Inhibition of endonuclease by d-2-(6'-methoxy-2'-naphthyl)-propionic acid (naproxen) is discussed as a possible therapeutic principle of the antiinflammatory action in polyarthritis. Infections by 'slow viruses" and mycoplasma have to be considered as possible etiologic factors for rheumatoid arthritis. The incorporation of the viral or mycoplasmatic DNA into the genetic material of the host cell depends on the function of endonucleases, which can be inhibited by naproxen. The advantages and the drawbacks of this type of mechanism of action are discussed.


[Steroid saving effect of naproxen].

[Steroid saving effect of naproxen]. Since for various reasons the Lansbury Index appeared inadequate to define the therapeutic efficacy of antirheumatic compounds, we chose to investigate in our trials the prednisolone saving effect in patients with rheumatoid arthritis. Our investigations with the new antirheumatic substance d-2-(6'-methoxy-2'-naphthyl)-propionic acid (naproxen) in most cases showed a prednisolone saving effect of 5 mg/day with a naproxen dose of 750 mg daily. In cases where a daily dose of 10 mg of prednisolone was necessary, a saving of 7.5 mg up to 10 mg was registered. But there were also failures and lesser saving effects. The steroid saving effect differs from one individual to another. In an additional study naproxen in a daily dose of 500 mg was compared with other antirheumatic agents (indometacin, azapropazon, and nifluminic acid) in patients not requiring steroids. The results were not uniform. In some cases naproxen was more effective, in other cases the substances mentioned were better. In these series joint function and subjective changes only were evaluated. Apart from a few cases of gastrointestinal side effects the drug was well tolerated.


[Experiences with the effect of naproxen in chronic and degenerative diseases as in overload conditions of the postural and locomotor system]. At the Orthopaedic University Clinic, Homburg, a total of 127 patients was treated with d-2-(6'-methoxy-2'-naphthyl)-propionic acid (naproxen) from June 1973 up to June 1974. The indications were chronic degenerative changes of the joints, muscles and tendons. In the first series naproxen was administered orally. In these 45 cases a very low rate of side effects was observed. Only 4 times nausea or vomiting occurred, which in one case had been caused by an overdosage. Generally tolerance was excellent and there was a very good relief of symptoms in early all patients. Particularly in those patients whose arthrotic alterations did not yet require surgical intervention the effect as to symptomatology was extremely good. In a second series initially 63 patients and, later on, another 19 patients were treated with naproxen suppositories. As before, concomitant medication was avoided. The therapeutic results were mostly very good to good, and only in a few cases no success was seen. It should be mentioned, however, that after application of the suppositories, a few patients noted a slight local burning after insertion of the suppository. Also blood in the feces and circulatory symptoms were reported. We believe that naproxen can achieve a very good improvement of subjective symptoms, particularly when combined with other therapeutic measures such as physiotherapy and intra- or periarticular injections. This drug should not only be used in the conservative treatment of degenerative joint diseases, but also -- as shown by our experience -- after palliative surgical procedures employed in the treatment of severe arthroses. Also in these cases a positive influence on the symptoms can be achieved.


Radioactive contamination of the environment and the possible consequences. To find the optimum solution to the problem of how to protect the environment from pollution by industrial waste, it is necessary, first and foremost, to obtain information on the existing levels of various forms of pollution and the damage caused by them. In this review data are given on all the main sources of contamination of the environment by radioactive substances. The pathways by which these substances reach and affect the human body are discussed, the doses incurred are characterized and the possible consequences of existing levels of exposure are assessed in the light of the latest data on the dose-effect relationship. The wisdom of treating the evaluation of radiation hazards arising from the use of atomic energy not in isolation but as part of a whole complex of ecological factors - including the use of conventional fuels for power generation and transport - is duly noted.


Changes in the rumen metabolism of sheep given increasing amounts of linseed oil in their diet. 1. Linseed oil was incorporated gradually into the diet of four sheep until the animals received 90 g additional fat/d. Attempts were made to measure changes in concentration of substances and rates of synthesis in the rumen directly, and by incubation of rumen contents in vitro (zero-time technique). 2. The high-fat diet increased the dilution rate and the volume of rumen contents and decreased the synthesis of diaminopimelic acid in the rumen. The number of protozoa decreased and the number of bacteria increased in the rumen of animals receiving the high-fat diet. 3. The concentration of volatile fatty acids (VFA) in the rumen decreased for sheep given the high-fat diet, but the capacity of rumen contents to produce VFA in vitro increased. 4. The incorporation of radioactivity from [14C]acetate into lipids during incubation of rumen contents vitro increased with the amount of linseed oil in the diet. The greatest proportional increase was with the bacterial fraction of rumen contents. 5. In the group of four animals used, one animal showed consistent differences in the magnitude of the measured varibles. This animal appeared to have a smaller rumen, a lower dilution rate and larger concentrations of some substances in the rumen. A higher proportion of fatty acids appeared to be synthsized by the micro-organisms from this animal.


The contribution made by school milk to the nutrition of primary schoolchildren. 1. The contribution of school milk to the nutrition of 396 Kent primary schoolchildren aged 8-11 years was assessed using information collected in a survey which included a weighed-diet record, a socio-economic questionnaire and a medical examination. 2. Over half the children (59% for boys, 54% for girls) drank school milk every school day of the diet-record week. 3. Children who drank school milk every school day, when compared with those not drinking it, had a significantly higher mean daily intake of liquid milk, a higher total daily intake of several important nutrients including animal protein, calcium, thiamin and riboflavin, and a diet richer in Ca and riboflavin (boys) and animal protein and Ca (girls). They were also less likely to have intakes of Ca and riboflavin below the recommended daily intakes for these nutrients, (Department of Health and Social Security, 1969). 4. The increased nutritional intake associated with school milk consumption was not related to any differences in height, weight, arm circumference or skinfold thickness. 5. There was no evidence that school milk consumption was associated with obesity (as assessed clinically).


Effect of metopirone on the synthesis of lung surfactant in does and fetal rabbits. The possible role of endogenous corticosteroids in the induction of synthesis of lung surfactant in both maternal and fetal rabbits was investigated. Metopirone (SU 4885), which specifically inhibits B hydroxylation in the adrenal gland, thus preventing endogenous cortisol production was used in this study. Pregnant rabbits received one of four treatment regimens: saline, metopirone, cortisone or metopirone plus steroid for 6 days before delivery. Studies of the lungs of the adult rabbits revealed that lung weights and percent dry weight were not influenced by drug injection. However, lung DNA content (mg/g) in the metopirone-treated group was higher than the control group, indicating an increase in cell number. Compared to the saline-treated group there was a significant decrease in lung phospholipid content in the other three groups (p smaller than 0.005). A decrease in lung lecithin and phosphatidylethanolamine was also noted in these three groups indicating that the inhibition was in the early steps of biosynthesis of lung lecithin. The specific activity of 14C-labelled palmitate in lung lecithin was not altered by drug treatment indicating that saturated fatty acid incorporation into lung lecithin is not influenced by metopirone, steroid or a combination of both drugs. Quasi-static deflation pressure-volume characteristics of the lung were also similar in all groups. However, lungs of animals receiving both metopirone and steroid had a small but statistically significant decrease in minimum surface tension (p smaller than 0.05). The change in surface tension did not correlate with a change in lung retractive forces or with lung lipid content and was, therefore, of dubious biological significance. Metopirone administration to pregnant rabbits did not alter surface active properties in the fetus from the 26th to the 29th day of gestation when compared to control fetuses. At day 30-31 gestation the offsprings of metopirone-treated rabbits had lung total phospholipid and lecithin contents, and deflation pressure-volume curves similar to control group, but minimum surface tension of minced lung extracts were high in about 60% of the fetal lungs studied (p smaller than 0.05). These results suggest that endogenous steroid production may play a significant role in the maturation of the fetal lung.


The Twin Cities biomedical consortium.

The Twin Cities biomedical consortium. Twenty-eight health science libraries in the St. Paul-Minneapolis area formed the Twin Cities Biomedical Consortium with the intention of developing a strong network of biomedical libraries in the Twin Cities area. Toward this end, programs were designed to strengthen lines of communication and increase cooperation among local health science libraries; improve access to biomedical information at the local level; and enable the Consortium, as a group, to meet an increasing proportion of its members' needs for biomedical information. Presently, the TCBC comprises libraries in twenty-two hospitals, two county medical societies, one school of nursing, one junior college, and two private corporations.


A description of the catalog division project at the College of Physicians of Philadelphia Library. This paper describes the procedures used at the Library of the College of Physicians of Philadelphia to divide its ninety-year-old dictionary card catalog. The division was necessitated by overcrowding, obsolete subject headings, and lack of a complete authority list which resulted in like materials being scattered throughout the catalog under several headings. Two catalogs were created: the historical-biographical catalog, representing all works published before 1950 and all works of historical or biographical nature; and the current catalog, containing all works published from 1950 on, excepting historical or biographical materials. The 1950-    catalog was further divided into name and subject catalogs, and the subject section was revised according to MeSH. The project was completed in about two years. As a result, searching time has been much reduced, and the library is able to take advantage of the annual revisions of MeSH to update the subject catalog.


A second cell type in Stannius bodies of two euryhaline telecost species. In the corpuscles of Stannius of sticklebacks and eels two cell types are described of presumably endocrine nature. The predominating type, comparable to the cells observed in other species, responds to variation in calcium content of the medium and possibly produces a hypocalcemic hormone. The second cell type is unreactive to calcium. Since it is more active in freshwater than in seawater specimens, this cell type is possibly involved in ionic regulation. It was not found in two seawater teleost species.


Tyrosinemia and tyrosyluria in healthy prematures: time courses not vitamin C-dependent. Tyrosyluria and for a part also tyrosinemia were studied in 60 healthy prematures of various birth weights and gestational ages. The first analyses were performed between the 6th and the 14th day after birth. A normal milk diet was given and the protein-intake was between 3 and 4 g/kg. After the first collection of urine half the patients received extra ascorbic acid, 100 mg/kg daily. Urinary analyses of tyrosine and p-hydroxyphenyl metabolites were performed once a week, until the excretion of p-hydroxyphenylpyruvic plus p-hydroxyphenyllactic acids was lower than 5 mmoles per gram creatinine. In 22 out of the 60 prematures (or 37%) a tyrosyluria of more than 5 mmoles/g creatinine and in 19 out of 44 (43%) patients analysed serum tyrosine was higher than 5 mg/100 ml at first analysis. No inverse correlation between tyrosyluria and tyrosinemia on the one hand and birth weight and gestational age on the other hand existed. But in children with a delayed intra-uterine development the incidence of tyrosyluria was higher as prematurity was more pronounced. Ascorbic acid had no effect on the rate of disappearance of tyrosyluria. It was concluded that the addition of extra vitamin C to the diet of prematures is not useful for the normalization of tyrosine metabolism.


Studies on human iodide peroxidase: its activity in various thyroid disorders. Iodide peroxidase activities in the human thyroid gland were measured in various thyroid disorders. The peroxidase activities in the thyroid gland revealed high values in Graves' disease, normal levels in thyroid adenoma and low values in thyroid carcinoma as compared to those in normal thyroid glands. A high activity of this enzyme was observed in toxic adenoma. The same results were observed whether 10% (W/V) homogenate or mitochondrial and microsomal fractions of the thyroid gland were used.


Ultrasonics in the diagnosis of thyroid disease. Ultrasonic A scans of the thyroid have been carried out on 47 patients with suspected thyroid disease. It was possible to measure the antero-posterior diameter of each lobe and to identify whether the tissue was homogeneous, nodular or cystic. Measurement of individual nodules or cysts was accurate to within 5 mm when compared with the tissue removed at operation. Ultrasonic examination was able to differentiate other lumps, in the neck from those arising in the thyroid gland. It is concluded that ultrasonic examination of the thyroid is a useful adjunct to other conventional tests and deserves to be used more widely.


Proliferative patterns in the mouse jejunal epithelium after fractionated abdominal x-irradiation. Cell proliferation was studied in the intestinal epithelium of mice exposed to fractionated abdominal X-irradiation. Exposures were separated by 12, 24, 48 or 72 hr. Labelled nuclei and mitotic figures per crypt using the crypt squash technique were determined at closely-spaced time intervals (1 to 96 hr) after 1, 2, 3, 5, 7 and 9 exposures. Cell cycle times including estimates of G-1, S, G-2 and M were determined at 12 and 24 hr. These data show that the intestinal epithelium has a remarkable potential to repair damage and recover following severe injury if sufficient time is allowed for the acceleration in proliferative activity. The damage-repair-recovery pattern, i.e., increase in size of proliferative population and acceleration of the generation cycle, is similar for single and fractionated exposures. The number of 300 R exposures which can be tolerated by a highly organized in vivo cell population is dependent upon time interval between fractions; e.g., when interval between fractions is 12 hr eight 300 R exposures kill all animals, but when the interval is increased to 72 hr some animals survive 20 doses, although time of death is highly variable. The compensatory recovery potential is maintained over a large number of exposures.


Ability of the leprous macrophage to accept cytophilic antibodies. The ability of leprous macrophages to accept cytophilic antibodies was not damaged. Blood macrophages derived from both types of leprosy formed rosettes with cytophilic antibody sensitized goat red cells. The rosette forming rates of tuberculoid (65.0%) and lepromatous macrophages (66.4%) were essentially the same as that of normal blood macrophages (68.8%).


Clinical studies on thyroidal autoantibodies. In an attempt to clarify autoimmune nature of Grave's disease and Hashimoto's thyroiditis, thyroidal autoantibodies have been studied on 86 cases of Grave's disease, 54 cases of Hashimoto's thyroiditis, 31 cases of simple goiter, 11 cases of primary hypothyroidism a-d 22 cases of thyroid neoplasia as well as on 364 healthy subjects.  Two kinds of tanned red cell hemagglutination tests were carreid out on each case.  One method using refined human thyroglobulin for sensitization of sheep red cells has been found to be specifice for anti-thyroglobulin antibody and to be frequently positive in Hashimoto patients.  However, in another method using human thyroidal microsomes (purified by ultracentrifugation) as sensitizing antigen, some heterogenous antibodies including anti-thyroglobulin antibody might be detected together with the antibody against the antigen proper to thyroidal micorsome (HF antigen)which is derived from hyperfunctioning thyroidal follicular cells of Grave's patients.  hAnti-HF antibody is frequently detected both in Hashimoto and Grave's patients.  In other thyroid diseases the titers of both thyroidal autoantibodies were generally low, though higher than in healthy subjects.  The effect of aging on thyroidal autoantibodies in healthy subjects was clearly observed in females but not in males.  From the results of these two test, it is possible to speculate that high=columnar and hyperfunctioning thyroidal follicular cells might exist focally in most cases of Hashimoto's thyroiditis.


The interaction of hemicholinium-3 (HC-3) with cholinomimetics and atropine. In either spontaneously beating or electrically driven atrial preparations of the guinea pig HC-3 (0.01-1 mM) inhibited negative inotropic responses to acetylcholine or carbachol. Although there was a parallel rightwards shift of the log concentration--response curves for acetylcholine or carbachol and no depression of the maximal response the type of antagonism was not competitive as the relationship between dose ratio -- 1) and concentration of HC-3 was not linear over the whole range investigated. A lesser degree of antagonism than expected for a competitive antagonist was observed with higher concentrations of HC-3. HC-3 was a more effective antagonist of responses to carbachol than to acetylcholine and pretreatment of animals with dyflos did not modify this difference. In addition, HC-3 was found to antagonize the inhibitory action of atropine on responses to acetylcholine and to a lesser extent carbachol. The results can be explained in terms of the interaction of HC-3 at a regulatory site distinct from the binding sites for cholinomimetics and atropinics. Interaction of HC-3 at the postulated site produces a noncompetitive antagonism of both agonists and competitive antagonists by modifying the affinities of the compounds for their respective binding sites.


A review of bromine determination in foods. Organic compounds containing bromine, including methyl bromide, ethylene dibromide, and 1,2-dibromo-3-chloropropane, have been used extensively for the fumigation of foods, or soils in which foods grow, making it necessary to determine residues of bromine and bromine-containing organic compounds. A large number of methods for the determination of bromine in foods, as organic, inorganic, and combined total bromide, have been developed. In methods for organic bromide, the bromine is converted to the inorganic form for measurement by titration, photometry, or other means. In recent years, instrumental methods have been developed in which the total bromine in the sample is determined, regardless of the state in which it exists. X-ray fluorescence and neutron activation analysis are the 2 instrumental methods used most widely. Residue data are presented for some typical bromine-containing samples.


Collaborative study of a rapid method for determing aflatoxins in cottonseed products. Eleven laboratories collaboratively studied a modification of the official final action AOAC method, 26.048-26.056, for determining aflatoxins in cottonseed products. An aflatoxin-negative meal, 6 contaminated meals, 4 contaminated meats (kernels) samples, and 2 ammonia-inactivated meals were used. Mean aflatoxin values, mug/kg, ranged from 6 to 223 (B1), 2 to 44 (B2), and 7 to 266 (total: B1 + B2). Only one laboratory reported a false-positive for the negative meal. The mean coefficients of variation for B1, B2, and total were 28, 56, and 29%, respectively, for meals; 35, 54, and 37%, respectively, for meats; and 35, 58 and 38%, respectively, for ammoniated meals. Statistical treatment of data from triplicate sets of meals and meats showed evidence for systematic error between laboratories. Since the modified method is considerably faster than the official method and yields precision estimates consistent with previous AOAC collaborative studies on determining aflatoxins, the method has been adopted as official first action.


Gas-liquid chromatographic determination of total cholesterol in multicomponent foods. A method is described for the determination of total cholesterol in multicomponent foods and also other products such as nonfat dry milk, dried whole egg solids, and certain candy bars. The lipid is extracted from the sample by a mixed solvent and saponified. The unsaponifiable fraction which contains the cholesterol and other sterols is extracted with benzene. An aliquot is evaporated to dryness and the residue is dissolved in dimethylformamide. The sterols are derivatized to form trimethylsilyl (TMS) ethers. The TMS-cholesterol derivative is quantitatively determined by gas-liquid chromatography, using 5alpha-cholestane as an internal standard. Nine laboratories participated in a collaborative study of the determination of total cholesterol in deviled ham sandwich spread, vegetable beef stew, corned beef hash, frozen chicken pot pie, pizza pepperoni, fish sticks, breaded shrimp, chocolate-covered candy bars, dried whole egg solids, and nonfat dry milk and the results are reported here. The coefficient of variation ranged from 5.64 to 23.2%, with an average coefficient of variation of 14.8%.


In vivo protein secretion by lung. Evidence for active secretion and interspecies differences. The present study is an attempt to determine (a) if the lung actively secretes protein into the surface-active fraction of lung lavage returns; (b) if there are interspecies differences in this secretory activity; and (c) if the amount of nonradioactive protein in the lavage surface-active fraction shows interspecies variation. I found that pilocarpine stimulates the release of radioactive protein into the lavage surface-active fraction of rabbits and that this pilocarpine effect is completely blocked by atropine. Inhibition of lung oxygen consumption by iodoacetate is associaged with a dose-dependent inhibition of the pilocarpine-induced secretion. Microtubules may be involved in this secretory process because colchicine inhibits the pilocarpine effect. Of the radioactive protein in the total surface-active fraction (tissue plus lavage returns), a greater percent appears in the lavage surface-active fraction at 2 and 4 h, after a pulsed injection [U-14C] leucine, in the mouse than in the rat, which in turn has a greater amount than the rabbit. There is also a difference in the amount of nonradioactive protein per square meter of alveolar surface area in the lavage surface-active fraction of different species: mouse greater than rabbit greater than cat greater than dog. The amount of nonradioactive protein per square meter of alveolar surface area in the lavage surface-active fraction is directly proportional to the species respiratory rate; the log of the nonradioactive protein in the lavage surface-active fraction is inversely proportional to the log of the species alveolar diameter. I conclude that the lung actively secretes protein into the lavage surface-active fraction, that this secretion is under neurohumoral regulation, and that respiratory rate and alveolar size may influence this secretory activity and the amount of protein in this surface-active fraction.


Beverage consumption patterns in New York State. Beverage consumption rates for consumers between twelve and sixty-five years of age in three New York cities were estimated, using a 24 hr. recall procedure with each of the 8,492 respondents. Individual consumers were interviewed to collect detailed data on the type and quantity of beverage, time of day, and place of consumption (home or away from home). Data on mean per capital consumption and market penetration were computed for seven beverage categories and are summarized according to age, sex, race, and market classifications. Data are also presented concerning consumption at home and away from home, during both meal and non-meal periods. Differences appeared in comparisons of adults vs. teenagers, males vs. females, and Upstate vs. New York City respondent.


Suppression of progesterone secretion in lactating rats by administration of ergocornine and the effect of prolactin replacement. In order to assess the stimulatory effect of prolactin on the secretion of progesterone from corpora lutea in lactating rats, ergocornine meleate (ECO; 1 mg/day), an inhibitor of prolactin secretion, was administered subcutaneously on days 6 and 7 of lactation in primiparous rats. By day 8 of lactation, the concentration of progesterone in ovarian venous blood fell to a undetectable level in the ECO-treated animals, while the concentration in the control animals was very high at this stage of lactation. The level of 20-alpha-hydroxypregn-4-en-3-one was significantly higher on day 8 of lactation in ECO-treated than in control rats. Lactational dioestrus was interrupted by treatment with ECO and vaginal oestrus appeared 3-4 days after the start of treatment. Administration of ECO caused deleterious depression of milk production and of food intake of mother rats. In the pair-fed control animals, lactation continued almost normally throughout the experimental period. Prolactin (1 mg/day) administered simultaneously with ECO increased progesterone to levels even higher than those in control rats and restored 20-alpha-hydroxypregn-4-en-3-oen levels to those of the controls. The effect of the drug on milk production was alleviated. The results strongly suggest that prolactin is the most important factor in maintaining the function of corpora lutea in the lactating rats.


Adverse reactions to intrathecal saline injection for control of pain. The authors report the results of a questionnaire regarding the use of hypertonic saline for the control of pain. Of 2105 patients so treated, nearly 11% had an adverse temporary symptom or sign, reported as an untoward reaction; slightly over 1% suffered a significant morbidity, of which paraplegia or quadriplegia was by far the most common, and two patients died (0.1%).


Hyperreactivity to cow milk in young children with pulmonary hemosiderosis and cor pulmonale secondary to nasopharyngeal obstruction. Six black infants and young children with high titers of milk precipitins were identified by screening the sera of 160 children with idiopathic chronic lung disease. None of the six had immunoglobulin deficiency, elevation of sweat chlorides, SS hemoglobin, or recurrent aspiration. All six children had typical manifestations of milk-induced pulmonary hemosiderosis: recurrent pulmonary infiltrates (6/6), hemosiderin-laden pulmonary macrophages (5/6), intermittent wheezing (5/6), eosinophilia (4/6), anemia (4/6), iron deficiency (4/4), failure to thrive (4/6), and elevated levels of serum IgE (4/4). Three children also had chronic rhinitis and eventually developed large adenoids, hypercapnia and acidosis during sleep, and right heart failure. Elimination of cow milk from the diet, symptomatic therapy, and adenoidectomy when indicated resulted in improvement of all six patients. Pulmonary hemosiderosis and some cases of upper airway obstruction with pulmonary hypertension appear to be two stages, early and delayed, of the same immunophysiologic process. Early dietary intervention may prevent the cardiovascular complications of this process.


The kinetics of methotrexate distribution in spontaneous canine lymphosarcoma. A mathematical model is presented to simulate the time-dependent uptake of methotrexate in spontaneous canine lymphosarcomas in vivo. Blood flow ratew in these tumors are high so that transport to the tumor is limited by cell membrane resistance. A significant amount of rapidly exchangeable methotrexate appears to exist in extracellular space loosely bound to proteins or cell membranes. Transmembrane drug transport follows Michaelis-Menten kinetics, wigh the maximum facilitated transport ranging from 0.002 to 0.007 mug/min/ml for the separate tumors studied and a Michaelis constant for transport equal to 0.2 mug/ml. This is in the range of Michaelis constants reported for normal tissues in rats in vivo and in several cell linnes in vitro.


Cardiac arrest related to anesthesia.  Contributing factors in infants and children. A collaborative retrospective study undertaken to investigate cardiac arrest related to pediatric anesthesia in seven institutions between 1960 and 1972 showed 73 instances in which anesthesia was thought to have been either directly responsible or had played an important contributing role.  About two thirds of these patients were successfully resuscitated.  Cases were found to fit into one of two major categories: cardiovascular and respiratory.  Among cardiovascular factors, blood loss, preoperative anemia, inappropriate administration of succinylcholine, and accidental administration of potassium were important contributing causes.  Respiratory factors included failure to maintain a patent airway and ventilatory problems.  In retrospect, most of these accidents were preventable.  Such information should indicate where research emphasis needs to be placed and that our current methods of teaching and training need to be reevaluated.


Management of hypertension.  Effect of improving patient compliance for follow-up care. A radomized controlled trial was conducted in a metropolitan teaching hospital to determine whether improving follow-up of emergency room patients who had hypertension led to improvements in their medical care and blood pressure control.  One hundred fourty four patients were randomly assigned into an intervention group and a control group.  In the former, a follow-up clerk assigned patients in returning for follow-up care.  Eighty-four percent of patients in this group and 63% of control patients returned to the clinic (P less than 0.1).  However, five months after the patients' emergency room visits, 51% of patients in the intervention group and 53% of control patients were normotensive.  There were more diagnostic and therapeutic measures in the intervention group, but long-term management was similar in both groups.  Improvement in follow-up may not be by itself lead to blood pressure control among hypertensive patients.


Hypertension.  Management in a prepaid health care project. Previous studies have shown that care for hypertension in clinical practice is not optimal.  This study consists of a review of medical records of 101 hypertensive patients enrolled in a community prepaid health care project, in which all direct costs to patients are eliminated and in which patients are known to have geographical access to care.  The results show that even under such conditions, there are deficiencies in what is done in the diagnosis and management of hypertension (process of care).  Furthermore, recorded blood pressures in the medical records indicate that 34% of identified patients had diastolic pressures greater than 95 mm Hg at the time of last visit for hypertension.


Severe hypertension.  Treatment with minoxidil. Seventeen patients who were partially or totally refractory to maximal doses of conventional antihypertensive agents were treated with minoxidil.  Three patients were receiving long-term maintenance dialysis.  Propranolol and diuretics were given to prevent reflex tachycardia and fluid retention.  Initial control of blood pressure was excellent in 16 patient.  In one patient, diastolic blood pressure remained unchanged (120 mm Hg) despite 60 mg of minoxidil and volume depletion.  In three other patients, secondary resistance developed, and the addition of guanethidine was necessary.  The main side-effects were fluid retention (in eight) and hypertrichosis (in ten), accompanied in some by a peculiar coarsening of the facial features.  Renal function stabilized or improved in most, and urine output increased in the three hemodialysis patients.  We conclude that minoxidil is a valuable drug in severe hypertension.


Outreach by primary-care physicians.

Outreach by primary-care physicians. Outreach can be accomplished by the primary-care physician if he institutes data systems that permit identification of cohorts of his patients by age, sex, diagnoses, and area of residence.  These systems were used by the Rochester Family Medical Program to identify and invite patients at risk to receive prophylactic influenza immunization, participate in an obesity treatment group, and receive screening tests for lead intoxication.


Sustained bacteremia and transvenous cardiac pacemakers. Five patients with transvenous cardiac pacemakers had sustained staphylococcal bacteremia (defined as bacteremia for at least 12 hours) two weeks to ten months after pacemaker insertion.  Three of the five patients had no evidence of an extravascular focus of infection at the time of stphylococcal bacteremia.  An additional patient had a petechial rash, which is unusual in staphylococcal bacteremia, unless endocarditis is present.  All patients were treated with antibiotics and drainage of the pacemaker packet when it was infected, removal of the pacemaker generator, or removal of the catheter electrode.  One patient without evidence of pocket infection was treated successfully with antibiotic therapy alone.


Acute myocardial infarction.  Prognostic value of white blood cell count and blood glucose level. Data obtained in the course of a nationwide study of patients with first acute myocardial infarction (AMI) demonstrated substantially higher hospital mortality among patients with leukocytosis or elevated blood glucose levels, or both.  It is suggested that the combination of these two measurements could be used as a handy diagnostic indicator in the evaluation of some AMI patients and as a criterion for the patients' immediate disposition to a coronary care unit, rather than to a general ward.


Penicillin-induced immune hemolytic anemia. Occurrence of massive intravascular hemolysis. A patient with penicillin-induced immune hemolytic anemia had massive intravascular hemolysis with hemoglobinemia and hemoglobinuria. Substantial amounts of complement components C3 and C4 were detected on the patient's red blood cells (RBCs), in addition to the usual IgG antibody to penicillin. The patient's serum demonstrated a high titer of antibody to penicillin (8,000), which did not cause hemolysis in vitro, but did cause complement fixation when incubated with normal serum. The presence of complement components on the patient's RBCs, and the finding that the serum fixed complement in vitro suggests that penicillin-antipenicillin immune complexes may have been present in the serum. We attribute the severity of the hemolysis to participation of the complement system in the hemolytic process and to the high titer of antibody to pencillin.


Startle reaction to air-bag restraints.

Startle reaction to air-bag restraints. Air bags in vehicles constitute a means of passive restraint for individuals involved in auto accidents. There is fear, however, that the inadvertent nonaccident-connected deployment of one of these air bags might substantially interfere with the handling of a vehicle in which such deployment occurred. We have found that while physiologic and physical evidence of startle accompanies such unexpected deployment, good control of the vehicle continues to be exercised by the test subjects under the conditions of our experimental protocol.


The postmortem examination. Scientific necessity or folly? Review of 252 autopsies on adult inpatients showed substantial differences between the major postmortem findings and the clinical diagnoses in 30 cases (11.9%). The clinical errors in at least half of these patients were of academic interest only. Errors in the diagnosis of malignant neoplasm occurred in 29 (25.7%) of 113 patients with cancer; however, all but three (2.7%) were of academic interest only. The results indicate that current diagnostic techniques may have decreased the value of the "routine" autopsy. Greater stress should be placed on the postmortem examination in selected cases rather than in a fixed percentage of deaths.


Endoscopy with endoscopic cholangiopancreatography. The combination as a primary diagnostic procedure. The combination of upper gastrointestinal endoscopy and endoscopic retrograde cholangiopancreatography was evaluated as a primary diagnostic procedure in 91 consecutive patients suspected of pancreatic or biliary tract disease. In 77 (85%) of the patients, the origin, nature, or extent of disease was established by endoscopy (13 patients), pancreatography (25 patients), or cholangiography (39 patients). This combined technique compares favorably with other means of diagnosing pancreatic or biliary tract disease.


The hyperperfused lung. Detection in congenital heart disease. Thirty-nine children with various cardiac abnormalities were examined with perfusion lung scintigraphy with technetium Tc 99m macroaggregated albumin. Nuclide accumulation within each lung, which is proportional to the division of pulmonary arterial flow, was determined. Twenty-six patients had hyperperfusion of one lung, with a particularly high incidence occurring with the tetraoloy of Fallot, pulmonary artery stenosis or atresia, and following surgical systemic-pulmonic anastomoses. Consistent detection of imbalance in pulmonary flow by inspection of chest x-ray films was possible when one lung received at least 2 1/2 times the blood flow of the opposite side; with angiography, flow imbalance could be recognized when flow in one lung exceeded flow in the other by only 1 1/2 times. The radionuclide quantitative method was a more sensitive means of detecting early cases of mismatched pulmonary blood flow than roentgenography, which was nonquantitative and required the presence of relatively gross perfusion abnormalities before visual perception was possible.


Help stamp out mandatory continuing education! Mandatory continuing education programs for health professionals, as they are now administered, are predictable failures. Such programs may destroy the will to learn. Objective studies indicate that current continuing education programs do not influence the methods of practice of the health professional. Current programs are primarily pedagogical, reflecting the philosophies and techniques of child-youth education. Present methods of program evaluation are sorely inadequate. Adults may be coerced into attendance, but learning and subsequent application of knowledge may not be forced. Future continuing education programs should be problem-centered. The adult practitioner must become actively involved in the planning and execution of these programs.


A surrogate system for informed consent. Since "informed consent" is frequently obtained in a clinical setting where the patient is anxious and overwhelmed with feelings, toward the physician, of awe, trust, and dependency, it is often of dubious value in protecting human subjects. We devised, as a possible alternative mechanism for uncovering patient views toward a specific research protocol, a surrogate system of consent. The surrogates' responses seemed more candid and diverse than the responses one usually hears in the "real" clinical setting. Potential applications of such a system lie in further study of the consent process, and as a means for individual investigators to better gauge consumer attitudes toward specific projects.


Corticosteroid therapy for the pregnant asthmatic patient. Corticosteroids were used during seventy pregnancies in 55 asthmatic patients. In this series there was one spontaneous abortion and 71 live births (including two sets of twins). There was no maternal, fetal, or neonatal deaths. On the basis of recorded gestation, slightly more premature births were noted in this series than would be expected in the general population. However, there was no increased incidence of toxemia, uterine hemorrhage, or congenital malformations when compared to the general population, Corticosteroids, when indicated for the treatment of severe asthma, do not appear to noticeably increase the risk of maternal or fetal complications, and thus should not be contraindicated in pregnancy.


Hyperglycemia during acute myocardial infarction. A six-year follow-up study. Fasting blood glucose (FBG) level and oral glucose tolerance (OGT) were determined in 169 patients within 72 hours of an acute myocardial infarction. Elevated FBG levels were found in 47.5% and a reduced OGT in 72.5%. Of 32 patients who died in the hospital, FBG value was elevated in 72% and the OGT was abnormal in 89%. Of 91 patients who survived longer than six years, the initial FBG level had been elevated in 33%, and the OGT had been abnormal in 67%. Eighty percent of the group with initially raised FBG values had either latent or overt diabetes, while more than 95% of the patients with initially normal FBG values had a normal OGT. Fifty-five percent of the patients with abnormal OGT during myocardial infarction showed normal OGT six years later. The FBG level shortly after an acute myocardial infarction is a better guide to prognosis and to the prediction of subsequent development of diabetes mellitus than the OGT test.


Limited form of Wegener granulomatosis. Eye involvement as a major sign. Bilateral uveitis was the initial manifestation of a limited form of Wegener granulomatosis in a 47-year-old man. Diagnosis was established by biopsy of a pulmonary nodule. Subsequently, evidence of lesions developed in the patient's central and peripheral nervous systems, but renal lesions were absent. Pulmonary lesions regressed on therapy with azathioprine and prednisone. Blindness ultimately resulted from retinal phlebitis, vitreous hemorrhages, and neovascular glaucoma.


Coronary heart disease in Western Collaborative Group Study. Final follow-up experience of 8 1/2 years. Clinical coronary heart disease (CHD) occurred in 257 subjects during eight to nine years of follow-up (average, 8 1/2 years) in a prospective study of 39- to 59-year-old employed men. Incidence of CHD was significantly associated with parental CHD history, reported diabetes, schooling, smoking habits, overt behavior pattern, blood pressure, and serum levels of cholesterol, triglyceride, and beta-lipoproteins. The type A behavior pattern was strongly related to the CHD incidence, and this association could not be explained by association of behavior pattern with any single predictive risk factor or with any combination of them.


Physician manpower and distribution. The primary care physician. This is a condensed version of the full report of the Coordinating Council on Medical Education on the Primary Care Physician. The full report is available on request from the coordinating Council on Medical Education, PO Box 7586, Chicago, IL 60680.


Today's scabies.

Today's scabies. In the past several years there has been a noticeable increase of scabies in the United States; the magnitude of this is not known. An expanding epidemic continues in most parts of the world. Scabies is frequently seen in many guises that may be difficult to diagnose: scabies in the clean, scabies incognito, nodular scabies, animal-transmitted scabies, scabies in infants, scabies with syphillis, and Norwegian scabies. If the diagnosis cannot be confirmed by identifying the mite, synthesis of suggestive features may establish the diagnosis. Recently adopted children from foreign countries, especially southeastern Asia, have had a high frequency of scabies, which may appear after the children arrive in the United States.  Acute glomerulonephritis may develop in patients whose scabetic lesions are complicated by a Virulent nephritogenic streptococcal strain.


Death patterns in sickle cell anemia.

Death patterns in sickle cell anemia. In Ibadan, Nigeria, 28 patients with sickle cell disease (hemoglobin SS and SC) died and were autopsied. Fifty percent of these had died by the age of 5 years, as did 21 (68%) with homozygous hemoglobin SS disease. No death occurred in infancy or childhood among the patients with hemoglobin SC disease. Serious intercurrent disease that could have been responsible for death was present in ten patients (36%). The type and frequency of intercurrent disease appears to be related to the environment.


Septic endocarditis and indwelling pulmonary artery catheters. A pulmonary artery catheter removed from a man with idiopathic cardiomyopathy yielded Staphylococcus aureus in culture, as did blood and sputum. Septic endocarditis of the right side of the heart was found at autopsy. A review of 438 autopsy reports in which an indwelling pulmonary catheter had been used and of another 493 reports preceding its use at our medical center suggests no association between the use of indwelling catheters in the right side of the heart and endocarditis in the left, although there is a risk of thrombotic endocardial vegetation formation in the right side of the heart, with possible infection or embolization.


Indwelling pulmonary artery catheters. Their relationship to aspetic thrombotic endocardial vegetations. To assess the incidence of aseptic thrombotic endocardial vegetations (TEV) after pulmonary artery catheterization with Swan-Ganz catheters we reviewed all autopsy reports for a two-year period in our hospital. In 413 autopsies there were five instances of aseptic TEV: 3 in 88 patients with Swan-Ganz catheters, 1 in 120 patients with central venous catheters, and 1 in the 205 patients without central vascular catheters. The incidence of TEV is significantly greater in patients with Swan-Ganz catheters than in other patients.


The prostaglandins.

The prostaglandins. The introduction of dinoprost tromethamine (Prostin F2 Alpha) as an abortifacient in the second trimester of pregnancy represents the first clinical use of a prostaglandin. Various synthetic analogues of the naturally occurring derivatives are being employed investigationally in the treatment of peptic ulcer, hypertension, asthma, and hypercalcemia. In the United States, dinoprost tromethamine is primarily administered intra-amniotically. Despite the fact that a substantial number of patients experience allergic reactions, hypertension, bronchospasm, nausea, vomiting, cramps, and diarrhea, the efficacy and relative safety of dinoprost tromethamine establish it as superior to intra-amniotic instillation of hypertonic saline. Cervical laceration, laceration or rupture of the lower uterine segment, retention of the placenta, and hemorrhage in part reflect the intensity of uterine contraction induced by dinoprost. Experience in administration improves the therapeutic response and diminishes adverse reactions.


Nonclostridial gas gangrene. Report of 48 cases and review of the literature. Gangrenous lesions accompanied by evidence of subcutaneous gas usually are diagnosed as "clostridial gas gangrene." The occurrence of nonclostridial gas gangrene has been infrequently reported and is thought to be relatively rare. Review of 278 admissions of diabetic patients with orthopedic vascular problems disclosed a 17% (48 patients) incidence of nonclostridial gas infections and a 3% (one patient) occurrence of clostridial gas gangrene. Clinical characteristics ranged from severe to benign toxicity. Appreciation of the causative organisms (usually mixed Gram-negative rod and enterococcus) of this syndrome is essential, especially in the diabetic patient, since appropriate antibiotic therapy and surgery can result in a low mortality (4%) and a high incidence (80%) of ambulatory, independent patients.


Liver disease in nonparenteral drug abusers. Liver function tests were performed in 500 young servicemen with a history of drug abuse. Serum glutamic oxaloacetic transaminase (SGOT) level was abnormal in 66% of 68 patients with a history of parenteral drug abuse. Forty-one percent of 432 patients with a history of only nonparenteral drug abuse also had elevated SGOT levels. A high incidence of liver disease in parenteral drug abusers is well established; however, to our knowledge, the magnitude of the problem in nonparenteral drug abusers has not been noted previously. Liver biopsy specimens in 34 of our patients showed either a classic viral hepatitis or a mild nonspecific hepatitis. Limited follow-up suggested a slowly resolving process. We conclude that hepatitis may be a common sequel to epidemic nonparenteral drug abuse.


Primary care within the academic tradition. In the rush to train primary-care physicians, the bioscience tradition must remain inviolate. At the same time, however, academic medicine should recognize that the actual practice of medicine has a special content and operational philosophy that is indispensable for patient care and in which, therefore, every student should be versed.


The bureaucrat. The taming of the DHEW.

The bureaucrat. The taming of the DHEW. America's dim view of the bureaucrat needs reassessment because professional standards review organizations (PSROs) and national health insurance will increase the amount of contact between physician and bureaucrat. Inevitable conflict between The Organization and the physician is aggravated by the government-business adversary relationship based on constitutionalism. With more public funds, the budget-based health institution may acquire more of the characteristics of bureaucracy. For better understanding, the bureaucrat is described, and his main types and natural history outlined. Contrasts between business and government as revealed by interchange of executives are reported. Remedies for better interaction are suggested, including liaison groups and use of the apolitical, career bureaucrat. Rules for dealing with bureaucracies are listed, including The Constituent's Letter.


Oral contraceptives in acute viral hepatitis. Thirty-four women took oral contraceptives during a major part, or throughout the course, of acute viral hepatitis. The acute illness and sequelae during the following year were compared to those of 34 matched control women with acute viral hepatitis who never took oral contraceptives. Statistical and clinical analysis showed no difference in severity of acute illness or frequency of sequelae. These findings suggest that oral contraceptives are not detrimental when taken during a course of acute viral hepatitis.


Serum creatine phosphokinase in leptospirosis. Serum creatine phosphokinase (CPK) and serum glutamic oxaloacetic and pyruvic transaminase (SGOT, SGPT) levels were determined in 61 patients with leptospirosis and 16 with viral hepatitis during the acute phase of illness. The CPK value was elevated in 29 leptospirosis patients and normal in all 16 hepatitis patients. Conversely, mean SGOT and SGPT levels were lower in leptospirosis patients. The CPK determination is a simple test that may provide diagnostic information in a jaundiced patient, particularly when characteristic manifestations of leptospirosis are absent. The pattern of greatly elevated CPK levels with only modest elevations in transaminase values in an acutely jaundiced patient should strongly suggest a diagnosis of leptospirosis.


Metabolic studies on metiazinic acid I. Absorption, distribution, excretion and metabolism in rats and rabbits. Absorption, distribution, excretion and metabolism after oral administration of 3-H-labelled metiazinic acid were studied. The administered radioactivity was excreted through both the urinary and fecal routes. The maximum levels of concentration in blood and most tissues were shown with 3 hr after dosing. The highest radioactivity was found in the kidney throughout all experiments. Relatively high radioactivity was observed in inflammatory-treated parts in rats. Unchanged compound, metiazinic acid S-oxide and these conjugates were found in urine and feces. Approximately 60% of the unchanged form was observed in plasma after 6 hr.


Venereal disease in a war environment: incidence and management. The improved control over most infectious disease does not extend to venereal infections, and these now provide the major medical problem encountered in wartime. This factor should be recognized when staff and facilities are being provided for wartime medical services. Unique problems of management of both physical and psychological illness may result from promiscuity in a foreign land during war, and specialist venereologists are as necessary as surgeons and physicians.


Chronic lymphocytic thyroiditis, thyrotoxicosis, and low radioactive iodine uptake. Report of four cases. To characterize four patients with thyrotoxicosis and a low radioactive iodine uptake, thyroid biopsies were performed, and iodine metabolism was studied. Histologic examination showed the presence of chronic lymphocytic thyroiditis, with no features of Graves's disease, in all. Detailed studies in one patient revealed insufficient metabolism of iodine to account for the clinical and chemical features of thyrotoxicosis, which implies that release of stored hormone by the inflammatory process causes the thyrotoxic state. The thyrotoxicosis in this entity subsides spontaneously. Thus, this form of thyrotoxicosis differs from the usual form found in Graves's disease in that histologie features of Graves's disease are absent, the radioactive iodine uptake is low, and specific antithyroid therapy is contraindicated. The observations further demonstrate that the radioactive iodine uptake remains a valuable tool in the diagnosis of thyrotoxicosis and the differentiation of its various forms.


The sterol hydrocarbons in edible oils.

The sterol hydrocarbons in edible oils. Since 1957 we have published the results of our research on the transformation of sterols in vegetable oils due the industrial treatment. During bleaching sterol hydrocarbons are formed which are partly removed due the deodorising. Hardening transforms them partly into other steroids. Thus the sterol hydrocarbons are also present in margarine. We have found that the content of those compounds amounted to a quantity of 0.023%. The apolar steroids are highly sensitive to the conditions of autoxidation. All margarines and edible oils contain not only steroid hydrocarbons but also the products of their oxidation and hydrogenation.


The effects of combined administration of cytembena and cyclophosphamide on the blood count and morphology of nucleoli in peripheral-blood lymphocytes in patients with malignant tumors. In patients with malignant tumors, changes in the blood count and morphological changes in the nucleoli in peripheral-blood lymphocytes were studied during treatment with Cytembena, Cyclophosphamide, or combinations of both drugs. After administration of Cyclophosphamide (400 mg i.v. daily for 10 days, then 100 mg orally daily), the counts of leukocytes, especially of neutrophils, sank (by 40% maximally), and the erythrocyte count and the haemoglobin content in blood sank moderately. In peripheral-blood lymphocytes, the proportion of ring-shaped nucleoli (stimulable to synthesis of RNA) reversibly sank, and the proportion of micronucleoli (nonstimulable) rose. After administration of Cytembena (400 mg i.v. daily for 10 days, then 200 mg i.m. at intervals of 2--4 days), neither the leukocyte counts nor the relative percentages of lymphocytic nucleoli signigicantly changed; the mean corpuscular haemoglobin content (MCH) transitorily increased (by 10 percent max.). In the group receiving combined cytostatics (Cytembena 400 mg i.v. daily for 10 days, then 200 mg i.m. at intervals of 2--4 days plus Cyclophosphamide 50 mg orally daily), the erythrocyte count and the haemoglobin content in blood sank moderately. In the population of peripheral-blood lymphocytes in this group, there sank the absolute counts of lymphocytes with ring-shaped nucleoli (by 44% max.) and those with micronucleoli (by 33% max.).


[Corticoids and alveolar surfactant. Experimental study]. The effect of cortisone on the production of surfactant was studied by measuring the tensioactive property of the alveolar fluid, evaluated with Pattle's method. The stability ratio (R.S.) values obtained in 12 guinea-pigs following cortisone administration were all within normal limits. In rabbits treated with prednisolone during a number of fast days, S.R. values were lower than normal in 9 cases out of 10. The results of this study would seem to exclude any influence of the administration of cortisone on the activity of the alveolar surfactant.


Mycotic aneurysms of the pulmonary artery and aorta. The clinical presentation and characteristic radiographic and angiographic findings in 6 patients with mycotic aneurysms of the pulmonary artery of aorta are presented. Radiographic findings that may suggest a mycotic aneurysm of the pulmonary artery include a rapid change in its coutour, which may be aneurysmal in character, and multiple septic pulmonary emboli or bacterial pneumonia. Patients with mycotic aneurysms of the descending thoracic aorta may have a middle or posterior mediastinal mass in close association with the aorta, and a pulmonary infiltrate may be seen surrounding the aneurysm. A barium swallow will often demonstrate esophageal displacement by the extrinsic mass.


Roentgen anatomy of the posterior horn of the lateral meniscus. The roentgen anatomy of the posterior horn of the lateral meniscus of the knee is presented with particular attention to the relationships between the popliteus tendon, joint capsule and meniscus. The popliteus tendon creates a tunnel as it passes obliquely through the posterior half of the meniscus creating two walls (medial and lateral) and a roof (superior attachment) and a floor (inferior attachment). The boundaries are readily visible on the double-contrast knee arthrogram. Familiarity with these relationships aids in the diagnosis of meniscal injuries.


A comparative study of the effects of dry vs. humidified ventilation on canine lungs. To compare the effects on canine ciliary and bronchial mucosal function of varying periods of ventilation with dry vs. humidified gas mixtures, 29 anesthetized dogs underwent 2, 4, and 6 hours of ventilation through a Carlen's double-lumen tube. Six dogs were evaluated by clearance studies, nine by differential bronchospirometry, six by surfactant studies, six by electron microscopy, and two by ventilation scanning. By means of two separate respiratory systems, dry gas (DG) was used to ventilate the right lung, and humidified gas (HG) ventilated the left lung in each dog. Serial chest roentgenograms showed more rapid clearance of inspired tantalum dust from the HG-ventilated lung in each of the six dogs, the disparity in clearance between the two lungs being more pronounced after longer periods of ventilation. The surface tension in DG-ventilated lungs increased fourfold, whereas in HG-ventilated lungs it increased only twofold as compared to preoperative values. Longer periods of ventilation did not change the surface tension appreciably in either DG- or HG-ventilated lungs. Scanning electron micrographs of bronchial mucosa from DG-ventilated lungs showed tangling and matting of cilia with a granular and stringy material attached to most cilia; these changes were much less pronounced in HG-ventilated lungs. Bronchospirometric studies showed an increase in ventilatory function in each of the lungs ventilated with the HG mixture (percent Vo2 on 100 percent oxygen increased 27.7 percent) to compensate for the decreased gas exchange provided by the contralateral DG-ventilated lung. Function in each of the lungs returned to normal within 24 hours. Ventilation scans with Xenon133 showed no apparent change in isotope uptake in the HG-ventilated lungs as compared to the DG lungs during the first 24 hours after ventilation. The observations from the present study suggest that ventilation of canine lungs with DG for 4 or more hours dries mucus and transiently retards mucociliary clearance and gas exchange. These changes may be minimized by ventilation with a humidified gas mixture. Application of these findings to patients undergoing prolonged general anesthesia and to lung preservation studies is suggested.


Health and disease in rural Ethiopia.

Health and disease in rural Ethiopia. Ethiopia, among the world's poorest countries, suffers from a full spectrum of health problems. A plastic surgeon and a public health physician present their experiences in Sidamo province in the Rift Valley.


The plasma prolactin levels in man during prolongation of darkness in the morning. The plasma prolactin levels were studied in 4 healthy subjects with a constant sleep-waking cycle and a constant activity schedule before and after experimental alteration of the dark-light cycle.  The subjects slept in the dark from 10.30 p.m. to 6.30 a.m.  During a control period of 10 days the subjects stayed in rooms which were well lighted after 6.30 a.m.  During the following 10 days darkness was prolonged by 4 hours until 10.30 a.m. Blood samples were obtained at 10.30 p.m., and each hour from 2.30 to 11.30 a.m. on days 9 and 10 of each period of investigation.  In all the subjects an increase of the plasma prolactin level occurred during sleep.  At about the time of waking the concentration fell rapidly.  There was no apparent shift in the waking-related decrease in the prolactin level during the experimental period with extended darkness.  Present data do not indicate that the dark-light transition in the morning is essential for the waking-related decrease in the prolactin level.