[Urologic complications in rectal surgery (author's transl)]. Urinary disorders after amputation or resection of the rectum are much more frequent than commonly supposed. Out of 239 patients they were noticed by 56.6%, undergoing amputation, and 36.6% after resection. Longterm disturbances were observed by 26.4% respect. 15.1%. The most important reason is injury of autonomic pelvic nerves and ganglia. Urinary bladder infection was verified in 22% respect. 8%. Furthermore urinary disorders may be caused by changing of bladder localization (bladder hernia), wound infection (especially of the sacral cavity), edema of the urethra, and exacerbation or manifestation of pre-existing urologic diseases. Compared to these, lesions of the urinary tract are of little importance. To prevent such complications, we postulate: 1. careful pre-operative urologic examination, 2. if possible mobilisation of the rectum along its borderlines (so-called Grenzlamellen of Pernkopf), 3. critical analysis of urologic disorders, removal of the urinary catheter as soon as possible, regular systemic prophylaxis of urinary infection, and therapy controlled by antibiogram, 4. adequate follow-up, and 5. urologic examination of all disturbances lasting longer than three months.


The anterior commissure in glottic carcinoma. The laryngeal anterior commissure is a specific anatomic area of the glottis which is often involved by cancer. Of 586 patients with glottic cancer, five (1 percent) had pure anterior commissure lesions and 175 (25 percent) had vocal cord tumors secondarily involving the anterior commissure. One of three of these anterior commissure tumors also had subglottic extension. Despite the presence of blood vessels and lymphatics in the anterior commissure, metastasis to regional lymph nodes in rare (8 percent). Patients with Stage 1 and 2 lesions were treated by hemilaryngectomy with satisfactory results (45/61 -- 74 percent). Only three patients had local recurrence after hemilaryngectomy. Patients with bilateral cord-anterior commissure lesions had the poorest survival and highest recurrence rate, even after total laryngectomy. Subglottic extension of these anterior commissure tumors did not correlate with survival. Survival and recurrence rates were conversely proportional to the stage of the tumor at presentation. Although the anterior commissure is a theoretical site for cancer breakthrough and lymphatic spread, its apparent significance lies in the fact that its involvement by glottic primaries represents only increasing tumor size and thus an advanced stage of disease.


The problem of advanced supraglottic carcinoma. Sixty-four cases of advanced supraglottic laryngeal carcinoma, and the possible therapeutic errors in these cases, have been analyzed. The available time for the investigation and treatment in these cases is short because of the ease and rapidity of spread of these tumors; thus, it is of great importance: that the nature, site and extent of the tumor is determined quickly; that the patient's general condition is determined and improved as far as possible and the patient receives treatment also for other diseases he may have; and that the tumor is radically eliminated whenever possible without delay. The main causes of poor results have been: late admission for treatment; inadequate (too conservative) surgery; and development of metastases during preoperative treatment which includes radiation.


Primary squamous cell carcinoma of the larynx. While many clinicians would intuitively believe that surgical treatment of laryngeal carcinoma is superior to irradiation, we have found that in many instances this is not the case. When the results of initial radiation therapy combined with the surgical salvage rates for irradiation failures are analyzed and compared with the results of initial surgery and subsequent salvage of surgical failures, the overall cure rates are quite comparable. This point has not been sufficiently emphasized in the treatment of laryngeal cancer. Its importance lies in the ability to offer a significant percentage of patients a form of treatment which carries with it much less functional morbidity without asking the patient to assume a greater risk with regard to the overall cure rate. This non-randomized retrospective study will analyze our experience in the treatment of laryngeal cancer with specific emphasis on the overall cure rate when megavoltage teletherapy is combined with surgical salvage of radiation failures.


Laboratory diagnosis of laryngeal disease. The most important method used in the laboratory diagnosis of laryngeal disease is histological examination of material removed at biopsy. Surgical and technical aspects of this procedure are discussed. A review of diagnoses made of laryngeal biopsies in a single year by the writer's laboratory is given together with a brief description of the pathology of the commonest non-malignant conditions. The handling of laryngectomy and block dissection specimens in the laboratory is described. The parts played by the cytology, bacteriology and virology laboratories in laryngeal diagnosis are briefly reviewed.


DNA contents of individual cells from squamous cell carcinomas of the larynx and tongue. In previous work a new method of histologic grading of malignancy in squamous cell carcinomas of the larynx was described. It was based on morphologic criteria representing the tumor cell population itself and the tumor host relationship. Nuclear polymorphism was revealed to be a very important factor for determining prognosis. This method of histologic grading of malignancy was in this work further analyzed by cytophotometric DNA determinations on individual cells obtained by scraping the surface of squamous cell carcinomas of the larynx and the tongue. Increased heterogenous cellular DNA distributions were found in cases with high histological malignancy grading. Cells in the carcinoma cases with a normal epithelial morphology had the same DNA content as that of control cells of normal buccal mucosa. Cells with higher DNA values all had malignant or suspicious morphology.


Stevens-Johnson syndrome: Twenty-three cases and their otolaryngologic significance. Stevens-Johnson syndrome is a symptom complex characterized by mucosal, ocular, and cutaneous lesions. Prodromal symptoms of upper respiratory infection or pharyngitis are most common. These are followed by target lesions of skin, sloughing of musous membranes, and ocular inflammation. Twenty-three cases are presented. Most patients (61 percent) were between 10 and 39 years of age. Relapses occurred in three patients. Five patients developed pneumonia, and there were two fatalities. Over one-half of the patients had serious ocular complications. The etiology of this syndrome is uncertain. Multiple allergic factors, drugs (especially long-acting sulfonamides), and infectious agents (most recently mycoplasma pneumoniae) have been implicated. This study does not support any single cause. The use of systemic steroids is generally accepted by most authors. The death rate in this study (10 percent) is essentially unchanged from early reports on patients without steroid therapy. The complications rate directly attributable to steroids is significant in this study group. The major complications of this syndrome are ocular. Aggressive topical management of ocular inflammation is required; however, the morbidity rate remains high despite these measures. The otolaryngologist should be aware of this syndrome as the early symptoms, and the acute complications may require his awareness of the natural and treated courses of this disease.


Human middle ear corpuscles -- A light and electron microscopic study. The human middle ear corpuscles originally described by von Troeltsch are examined by means of light microscopy in 124 subjects, and electron microscopy in 27 subjects. While the corpuscles are not observed in all 19 individuals under age six, and in all 20 adults who had a history of suppurative otitis media, an average of six corpuscles per temporal bone is found in 98 percent of 83 adult subjects who had no history of middle ear disease. Two-thirds of the corpuscles are located in the mastoid, and the remainder in the middle ear. Often, they become bifurcated or trifurcated. Although light microscopy shows that the corpuscle is formed by lamellar capsules and a central core resembling pacinian corpuscles, electron microscopic study failed to confirm that this structure is a typical pacinian corpuscle. Subsequently, possible physiological significance of this corpuscle is discussed.


Unilateral deafness with subsequent vertigo. The association between the characteristic clinical picture of endolymphatic hydrops and pre-existent profound sensori-neural hearing loss of long duration, has not been previously reported. Several cases are reported to illustrate this clinical syndrome. Labyrinthectomy was found to be curative. A plea is made for better recognition of this clinical entity.


Anticonvulsant-induced lymphoma.

Anticonvulsant-induced lymphoma. Patients with cervical adenopathy of obscure etiology may present a diagnostic problem to the otolaryngologist. The hydantoin family of anticonvulsants is a rare cause of adenopathy that may range from histologically simple lymphoid hyperplasia to true lymphoma. Between these two extremes is a benign clinical entity with the histologic characteristics of lymphoma. A patient on diphenylhydantoin (Dilantin) therapy developed bilateral true vocal cord paralysis and cervical adenopathy. On pathological examination the lesion was interpreted first as malignant lymphoma and later as hydantoin-induced pseudolymphoma. He has now been followed for over two years. Hydantoin-induced adenopathy may vary clinically from a benign condition to a true lymphoma. The malignant form may present long after the anticonvulsant treatment is discontinued. A 10-fold increase in the expected incidence of malignant lymphoma in epileptic patients on hydantoin therapy has been reported; therefore, these patients required long-term follow-up. The otolaryngologist should be aware of this rare clinical entity as an unusual cause of cervical adenopathy associated with vocal cord paralysis.


Constituents of West African Medicinal Plants. IX. Dihydrocubebin, a new lignan from Piper guineense. An extract of the leaves of Piper guineense Schum. and Thonn. afforded a new lignan, dihydrocubebin, which was characterized by its spectral properties and identified by direct comparison with a reference sample obtained by catalytic hydrogenation of sesamin.


A survey of the plants of Orissa (India) for tannins, saponins, flavonoids and alkaloids. One hundred and thirty-eight plant samples collected from various parts of Orissa were studied for the presence of tannins, saponins, flavonoids and alkaloids. Forty-six samples were found to be positive for tannis, twelve for saponins, fifty-eight for flavonoids and fourteen of alkaloids.  The presence of alkaloids in five species is reported for the first time. The tannin content of nine samples was found to be between 3 to 10.5 percent.


Specificity of digestive lipases in hydrolysis of wax esters and triglycerides studied in anchovy and other selected fish. The physiological specificity of fat digestion in several species of marine fish was studied by incubating a variety of synthetic and natural lipid substrates in fish intestinal fluid. Wax ester and triglyceride hydrolyses were studied in vivo and in vitro. In vivo feeding studies showed triglyceride hydrolysis and reesterification in the gut occurred 4 times faster than wax ester metabolism. In vitro comparisons of wax and triglyceride lipolysis always showed triglycerides to be hydrolyzed faster than wax esters; however, wide variation in the ratio occurred among different batches of intestinal juice. Ca. 50% of the 2 monoglycerides formed in the lipolytic sequence were hydrolyzed. Esters of lipase resistent fatty acids (20:4 and 20:5) were cleaved faster than normal fatty acid esters (18:2 and 18:3). Two of the species studied, the northern anchovy, Engraulis mordax and the jack mackerel, Trachurus symmetricus, empty lipase(s) into their gall bladders and produce-phospholipid free bile.


Effect of the nature and amount of dietary energy on lipid composition of rat bone marrow. The effect of the nature and amount of dietary calories on the lipid composition of bone marrow of rats was studied. Male weanling rats were fed 3 isocaloric diets, containing high carbohydrate, normal protein, and high protein, and a fourth high fat diet for 49 days. Feeding of the high carbohydrate, high protein, and high fat diets caused a significant increase in the level of total lipids compared to the normal protein diet. This increase of total lipids was due primarily to the increase in the level of triglycerides. There was no significant difference in fatty acid composition of either nonpolar or polar lipids of bone marrow among rats fed high carbohydrate diet and those fed normal protein diet. A comparison of fatty acid compositions between bone marrow lipids of rats fed high protein diet and the other 2 isocaloric diets revealed that the proportion of palmitic acid was higher and the proportion of oleic acid was lower in animals fed high protein diet than in animals fed the other 2 diets. Compared to the 3 isocaloric low fat diets, dietary feeding of high fat diet caused a decrease in the proportion of palmitic and palmitoleic acids and an increase in the proportion of oleic and linoleic acids in total fatty acids of both nonpolar and polar lipids.


Fluorescent products and polyunsaturated fatty acids of human testes. Lipid soluble fluorescent pigments from human testis were fractionated by silicic acid column chromatography and silica gel thin layer chromatography. Fluorescence analyses revealed a family of at least 3 compounds with similar fluorescence properties, including excitation and emission maxima, reversible fluorescence quenching by alkaline pH, and fluorescence quenching by heavy metal chelation. These fluorescence characteristics strongly indicated the presence of the conjugated Schiff base fluorophore-N=C-C=C-N-. The chromatographic separations employed enabled a more definitive fluorescence characterization of the lipid soluble pigments known to accumulate late in tissues with age and as a result of lipid peroxidation. Total lipids and fatty acid composition of the total lipids were determined. Polyenoic acids constituted about 40% of the total fatty acids. Histological examination of the tissues revealed some degeneration and edema, but significant spermatogenesis and normal complement of Leydig cells.


Positional specificity of gamma-ketol formation from linoleic acid hydroperoxides by a corn germ enzyme. We have shown unequivocally that the positional specificity of gamma-ketol formation by a corn germ enzyme was different from that observed previously by others with an alfalfa seedling enzyme. When the pure positional isomers of linoleic acid hydroperoxide served as substrates, the corn germ enzyme formed one of two gamma-ketols: 12-oxo-9-hydroxy-trans-10-octadeconoic acid from 13-hydroperoxys-10-octadecenoic acid from 13-hydroperoxy-cis-9,trans-11-octadecadienoic acid (99+% pure) and 10-oxo-13-hydroxy-trans-11-octadecenoic acid from 9-hydroperoxy-trans-10,cis-12-octadecadienoic acid (96% pure). Also isolated from these reactions was one of two alpha-ketols commonly found as a result of catalysis by linoleic acid hydroperoxide isomerase: 12-oxo-13-hydroxy-cis-9-octadecenoic acid from the 13-hydroperoxide and 10-oxo-9-hydroxy-cis-12-octadecenoic acid from the 9-hydroperoxide. Evidence is offered that gamma-ketol formation is catalyzed by linoleic acid hydroperoxide isomerase, the same enzyme responsible for alpha-ketol production.


Phosphatidyl choline: Donor of 18-carbon unsaturated fatty acids for glycerolipid biosynthesis. Kinetics of radiocarbon inforporation into the phyosphatidyl choline of pumpkin leaf fed 1(-14)C-acetate at low light intensity were strongly suggestive of lipid bound fatty acids acting as substrates for desaturase enzymes. After pulse labeling in direct sunlight with the same precursor, phosphatidyl choline and phosphatidyl glycerol contained up to 90% of total glycerolipid radiocarbon at the shortest sampling times. Subsequent loss of radiocarbon from phyosphatidyl choline and a corresponding gain in other glycerolipids is taken to indicate a net flow of long chain fatty acids through phosphatidyl choline and into other lipids. It is proposed that there may be 2 separate synthetases in leaf tissue, one producing oleic and the other palmitic acids as their end products. Oleic acid is transferred almost exclusively to phosphatidyl choline where it is further desaturated to linoleic and linolenic acids before being made available for the biosynthesis of other lipids. Palmitic acid is transferred mainly to phosphatidyl glycerol, where it is desaturated to trans-delta3-hexadecenoic acid.


Inhibitive effects of structurally modified azasteroids and related nitrogen containing steroids on insect growth and development. A number of azasteroids and other nitrogen containing steroids with a modified nucleus or side chain were prepared and tested for their inhibitory effects on the growth and development of several species of insects. Structure-activity studies showed that compounds with a structurally related steroid nucleus and side chain were approximately equal in inhibitory activity for a particular species. The replacement of the tertiary amino group in the side chain of the 5beta-steroid with other nitrogen substituents, such as nitro, cyano, acetylamino, or a quaternary ammonium salt, resulted in a considerable loss of inhibitive activity in the tobacco hornworm or the yellowfever mosquito. However, certain modifications of the azasteroid nucleus resulted in compounds that still retained high biological activity. As a result, a compound was synthesized that lacked the A and B rings of the steroid nucleus and that inhibited insect growth, molting, and metamorphosis and the delta24-sterol reductase enzyme system of the tobacco hornworm.


Enzymatic conversion of 5alpha-cholesta-7, 14-dien-3beta-ol to 5alpha-cholesta-8, 14-dien-3beta-ol. 5alpha-Cholesta-7, 14-dien-3beta-ol, previously shown to be efficiently converted to cholesterol upon incubation with rat liver homogenate preparations under aerobic conditions, has been studied as to its possible conversion to 5alpha-cholesta-8, 14-dien-3beta-ol. Efficient conversion was observed upon incubation in the presence of washed mictosomes of rat liver under anaerobic conditions. This observation is of importance in consideration of possible metabolic pathways in the biosythesis of cholesterol.


Studies on tocopherol derivatives: V. Intestinal absorption of several d,1-3,4-3H2-alpha-tocopheryl esters in the rat. Twelve d,1-3,4-3H2-alpha-tocopheryl esters were synthesized from d,1-3,4-3H2-alpha-tocopherol. They were acetate, propionate, butyrate, isobutyrate, caprylate, palmitate, acid succinate, benzoate, nicotinate, o-hydroxybenzoate, o-acetoxybenzoate, and pivalate. The hydrolysis of these esters with bile-pancreatic juice and with 9,000 x g supernatant of small intestine and liver homogenates of rats was examined. When these esters were incubated in small intestine or liver supernatants, hydrolysis occurred at a similar rate. In the incubation experiments, alpha-tocopheryl acetate, propionate, butyrate, isobutyrate, caprylate, palmitate, and acid succinate were classified as an easily hydrolyzable group. Alpha-tocopheryl benzoate and nicotinate were in a moderately hydrolyzable group. O-hydroxybenzoate and pivalate, which resisted hydrolysis, were in a scarcely hydrolyzable group. O-acetoxybenzoate was easily hydrolyzed to the o-hydroxybenzoate. Hydrolysis on straight chain fatty acid esters of alpha-tocopherol easily occurred in bile-pancreatic juice. In in vivo experiments, the lymphatic absorption rate of 6 esters, acetate, palmitate, acid succinate, nicotinate, o-hydroxybenzoate, and pivalate, was measured on thoracic duct fistula rats. Easily hydrolyzable esters were recovered mostly in lymph as alpha-tocopherol, whereas, an ester which strongly resisted hydrolysis, such as pivalate, appeared mainly unchanged. This fact suggested that hydrolysis of alpha-tocopheryl esters was not necessarily a prerequisite for intestinal absorption. The percentage of absorption of slowly hydrolyzed esters in lymph was relatively lower than that of moderately or easily hydrolyzable esters.


Analysis of methylsterol fractions from twenty vegetable oils. The 4-monomethylsterol and 4,4-dimethylsterol fractions were separated from the unsaponifiables of 20 vegetable oils by preparative thin layer chromatography, and their compositions were determined by gas liquid chromatography. Tentative identification of the individual components of these fractions was carried out by gas liquid chromatography and combined gas liquid chromatography-mass spectrometry. Among 4-monomethylsterols, obtusifoliol, gramisterol, and citrostadienol occur abundantly in most of the oils. Cycloeucalenol also occurs in some of the oils as a major component of 4-monomethylsterols. Other 4-monomethylsterols tentatively identified are: lophenol, 31-norlanosterol, 31-norcycloartenol, and 31-norlanostenol and/or 4alpha-methylzymostenol. Among 4,4-dimethylsterols, cycloartenol and 24-methylenecycloartanol followed by beta-amyrin and cycloartanol are common to most of the oils. Butyrospermol, alpha-amyrin, lupeol, and cyclobranol together with a 4,4-dimethylsterol, presumably lanostenol, occur in some of the oils. Cyclolaudenol is present in poppy seed oil. Besides these compounds, each of the oils contains some unidentified members of 4-monomethylsterols and 4,4-dimethylsterols. The methylsterol fraction of capsicum seed oil as compared with that of the other oils is characterized by its very high content of lophenol and cycloartanol together with three other members, presumably 31-norlanostenol, 4alpha-methylzymostenol, and lanostenol.


Dietary alteration of fatty acid composition of lipid classes in mouse mammary adenocarcinoma. The composition of total fatty acids in serially transplanted mammary adenocarcinomas of C3H mice which were fed a fat free diet or a stock diet containing 4% fat for 8 weeks were significantly different, although fatty acid amounts were similar. The difference in composition was manifested in the triglyceride, phosphatidyl choline, and phosphatidyl enthanolamine fractions. Tumors of mice fed fat free diet has appreciable amounts of eicosatrienoic acid, whereas neoplasms of stock diet fed animals had none. In addition, higher levels of oleic acid and lower contents of linoleic acid were found in tumors from mice fed fat free diet than in those from mice fed the stock diet. Thus, mechanisms which maintained the triglyceride fatty acid composition in some tumors, such as 7288CTC hepatoma, were not observed in mouse mammary adenocarcinomas, and, therefore, were not a general phenomena associated with carcinogenesis.


Composition of liver lipids of the rat during pregnancy and lactation. Triglyceride concentrations in rat liver rose during late pregnancy, declined at peak lactation, and then rose again during involution. The percentage of oleate in the triglycerides rose at peak lactation, but that of linoleate fell. Although phospholipid concentrations were unchanged, the percentage of palmitate in this fraction rose, and those of stearate and arachidonate fell during pregnancy and lactation. These changes may be related to the changes in lipogenesis and fat mobilization that occur during pregnancy and lactation.


Pertussis.

Pertussis. Pertussis as an infectious disease exhibits a number of unusual features, both with respect to its epidemiology and to the interaction of the bacteia with the infected host. Evidence that a virus may in some cases be the etiology of the syndrome has been reviewed and seems to be have been established in certain instances. Pertussis caused by a virus would not be difficult to accept insofar as the respiratory manifestations of the disease are concerned. It is difficult, however, to reconcile the hematologic changes of pertussis with what is presently known about the usual virus infection of humans. The clinical syndrome itself is suficiently unique as to be recognized in most cases. The use of antibiotics has considerably reduced the mortality of the disease by allowing treatment of complications. The other serious complication of disease, pertussis encephalopathy, remains a problem. The possible occurrence of hypoglycemia during pertussis has been noted and deserves further documentation especially in that it may contribute to the encephalopathy...


Subdural empyema: analysis of 17 recent cases and review of the literature. Subdural empyema is an intracranial infection that has remained difficult to diagnose and to treat. Seventeen patients with this infection, treated between 1967 and 1974, are analyzed and compared to published series with particular regard to diagnosis using newer procedures and treatment, considering the primary focus of infection. The infection is usually located in the supratentorial spaces, is often bilateral, and results most often from para-nasal sinusitis (single most common cause), otitis, neurosurgical operative infections, and meningitis in infants. Patients suffering from subdural empyema generally present with rapid onset of depressed sensorium, seizures, focal neurological deficits, and signs of increased intracranial pressure, following a period of days to weeks characterized by headache and fever. All 17 of our patients demonstrated localizing neurological signs and 16 manifested either fever or leukocytosis. Diagnostic studies, except for cerebral arteriography, do not reliably corroborate or exclude the diagnosis. Cerebral arteriography established the diagnosis and defined the location and extent of the empyema in all of our cases. The EEG and brain scan produced frequent false-negative and/or non-localizing results in 10 and 8 patients, respectively. The cerebrospinal fluid was abnormal from all 15 patients examined by lumbar puncture, but the findings were similar to those in other infectious and non-infectious central nervous system diseases. Signs of transtentorial herniation developed within eight hours following lumbar puncture in three of seven patients who had exhibited signs of increased intracranial pressure before the procedure was performed. Bacterial cultures were positive in 13 of our cases. A review of our data and that of other studies indicates that the organisms associated with subdural empyema are consistent with those expected from infections of the primary site; e.g. sinusitis, otitis, meningitis, site of prior neurosurgery. A therapeutic approach is suggested which emphasizes specific antibiotic regimens appropriate to the primary site of infection and prompt neurosurgical intervention with evacuation of the subdural spaces bilaterally. In general, combination antimicrobial therapy employing high parenteral doses of penicillin G, a semi-synthetic penicillinase-resistant penicillin and chloramphenicol is recommended.


Deep mycotic infection in the hospitalized adult: a study of 123 patients. A prospective study of patients hospitalized in a large Veterans Administration Hospital between November 1963 and November 1973 revealed 123 patients with deep mycotic infections. The incidence of these infections almost doubled during the last 5 years. Candida (55 patients) and Aspergillus (26 patients) were the major causative agents. Nine other fungal caused infection in the remaining patients. Candidemia was rare prior to the introduction of commerical percutaneously-inserted venous catheters in 1965. The incidence increased further following the introduction of parenteral hyperalimentation in 1969, and Torulopsis fungemia (5 patients) appeared for the first time. Invasive pneumonia caused by spore-forming Aspergillus decreased when patients were moved from an old, naturally-ventilated hospital to a new, mechanically-ventilated one. The air in both hospitals was sampled on one occasion for the presence of fungal spores, and spores of Aspergillus fumigatus were detected only in the old hospital. Our experience suggests that hospital-acquired Aspergillus infection of the lung might be eliminated if all incoming hospital air is filtered, properly vented, and not recirculated. Efforts to decrease hospital-acquired fungal infections include vigorous infection control procedures for intravenous therapy, judicious use of any therapy that predisposes to infection, and further evaluation of improved mechanical control of hospital ventilation.


Effect of dexamethasone on thyroid hormone response to TSH. The effect of short-term dexamethasone administration (8 mg daily for 3 days) on thyroid hormone response to exogenous TSH (bovine TSH, 5 IU i.m.) was studied in 16 euthyroid volunteers. Serum T3 and T4 concentrations were measured by radio-immunoassay prior to and 2, 6, 12, 24, and 49 hr after bTSH injection, both under basal conditions and during dexamethasone treatment. In all subjects bTSH administration raised both T3 and T4 concentrations significantly. Dexamethasone treatment induced a slight depression of endogenous TSH (m +/- SEM = 2.0 +/- 0.4 versus 1.6 +/- 0.3 muU/ml) and T4 (6.8 +/- 0.4 versus 6.1 +/- 0.2 mug/100 ml) basal values and a significant decrease in T3 value (1.16 +/- 0.09 versus 0.64 +/- 0.06 ng/ml, p = 0.005). The mean increment of both T3 and T4 after bTSH injection was percentually unchanged during dexamethasone treatment but, due to lowered basal value, T3 levels at each time interval after TSH + dexamethasone were significantly lower than the corresponding values observed after TSH alone. The present data show that high dexamethasone doses decrease T3 serum levels significantly without inhibiting T3 response to TSH stimulation. Only a slight lowering was observed in T4 levels.


Stimulation of thyrocalcitonin secretion by ethanol in patients with medullary thyroid carcinoma--an effect apparently not mediated by gastrin. We have compared the effects of oral and intravenous ethanol on the secretion of both thyrocalcitonin and gastrin in five patients with medullary carcinoma of the thyroid. Ethanol caused a moderate rise in plasma thyrocalcitonin to 316% +/- 343% of baseline when given intravenously and to 197% +/- 106% of baseline when given orally. Only oral ethanol caused a measurable rise in serum gastrin levels. Serum calcium did not change significantly from baseline during either oral or intravenous administration. The results suggest that stimulation of thyrocalcitonin secretion by ethanol is not secondary to increased secretion of gastrin nor to the induction of hypercalcemia. Neither oral nor intravenous ethanol appears to be as effective as intravenous pentagastrin in testing for the presence of medullary carcinoma.


The development of a glucose clamp.

The development of a glucose clamp. A reliable control system was developed for clamping (i.e., holding at a steady level) the concentration of blood glucose in the hyperglycemic region of a normal nonanesthetized dog. The system is based upon, and hence largely validates, a mathematical model of the canine glucoregulatory mechanism which was assembled from the results of experiments in which radioisotopes were used. The operation of the clamp, however, does not require the use of radioisotopes. The glucose clamp is a tool which may be applicable clinically in the measurement of glucose turnover and in the laboratory in the study of the effects of glucose turnover of variable insulin with constant glucose levels.


The effect of somatostatin on plasma noradrenaline and plasma adrenaline concentrations during exercise and hypoglycemia. The effect of somatostatin, on the secretion of noradrenaline and adrenaline was studied in eight normal subjects during exercise and in insulin induced hypoglycemia. Plasma growth hormone response to exercise and hypoglycemia was almost totally suppressed by somatostatin. Plasma noradrenaline during exercise tended to be lower during the infusion of somatostatin but the difference was not significant. During the infusion of somatostatin the secretion of adrenaline was increased. This was seen during exercise but was much more pronounced during hypoglycemia. The blood glucose concentration attained after insulin injection was lower during the infusion of somatostatin and evidence is presented which indicates that the higher adrenaline values during hypoglycemia were due to the lower blood glucose values attained. In conclusion the secretion of catecholamines are not inhibited by a dose of somatostatin which nearly totally suppresses the secretion of growth hormone.


Inhibition of lipoprotein lipase by uremic plasma, a possible cause of hypertriglyceridemia. In an attempt to define pathogenesis of the previously described impaired triglyceride (TG) removal in uremia, the effects of the addition of normal and uremic plasma on the activity of lipoprotein lipase (LPL) from rat epididymal adipose tissue were examined. Six uremic patients on chronic dialysis and 13 normals were studied. Adding increments of normal and uremic plasma increased the LPL activity to maximal levels when 0.1 ml of plasma was added. Larger aliquots of uremic plasma produced marked inhibition of LPL activity. This inhibition was not observed with the normal plasma. When increasing amounts of uremic plasma were added to an incubation mixture already maximally activated by 0.1 ml of normal plasma, inhibition of LPL was again observed. This inhibition was still present in uremic plasma which had been dialysed against cold saline. The inhibitor was in the lipoprotein-free (d greater than 1.225) fraction of the plasma. The results indicate that uremic plasma has an LPL inhibitor which is probably a protein and may play a role in the pathogenesis of uremic hypertriglyceridemia.


The role of glucagon in the pathogenesis of the endogenous hyperglycemia of diabetes mellitus. The effect of glucagon suppression by somatostatin upon endogenous hyperglycemia was studied in three forms of experimental insulin deficiency in dogs: alloxan diabetes, total pancreatectomy, and diazoxide administration. In six insulin-requiring alloxan-diabetic dogs deprived of insulin for 24 hr, mean plasma glucose declined to 77% +/- 6% of the baseline level of 350 +/- 41 mg/dl during 3 hr of glucagon suppression, significantly below the unsuppressed saline controls (p less than 0.01-0.05). When somatostatin was discontinued, glucagon rose and glucose increased 21% (p less than 0.05) in 30 min. Significant correlation between maximal changes in glucagon and glucose was observed (r = 0.81; p less than 0.001). Even during a 1-hr alanine infusion in such dogs, glucose declined an average of 36 +/- 9 mg/dl, instead of rising 51 +/- 7 mg/dl as in unsuppressed controls. Maximal changes in glucagon and glucose were correlated (r = 0.85; p less than 0.01). In eight depancreatized dogs pretreated intravenously with continuous insulin and glucose infusions, withdrawal of insulin was followed by a rise in extrapancreatic glucagon; mean plasma glucose rose from 212 +/- 43 to 415 +/- 80 mg/dl 270 min after the end of the insulin infusion. However, when glucagon was suppressed after insulin withdrawal, glucose remained below 240 mg/dl, significantly less than the controls (p less than 0.005); when somatostatin was stopped, glucagon rose and glucose increased 88 +/- 19 mg/dl within an hour. The rises in glucagon and glucose were significantly correlated (r = 0.68; p less than 0.05). Glucagon suppression by somatostatin during diazoxide-induced blockade of insulin secretion in four normal dogs reduced hyperglycemia significantly but did not prevent it. The results support the hypothesis that a relative or absolute excess of glucagon, as well as a relative or absolute deficiency of insulin, is etiologically important in the development of endogenous hyperglycemia in diabetes mellitus, the hyperglucagonemia probably mediating the glucose overproduction.


Turnover of plasma free stearic and oleic acids in resting and exercising human subjects. Turnover rates and metabolism in the legs and the splanchnic region of free stearic and oleic acid have been studied in five healthy male volunteers at rest and during bicycle exercise. A continuous infusion of 14C-labeled stearic acid and tritiated oleic acid was given intravenously. At rest, the fractional turnover was the same for the two acids; the fractional leg uptakes were also similar, while fractional uptake in the splanchnic region was 80% higher for oleic than for stearic acid. The response to exercise differed between the two acids: the arterial concentration of stearic acid fell, its fractional turnover and fractional leg uptake became higher than for oleic acid, and its fractional uptake in the splanchnic region increased, while that of oleic acid remained unchanged. It is concluded (1) that stearic acid turnover in the postabsorptive state is similar to that of the main part of the FFA fraction and (2) that the decrease in stearic acid concentration during exercise can be explained by an increased removal in excess of that for other FFA.


Activity of various endogenous compounds and pharmacologic agents at a  glucose-oxidizing platinum electrode. The specificity of a glucose-oxidizing platinum electrode system was investigated in vitro using selected metabolic compounds and a wide range of pharmacologic agents. Many compounds were found that either augmented or inhibited the glucose effect on the electrode system, but relatively few had substantial effects at reasonable plasma levels. Should the platinum electrode system be incorporated into an artificial beta cell for diabetic patients, graduated clinical trials might be necessary for every new medication taken by the patients.


Low oestriol excretion: incidence, significance and treatment in an obstetric population. In a series of 6,361 consecutive patients, low oestroil excretion late in pregnancy was detected in 871 cases (13-6%) and was associated with significantly increased incidences of still birth (P less than 0-001), neonatal death (P less than 0-001) and intrauterine growth retardation (P less than 0-001). Persistently low oestriol excretion occurred in approximately 3% of patients and two-thirds of these were suitable for conservative treatment with intravenous infusion of dextrose (25%) and fructose (20%) (2 1. of each in 48 hours). In 97 of 147 patients (65%), low oestriol excretion was favourably affected by this regimen, with significantly improved perinatal results (P less than 0-001).


The AAMI contract approach to standards development. In summary, the AAMI approach enables the FDA to utilize all available resources needed to identify critical characteristics that should be subjected to standards; to develop rationale for those parameters that should not be subjected to standards; and to develop standards in those areas where standards should be developed. During the process, appropriate checks and balances are available because of AAMI's multidisciplinary approach, which is not available using other approaches. The AAMI approach is extremely participatory and, consequently, will result in the production of a standard that will be acceptable to the largest number of people without compromising critical safety and efficacy considerations.


Children born from pregnancies complicated by subnormal oestriol excretion--first year. This paper is the first of a series concerning the follow-up of children whose mothers had subnormal oestriol excretion during pregnancy. The incidences of still births, neonatal deaths, dysmaturity and major and minor congenital malformations were significantly increased in pregnancies complicated by one or more subnormal oestriol value. Growth parameters and developmental progress were measured of 136 infants who attained the age of one year, and it was encouraging to find that no gross departures from normal were observed.


Surgical treatment of aortic valvular disease in rheumatoid arthritis. Two patients with severe rheumatoid arthritis and aortic regurgitation, developed progressive symptoms of left ventricular failure. Symptoms were inadequately controlled by medical therapy. Surgical treatment was at first considered with great reluctance because of the theoretical risk of operative and postoperative complications in patients with a diffuse disease of connective tissue. The suspected complications did not materialize. Valvular replacement should be considered in patients with severe valvular disease associated with rheumatoid arthritis.


Severe depression in young adolescents. A report of five cases. The clinical features of depressive illnesses in five boys aged 14 and 15 years are described. The early stages of the illnesses were not noticed by others. Each made serious suicide attempts which resulted in their hospitalization. After this, a depressive state was revealed in each case, which in its depth and persistence was very similar to the major depressive illnesses of adults. Aetiological factors are discussed.


Clinical experience with verapamil.

Clinical experience with verapamil. Verapamil administered by the intravenous route restored sinus rhythm in 33 out of 40 episodes of supraventricular tachycardia. The drug was also effective in reducing ventricular rate in patients with atrial fibrillation. Intracardiac conduction studies using His bundle electrograms showed prolongation of atrioventricular nodal conduction in eight out of nine cases after 5 mg of verapamil were given. The distal conduction was unaffected. Bradycardia and hypotension occurred in two cases and responded promptly to intravenous administration of atropine. Verapamil is an effective antiarrhythmic agent which is, in general, free from significant side effects.


Arsenic poisoning from anti-asthmatic herbal preparations. Arsenic poisoning, a disease of the past, was recently found in 74 patients in Singapore over a 15-month period. Most victims (70%) had a chronic form of poisoning and 64% of the cases were caused by a local anti-asthmatic herbal preparation containing 12,000 ppm of inorganic arsenic sulphide. The other patients were poisoned by six other brands of herbal preparations used for the treatment of asthma and a variety of other illnesses. Subsequent investigations revealed another 22 other brands of Chinese herbal preparations containing high concentrations of inorganic arsenic ranging from 25 to 107,000 ppm, of which most were imported. Nearly 40% of the patients had taken the medicine for less than six months, but the others had a longer history of exposure ranging from one to 15 years. Systemic involvement was confined mainly to the skin (91%), nervous system (51%), gastrointestinal system (23%) and blood (23%). Malignancy of the skin was present in six patients, and of the visceral samples, toxicological confirmation was found in half of the cases investigated. There was no correlation between the clinical status of the patients and their tissue arsenic content. The importance of arsenic poisoning by herbal preparations is discussed, as there are no known reports of their association.


Liver dysfunction and tea eating.

Liver dysfunction and tea eating. A case report is presented of a patient who had liver fibrosis, splenomegaly and ascites, associated with the habit of nibbling tea leaves. The splenomegaly and the ascites remitted when she ceased eating tea, but liver fibrosis is still present 15 years later. No other cause for the liver disorder was found.


Ventricular septal deffect and aortic imcompetence: clinical and haemodynamic study of 12 cases. The incidence of aortic incompetence complicating ventricular septal defect has been estimated as varying from 2-5% (Glasser et alii, 1972) to 5% (Nadas et alii, 1964). Although numerous publications have appeared describing the clinical, pathological and surgical aspects of this syndrome in different parts of the world, documentation of its occurrence in Asian patients has been rare except for reports from Japan (Tatsuno et alii, 1973; Mizuno and Saegusa, 1967). This paper describes our experience of 12 cases collected over 10 years.


Social aspects of pregnancy--Canberra survey. A group of women, resident in Canberra and whose babies were born at the Canberra Hospital, responded to a questionnaire covering selected social aspects of pregnancy. They were divided into "middle class" and "working class" categories on the basis of their husbands' occupations. Those from the "middle class" sample were more willing to breast feed their babies, more diligent in attendance at antenatal classes and were more likely to have their husbands present with them during labour. There did not appear to be a significant class difference in whether the husbands remained in the labour ward for the birth of the baby. More wives would like their husbands to remain for the birth event than in fact actually do so.


Heat gain in the treatment of accidental hypothermia. In two cases of accidental hypothermia, heated humidification of the inspired gases and warming of fluids administered intravenously was associated with an increase in the deep body (core) temperatures at rates of 0-5 degrees to 1-0 degrees C per hour. The first case demonstrated that heat was transferred selectively to the body core, as temperatures here rose during the first three hours of treatment, while skin temperatures remained low. The second patient gained less than 0-1 degrees C per hour when treated "passively" by means of surface insulation with unheated blankets. The introduction of "active" measures was followed by a more rapid gain. It is suggested that heat supplied to the body core by these measures provides effective additions to metabolic production, particularly when the deep body and cardiac temperatures are at their lowest.


[Clinic and therapy of the so-called hyperosmolar syndrome in childhood (author's transl)]. The so-called hyperosmolar syndrome is the most severe form of imbalance of osmolarity. From 1971 to May 1973 we observed 27 children with this disturbance, which until recently had mortality rate up to 30%. In the presented material the diagnostic and therapeutic possibilities of the excessive hyperosmolar syndrome in childhood is discussed. The rapid establishment of clinical diagnosis supported by laboratory findings is necessary to start immediate and effective therapy. Prophylaxis and treatment of cerebral edema with dexamethasone is of equal importance to primary emergency therapy and reanimation. This new therapeutic concept has proved to be excellent in the treatment of the disturbance. 2 of 27 children died: One of these presented on admission with sign of irreversible brain damage, while the other developed the clinical picture of severe subdural hematome during the phase of rehydration.


[Syncopal convulsions with myocarditis in childhood. A case contribution to the transitory pacemaker treatment of myocarditis-induced heart block]. A ten-year-old girl was admitted to hospital with convulsions due to Adams-Stokes syndrome as a complication of complete heart block. A rheumatic myocarditis was causing the conduction defect. As a temporary measure a pacemaker was used to treat the extremely serious condition. In addition, cortisone, antibiotics and antiphlogistics were given for treatment of the underlying disease. The child was discharged from hospital in good condition with a long-term therapy of penicillin.


[Mediastinal tumors of childhood (author's transl)]. Among 147 operatively treated tumors of the mediastinum there were 14 infantile tumors. 6 of these were malignant. The poor prognosis can only be improved by early diagnosis and early radical surgery. The problems of diagnosis and treatment are discussed.


[Allergic reactions to the house-dust mite in children with obstructive disease of the respiratory tract (author's transl)]. 160 children with obstructive allergic disease of the respiratory tract were tested with the modified pricktest. 58 showed positive reactions to the house-dust mite. Typically, in the case history of these children, is the presence of the complaints throughout the year, especially at night and not in particular seasons. Although, the modified pricktest could be negative in children under 4 years of age, in later years an allergen could be found. Children who have typical-complaints in their case-history, but show weak cutaneous reactions, are admitted in hospital, and a bronchial provocationtest is carried out to study the action of the allergen on the affected organ. 28 of the 58 children with house-dust mite allergy showed only weak positive cutaneous reactions and had mild complaints. Avoidance measurements brought in almost 80 p.c. of these cases good results. We recommended specific hyposensibilisation for the remaining 30 patients; in 22 of these cases the recommendation was carried out. The positive effect of the specific hyposensibilisation was proved when compared to a controll series.


[Clinical evaluation of Australia-antigen detection (author's transl)]. The detection of Australia antigen is considered as indication for the presence of a hepatitis with a long incubation period (hepatitis B). Thereby, these findings are getting a considerable diagnostic and prognostic importance. Attempts are made by means of serological and clinical data from permanent blood donors and liver patients to demonstrate the importance of Australia antigen findings with regard to the prevention of transfusion hepatitis and to the clinical evaluation of acute and chronical hepatitis. Furthermore, the role of Australia antigen detection for diagnosis of liver-complaint is discussed.


[Electrocardiographic changes in electrolyte imbalance. Part 1: Alterations in serum potassium (author's transl)]. 163 patients (95 hypokalemic, 48 hyperkalemic, 20 healthy) were examined. Electrocardiographic patterns of hypokalemia were evident in 46 p.c. of all patients with serum potassium less than 3,5 mval/l. Patients without cardiac disease showed signs of hypokalemia in the ECG in 68 p.c., those cases with extremly low serum potassium (less than 2,5 mval/l) in 81 p.c. In patients without cardiac disease a good correlation could be observed between ST depression and T wave inversion on one side and serum potassium level below 3,5 mval/l on the other side. The T/U ratio was found to be below unity in only 9 p.c. in mild hypokalemia, but in 82 p.c. in severe hypokalemia. ECG pattern of hyperkalemia could be found in 29 p.c. of all patients with serum potassium levels greater than 5,1 mval/l. These signs were evident in patients without cardiac disease in 29 p.c. in mild hyperkalemia, but in 75 p.c. in severe hyperkalemia. Patients suffering from cardiac disease, however showed the correspondive ECG changes of hyperkalemia only in 5 p.c. There is a good correlation between the P, and T-wave-amplitude and the serum potassium level greater than 5,1 mval/l. According to our findings it can be stated, that the ECG changes in patients with cardiac disease tend to hide the correspondive changes of potassium disorder.


[Vitamin A absorption test. I. Pancreatic insufficiency and sprue (author's transl)]. The vitamin A absorption test and its interaction with the secretin-pancreozymin test, the d-xylose absorption test, fecal fat content and the small intestine biopsy are estimated on their significance in the diagnosis and course of sprue and pancreatic insufficiency. The investigation includes 39 patients with different stages of pancreatic insufficiency and 10 patients with sprue. First it results relatively wide spread normal values in a control collective with sometimes unexplained low values, the significance of the vitamin A absorption test as screening test therefore is limited. Secondly the absent rise after vitamin A ingestion in serum after 3 and 6 hours favours the diagnosis of sprue, correlates with the histological findings of the mucosa and appears more reliable than the d-xylose test. Thirdly this test seems to allow the differentiation between malabsorption and maldigestion when steathorroe is proved: In contrast to sprue-syndromes pancreatic insufficiency shows significant reduced 3 hour values at subnormal 6 hour values after vitamin A ingestion.


[Vitamin A absorption test. II. Diseases of the liver, the extrahepatic biliary system and the stomach (author's transl)]. It is reported on the estimation of the vitamin A absorption test in 17 patients with chronic liver diseases, 26 patients with diseases of the extrahepatic biliary system, and in 12 patients with diseases of the stomach. In the latter there are no changes in the vitamin A test. On the contrary patients with diseases of the liver and biliary system show differences in the serum vitamin A levels. A separate consideration of active liver cirrhosis and active cholangitis indicates individualities in the constellation of the 3 and 6 hour values after vitamin A ingestion: in liver cirrhosis the first value is normal while the 6 hour value seems significant lowered so that the maximum vitamin A concentration is found near 3 hours. In active cholangitis both values are reduced, the first one more than the second one. The reason is to be seen in a decrease of the conjugated bile acids, whereas in the group of liver diseases an interpretation is somewhat problematic. It is to discuss whether these results depend on the development of portal hypertension, while the intestinal absorption seems normal and liver damage only of secondary importance. The fact that this test is influenced by diseases of the liver and biliary system shortens its significance as a screening test for malabsorption or maldigestion though a further differentiation between sprue and pancreatic insufficiency seems possible.


[Determination of chymotrypsin in the stool by succinyl-L-phenylalanin-P-nitraniliden (Suphepa) in the diagnosis of pancreatic diseases (author's transl)]. A specific substrate (Suphepa), which is well known in duodenal chymotrypsin determination (pancreozymin-secretin-test), is also suitable for the enzyme determination in stools from patients suspected of having a pancreas insufficiency of exocrine nature. The median value of 353 fecal chymotrypsin determination of 180 normal persons was 137 mug/g of native stool. There is a good correlation in comparing the fecal with the duodenal chymotrypsin: Out of 30 comparable patients, 10 patients had pathological values for the duodenal and fecal chymotrypsin determinations, whereas 18 patients had normal values. According to the results of the pancreozymin-secretin-test, false normal stool results were recorded for two patients. No false positive stool values were recorded for the comparative collective. The great accuracy, the modest instrumental expense and the negligible inconvenience for the patient are good in line with the requirements for a screening test.


[Significance of the chronic abuse of bromoureide containing hypnotics. Simple chemical methods for its detection (author's transl)]. The abuse of bromoureide (= bromocarbamide) containing sedatives gains increasing clinical relevance. Up to 50% of acute intoxications nowadays are caused by suicidal ingestion of bromocarbamides. The symptoms of the chronic intoxications are due to ionised bromide split off from the organic molecule and slowly accumulating in the organism. Due to the extremely long biological half-life of the bromide ion the chronic ingestion of bromocarbamides can be demonstrated easily and for long periods by determining the concentration of free, i.e. ionised bromide in serum or saliva. Simple and rapid methods suitable for screening purposes are discussed and the results of routine determinations of serum bromide in a psychiatric-neurological department are presented.


[Metabolic myelosis (author's transl)].

[Metabolic myelosis (author's transl)]. 102 patients suffering from metabolic myelosis were studied clinically. Among the early signs and symptoms, pins and needles, freezing or burning feet, and impaired kinaesthesia were the most frequent ones. With the syndrome progressing, motor disturbances of supramotoneuronal character developed. Every third patient had neurogenic ischuria. Examinations of the cerebrospinal fluid did not reveal any deviation characteristic or "typical" of myelosis. Different pathogenic factors were detected by analysis according to the rules of internal medicine. However, no single factor defining myelosis aetiologically could be discovered. The majority of cases suggested that the metabolic steady state decompensated by the coincidence of more than one factor, thus initiating myelosis. The following pathogenic factors were observed frequently: Malabsorption, abuse or intoxication, liver cell damage, neoplasm. The great variety of pathogenic factors emphasizes that metabolic myelosis must be counted among the polygenetic identical reactions of the central nervous system. These are the organism alarming signals and they require comprehensive general examinations.


[Treatment of obesity by behavior therapy (author's transl)]. Many possibilities are discussed to influence abnormal eating behavior by methods of behavior modification by learning principles. Amongst the usually employed procedures of operant conditioning, of self-control, of aversive stimuli and behavior modification by contract as new methods are used: learning by models and self-determination (giving marks as in school) of eating behavior. The proceedings are illustrated by 5 own cases (children between 9 and 13 years old). Success for longer periods was only obtained in 3 cases where a self-control program was practised.


[Pathobiochemistry of galactosemia and usefulness of the Gt system in expert opinions (author's transl)]. We investigated the genetic polymorphism of galactose-1-phosphate-uridyl-transferase (Gt) of 525 blood samples from Southern Germany. The gene frequencies of Gt1 are 0.9581 and of Gt2 0.0623. Comparing the gene frequencies of galactosemia (0.006), GtD (0.06), Gt1 (0.9581) and Gt2 (0.0623), we see that the gene frequencies of GtD and Gt2 are nearly identical. In expert opinions that Gt is a system of insufficient information.


Boron neutron capture therapy for the treatment of cerebral gliomas. I. Theoretical evaluation of the efficacy of various neutron beams. The technique of boron neutron capture therapy in the treatment of cerebral gliomas depends upon the selective loading of the tumor with a 10B-enriched compound and subsequent irradiation of the brain with low-energy neutrons. The charged particles produced in the 10B (n,alpha) 7Li reaction have ranges in tissue of less than 10 mum so that the dose distribution closely follows the 10B distribution even to the cellular level. The effectiveness of this therapy procedure is dependent not only on the 10B compound but on the spectral characteristics of the neutron source as well. Hence, an optimization of these characteristics will increase the chances of therapeutic success. Transport calculations using a neutral particle transport code have been made to determine the dose-depth distributions within a simple head phantom for five different incident neutron beams. Comparison of these beams to determine their relative therapeutic efficacy was made by the use of a maximum useable depth criterion. In particular, with presently available compounds, the MIT reactor (MITR) therapy beam (a) is not inferior to a pure thermal neutron beam, (b) would be marginally improved if its gamma-ray contamination were eliminated, (c) is superior to a partially 10B-filtered MITR beam, and (d) produces a maximum useable depth which is strongly dependent upon the tumor-to-blood ratio of 10B concentrations and weakly dependent upon the absolute 10B concentration in tumor. A pure epithermal neutron beam with a mean energy of 37 eV is shown to have close to the optimal characteristics for boron neutron capture therapy. Futhermore, these optimal characteristics can be approximated by a judiciously D2O moderated and 10B-filtered 252Cf neutron source. This tailored 252Cf source would have at least a 1.5 cm greater maximum useable depth than the MITR therapy beam for realistic 10B concentrations. However, at least one gram of 252Cf would be needed to make this a practical therapy source. If the moderated 252Cf source is not 10B filtered, the resultant neutron beam has characteristics similar to those of the MITR beam with no gamma-ray contamination. For usch a beam, 100 mg of 252Cf would produce a flux of 2.4 X 10(8) neutrons/(cm2 sec), which is an intensity suitable for therapy applications.


Electrostatic fields in ionography.

Electrostatic fields in ionography. There is renewed interest in diagnostic radiology in electrostatic methods of imaging, such as xeroradiography and ionography. This is due to the fact that edge contrast can be achieved, aiding in the visualization of soft tissue tumors. In analyzing the image forming properties of these system, we chose to solve the electrostatic problems by the method of images. We present methods and recursion formulas for calculating electrostatic fields due to (a) any charge distribution on a slab of dielectric (the solution involves a single infinite series) or (b) the same as the above with the introduction of an additional ground plane parallel to the dielectric surface (the solution now involves double infinite series). Analysis of these fields suggests new methods of controlling edge contrast and development configurations where the field which penetrates through the foil is used to produce the final image rather than the field above the charged surface.


Simple method for the generation of organ and vessel contours from roentgenographic or fluoroscopic images. A simple method is described for outlining or contouring any area defined by a change in film density or fluoroscopic screen intensity. The entire process, except for the positioning of an electronic window, is accomplished using a small computer having appropriate software. The electronic window is operator positioned over the area to be processed. The only requirement is that the window be alrge enough to encompass the total area to be considered.


Loss of field flatness in AECL teletherapy units form misadjustment of the collimator. Atomic Energy of Canada Limited 60Co teletherapy units have adjustable collimator hinges to adapt to source diameters from 0.75 to 2.50 cm. Adjustment of the collimator hinge to the manfacturer's settings can cause a loss of radiation field flatness as high as 20% for large fields. The recommended settings appear to clip the top corners of tall source capsules. Opening the hinge adjustment restores field flatness, without changing penumbra or the inverse square law behavior of the teletherapy unit.


Laser modification to an x-ray collimator: an aid in positioning patients for neurosurgical and radiographic procedures. In high-ambient-light levels such as are found in operating rooms, and at long target-to-patient distances, the cross lines and light field projected from conventional x-ray collimators are not easily visible and proper patient positioning is difficult. The collimators on two mutually perpendicular x-ray units have been modified by replacing the incandescent bulbs with lasers and adjusting the lasers to be coaxial with the x-ray beams. These modifications have been coupled with a third wall-mounted laser to facilitate patient positioning for stereotaxic thermal hypophysectomy. The use of the laser-modified collimators has resulted in considerable saving of time for the operating team and has markedly reduced patient anesthesia time. The laser-modified collimator has also been found useful in positioning patients for other radiographic procedures in the operating room and has virtually eliminated retakes due to malpositioning.


Modulation transfer function of a finite scanning microdensitometer slit. Inherent in the line-spread function approach in modulation transfer function (MTF) determinations is the use of a microdensitometer to scan the density pattern resulting from the line exposure. In such a procedure, loss of fidelity in the distribution being scanned is expected. This loss is due in part to the use of a finite-width scanning slit. In spite of the central role of the scanning slits in the MTF determination, little if anything has appeared in the literature from which one can quantitate the effect of a scanning slit on the MTF determination. This paper analyzes the loss of response attendant with use of scanning slits of differing widths. Specifically, the MTF of a finite scanning slit is derived. A method for correcting for loss of response, given a specific slit width, is indicated on the basis of the chain-multiplication property of MTFs. The current practice of using a 10-mum width for film-screen combinations is shown to be justified. Results can be generalized to any configuration scan slit. In addition, it may also be applied to any generalized sampling or display-type slit.


Saturation curve in gases of high atomic number at pressures up to 8 atm. I. Krypton and xenon. The saturation curve has been studied in xenon and in krypton up to a pressure of 8 atm. An empirical formula has been found that describes the fraction of current collected over a wide range of voltages, pressures, ionization intensities, and electrode spacings. This is of practical value in the design of ionography chambers. For krypton the collection fraction fKr = (1 + 0.25eta-1.74)-1, and for xenon fXe = (1 + 0.16eta-1.88)-1, where eta = Fp-0.7Vd-2q-1/2 with F = 3.61 X 10(-7) and 2.50 X 10(-7) for krypton and xenon, respectively. The ranges of the variables covered in the experiments were p = 1-8 atm, V = 5-25000 V, d = 0.3-1.3 cm, and q = 4 X 10(-9)-6 X 10(-8) A/cm3.


X-ray scatter background signals in transmission radiography. With monoenergetic x-ray beams incident on polystyrene phantoms, the spectra of the tramsmitted x rays were measured with a scintillation spectrometer. The scattered and unscattered components of the transmitted x-ray fluence at a point on the beam axis were determined as a function of (i) the incident x-ray energy (18, 22, 32, 49, 58, 69, and 660 keV), (ii) the phantom thickness (5.3, 10, and 21 cm), (iii) the scatter solid angle determined by the exposed area of the phantom and the separation distance of the image plane (0.090, 0.31, 0.66, 1.8, 3.5 4.3, 4.8, and 5.1 sr), and (iv) the beam diameter at the image plane (25, 17, and 10 cm). The results indicate that, as the incident x-ray energy decreases from 660 to 30 keV, the contribution of the scattered component to the transmitted fluence increases from approximately 50% to 90% for the 21-cm phantom and from 21% to 50% for the 5.3-cm phantom. For typical cases, the data show the effect of the scatter component on the ratio of the image to the background signals. In addition, the examples show that optimum conditions for maximizing this signal ratio may be obtained by a careful selection of the incident x-ray energy for low-, medium, and high-contrast objects.


Effect of microdensitometer scan slit misalignment in MTF determinations. To determine the modulation transfer function (MTF) of a radiographic film or film-screen system, it is common to expose the system to a line source and scan the result with a microdensitometer. The question arises as to how the MTF determination is affected by such factors as microdensitometer slit width and possible misalignment of the slit with the line pattern being scanned. In any experiment, some degree of misalignment can be expected. This paper analyzes the resulting problem and derives an expression for the MTF of slit misalignment and slit width: MTF = [sin[2pif(L/2)]/2pif(L/2)] X (sin[2pif[H sin(theta/2)[[/2pif[Hsin(theta/2)[[), where L is the slit width, H the slit height, theta the angle of misalignment, and f the spatial frequency variable. The left-hand factor of this product is the MTF of a finite slit width, while the right-hand factor is the MTF of misalignment. It is shown that, for radiographic film-screen combinations, small-angle misalignment up to 0.25 degrees is not serious with 1.5-cm-long slits, while such a misalignment may become serious in highbandwidth systems such as nonscreen films.


Intensifying screen for xeroradiography. A high-atomic-number rare gas has been incorporated into xeroradiographic cassettes in order to increase the sensitivity of the process to x radiation. Preliminary results indicate that krypton gas at 1-atm pressure increases the sensitivity by approximately a factor of 2 in the mammography energy region.


Maintenance of condenser-ion chamber calibration. Readings made with condenser-ionization chamber systems are frequently suspect because significant changes in calibration can occur without being evident in the normal use of the instruments. These changes can be traced to physical causes that alter the voltage sensitivity of electrical capacitance. Thus, measurement of these electrical parameters will indicate whether or not a change in calibration has occurred. Formulas are presented of calculating such changes and determining which parameter is responsible. Good agreement was obtained between the results of calculations with these formulas and the results of radiation measurements made with a Victoreen Condenser R-Meter after several components had been deliberately maladjusted.


Exposure values around an x-ray scanning transaxial tomograph (EMI scanner). Measurements of exposure accumulated in a one-month period in and around a scanning x-ray transaxial tomograph are reported. For the unit studied (the EMI neurological scanner) values measured indicate that the shielding required is "minimal."


New device for accurate measurement of the x-ray intensity distribution of x-ray tube focal spots. A new device has been developed with which the focal spot distribution can be measured accurately. The alignment and localization of the focal spot relative to the device are accomplished by adjustment of three micrometer screws in three orthogonal directions and by comparison of red reference light spots with green fluorescent pinhole images at five locations. The standard deviations for evaluating the reproducibility of the adjustments in the horizontal and vertical directions were 0.2 and 0.5 mm, respectively. Measurements were made of the pinhole images as well as of the line-spread functions (LSFs) and modulation transfer functions (MTFs) for an x-ray tube with focal spots of 1-mm and 50-mum nominal size. The standard deviations for the LSF and MTF of the 1-mm focal spot were 0.017 and 0.010, respectively.


Method for gantry angle repositioning on rotational teletherapy equipment. Repositioning errors for given angles have been found to be as large as +/-0.5 degrees. Errors of this magnitude are undesirable and unnecessary. To overcome this difficulty, a small laser was mounted to the counterweight of our accelerator with its light beam projected at 90 degrees to the axis of the x-ray beam. The light beam is used as a lever arm to indicate large distances (0.125 in.) for small changes in gantry angle (0.1 degrees). Gantry angles can easily be respositioned within 0.1 degrees. Routine use of the laser beam indicator has reduced the time taken to reposition the gantry.


Treatment of ruptured ileum and peritonitis in a cat. Ischemic necrosis and rupture of the ileum caused by avulsion of the mesentery occurred in a 6-month-old cat following blunt trauma of the abdomen. The damaged section of intestine was resected and an anastomosis was performed using a single layer edge-to-edge suturing technic. Diffuse peritonitis was treated by peritoneal lavage and instillation of antibiotics into the peritoneal cavity at the time of surgery. The cat's recovery was uncomplicated. A rationale is provided for the suturing technic and peritoneal lavage at the time of surgery.


A simple method for making new transducing lines of coliphage lambda. A variety of novel transducing lines of phage lambda can be obtained by induction of a mixed culture of abnormal lysogens. Such a culture is simply made by mass lysogenization of a host lacking the normal prophage attachment site.


Cryptic mutations: their predicted biochemical basis, frequencies and effects on gene conversion. Cryptic mutations are undetected base changes in genetic DNA (or hereditary RNA). Some kinds of base change are normally undetected; others may or may not be detected, depending on experimental conditions, procedures and genotypes. Cryptic mutations could affect gene conversion results because when heterozygous they cause mismatched base pairs in hybrid DNA in the same way as known mutations, but the experimenter is unaware of them. Cryptic heterozygosity will usually be much more frequent in heterothallic than homothallic organisms. The effects of cryptic mutation heterozygosity on recombination and conversion of known mutations are predicted with reference to co-conversion, map expansion and polarity. Relevant evidence is considered.


Studies on the mechanism of electron trasport in the bc1-segment of the respiratory chain in yeast. III. Isolation and characterization of an antimycin resistant mutant ANT 8 in Schizosaccharomyces pombe. 1. A mutant (ANT 8) of Schizosaccharomyces pombe which shows resistance to antimycin both in vivo and in vitro is characterized biochemically and genetically. 2. In crosses of ANT 8 with auxotrophic strains, resistance to antimycin segregates 2:2 indicating that resistance is conferred by a single nuclear gene. Diploids heterozygous for the resistance gene, however, show segregation of the resistance and sensitivity during mitosis. Possible reasons for this segregation are discussed. 3. Compared with the wild type, the NADH oxidase of ANT 8 requires 13 times as much antimycin for 95% inhibition. After addition of ubiquinone-3, electron transport which is less sensitive to antimycin is found only in the mutant. 4. The resistance of the mutant ANT 8 si due to the much weaker binding of antimycin to mitochondria. As in the wild type, two antimycin binding sites can be separated by binding studies. From the inhibition curves it is evident that binding of antimycin to oxidized mitochondrial particles does not correspond with its inhibitory effect on the partly reduced enzyme in kinetic studies. 5. The peak of the b-cytochrome absorbing at 560.2 nm at 77 degrees K in the wild type is shifted to 561 nm in the mutant. 6. A special preparation method for mutant mitochondrial particles is described, yielding highly active enzymes and CO-insensitive cytochromes. 7. The results are discussed with reference to the components in our model of the respiratory chain, which may be responsible for this type of resistance.


Two separated nucleolus organizers on the Drosophila hydei Y chromosome. By genetical, cytological, and filter saturation hybridization methods it is shown that the Y chromosome of Drosophila hydei contains two separate nucleolus organizers, one on the short arm, the second near the tip of the long arm.


Rec-mediated recombinational hot spot activity in bacteriophage lambda. IV. Effect of heterology on Chi-stimulated crossing over. A Chi mutation in phage lambda stimulates Rec-mediated crossing over more to one side of itself than to the other; stimulation, which is maximal near Chi, can occur at some distance from the Chi site as well. A gross heterology differentiating the two recombining parents does not interfere with the distant Chi-stimulated crossover whether the heterology is at the Chi site or between the Chi site and the distant interval in which recombination is monitored. These conclusions hold whether recombination is measured "genetically" in standard crosses or "physically" in density-labeled crosses conducted in the absence of DNA replication.


Spectral characteristics of the bioluminescence induced in the marine fish, Porichthys notatus by Cypridina (ostracod) luciferin. Specimens of Porichthys notatus, which are naturally luminous along the coast of California, are non-luminous in Puget Sound. However, luminescence capability may be induced in the adult Puget Sound Porichthys by the administration of purified Cypridina (ostracod) luciferin, synthetic Cypridina luciferin, or Cypridina organisms. The bioluminescence emission spectra produced by the Puget Sound fish following induction is similar, if not identical, to that of the naturally luminous Porichthys notatus from California waters (maxima: 485 and 507 nm).


Chromatin-associated RNA content of heterochromatin and euchromatin. Chromatin from TLT hepatoma cells, mouse liver cells, and mouse brain cells was fractionated by differential centrifugation into a pellet, enriched with heterochromatin, and a supernatant, enriched with euchromatin. The pellet was found to contain more than twice as much of a particular species of chromatin-associated RNA per milligram chromatin DNA as did the supernatant. This chromatin-associated RNA was also found to be associated with the transcriptionally inactive chromatin of mature avian erythrocytes. Bull sperm, whose genome is known to be completely inactive, was used as the source in the preparation of sperm heads. Bull sperm head RNA appeared to consist of a single, low molecular weight species which migrated on polyacrylamide gels at a rate just slightly slower than the aforementioned chromatin-associated RNA. The results are interpreted as indicating that this chromatin-associated RNA is more prevalently associated with the heterochromatic fraction of chromatin. It is postulated that this chromatin-associated RNA might constitute a structural component of heterochromatin.


Experiences with the dominant lethal test in female mice: effects of alkylating agents and artificial sweeteners on pre-ovulatory oocyte stages. Pre-ovulatory oocytes are especially sensitive to mutagenic influences. Since post-dictyotene oocytes are not subject to selection and elimination before fertilization, they may reveal mutagenic effects directly and unrestrictedly. Presuming that a chemical is administered at pro-estrus to female mice one can conclude that the substance or its active metabolite has the chance to reach the gamete during the sensitive pre-fertilization stages. We proved the usefulness of the test system by investigating the effects of alkylating agents. A second step was to investigate other substances. The following treatments induced dominant lethal effects: methyl methanesulfonate 100 mg/kg i.m., cyclophosphamide 200 mg/kg per os, triaziquone 0.25 mg/kg i.p. In contrast, the following agents were ineffective and can be classified as not mutagenic in this method: sodium cyclamate 10 000 mg/kg per os, saccharine sodium, 10 000 mg/kg per os, cyclohexamine sulfate 150 mg/kg per os, ethanol 5 ml/kg per os.


Some aspects of the detection of potential mutagenic agents in Drosophila. The Drosophila system is a valuable test for detecting and characterizing mutagenic agents. Tester strains are available or can be synthesized for determining almost all types of genetical change ranging from gene mutations to chromosome rearrangements in a great variety of cell types of both sexes. Metabolic activation of all groups of indirect mutagens tested so far (aryldialkyltriazenes, cyclophosphamides, nitrosamines, azo-, hydrazo- and azoxyalkanes, aflatoxins, and polycyclic hydrocarbons; about 35 representatives in all), gives strong although indirect support for the considerable metabolizing ability of Drosophila. This capability would be expected from comprehensive biochemical data on bioactivation of foreign compounds in other insects. From a comparison of which types of genetical change are induced at high, low and threshold concentrations, it appears that lethal tests remain the most reliable method for any screening program. Mutagenic agents such as diethylnitrosamine, hycanthone and certain triazenes, which are highly efficient in the induction of recessive lethals (gene mutations and/or deficiencies), would not have been detected in Drosophila if chromosome breakage were the only indicator for mutagenic activity. Moreover, for several mono- and polyfunctional agents, the lowest dose which is still genetically active was definitely lowest for recessive lethals when compared with dominant lethals, chromosome rearrangements or loss. If a new mutagen is discovered by a screening procedure using Drosophila, an accurate picture of its ability to cause either or both gene mutations and chromosome aberrations can be drawn. Such work will be valuable in helping to clarify similar problems in mammalian systems. For instance, it was important to learn that mutagens of the nitrosamine type apparently fail to produce breakage events in Drosophila. Similarly, three cyclophosphamides appeared not to have chromosome breaking ability. However, from a more detailed study, in which a series of concentrations was used, it became obvious that a penetration effect or, more likely, a rate-limiting factor in bioactivation, was the cause of the negative results obtained with these agents.


Mammalian cell transformation and cell-mediated mutagenesis by carcinogenic polycyclic hydrocarbons. The introduction of a polycyclic hydrocarbon such as benzo(alpha)pyrene (BP) into normal golden hamster embryo cell cultures results, in addition to cytotoxicity, in malignant cell transformation. Studies on the effect of different doses of BP on the normal cells showed that the frequency of transformed colonies was directly related to the dose of the carcinogen. Analysis of this dose-response curve suggests a one-event ("one-hit") response for transformation by this carcinogen. The one-event response for transformation by carcinogenic polycyclic hydrocarbons and the fact that these carcinogens bind to DNA in susceptible cells suggests that transformation can involve a single alteration in the genetic constitution of the treated cells. Carcinogens may, therefore, produce somatic mutations, some of which may involve the genes that control malignancy. Recently, considerable progress has been made in developing models for the study of chemical mutagenesis in mammalian cells. Using resistance to 8-azaguanine as a marker, positive correlations between mutagenicity and transformation were obtained with chemically reactive carcinogens such as N-acetoxy-N-2-fluorenyl-acetamide, N-methyl-N'-nitro-N-nitrosoguanidine and K-region epoxides of polycyclic hydrocarbons. However, no such correlations were obtained with the carcinogenic polycyclic hydrocarbons themselves, since the cell lines used in chemical mutagenesis do not metabolize these carcinogens. In order to obtain better correlations, we have developed a cell-mediated mutagenic assay with carcinogenic hydrocarbons in which Chinese hamster cells, which are susceptible for mutagenesis, were co-cultivated with lethally irradiated rodent cells that can metabolize these compounds. Using this cell mediated assay, we obtained mutagenesis with the carcinogenic hydrocarbons 7,12-dimethylbenz(alpha)anthracene (DMBA), BP, 3-methylcholanthrene and 7-methylbenz(alpha)anthracene; the most potent carcinogen, DMBA, gave the highest frequency of mutations. The polycyclic hydrocarbons, pyrene and benz(alpha)anthracene, which are not carcinogenic were also not mutagenic. We have therefore demonstrated a relationship between the carcinogenecity of polycyclic hydrocarbons and their mutagenicity in mammalian cells, without having to isolate their reative metabolic intermediates. It should be possible to use in this system human cells from different organs and individuals to screen for environmental chemicals hazardous to humans which have to be metabolically activated.


Legislative and technical aspects of mutagenicity testing. A brief account is given of the history of the legislative acts that give responsibility to the U.S. Food and Drug Administration (FDA) for ensuring the safety of foods, drugs, and cosmetics. Within the present legislative framework the FDA has the authority to impose regulations which are designed to ensure the safety of all foods, drugs, and cosmetics. The existing legislative authority is adequate for this purpose; however, the difficulty lies instead with technology and the inadequacy of scientific perspective in the emerging area of mutagenicity testing. Earlier efforts in development of mutagenicity screening systems culminated only a few years ago in the proposal to use the host-mediated assay, somatic cell cytogenetics, and dominant lethal tests collectively. Subsequent research efforts indicated that there were serious practical and scientific deficiencies in using this approach. More recently a new proposal, the tier system, has been suggested as an alternative measure. The proposed tier system at FDA consists of three testing levels of increasing complexity. The first tier is an initial screening effort using techniques having maximum sensitivity that are also useful for large-scale, rapid testing. The second tier is designed to identify and confirm that the presumptive mutagens detected in the first tier are truly mutagenic for higher organisms, most especially, for mammals. The third tier would be devoted to explicit genetic tests in mammals designed to ascertain the imposed risk to man by the introduction of a mutagen in our environment. The FDA is currently involved in a number of research activities in the area of mutagenicity safety screening which will explore the adequacies and possible deficiencies of the tier system approach. These efforts are described for our in-house activities, our contract activities, and our cooperative and collaborative activities with other government agencies and institutions.


Lymphocytotoxic antibody in inflammatory bowel disease. A family study. The prevalence of lymphocytotoxic antibody in inflammatory bowel disease is 40 per cent. Twenty-seven of 90 relatives of 23 probands with the disease (30 per cent) demonstrated lymphocytotoxic antibody, as contrasted with only three of 69 control family members (4 per cent) (P less than 0.0001). Decreased lymphocytotoxicity against lymphocytes from patients with inflammatory bowel disease as compared to normal donor lymphocytes previously demonstrated in the serum of probands was also observed in the serums from family members of the probands. Nineteen of the 48 household contacts of probands (40 per cent) were positive for antibody, whereas eight of 42 nonhousehold contacts (19 per cent) demonstrated it (P less than 0.05). Eight of 16 spouses (50 per cent) of probands showed antibody. The increased prevalence of lymphocytotoxic antibody in family members of probands and its occurrence mainly in household contacts (consanguineous and non-consanguineous) may indicate the exposure of probands and their family members to a common environmental agent.


Association of exogenous estrogen and endometrial carcinoma. To determine the association between the incidence of endometrial cancer and the use of estrogen in menopausal and post-menopausal women, we retrospectively compared 317 patients with adenocarcinoma of the endometrium with an equal number of matched controls having other gynecologic neoplasms; 152 patients used estrogen, as compared to 54 of 317 controls. Thus, the risk of endometrial cancer was 4.5 times greater among women exposed to estrogen therapy. When estrogen use was adjusted for concomitant variables such as obesity, hypertension, diabetes, parity, referral pattern, age at diagnosis, year of diagnosis and other gynecologic neoplasms, the magnitude of the increased relative risk was associated with several of these variables, and was highest in patients without obesity and hypertension. Exogenous estrogen therapy is associated with an increased risk of endometrial carcinoma, but this increased relative risk is less apparent in patients with physiologic characteristics previously associated with an increased risk.


Prospective comparison of indirect methods for detecting lactase deficiency. To compare sensitivity, specificity and convenience, four indirect methods of detecting lactase deficiency were tested prospectively in 25 subjects with biopsy-proved lactase deficiency and in 25 with normal lactase activity. After ingestion of 50 g of lactose, containing 1-14Clactose, breath hydrogen was abnormally elevated in all 25 lactase-deficient subjects (greater than 0.30 ml per minute at two hours); breath 14CO2 was below the normal range in 23, and in 19 the plasma glucose increased by less than 20 mg per deciliter. When lactose and ethanol were given together, the rise in plasma galactose remained less than 5 mg per deciliter in 24 of the lactase-deficient subjects. The specificity of the four tests was excellent, with only one false-positive plasma glucose test. Measurement of breath hydrogen is sensitive and specific, and does not require ethanol or isotopes. It is noninvasive, and is not influenced by gastric emptying or metabolic factors. We believe it to be the most suitable test for population screening for lactase deficiency.


Prostaglandins as mediators of hypercalcemia associated with certain types of cancer. We investigated the role of prostaglandins in the hypercalcemia associated with neoplasia. In patients with hypercalcemia and solid tumors the excretion of the major urinary metabolite of the E prostaglandins, 7 alpha-hydroxy-5, 11-diketotetranorprostane-1, 16-dioic acid (PGE-M), was significantly greater than normal, P LESS THAN 0.01 (median of 58.4 and 7.1 ng per milligram of creatinine respectively). Slightly elevated values were seen in normocalcemic patients with solid tumors (14.3 ng per milligram). The levels of the metabolite were normal in hypercalcemic patients with either hematologic neoplasia or primary hyperparathyroidism. Immunoreactive parathyroid hormone was undetectable in the plasma of all hypercalcemic patients with solid tumors. Inhibition of prostaglandin synthesis by aspirin or indomethacin reduced excretion of both the urinary metabolite and serum calcium in six hypercalcemic patients with solid tumors and elevated excretion of the metabolite. These findings support the concept that prostaglandins are mediators of the hypercalcemia caused by certain solid tumors.


Testing the physician's knowledge of antibiotic use: Self-assessment and learning via videotape. Because recent reports suggest that physicians in the United States do not use antimicrobial agents properly, we analyzed scores for the first 4513 physicians viewing the National Antibiotic Therapy Test, a nationally televised self-assessment test on the diagnosis and treatment of infectious diseases. The 75-minute videotape test, produced by the Network for Continuing Medical Education, contained three section: a 10-question pre-test, a 25-question teaching test, and a 15-question post-test. Scores were tabulated according to the specialty, years in practice, and volume of patients seen. The mean correct score was 68 per cent for all 50 questions, 55 per cent for the 10 pre-test questions, and 71 per cent for the 15 post-test questions. Physicians in practice for one to five years, residents and internists scored better than other subgroups. Answers to questions indicated deficiencies of knowledge and the need for further postgraduate education in the use of antibiotics.


Nosocomial respiratory syncytial virus infections. We studied the frequency and severity of respiratory syncytial virus infections acquired nosocomially on an infants' ward during a community outbreak. Every three or four days all infants and staff were examined, and specimens were obtained for viral isolation. During two months, 14 of 44 contact infants acquired the virus. All were ill, and four had pneumonia. Infected infants had a significantly longer mean hospital stay (21.5 days) than uninfected ones (9.2 days, P less than 0.001). Risk of nosocomial infection could not be related to age or to underlying disease, but was linked to length of hospitalization: 45 per cent of infants hospitalized for one week or more became infected, and the percentage increased with length of stay. Ten of 24 staff members also acquired the virus and appeared to play a major role as virus carriers. Nosocomial respiratory syncytial virus infection poses a major risk for hospitalized infants and adds to hospital costs.


Nephrosis and papillary necrosis after pyelonephritis. We present a case of nephrotic syndrome complicating acute pyelonephritis in a 45-year-old man. His first attack of acute bacterial pyelonephritis had two unusual features: transient nephrotic syndrome and chronic recurrent episodes of papillary necrosis. The former, which lasted for two weeks, was characterized by edema, excretion of 7.7 g of urinary protein per 24 hours and hypoproteinemia (1.8 g per 100 ml). A percutaneous renal biopsy two weeks after the height of the nephrotic state showed normal glomeruli by light and electron microscopy and immunohistologic studies. Interstitial changes were noted. Over two years the patient has passed approximately 50 fragments, characterized as necrotic tissue containing tubular structures. He has no evidence of diabetes mellitus, urinary-tract obstruction or ureteral reflux, analgesic abuse or atypical vasculitis. He is afebrile but has recurrent bacteriuria despite antibiotics. This case demonstrates that acute pyelonephritis must be added to the list of diseases causing the nephrotic state.


Tertiary structural differences between microbial serine proteases and pancreatic serine enzymes. Although primary structural homology between bacterial serine proteases and those from the mammalian pancreas is slight, two-thirds of the residues in the bacterial enzyme SGPB as seen at 2.8-A resolution, adopt a similar polypeptide chain conformation to that of the chymotrypsin family. The three major regions of difference show how this family of proteolytic enzymes has developed from the more primitive bacterial to the relatively sophisticated pancreatic enzymes.


Regulation of cell cycle stage-specific transcription of histone genes from chromatin by non-histone chromosomal proteins. RNA transcripts from chromatin of S phase but not G1 cells contain histone-specific sequences. Chromatin reconstituted with S phase non-histone chromosomal proteins transcribes histone messenger RNA sequences whereas chromatin reconstituted with G1 non-histone proteins does not. These results suggest that transcription of histone genes is regulated during the cell cycle and that non-histone proteins have a key role in this regulation.


Polarity of structure and of ordered nerve connections in the developing amphibian brain. Tectal polarity for retinal connections remains reversible long after the anatomical pattern of neural structures has been determined. Cells in the diencephalon seem to control this polarity. Following certain embryonic operations, the diencephalon developed behind the tectum. In such cases, the polarity of the retino-tectal projection was reversed.


[Biophysics of vision].

[Biophysics of vision]. Light snesory cells are sensitive photon-counting devices. The mechanism by which the light stimulus is transduced to nervous excitation is described. The absorption of a photon by the visual pigment-rhodopsin, a chromoprotein-causes a photo-chemical reaction, which is followed by a cascade of dark reactions of rhodopsin. One of these reactions triggers conductivity changes in the membrane of the visual cell, which results in a transient voltage impulse across the cell membrane. The magnitude and time course of this electrical signal contain the information of the light stimulus. The molecular mechanism of visual excitation can now be investigated experimentally.


[Specific crystal structures of carcinogenic hydrocarbons]. Carcinogenic polycyclic aromatic hydrocarbons differ from the noncarcinogenic hydrocarbons by a two-dimensional structural pattern of specific crystal faces. The significance of this structural pattern is envisaged as being a matrix for the specific two-dimensional adsorption of biogenic macromolecules. It is assumed that the specific adsorption may manifest the primary reaction of these carcinogenic compounds.


Rolling round bottle culture of HmLu-1 cells and the production of bovine ephemeral fever virus. An attempt was made to cultivate HmLu-1 cells in a rolling round bottle. As a result, the optimum conditions of cultivation were found to consist in the number of cells transplanted per bottle being 1 X 10(8), the volume of growth medium per bottle being 250 ml, and the velocity of rolling being 6 revolutions per hour. It was possible to make a monolayer of cells develop all over the glass surface under these conditions. A preliminary experiment was carried out to clarify the production of virus in the tube culture. In it, the highest virus titer was obtained two days after inoculation of a 4-day-old culture with a 1:100 dilution of stock virus. On the other hand, when the 4-day-old culture cells in the rolling round bottle were inoculated with virus suspension and when 100, 500, or 800 ml of maintenance medium was added to each bottle, there was little difference in virus titer obtained among the culture bottles. Then the virus yield per cell was compared between the rolling round bottle culture method and the stationary square bottle culture method. The highest virus titer was reached two days after virus inoculation, regardless of the culture method. The virus yield was 1.9 times as high in the rolling method as in the stationary method. From the results mentioned above, it was clarified that the rolling round bottle culture method made it possible to obtain a large amount of bovine ephemeral fever virus at a high titer in a labor-saving manner.