[Diagnosis of hypertension in childhood]. A significant increase in arterial blood pressure is considerably less common in childhood (as compared with adults), and, to a larger degree, is high-grade. The mild forms more frequently reverse spontaneously, and severe cases are more often asymptomatic. It is of a secondary nature in a much larger percentage (preponderantly of renal, but also of vascular, adrenal or other demonstrable etiology), i.e., susceptible to causal therapy. The growing interest within pediatrics in problems of primary (essential) hypertension with regard to epidemiology, etiology, pathogenetics and prognosis (!), lends additional importance to the particular difficulties involved in reliable blood pressure measurement and control, and additionally, the question of a useful definition of the criteria for pathological blood pressure increases, which is relatively uncertain in children (moreover, the normal values are highly age-dependent). The symptomatology of arterial hypertension shows certain age-specific characteristics. In the secondary forms, the underlying disease is ofter far advanced at the moment of manifestation and, even more so, of completion of the diagnosis. Certain risk factors (obviously also relevant for the later years of life) related to primary hypertension, the incidence of which is still quite controversial, can already be detected in childhood (familial and hereditary factors).


[Cervix cerclage surgery. A way for reducing prematurity]. Indications and results of 202 cerclage-operations are reported. There are prophylactic as well as therapeutic indications for a cerclage-operation. Regarding the results it is obvious that prophylactic cerclage has better prepossessions for a normally terminated delivery. Therapeutic cerclages show best results when performed within the 15th to 27th week of pregnancy. A cerclage performed after the 32nd week of pregnancy shows no statistically significant reduction of early delivery but only a postponing of the delivery-date into a phase of better survival chance for the child. A reduction of the early delivery rate is regarded to  be effective by prophylactic as well as therapeutic cerclages up to the 27th week of pregnancy.


[Continuous lumbar peridural anesthesia in obstetrics]. Review of 1000 continuous peridural anesthesias during labor and delivery. Reasons and conditions for the application of this analgetic procedure in our delivery rooms are discussed. The duration of labor and delivery is reduced by this method. The rate of vacuum extraction and forceps delivery is slightly increased. The rate of cesarean section is independent of this procedure. No adverse effects on the fetus were found. We obtained complete analgesia in 93 per cent of the cases. Severe complications were not observed.


[Dynamic measurement of blood pressure in human nailfold capillaries]. Dynamic blood pressure was measured in 33 human finger nailfold capillaries after direct cannulation with glass micropipettes by means of a resistance servonulling pressure measuring method. ECG, finger pulsations and respiratory thorax excursions were monitored simultaneously. All recordings exhibited pulsatile oscillations related to the cardiac rhythm. These oscillations resembled the wave forms of arterial pulsations with steep upstroke and dicrotic notch when the pressure amplitudes were above 10 mmHg. There was no apparent dependence on respiration. In 12 instances pressure fluctuations with frequencies ranging from 0.2 down to 0.07 Hz were observed in both the arteriolar and venular limb. Blood pressure in human skin capillaries is pulsatile and subject to remarkable fluctuations in the arteriolar as well as in the venular limb, systolic pressure values ranging from 14 to 71 mmHg and from 11 to 52 mmHg respectively.


[Regeneration of the gastric and intestinal mucosas]. The physiological cell renewal of gastrointestinal mucosa is regulated in man as in animal through certain mechanisms with measurable kinetic data. Pathologic mucosal alterations, metabolic disorders, pharmacological agents etc. clearly affect the regenerative processes of the gastrointestinal epithelium. Gastrin and pentagastrin stimulate the growth not only of the parietal cells, but also of the superficial epithelium of the gastric mucosa, whereas secretin does not change cell growth. Glucocorticoid steroids inhibit epithelial regeneration in all parts of the gastrointestinal tract. 5-fluorouracil has a similar effect but acts at a different site in the regeneration cycle. Epithelial cell proliferation of the gastric and intestinal mucosa is likewise inhibited in an uremic condition. In inflammatory changes in the human gastric mucosa epithelial cell hyperproliferation relative to the severity of gastritis and anomalous proliferation within regions of dysplasia can be demonstrated. Foveolary hyperplasia in Ménétrier's disease occurs on the basis of excessive hyperproliferation with displacement of regeneration zones.


[Adaptation of statistics to medicine].

[Adaptation of statistics to medicine]. In respect of the useful way of questioning and the properties of medical data rank tests and rank scores tests fit better than the so-called standard tests. Yet, rank tests in their wide variety are so far too poor for our medical purposes. Therefore some urgently needed methods for data analysis have been developed.


[Management of gastrointestinal diseases using a motility-regulating preparation. Results of a field study using bromopride (Viaben) conducted by 530 general practitioners on 4182 patients]. Abnormalities of oesophago-gastro-intestinal motoricity play an important etiologic role in various affections of stomach, intestine, oesophagus and associated complaints. The new monosubstance bromopride produces a selective action restoring the basal motility of stomach, pylorus, duodenum and of the lower oesophageal sphincter to normal. The effect and tolerance of Viaben (bromopride) were examined in an open field study on 4182 subjects. The drug was given in average doses of one capsule three times a day. The results were assessed as very good in 37.9% of cases, and as good in 47.9%. No change was seen in 12.2%, while only 2.0% were aggravated. 64.7% of all patients benefited within the first fortnight. Nausea, vomiting and intolerance to drugs even disappeared in the first days of treatment. Individuals exhibiting a nervous, irritative stomach also had a rapid response to the drug. Pain, which is a fairly common complaint, passed off quickly. Side effects were seen in 6.8% of cases. However, the question whether they were due to the treatment, is not easily answered in an open study. The most common side effect was tiredness (3.7%), which was reported to be mild in some cases. The dyskinesia observed in subjects treated with other ortho-substituted benzamides was only seen in 0.4% of all patients.


[Hyperbilirubinemias; diagnostic and therapeutic aspects]. In the newborn functional disturbances of bilirubin metabolism may be threatening for the life of affected infants. Apart from states with massive overproduction of bilirubin caused by hemolytic crisis functional hyperbilirubinemias in adults represent preponderant hereditary disorders (Gilbert's syndrome, Dubin-Johnson-syndrome, Rotor-syndrome), full compatible with normal life span. Affected subjects are considered as normal persons and should be advised to live a normal life, avoiding however all well-known exogenous factors which may exacerbate the disease. The important clinical and characteristic diagnostic criteria of the mentioned disorders of bilirubin matabolism as well as the possibilities of their symptomatic therapy are discussed.


[The Reiter syndrome. 2. Diagnosis, therapy, prognosis]. The incomplete form, the so-called Reiter-trias (three-fold Reiter's syndrome) and the form supplemented by skin- and mucous-membrane-lesions are presented. Iritis, conjunctivitis, urethritis as well as visceral complications are being discussed referring to their appearance and frequency. Of essential importance seems to be a specific analysis which will bring to light the often fleeting (eyes, urogenital-region) or willingly concealed (urethritis) symptoms. A differential diagnosis, recommendations for therapy and a prognostic outlook are concluding this short demonstration of Reiter's syndrome.


[TSH-screening program for congenital hypothyroidism. Experiences with early thyrotropin (TSH) screening]. 14,919 newborn infants were screened for congenital hypothyroidism within the last 5 years using a sensitive TSH method. 10 infants with congenital hypothyroidism were discovered thus presenting a frequency of 1:4500. Four of these infants showed abnormally high TSH levels and normal thyroxine levels. The determination of TSH in cord blood--or combined with the screening program for phenylketonuria--in eluate of dried filter paper specimens is the most sensitive test for primary hypothyroidism without false negative results and a low false positive recall rate of 0.16%. After initiation of therapy with thyroxine the TSH level falls unless therapy is delayed for longer. In the latter case TSH levels may remain elevated for several months despite therapy with thyroxine. We would suggest to start therapy with triiodothyronine for up to 14 days prior to initiation of the usual thyroxine therapy.


[Congenital hypothyroidism].

[Congenital hypothyroidism]. The clinical picture of congenital hypothyroidism in the newborn period as well as in infancy is presented. Those signs and symptoms are particularly emphasized which in spite of being clearly present in the newborn are frequently not registered and mostly not correctly interpreted. This is meant to aid in earlier clinical diagnosis of congenital hypothyroidism. Furthermore, guidelines for diagnostic work-up, therapy and follow-up are presented. For an optimal mental and neurological prognosis early treatment is of paramount importance.


[Diet therapy in chronic kidney failure]. The dose of proteins of high biological value and eventually the use of selective diet with protein mixture of highest value such as the potato-egg diet, the dose of essential aminoacids as part of the so-called Sweden-diet and finally the application of ketoanaloges of essential aminoacids, all these measures make possible a removal of all uraemic symptoms as well as a long lasting rehabilitation inspite of a strongly restricted renal detoxication.


[Chlamydia infections of the urogenital system]. During the last years Chlamydiae have been increasingly recognized as an important cause of urogenital infections. This paper is concerned with the classification, microbiology, cultivation and clinical findings of Chlamydiae, especially Chlamydia trachomatis, as causative agents of genital tract diseases.


[Complications following mediastinoscopy. Prevention and therapy]. Mediastinoscopy, being practised since 20 years, is a research method giving a high degree of information and during this time has become indispensable in diagnosis of diseases of the chest. The close neighbourhood of vital organs, small and easily vulnerable blood vessels and nerval tissues of functional importance first seemed to burden this method of investigation with an incalculate risk. But subtle operative technique with its instruments by Carlens and others let the number of complications remain remarkably small even in great collective statistics. The number of lethal complications ranged below 0.2%, more severe ones about 1%. But in these latter ones one almost always succeeds in achieving a restitutio ad integrum bei performance of consequent after-treatment. The more frequent mediastinoscopic investigations are performed in regions of marked pathologic changes, the higher is the number of described complications. But it must be considered that in many cases the more perilous and functionally straining thoracotomy can be avoided using mediastinoscopy. Complications occurring most frequently are described and possibilities of therapy are discussed.


[Prognosis and therapy of peripheral facial nerve paralysis. Electrodiagnostic ways of evaluation]. The function of the facial nerve can be examined by four electrodiagnostic methods. In the nerve excitability test and electroneurography with determination of the distal latency the facial nerve is stimulated over the stylomastoid foramen. Chronaximetry and electromyography are performed in the muscles. Whereas chronaximetry renders an impression of the severity of neural lesion, electromyography can also determine the onset of reinnervation activity. Early prognosis within 6 days of onset can be determined only by nerve excitability test and electroneurography, preferred by us, which assesses the muscle potential. If the potential amplitude decreases more than 35% within two days and the muscle potential disappears between the fourth and sixth day, total degeneration of the nerve with poor prognosis is indicated. Such data can be gathered by at least two electrodiagnostic investigations preferably on the third day after onset and one to three days later. The cosmetic disfigurement through peripheral facial nerve palsy poses immediately the question of prognosis and of the therapeutic possibilities. Usually, this question can be answered by clinical examination alone. As soon as paralysis of facial muscles exists, prognostical statements can be made by electrodiagnostical methods alone. Because of the possiblility of operative treatment it is necessary to assess the infavorable courses early.


[Nystagmus as a diagnostic criterium in neurology]. The most frequent seen nystagmus is jerk nustagmus. It is a versional eye movement comprising a quick and a slow phase. For diagnostic reasons it is very important to know the connections involved in vestibulo-oculomotor control. Besides peripheral, labyrinthine disturbances the observation of nystagmus is a very good tool in the topodiagnosis of the brain stem and mesencephalon. By ENG recordings, which normally should be used only after clinical examinations according to Frenzel and Jung, we can find much more better and reliable results in clinical topodiagnosis. Further tests of vestibulo-oculomotor function (rotation, optokinetic tests e.g.) offer the possibility of a discriminating topodiagnosis of the brain stem. This means an efficient use in clinical neurology. Following these considerations examples of single cases including ENG recordings are given.


[Measurement and evaluation of industrial noise]. Different methods for measurement and assessment of industrial noise are discussed. It is shown, that momentary the best approach to stress caused by noise is the "Trakt-Maximalpegel-Verfahren" with a cycle time of 5 s. For more exact description of acoustic recording of sound level and harmonic analyzis are indispensable.


[Reduced blood supply of the vestibular centers. Clinical and experimental studies]. To explain the origin of the narrow nystagmus writing (petite écriture) selected patients with hypoxemia were examinated using the pendular rotating test and ENG. Blood gas analysis was used to determine pO2 reduction. The decreased oxygen saturation was corresponding to the decreased amplitude of nystagmus. In a second experiment with alert rabbits the inspired gas mixture was altered to obtain hypoxia (8% O2+ 92% N2, controlled with blood gas analysis). A significant reduction from the normal nystagmus reaction was observed. This reduction in the amplitude (about 50%) is immediately reversible by giving oxygen. These experiments were repeated with each animal several times, the results being reproductible. There is a significant decrease  in amplitude of nystagmus through the influence of hypoxia.


[Pathophysiology and therapy of perinatal asphyxia in a mature newborn]. Based on modern knowledge about the pathophysiology of perinatal asphyxia a new concept of therapy is discussed. Besides cardiopulmonary resuscitation for the initial shock reaction the therapy of secondary complications according to the multi-system-reaction is emphasized. After the description of the correlation of partial asphyxia and the development of neurological defect syndromes in animal models the necessity of a "cerebral resuscitation" is mentioned.


[The biliary excretion of azlocillin].

[The biliary excretion of azlocillin]. The excretion of azlocillin into the human biliary tract was investigated in 8 patients with a T-tube in the common bile duct after intravenous injection of 2 g. Samples of serum and common duct bile were assayed from 15 min to 12 hours after injection. Biliary tract levels generally run parallel to serum levels but were about 15 times higher than those. Peak levels in T-tube bile averaged 1137 mg/l 60 to 90 min after administration. 12 hours after administration there were still mean concentrations of 13 mg/l to be found. It is concluded that azlocillin concentrations in bile exceed for a long time the minimum inhibitory concentrations for gram-negative and gram-positive causative organisms (above all E. coli, enterococci, Klebsiella spp., Proteus spp., staphylococci) of biliary tract-infections.


Effect of metaproterenol on ketone body metabolism of the forearm in healthy and diabetic subjects. Muscular ketone body metabolism was studied by the registration of arterial-deepvenous concentration differences of glycerol, beta-hydroxybutyrate and acetoacetate, and of muscular blood flow in 53 healthy volunteers and 23 juvenile diabetics. In six subjects of each group substrate metabolism was also investigated during the intrabrachial arterial infusion of metaproterenol (0.4 microgram/min). Identical rates of muscular glycerol release and ketone's fractional extraction were obtained in healthy and diabetic subjects during the basal period. A significant correlation between muscular ketone extraction and arterial ketone concentration was calculated in both groups. During the infusion of metaproterenol the diabetics, unlike the controls, revealed enhanced muscular glycerol output and reduced fractional extraction of beta-hydroxybutyrate. These findings are in line with the present view that the impairment of muscular ketone body utilisation in diabetic ketoacidosis may at least partly be due to enhanced muscular lipolysis.


On the effect of insulin on glucose-6-phosphate dehydrogenase and fatty acid synthetase activity in mouse liver. Regulation of glucose-6-phosphate dehydrogenase and fatty acid synthetase activity in mouse liver is examined in diabetic and normal mice. Up to a 4-fold increase of both enzymes can be observed in streptozotocin diabetic mice when transferred to a fatless, inducing diet. Administration of insulin does not increase enzyme activity at several doses and under a variety of conditions. This is a strong indication that insulin is not a necessary component of the induction system.


The use of perfused rat intestine to characterise the glucagon-like immunoreactivity released into serosal secretions following stimulation by glucose. Isolated perfused intestine of rat was used to demonstrate the glucose-stimulated release of glucagon-like immunoreactivity (GLI) into serosal secretions. The released GLI was characterised using immunoaffinity chromatography on columns of immobilised antibodies specific for the N (residues 1 to 18) and for the C (residues 19-29) terminal portions of glucagon followed by gel-filtration. The immunoreactivity was present in a variety of molecular species. These include a large GLI which has a molecular weight about 12000 and binds to antibodies specific for the N-terminal portion of glucagon and two polypeptide fractions with molecular weight closer to that of glucagon. While one fraction of the small GLI boun both to antibodies specific for the C-terminal and N-terminal portions of glucagon the other bound only to the former antibodies. The relevance of these findings to the origins of circulating GLI and the possible precursor relationship between large and other forms of GLI is discussed.


Serum T4, T3 and reverse T3 during treatment with propranolol in hyperthyroidism, L-T4 treated myxedema and in normal man. Serum concentrations of T4, T3 and reverse T3 were studied in two hyperthyroid groups (n = 13 and 11), in a group of normals (n = 9) and in a group of L-T4 substituted patients (n = 7) with severe pretreatment hypothyroidism. Serum T4 did not change except in one of the hyperthyroid groups change to in which a slight decrease was found. In all groups a significant fall in serum T3 and a significant rise in serum reverse T3 were found. An expected increase in serum TSH in the normal and in the L-T4 substituted groups could not be demonstrated.


Effects of levodopa and dopamine on plasma 11-hydroxycorticosteroid concentrations in mice. The effects of levodopa on the plasma concentration of 11-hydroxycorticosteroids and glucose were examined in mice. In fasted, nialamide treated mice, but not in fed mice, levodopa produced a significant decrease in the plasma concentration of 11-hydroxycorticosteroids. This was accompanied by a significant and marked decrease in the plasma glucose concentration. These effects of levodopa could be mimicked by relatively small doses of dopamine injected intracerebroventricularly but not intravenously. The integrity of the hypothalamic-pituitary adrenal axis in nialamide-treated mice was suggested by the elevation in plasma 11-hydroxycorticosteroids produced by fasting or by insulin induced hypoglycaemia. These results indicate that in the mouse, as in other species, levodopa can inhibit stress provoked increases in the secretion of 11-hydroxycorticosteroids.


Increase of serum potassium in the upright posture in selective hypoaldosteronism. The effect of a 4 hr upright posture on serum potassium (SK) levels was investigated in a certain group of hospitalized renal patients with selective hypoaldosteronism and in healthy subjects. Significant (p less than 0.001) postural increase in SK (0.4 MMol/L) was found only in the 3 young patients with chronic glomerulonephritis and hypoaldosteronism who presented with hyperkalemia (5.84 +/- 0.13 mMol/L) as outpatients, but showed a marked improvement toward normokalemia (4.95 +/- 0.13 mMol/L; p less than 0.001) within the hospital without any specific treatment. In healthy persons in the fastqng condition the influence of the upright position of short duration (45 min) was also studied on SK and a very small but significant increase (0.15 mMol/L) was found. It was concluded: 1. the postural SK INCREASE MAY OFFER AN--AT LEAST PARTIAL--EXPLANTATION FOR THE "OUTPATIENT HYPERKALEMIA", 2. The normal activity of renin-angiotensinaldosterone system may play a role in the counteraction of the trend for SK rise in the upright posture.


Effects of adrenergic blockade on plasma catecholamine levels during adrenaline infusion. Alpha and beta adrenergic blocking drugs were administered, either singly or in combination, prior to a 3hr adrenaline infusion (2 microgram kg body wt-1 min-1)), Animals were premediated with either phenoxybenzamine (1 mg kg body wt-1 min-1). Phenoxybenzamine did not affect circulating adrenaline levels, but propranolol, either alone or in combination with phenoxybenzamine, resulted in a significant reduction in plasma adrenaline levels when compared with the control unblocked situation of adrenaline infusion without premedication. The results provide a possible explanation for the protective effect of combined adrenergic blockade in shock situations.


Fetal blood calcium response to maternal hypercalcemia induced in the cow by calcium infusion or by solanum glaucophyllum ingestion. Bovine fetuses chronically catheterized in utero during the last month of gestation were used to study the relationships of maternal-fetal calcium and phosphate levels. Calcium infusion into the pregnant cows induced a rapid and marked increase in maternal plasma calcium but no change in fetal plasma calcium concentrations. Oral administration of Solanum glaucophyllum to the mother for 6 days raised the plasma concentrations of calcium and phosphate in both the mother and the fetus.


Effect of oral contraceptives on folate economy--a study in female rats. Daily administration of one tenth of a tablet of Ovulen-50 (ethinodiol diacetate, 1 mg, ethinylestradiol, 50 microgram) to adult female rats resulted in an increase in the liver and kidney folate levels, increased urinary excretion of folate and a fall in serum folate while red blood cell folate levels remained unaffected. The tissue folate levels did not indicate adverse effect of OCA on folate economy of the body.


Gluconeogenesis in perfused livers of genetically obese-hyperglycemic (ob/ob) mice. Hypertrophy of liver cells, as measured by decreased mg DNA per g wet liver, from obese mice (C57BL/6J ob/ob) was associated with a marked increase in triacylglycerol content per g wet liver when compared with control lean mice (C57BL/6J ?/+). The difference between the rates of net glucose production from lactate in isolated perfused livers from obese and lean mice was small when expressed per g wet liver. However, calculation of these rates either on a DNA or body weight basis indicated that the rate of gluconeogenesis in livers from obese mice was twice that of lean mice. Using perfused livers from lean mice, the ratio of net uptake of C3-substrate to gluconeogenesis indicated that a major proportion of lactate disappearing from the perfusion medium could not be accounted for in the appearance of glucose; but using the perfused livers of obese mice, almost all of the net lactate disappearance could be accounted for by a net increase in glucose production.


Deuterium-labeled steroids for study in humans. II. Preliminary studies on estrogen production rates in pre- and post-menopausal women. 6,7-Dideuterio-3-hydroxy-1,3,5(10)-estratrien-17-one (dideuterio-estrone) and 4-deuterio-1,3,5(10)-estratriene-3,17 beta-diol (monodeuterio-17 beta-estradiol) were used for the estimation of estrogen production rates in pre- and post-menopausal women. The results are concordant with those obtained by radioisotope administration as reported in the literature. This preliminary study suggests that one or more steroids labeled with one or multiple deuterium and/or other stable isotopes may be employed for the measurement of production rates of steroid hormones which are derived from multiple precursors.


Metastatic tumours in the testis.

Metastatic tumours in the testis. In a prospective autopsy study of male subjects with solic malignant neoplasms, six were shown to have metastatic deposits within the testis (2.5%). These were metastases from carcinoma of the prostate (two cases), melanoma (two cases), bronchial carcinoma (one case) and pleural mesothelioma (one case). In addition, four of 29 leukaemic patients and six of 28 with non-Hodgkin's lymphoma showed testicular involvement. The metastases from the solid tumours presented in solitary nodules, as multiple nodules or as a diffuse involvement. Microscopically, these were represented by tumour cells within the interstitial tissue without involvement of the seminiferous tubules; interstitial tissue and tubular involvement, and tumour confined to the seminiferous tubules respectively.


Peutz--Jeghers syndrome with pseudoinvasion of hamartomatous polyps and multiple epithelial neoplasms. The risk of malignant change developing in the hamartomatous polyps in Peutz-Jeghers syndrome is widely held to be negligible. However an association with tumours of the upper gastro-intestinal tract, ovary and other diverse multiple neoplasms is now recognized. Previously reported cases of malignant change in Peutz--Jeghers polyps may represent 'pseudoinvasion' and we report such a case. This was associated with carcinomas of the bile ducts, left tonsil and a papillary adenoma of the pancreatic duct. It lends further support to the view that there may be a genetic predisposition to the development of neoplasms in this condition. Pathologists and clinicians must be aware of this entity of 'pseudoinvasion' in order to avoid unnecessarily radical surgery in Peutz-Jeghers syndrome.


The nature of retest reaction in delayed hypersensitivity. I. Light microscopic changes in the skin of the eyelid. The retest reaction is a variant of delayed hypersensitivity where in repeated application of an antigen at the same site leads to an intense eosinophil leucocytic infiltration. This reaction has been produced experimentally for the first time in the eyelids of rabbits and guinea-pigs and it is possible that such a mechanism is implicated in a variety of clinical ocular conditions in which IgE does not appear to feature. It was also found that tissue reaction was modified in the absence of suppressor cells, these having been temporarily inhibited by pretreatment of the animals with cyclophosphamide.


Oxyuris granulomas of pelvic peritoneum and appendicular wall. Infestation with Enterobius (Oxyuris) vermicularis is very common but seldom produces lesions and even more rarely causes granulomas. Two cases of oxyuris granulomas/nodules), one in the serosa of ovaries and left fallopian tube in a female of 32-years and the other in the submucosa of the appendix in a 10-year old girl are identified by the presence of true necrotizing granulomas containing the parasite. The pathogenesis and differential diagnosis of abdominal granulomas is discussed.


A cost containment committee can help cut overall costs. The cost containment committee at the University Hospital of Jacksonville has served many purposes. For example, through its activities, managers have gained a better sense of the overall needs of the institution, and the medical staff has learned how complicated resource allociation can be.


Providers have failed to work for continuity. Continuity of patient care between different health care settings has been advocated for nearly 20 years, but little has been done to effect it. The study described here emphasizes the current lack of effort by health care providers in hospitals and nursing homes to find a workable solution.


Management peer review audits efficiency. A medical center's voluntary management audit program helps to assess and to ensure efficient and effective institutional and departmental management.


NIH panels analyze issues on technology. Experts at NIH's "consensus development" technology assessment conferences study a wide range of issues and make recommendations to help guide users of medical technologies.


'TEAM' up for technology assessment.

'TEAM' up for technology assessment. Recently, the technology evaluation and acquisition methods (TEAM) project was launched to study the current state of the art of decision making in hospitals.


Small hospitals manage clinical equipment. Small hospitals can develop clinical engineering programs that meet their needs by using regional shared clinical engineering services or by hiring engineering technicians.


Cooperation is key to future needs.

Cooperation is key to future needs. Can the hospital industry reconcile manufacturers' entrepreneurial prerogatives with public desire to have safe, tested, cost-effective technologies?


Planning system has corporate overview.

Planning system has corporate overview. The Clarkson Management System (CMS) provides for appropriate participation of managers in all major plans and a common understanding of the impact of all plans on the total organization.


Reimbursement shapes market for technology. Methods of reimbursing health care providers affect their decisions about adoption and use of new medical technologies, but how they can elicit good decisions is unclear.


Patient leverage theory proves to be false. The assumption that hospitals must procure new technologies to recruit and retain physicians appears to be false, according to the study done by these authors.


Auditing dietetic services (second of a series). In this second article of a four-part series on auditing dietetic services, the authors focus on a monodisciplinary nutritional care audit. After defining the purpose of such an audit, a step-by-step description is given of how the audit should be carried out from developing standards and criteria to conducting a review audit to measure improvement.


Remodeling on a shoestring improves pharmacy's efficiency. A hospital's pharmacy renovated its existing outdated and highly restricted departmental space to help ensure more efficient operation until the master plan for hospitalwide improvements could be completed and implemented. This temporary renovation was accomplished at very low cost and yielded improvements ranging from better use of space and personnel to better communication between the nursing and the pharmacy departments.


Method for calculating costs of steam sterilization devised. Through a study at 10 hospitals located throughout the United States, a method for determining the costs of operating steam sterilization equipment was devised and tested. Any hospital central sterile supply manager can use this method to monitor his sterilizers' cost per hour of operation and cost per load.


Cost containment: a national policy.

Cost containment: a national policy. Guaranteeing access to high-quality care became a firmly established national policy with the advent of Medicaid and Medicare programs. However, since 1970, the federal government has gradually shifted the emphasis of national policy on hospital care. Cost containment efforts on the part of President Carter's Administration have made cost containment, rather than guaranteed access, the major national policy on hospital care.


Changing the course of things: costs enter medical education. The costs of health care, and the physician's role in generating them, are subjects that more and more often are being taught in medical schools and graduate medical training programs. Virtually all of these programs are focused on physicians' use of hospital services, particularly diagnostic procedures, but there is a wider goal: development of a different physician attitude toward cost, quality of care, alternative treatments, and how they all interrelate.


Strategic strike management helps hospital to carry on. During a strike, a hospital's administration has the responsibility for minimizing disruption of patient care. Preparation for a strike should include development of a contingency plan whereby additional duties are assigned equitably among staff members, lines of communication are reinforced, and services are shared with neighboring hospitals.


Cost-consciousness prompts three-phase education service. During a one and one-half year period, an acute care community hospital implemented a patient education service, a major goal of which is to provide programs that have a revenue-generating potential. The three distinct phases of the plan--research and development, implementation and evaluation, and expansion--are described herein.


The kidney in health and disease: VIII. Renal concentrating and diluting mechanisms. The capacity to elaborate urine either more dilute or more concentrated than the plasma from which it is derived enables the kidney to regulate the solute concentrations and hence the osmolality of body fluids within narrow physiologic limits despite wide fluctuations in salt and water intake. The underlying mechanisms are examined in detail, with emphasis on the role of urea in the countercurrent system of Henle's loop.


Diet and diabetes mellitus.

Diet and diabetes mellitus. Optimal control of any stage of diabetes is possible only with optimal dietary management. Furthermore, in 90% of stable patients who comply with regimens like those described, this dietary approach alone will suffice for control.


Fetal breathing: its physiologic and clinical implications. The respiratory movements the human fetus makes in utero can be detected and used as a valuable aid in determining fetal well-being. Their presence or absence, amplitude, and duration can all provide important information. Their absence, however, does not carry a poor prognosis unless other indices of fetal status, such as the nonstress test and oxytocin-challenge contraction-stress test, are also abnormal at the same time.


Buerger's disease involving the celiac artery. A young male with Buerger's disease who had previously required a left leg amputation died in renal failure and sepsis. Postmortem examination revealed an obliterative lesion of the celiac artery, which resulted in hepatic, splenic, and pancreatic infarctions. Celiac artery involvement represents an unusual manifestation of thromboangiitis obliterans.


Transvascular endomyocardial biopsy in infants and small children. Myocardial findings in 10 cases of cardiomyopathy. Transvascular endomyocardial biopsy specimens from nine children with congestive cardiomyopathy and one with hypertrophic cardiomyopathy were studied by light microscopy using sections 1 mu thick cut from Epon embedded tissue and by electron microscopy. There was a disparity between the severity of the physiologic impairment and the morphologic abnormalities. Interstitial fibrosis was present only in the one case in which significant viral antibody titers were obtained. The sizes of the cardiac muscle cells varied abnormally in all specimens. Cardiac muscle cells in two patients contained abnormal mitochondria, and a leptomeric fibril was found in one patient. Virologic cultures of the tissues were negative and no viral particles were identified by electron microscopy. An attempt was made to correlate the clinical and pathologic findings.


The spectrum of eosinophilic infiltration of the gastrointestinal tract and its relationship to other disorders of angiitis and granulomatosis. Six cases of eosinophilic infiltration of the gastrointestinal tract were studied. Three cases were of the diffuse infiltrative variety (eosinophilic enteritis, two cases; eosinophilic peritonitis, one case), and three cases were of the circumscribed variety (so-called inflammatory fibroid polyp). Two of the infiltrative lesions showed necrotizing granulomas identical to those described by Churg and Strauss; one of the two also showed active vasculitis. One circumscribed lesion occurred in a patient with polyarteritis nodosa. Necrotizing eosinophilic granulomas were also noted in this lesion. Our observations suggest that the two forms of eosinophilic infiltration of the gastrointestinal tract are parts of a disease spectrum. Supporting evidence in the literature is presented. The relationship of this group of eosinophilic lesions to the hypereosinophilic syndrome, allergic granulomatosis and angiitis of Churg and Strauss, and polyarteritis nodosa is discussed.


Histologic and morphometric study of chronic gastritis in alcoholic patients. The effect of chronic alcohol ingestion on the gastric mucosa was determined in 96 patients in whom gastroscopy was performed because of upper gastrointestinal symptoms. Seventy-two patients were classified as alcoholics and 24 patients as nonalcoholics. In all cases biopsy specimens were taken from the fundus and antrum. The diagnoses of chronic superficial and atrophic gastritis were based on conventional histologic criteria and a morphometric technique utilizing quantitation of the chronic inflammatory cells in the lamina propria. Alcoholic patients were found to have a higher incidence of chronic gastritis of the antrum than nonalcoholics (p less than 0.001). Fundic involvement was also more common, probably accounting for the decreased gastric acid output described in chronic alcoholic patients. Finally, gastritis was more severe in the alcoholics; below 45 years of age chronic atrophic gastritis was seen only in alcoholics. We conclude that chronic gastritis develops more frequently in alcoholic patients and evolves into chronic atrophic gastritis at an earlier age than in nonalcoholic subjects.


Ultrastructure of benign cartilaginous tumors of intraosseous origin. The ultrastructure of chondroblastoma, chondromyxoid fibroma, and enchondroma is described. In chondroblastoma the tumor cells often show nuclear indentations and a thick nuclear fibrous lamina, and have features indicative of poorly differentiated cartilaginous cells. Chondroblastoma is a tumor thought to arise from immature chondrocytes related to the epiphyseal cartilage. In chondromyxoid fibroma the cells are pleomorphic with irregular cell processes and scalloping of the cell membrane. The nuclei are also often indented and demonstrate the presence of a thick nuclear fibrous lamina. The matrix consists of proteoglycan granules and fine fibrils. The large bizarre atypical cells often seen in this tumor, except for their size, do not differ from the typical cells. Chondromyxoid fibroma arises from cells related to the epiphyseal cartilage and demonstrates moderate degrees of cartilaginous differentiation. The close relationship between chondromyxoid fibroma and chondroblastoma is emphasized. The nuclear irregularities and the presence of a thick fibrous lamina are features shared by these two lesions. The tumor cells of enchondroma have features of well differentiated cartilage, and the pericellular matrix tends to be sparse around most cells. In addition to proteoglycan granules and fine fibrils, the matrix contains many dense membrane bound bodies. Numerous tumor cells undergoing necrosis are noted. Studies comparing enchondroma and well differentiated chondrosarcoma show no morphologic differences and both tumors have similar features. The application of electron microscopy does not provide pathognomonic features to distinguish between these lesions. However, it helps to correlate the ultrastructural findings with light microscopy.


Sphenoidal pituitary adenoma.

Sphenoidal pituitary adenoma. A 62 year old female died of a chromophobe pituitary adenoma of the sphenoid bone. A normal pituitary gland was present within the sella turcica. She also had a chief cell parathyroid adenoma, a papillary thyroid carcinoma, and an ovarian thecoma (multiple endocrine neoplasia syndrome).


An ultrastructural demonstration of the agent of Legionnaires' disease in the human lung. The authors have provided ultrastructural demonstration from human material of a small rod shaped organism that represents the causative agent of Legionnaires' disease. The organisms are found mainly in intracytoplasmic vacuoles of alveolar cells. They have a thin outer cell wall and a more delicate plasma membrane. On the basis of morphology, arguments are presented to classify these unusual organisms as rickettsia-like.


Benign lymphoepithelial lesion (Mikulicz's disease) of the salivary gland: an ultrastructural study. An ultrastructural study of a benign lymphoepithelial lesion of the parotid gland demonstrated that the so-called epimyoepithelial cell islands were sharply demarcated from the surrounding parenchyma by a thick basement membrane containing collagen fibers. The hyaline material seen by light microscopy within the islands was ultrastructurally similar in appearance to this delimiting basement membrane. The epithelial cells within the islands were united by well formed desmosomes and many had prominent tonofilament bundles, but myogenic differentiation was not observed. Hydropic degeneration was not seen in these epithelial cells; cells with a perinuclear clear space seen by light microscopy corresponded to large lymphoid cells ultrastructurally.


Variable substructure in the secondary constriction of the human chromosome 1. The secondary constriction in human chromosome 1 consists of a proximal segment stained by the GC-specific fluorochrome mithramycin and a distal segment stained by such fluorochromes as DAPI or DIPI, which show enhanced fluorescence intensities in AT-rich regions of the chromosomes. A study involving 21 individuals revealed that both parts are independently involved in length variability. In two cases, two GC-rich regions separated by an AT-rich segment and an additional distal AT-rich part were found.


A case of D13 ring chromosome.

A case of D13 ring chromosome. A case of D ring chromosome identified with trypsin banding as a 13 with loss of the bands p12 and q34 is reported. The clinical features characteristically associated with the loss of these specific segments were present.


Partial monosomy of the long arm of chromosome 16: a distinct clinical entity? A 7-month-old male child with a de novo, seemingly balanced reciprocal 5p/16q translocation and karyotype 46,XY,t(5;16) (p14;q21), resulting from a maternal meiotic error, is described. The clinical findings in this patient are strikingly similar to those in the only patient with partial deletion 16q hitherto described, [del(16)(q21)], indicating that during the 5p/16q rearrangement, 16q material was lost and suggesting that partial or total deletion of the long arm of chromosome 16 distal to band q21 is accompanied by a distinct clinical phenotype.


Langer type of mesomelic dwarfism as the possible homozygous expression of dyschondrosteosis. A male newborn with the typical Langer type of mesomelic dwarfism is presented. The finding of a variable degree of Madelung's deformity and mesomelic shortening in both parents and in the maternal family tends to support the hypothesis that this type of mesomelic dwarfism may be the clinical manifestation of a homozygous state for dyschondrosteosis.


Partial trisomy 10q: a recognizable syndrome. Five cases from two nonrelated families with partial trisomy 10q due to a reciprocal translocation t(10;17)(q25;p13) and t(10;11)(q24;q23), respectively, are reported. The phenotypic findings are compared with those of 17 previously published cases; the clinical data justify the conclusion that cases with trisomy 10q show a specific syndrome of mental retardation and malformation characterized by psychomotor retardation, growth retardation, hypotonia, high forehead, flat face, fine and arched eyebrows, antimongoloid slant of the eyes, narrow palpebral fissures, hypertelorism, short nose, bow-shaped mouth, short neck (kypho)scoliosis, and in some cases microcephaly.


Biochemical characteristics of Ehlers-Danlos syndrome type VI in a family with one affected infant. The parents of a child with the clinical symptoms of Ehlers-Danlos syndrome type VI were identified as third-degree cousins. Biochemical analysis of the dermis of the patient revealed a complete lack of hydroxylysine in the dermal collagen. The dermis of both parents contained only half the amount of hydroxylysine found in healthy individuals. Hydroxylation of prolyl residues was normal in the skin of the patient and his parents. Investigation of the collagen synthesized by fibroblasts derived from the skin of the patient showed a normal proportion of type I and type III collagen. However, while hydroxylation of prolyl residues was normal in type I and type III collagen, hydroxylation of lysyl residues was markedly lower than normal in both type I and type III collagen.


A homozygote for a serum albumin variant of the fast type. A healthy, 10-year-old male born in Milano to a family from Southern Italy (Puglia) was found to be a homozygote for an albumin variant of the fast type. His parents are half-first cousins. Their common grandfather, the parents, one sister, and three brothers of the child were all heterozygotes for the same albumin variant. This seems to be the first case of a homozygote for a fast albumin variant described in Europe.


Effects of various cyclophosphamide concentrations in vivo on sister chromatid exchanges (SCE) and chromosome aberrations of Chinese hamster bone marrow cells: comparison of two methods measuring the mutagenicity of a test compound. The in vivo SCE formation and the induction of chromosome aberrations in the bone marrow of Chinese hamsters (Cricetulus griseus) were studied after various concentrations of cyclophosphamide, and the sensitivity of the two test methods was compared. The administraiton of 1.0, 5.0, 13.3, 25.0, and 40.0 mg/kg body weight induced a dose-dependent increase in SCE. The frequency of chromosome aberration, however, was not increased significantly with doses of 1.0 and 5.0 mg/kg body weight. Only with doses of more than 13.3 mg is a significant induction of chromosome aberrations seen. Therefore the SCE test system seems to be 10 times more sensitive than the induction of chromosome aberrations in the same cell type.


Sister chromatid exchanges and aging. III. The effect of donor age on mutagen-induced sister chromatid exchange in human diploid fibroblasts. Although baseline levels of SCE appear to be similar in metaphase cells derived from young and old human skin fibroblast cultures, a significant decline in both MMC- and AAAF-induced sister chromatid exchanges was observed in the older cell populations. Considerable variation exists in the levels of MMC-induced SCE between individual cell cultures. However, parallel examination of several cell strains from young and old donors confirmed the decrease in mutagen-induced SCE frequencies in older cell populations.


Serum zinc levels in heterozygous carriers of the gene for acrodermatitis enteropathica: identification of a carrier state is not possible. Three cases of acrodermatitis enteropathica (a.e.) from two nonrelated families are described. Two siblings had characteristic symptoms of a.e. in childhood. Both survived to adulthood without treatment, at which time the clinical picture became uncharacteristic of a.e. Even so, the serum zinc levels confirmed the diagnosis in both cases. The third case showed classic symptoms of a.e.; the patient had a greatly reduced serum zinc level and responded at once to treatment with zinc sulphate. Heterozygous carriers of the gene for a.e. have often had slightly reduced serum zinc levels. The value of this test could probably be improved by correcting the normal range of serum zinc for factors known to influence this, such as the patient's age and serum albumin level. The normal range ought also to be corrected for diurnal and postprandial variations of serum zinc.


Isoelectric focusing of rare transferrin (Tf) variants and common TfC subtypes. TransferrinC (TfC) subtypes were determined by isoelectric focusing (PAGIF) on samples from 90 carriers of the TFB and TfD alleles. In all cases of CB and CD heterozygotes only one of the two common subtypes of the TfC allele, TfC1 or TfC2, was observed. This is considered strong support for the hypothesis of two common alleles at the Tf locus. The different isofocusing patterns of rare B and D variants are compared with the results obtained after agarose gel electrophoresis (AGE).


Isoelectrofocusing of erythrocyte galactose 1 phospho uridyl transferase in a family with both galactosemia and Duarte variants. A family with the presence of the genes for both galactosemia and the Duarte variant is described. Galactose 1 phospho uridyl transferase has been studied not only by electrophoresis on starch gel, but also by isoelectro-focusing on thin-layer acrylamide. Normal and variant transferases were resolved into three bands, the isoelectric point of which was between 5.40 and 5.10 for the normal subjects, and between 5.25 and 4.95 for subjects with the Duarte variant.


PTC-tasting ability in populations living in Kirghizia with special reference to hypersensitivity: its relation to sex and age. The dimorphism in sensitivity to PTC, with a dilution scale up to 29, was studied in 320 male and 320 female Kirghiz students, 45 male and 200 female Russian students in Frunze, and in 734 Kirghiz schoolchildren in a high-altitude area of South Kirghizia. Gene t frequency was 0.44 for the Kirghiz students, 0.56 for the Russian students, and 0.54 for the Kirghiz schoolchildren. In all the groups studied it was established that such factors as sex and age have no modifying effect on sensitivity to PTC and the pattern of the distribution of sensitivity. In all the groups the frequency of 'tasters' exceeded that of 'nontasters.' Among the Kirghiz students there was a very small percentage (1.2%) of hypersensitive subjects (dil. No. 18), while 14.1% of the Kirghiz children of one Kyzyl-Dzhar school were hypersensitive. Genealogical studies showed that all the hypersensitive subjects belonged to one small stock and lived in the same village. Family studies of probands suggest the existence of a new (third) allele (T2) which determines hypersensitivity to PTC.


The electroencephalogram (EEG) as a research tool in human behavior genetics: psychological examinations in healthy males with various inherited EEG variants. II. Results. The results of psychological examinations on 298 adult male probands with various inherited EEG variants are described. They may be summarized as follows: 1) The low-voltage (N) group scored high in intelligence tests, especially in spatial orientation. Personality scores revealed this group as 'normal', extravert, group-dependent, and not very energetic. 2) The borderline low-voltage (NG) group showed slight weakness in abstract thinking, short-time memory, and motor skills and a relatively strong tendency to have 'neurotic' complaints. Reaction time and motor skills were poor. 3) The occipital fast alpha-variants (BO) group performed very well in tests of abstract thinking and motor skills. 4) The monotonous alpha (R) group showed average performance in most intelligence scores but above-average in short-time memory and in precision under stress conditions. Personality scores indicated high spontaneous activity and toughmindedness. 5) The BG (fronto-precentral beta-group) category showed very low MMPI scores, indicating little neurotic tendency. Intelligence could be above average. 6) The diffuse beta (BD) group scored low in intelligence tests, especially in spatial orientation, and had a high error rate in tests measuring concentration and precision. Most differences were relatively small; the whole range of test scores could be found in all EEG groups.


The electroencephalogram (EEG) as a research tool in human behavior genetics: psychological examinations in healthy males with various inherited EEG variants. III. Interpretation of the results. Interpretation of the results from psychological examinations of 298 probands with inherited EEG variants requires (1) critical evaluation of previous literature on psychological EEG correlates, (2) knowledge of the main concepts and experimental approaches for elucidating the basic mechanisms of EEG rhythms, (3) discussion of previous attempts to link psychological variation in human populations with corresponding variation in brain function, and (4) interpretation of results from considerations at these three levels with the data from our own study. At the first level (previous psychological studies), comparison with Schmettau's study proved to be especially revealing: Her conclusions about personality correlates with high alpha-index and with "flat" EEGs were very similar to ours with the monotonous alpha- (R) and low-voltage (N) EEGs, respectively. Her EEG type with high beta-index overlaps with our beta-diffuse (BD) type; a tendency to psychasthenia and low resistance to stress is less obvious in our group, but is expressed indirectly by reduced speed and accuracy in tests requiring attentiveness and persistence. The correlation between alpha-frequency and intelligence found in other studies was confirmed by the especially high intelligence scores of our group with occipital fast alpha-variants (BO). At the second and third levels of the discussion (EEG mechanisms; neurophysiological theories), the cooperation of cerebral cortex (EEG battery), thalamus (pacemaker), and ARAS (tonic arousal) is discussed, and the personality typologies of Eysenck and Claridge are mentioned. From this and other evidence, the following hypotheses are discussed: 1) The personality profiles of the R group are influenced by high activity and efficiency of the thalamic alpha-pacemaker(s), which leads to a high degree of modulation, selection, and amplification of afferent stimuli. 2) In the countertype of this EEG variant, the N EEG, a low modulation and amplification by the thalamic alpha-pacemaker is assumed. This leads to relatively low intensity of feeling and to low spontaneous activity, but to faster information processing. Combined with an increased level of tonic arousal in the ARAS, it may cause certain 'neurotic' complaints (our low-voltage borderline (NG) group). 3) The EEG with diffuse beta-waves (BD) is caused by a high level of tonic arousal in the ARAS, which tends to distrub the thalamocortical circuit. This leads to reduced stress resistance and to impairment of intellectual functions, especially space perception. Due to limited evidence, the next two hypotheses are advanced only tentatively: 4) alpha-rhythm with very high frequency 16--19 c/s) leads to improvement of information processing and, hence, to high intellectual performance and motor dexterity. 5) Probands with frontoprecentral beta-groups (BG) show no psychological signs of increased tonic arousal; therefore, these beta-groups are caused not by increased tonic arousal of the ARAS, but by a genetic variant of a thalamic subsystem.


Production of endogenous D-glucaric acid and oxidative N-demethylation of amidopyrine in man: lack of correlation. In adult male subjects there was no positive correlation between the 24-hr urinary excretion of D-glucaric acid (D-GA) and the metabolic formation of 4-aminoantipyrine (AAP) from amidopyrine. It is concluded that in man the urinary D-GA excretion rate cannot be regarded in general as an indirect measure of the activity of microsomal drug conversion by means of mixed-function oxidases (MFO). Normal urinary value for D-GA: 16.3 +/- 1.5 (mean +/- SEM) mumols saccharo-1,4-lactone/24 hr as equivalent.


Dihydralazine therapy and acetylator phenotype. The acetylator phenotype was studied in 21 hypertensive patients receiving chronic treatment with dihydralazine and other antihypertensive drugs. Plasma dihydralazine concentrations were measured 6 hours after the morning dose of the drug. There were no significant differences between the slow and fast acetylators 1) in the daily dose of dihydralazine needed, 2) in the concentrations of dihydralazine achieved in plasma, 3) in the dose/concentration-relationship of dihydralazine or 4) in the appearance of side effects. Antinuclear antibodies were found in five patients. Four of them were fast acetylators. The lowest dose/concentration relationship was found in a patient with impaired renal function. According to these results the acetylator phenotype seems to be an unimportant factor in therapy with dihydralazine. More investigation will be needed in order to elucidate the metabolism of dihydralazine.


Pharmacodynamic and spirometric responses to a sustained-release theophylline capsule. A prolonged therapeutic effect following a single oral dose of theophylline and maintenance of an adequate therapeutic blood level of theophylline is an important factor in the management of chronic bronchial asthma. Eighteen adult asthmatics, nine of whom were females and nine males, aged between 21-53 years, were given a sustained release theophylline capsule, 250 mg, every 12 hours and pulmonary mechanical functions as well as serum theophylline levels were studied. All patients received Elixophyllin Elixir, 250 mg, and their serum level as well as pulmonary functions were studied and compared to those after receiving the sustained release capsules. In these patients, after isoproterenol inhalation, an average of 25.6% improvement in FEV1 was observed while after placebo there were very minimum changes. At the steady-state of sustained release theophylline capsule administration, an average of 20% improvement of FEV1 was observed at the five hour period and sufficient bronchodilation expressed as FEV1 was observed for a 10-12 hour period. Indeed, a sustained release theophylline capsule fulfilled the requirement that it adequately maintained therapeutic theophylline level of the blood and improved bronchodilation lasting up to 12 hours.


[The propagation of aminoglycoside transferases in gram negative bacteria]. Molecular genetic and enzymatic studies on Gram-negative bacteria from hospital specimens give the following picture on surveillance of aminoglycoside transferases: The most frequent enzymes inactivate streptomycin only, AAD- (3'') and APH-(3''). Only 15% of the isolated enzymes inactivate gentamycin, tobramycin, sisomycin or amikacin. The most frequent of these are AAD-(2'') with 7% and AAC-(6') IV with 3%, both enzymes inactivate a wide range of substrates. The high frequency of streptomycin inactivating enzymes is due to the high incidence of linked resistance markers. A plasmid rPB1 is described, that is present in about 10% of all clinical isolates of E. coli. It has a molecular weight of 4. 1 Mdal and typical restriction pattern.


First-pass effect of coumarin in man.

First-pass effect of coumarin in man. Blood level versus time data upon i.v. and p.o. administration of coumarin in a cross-over study have been analyzed for extent of bioavailability (EBA) and first-pass effect (FPE). In whole blood the parent drug, coumarin (C), and its main metabolite, 7-hydroxycoumarin (7HC), after hydrolysis of the glucuronide were determined. Comparison of the areas under the curve (AUCO leads to infinity) for C and 7HC upon i.v. and p.o. administration revealed that all of the drug is absorbed; however, only approximately 2-6% of C reaches systemic circulation in intact form. Hence, extensive first-pass effect must be assumed. The fraction of unchanged drug reaching systemic circulation predicted from the i.v. study fFPE varied between 0 and 38% assuming a liver blood flow rate (LBF) of 1.53 1/min. When corrected for individual LBF the fPFE varied between 2.5 and 13%. The question whether the FPE is only due to metabolism in the liver or in part due to biotransformation in the intestinal lumen, gut wall and/or portal blood will be the subject of a further paper. It is suspected that C is the pro-drug and 7HC the pharmacologic active moiety.


Poly-N-acrylylpyrrolidine. A new resin in peptide chemistry. Entirely beaded poly-N-acrylylpyrrolidine-co-bisacrylyl-1,2-diaminoethane-co-N-acrylyl-1,6-diaminohexane.HCl(PAP), a new resin on which to perform peptide chemistry, has been prepared by reverse phase suspension polymerization in quantitative yield. In addition to being a superior support to polystyrene, albeit readily adaptable to current techniques of peptide synthesis, its versatility has been furthur extended by the introduction and use of new peptide-to-polymer linking groups, which allow the use of the bidirectional approach to peptide chemistry. One such linkage, which connects the side chain of cysteine to PAP via an acid resistant S-carbamoyl bond, was used in a bidirectional synthesis of deamino-oxytocin. PAP solvates and swells in solvents with wide-ranging polarities, including aqueous media. Thus, peptide coupling reactions were performed in organic media of high and of low polarity as well as in aqueous solution.


Use of thiocyanic acid to form 2-thiohydantoins at the carboxyl terminus of proteins. The chemistry of the formation of 2-thiohydantoins on the carboxyl terminal of peptides or proteins was investigated. It was found that thiocyanic acid was much more reactive for the formation of 2-thiohydantoins than were the thiocyanate salts. The physical reasons for this observation are explained. The kinetics of the reaction of a number of proteins, and some of their fragments, with thiocyanic acid were also determined. Simple and safe procedures for the preparation of anhydrous thiocyanic acid solutions were devised. The prospective application of these procedures to sequencing from the carboxyl terminal of a polypeptide is discussed.


Syntheses and biological activities of methoxinine-analogues of the C-terminal octapeptide of cholecystokinin-pancreozymin. The C-terminal octapeptide of cholecystokinin-pancreozymin and its analogues in which the methionine residues were successively replaced by methoxinine have been synthesized. When these analogues were tested for their gallbladder-contraction activity in an in vitro system the following relative potencies were observed: [Mox3]-CCK-PZ 8 (95%), [Mox6]-CCK-PZ 8 (5%) and [Mox3, Mox6]-CCK-PZ 8 (2%).


Synthesis of oxytocin using iodine for oxidative cyclization and silica gel adsorption chromatography for purification. Oxytocin (OT) was synthesized employing the solid phase method. Resins made of copolymers of polystyrene-1%-crosslinked with divinylbenzene gave better yields (73-95%) of Z-Cys(Bzl)-Tyr(Bzl)-Ile-Gln-Asn-Cys(Bzl)-Pro-Leu-Gly-NH2 (I) than 2%-crosslinked resins (10--56%). Reduction of I with Na-liq.NH3 and oxidation with I2-MeOH at -40 degrees minimized dimer and polymer formation, and resulted in good yields (49--54%) of OT. The large volumes of MeOH required when several grams of I are reduced and then oxidized were rapidly evaporated in vacuo, and the residue was desalted by dissolving the peptide in a small volume of glacial acetic acid and filtering to remove the salt. OT was purified by adsorption chromatography on a silica gel column with combinations of MeOH-CHCl3 of graded polarity. Oxytocin elutes with 33% MeOH-CHCl3. After two purification steps by adsorption chromatography, the resulting OT was found to be homogeneous. The hormone was characterized chemically and found to be active biologically.


Comparison of Bungarus caeruleus venom with the venom from which a putative cholinergic ionophore marker was isolated. Comparisons are described between Bungarus caeruleus venom and the actual venom from which a putative marker for the cholinergic ionophore, called ceruleotoxin, was isolated. The venoms are shown to be different by two procedures for ion exchange chromatography and by isoelectric focusing on polyacrylamide gel. The activities of the purified "ceruleotoxin" as an inhibitor of acetylcholine receptor-mediated ion flux and as a phospholipase have been reported (Bon & Changeux, 1977b). The results reported herein suggest that this toxin is from an unknown origin.


Sorghum proteinase inhibitors. 2. Mode of interaction with serine proteinases. Investigations have been carried out on the complex formed between sorghum Inhibitor III and alpha-chymotrypsin by physico-chemical methods. An apparent dissociation constant (Ki) of 4.0 X 10(-8) M has been calculated for the complex. This enzyme-inhibitor complex was isolated by gel filtration on Sephadex G-75 and a molecular weight of 48,000 was estimated for the complex. The formation of the complex was accompanied by spectral changes in the 270--300 nm region of the spectrum. Preliminary evidence suggests that the sorghum Inhibitor III is structurally altered when it is incubated with alpha-chymotrypsin. Catalytically inactive derivative of alpha-chymotrypsin and trypsin, as well as their zymogens, did not interfere with the activity of the sorghum inhibitor towards the native enzymes. Sorghum Inhibitor I was shown to be a 'double-headed' inhibitor since it inhibits both trypsin and alpha-chymotrypsin independently.


An analysis of side-chain conformation in proteins. The crystal structures of a number of globular proteins are currently available. An analysis of the distribution of side-chains among different allowed conformations in these proteins has been carried out. The observed conformations of individual residues are discussed on the basis of well-known stereochemical criteria. The population distribution of side-chains in different allowed regions in conformational space can be explained largely on the basis of simple steric considerations. In addition to examining the conformational behaviour of individual residues, some population distributions of conformational angles of general interest involving groups of residues have also been analyzed.


Studies on polypeptides. XXIX. Synthesis of the N-terminal tetradecapeptide sequence of ribonuclease A, incorporating beta-(3-pyridyl)-L-alanine at position 12. A description is given of the synthesis by fragment condensation of 12-(3-Pyd) Ala S-peptide (1--14), the 1--14 peptide sequence of ribonuclease A in which the histidine-12 residue is replaced by beta-(3-pyridyl)-L-alanine. The peptide binds strongly and stoichiometrically to S-protein; the resulting complex is enzymatically inactive.


Diabetogenic action of human growth hormone. Synthesis and activity of C-terminal fragments. Three peptides corresponding to the C-terminal region of human growth hormone have been synthesized by the solid-phase method: HGH-(177--191), HGH-(178--191) and HGH-(179--191). The diabetogenic activities of these synthetic peptides are reported. The data indicate that extension of HGH-(179--191) at its NH2-terminus is required for in vivo activity. The reduced and S-carbamidomethylated form of HGH-(177--191) was also active, indicating that the disulphide bond is possibly not a prerequisite for biological activity.


Synthesis and biological effect of the C-terminal pentapeptide amide of avian pancreatic hormone III (APP). Model building studies and analogies drawn from peptides of similar biological activity have indicated that the C-terminus of avian pancreatic hormone III may possess significant biological information. To test this hypothesis, the C-terminal pentapeptide amide sequence has been synthesized by the Merrifield method. The synthesis, purification and characterization of this compound are reported here in detail. In vivo studies indicate that this synthetic segment possesses none of the secretogogic activity of the parent hormone; rather, it reduces "gastric" secretion levels even in the presence of the intact hormone.


Cyclic peptides. VI. Asymmetric hydrogenation of dehydroalanine or dehydroaminobutanoic acid residue in cyclodipeptides. Several cyclo(-L-aminoacyl-deltaAla-) (aminoacyl = Ala, Val, Leu, Phe, Pro and Lys (epsilon-Ac)) were prepared by tosylation and successive detosylation of cyclo(-L-aminoacyl-L-Ser-), which were synthesized via the Nitecki and Fischer methods. Hydrogenation of the double bond of dehydroalanine residues in cyclodipeptides was carried out using Pd black in methanol at 1-atm pressure and room temperature. The degree of asymmetric hydrogenation was assessed by determining the amounts of L- and D-alanine by a modified Manning and Moore procedure. When L-valine was used as a chiral source, L-alanine residue with chiral induction of 98.4% was derived from cyclo(-L-Val-deltaAla-). L-Amino acids other than L-proline also were effective in inducing remarkable asymmetric hydrogenation. Hydrogenation of alpha,beta-dehydro-alpha-aminobutanoic acid residues in cyclodipeptides produced L-alpha-aminobutanoic acid residues with effective chiral induction to the same extent as observed with dehydroalanine residues. Optically pure l-alanine was prepared from cyclo(-L-Lys(epsilon-Ac)-deltaAla-) via asymmetric hydrogenation. A mechanism of chiral induction is discussed.


Protein densities.

Protein densities. The calculation of protein densities from atomic coordinates is not straight-forward and requires very careful attention to the determination of the protein-solvent boundary. Interior densities are more readily obtained and are in reasonable agreement with those estimated from solvent accessibility studies. The interior of globular proteins has very significant density inhomogenities on a scale of 100--1000 A3. The interior densities range from less than 0.5 g/cm3 to over 3 g/cm3. The low local densities are primarily associated with clusters of nonpolar sidechains while the high local density regions arise from the protein backbone secondary structures: helices and beta sheets. We show a rough correlation between local density and local polarity.


Isolation and characterization of fin whale prolactin. A highly purified prolactin preparation has been obtained from fin whale pituitaries by extraction with acid acetone. salt precipitation, isoelectric fractionation, and exclusion chromatography on Sephadex G-100 and ion-exchange chromatography on DEAE-CELLULOSE. Fin whale prolactin was isolated in a yield of 250 mg/kg wet weight tissue. It was found to have a molecular weight (SDS disc gel electrophoresis) of 23,600 daltons and an alpha-helix content (circular dichroism) of 50%. The amino acid composition and circular dichroism spectra were very similar to those of porcine prolactin. The partial amino acid sequence has been determined by the method of fluorescein-isothiocyanate. Fin whale prolactin was found to be 80% as potent as ovine prolactin with regard to pigeon crop-sac assay.


Studies on protein folding, unfolding and fluctuations by computer simulation. III. Effect of short-range interactions. The theoretical model of proteins on the two-dimensional square lattice, introduced previously, is extended to include the specific short-range interactions. Attractive long-range interactions with various specificities and non-specific repulsive long-range interactions in the form of self-avoidance of the polymer chain are also operative in the model. Dynamics of the model protein is studied by a Monte Carlo method. The short-range interactions are found to accelerate the folding and unfolding transitions. Non-specific part of the attractive long-range interactions have a competing effect of decelerating the transitions. When the short-range interactions are weighted beyond a certain extent over the attractive long-range interactions are weighted beyond a certain extent over the attractive long-range interactions, the all-or-none character of the folding and unfolding transitions is destroyed. How the destruction proceeds is quantitatively expressed in terms of the S-H curves. The limiting case of dominance of the specific short-range interactions over the attractive long-range interactions is studied in detail. The lattice polymer in this limit does not behave like a globular protein at all. This observation leads to a reexamination of the currently popular notion of the dominance of the short-range interactions. A new concept of consistency is proposed to replace it. Possible mechanisms of the acceleration of the transitions by the specific short-range interactions are discussed.


Studies on the coupling rates in liquid-phase peptide synthesis using competition experiments. Competition experiments were carried out in order to determine relative reaction rates, Vrel, for the peptide-forming step. Using the liquid-phase method of peptide synthesis a model system was developed to investigate the influence of coupling method, amino component, derivatization and solvent upon Vrel. According to a standard procedure, Vrel for all 20 commonly occurring amino acids were established. A strong dependence of Vrel upon steric effects of the coupling components was found. The data obtained may serve as a guideline for optimizing the reaction conditions in peptide synthesis.


Affinity chromatographic purification of papain. The reinvestigation of the affinity chromatographic method of purifying papain has been carried out. It has been reported that papain could be purified by taking advantage of the affinity of the enzyme for the insolubilized peptide inhibitor, agarose-Gly-Gly-Tyr(Bz)-Arg. Using pure tetrapeptide obtained commercially and standard coupling procedures, a significant purification of papain could not be achieved. Both active and nonactivatible enzyme bound to a column prepared in this manner were eluted together by the use of deionized water. An affinity medium with properties similar to those reported by Blumberg et al. was obtained by removal of the benzyl group on tyrosine prior to coupling with agarose. The deprotected tetrapeptide was also synthesized by an independent route and inhibition constants for the binding of the protected and deprotected tetrapeptide to papain were determined in kinetic experiments.


H and 13C nuclear magnetic resonance spectra of some peptides with fibrinogen-like reactivity. The 1H and 13C spectra of four peptides, L-Phe-Val-Arg-pNA, D-Phe-Val-Arg-pNA, L-Phe-Pip-Arg-pNA and D-Phe-Pip-Arg-pNA (pNA = p-nitroaniline, Pip = pipecolic acid residue), have been examined, and deductions made about their conformation in solution. The D-Phe peptides, which are cleaved especially rapidly by thrombin in water, have structures (in deuterated DMSO) in which the aromatic ring of the D-Phe residue is folded back over the Val or Pip residue. This arrangement is not found in the L-Phe peptides. It is proposed that this feature (in which Phe could be situated near Val and near the Arg-Gly bond of the A alpha chain in the three-dimensional structure of fibrinogen) may be especially advantageous for binding to the enzyme.


Facile thiolytic removal of the o-nitrophenylsulphenyl amino-protecting group. 2-Mercaptopyridine was used to effect the selective, mild and efficient cleavage of the o-nitrophenylsulphenyl amino-protecting group from several amino acids and peptides. By utilization of this reagent a stepwise synthesis of the tetrapeptide Thr-Lys-Leu-Arg([Leu3]tuftsin) was successfully achieved. The potential use of 2-mercaptopyridine in mechanized peptide synthesis via the polymeric reagents approach is discussed.


Distance constraints on macromolecular conformation. Many physico-chemical studies are made on proteins to determine something of their solution conformation. For example the coat protein of Tobacco Mosaic Virus has been subjected to more non-crystallographic experimental studies to determine its native conformation than perhaps any other protein. Yet the sum of the experimentally determined constraints on its tertiary structure are surprisingly inadequate to fix its conformation. We are able to detect and remove minor inconsistencies in the data and then calculate a sampling of conformations consistent with all the data, which differ among themselves by r.m.s. deviations of the respective interresidue distances ranging from 5.7 angstrom to 15.8 angstrom. Some individual interresidue distances differ by as much as 50 angstrom from structure to structure. In order to restrict the range of possible conformations to something corresponding to the errors in a 10 angstrom resolution X-ray crystal structure, chemical and spectroscopic studies will have to be much more detailed than anything done to date. Our calculations appear to be useful in deciding which further experiments would be most productive.


Solid phase synthesis of 13-lysine-apamin, 14-lysine-apamin and the corresponding guanidinated derivatives. In order to study the importance of arginine residues 13 and 14 in apamin, the bee venom neurotoxin, four analogues, [Lys13]-apamin, [Lys14]-apamin, [Har4, Har13]-apamin and [Har4, har14]-apamin were synthesized and tested with respect to their neurotoxicity. The two lysine-apamins were prepared by the solid phase method on benzhydrylamine resins. Before oxidation to disulphides, the (S-Acm)4-peptides were isolated and characterized. Portions of the purified lysin peptides were converted to homoarginine analogues by guanidination. The four apamin analogues were lethal, but the lethal doses differed significantly. The results demonstrate that the arginine residue at position 14 is more important for the high toxicity than is the one at position 13. The circular dichroism (CD) spectrum of [Lys13]-apamin was identical with that of apamin itself, whereas the spectrum of [Lys14]-apamin showed certain deviations.


Synthesis of Nalpha-formyl-Met-Leu-Phe-OH: an inducer of chemotaxis in peritoneal polymorphonuclear neutrophils. A chemotactic peptide CHO.Met.Leu.Phe.OH has been synthesized classically using the mixed anhydride procedure. The formyl group was introduced by coupling formic acid in the presence of dicyclohexylcarbodiimide to the partially protected triptide. The final product was obtained by treatment of the intermediate CHO.Met.Leu.Phe.OBzl with hydrogen fluoride. The ED50 of the peptide in the Boyden chamber assay was 7 x 10(-11) M; in the lysozyme release assay 2.4 x 10(-10) M and in the beta-glucuronidase release assay 2.6 x 10(-10) M. In a radioreceptor assay the ID50 of the peptide was 3.3 x 10(-10) M.


Improved procedure of purification of inorganic pyrophosphatase from Bacillus stearothermophilus. An improved method for isolation of inorganic pyrophosphatase (EC 3.6.1.1) from Bacillus stearothermophilus is described. The enzyme was purified to more than 90% after two chromatographic steps. A molecular weight of 140,000 daltons was estimated by density gradient centrifugation. The isoelectric point was found to be 4.0.


Induced helical conformation of ionic polypeptides by phospholipids solubilized in a nonionic surfactant solution. Phosphatidylcholine that has been solubilized in hexadecylpoly (oxyethylene) ether can induce a coil-to-helix transformation for poly (L-glutamic acid) in neutral solution. Similarly, solubilized phosphatidylserine promotes a helical conformation of poly (L-lysine) at neutral pH through complex formation. The mixed micelles of a phospholipid and a nonionic surfactant are thermodynamically stable and do not separate on standing. The nonionic surfactant here has no effect on the conformation of the two polypeptides.


Stereochemical studies on cyclic peptides. Part X. Conformational analysis of hydrogen bonded cyclic pentapeptides. Conformational aspects of 4 leads to 1 hydrogen bonded cyclic pentapeptides are considered in this paper from the point of view of "contact criteria" and potential energy calculations. Three types of such hydrogen bonded conformations, designated A1, A2 and B, are possible, involving some amount of strain on the bond angles. The energy of hydrogen bonded cyclopentaglycyl is somewhat less than that of the five-fold symmetrical conformation. The stereochemical feasibility of introducing L- and D-alanyl resudues in these structures has also been studied and the possible types for different sequences of alanyl residues have been determined. The results are discussed further in the light of the limited data available from crystal structure and nuclear magnetic resonance studies on cyclic pentapeptides.


Development of Bruch's membrane in the chick: an electron microscopic study. The development of fibrous connective tissue in Bruch's membrane within the choroid of chronologically staged chick embryos was observed by means of transmission electron microscopy. The appearance of these connective tissue elements follows an orderly developmental sequence. The first component of Bruch's membrane to appear is a continuous basal lamina at the basal surface of the presumptive retinal pigment epithelium (RPE) at 21/2 days. Microfibrils and associated amorphous material are present in the adjacent connective tissue space. A discontinuous inner collagenous layer is observed at the basal aspect of the RPE during the fourth day. A definitive elastic layer is present during the ninth day and becomes more apparent following subsequent stages of development. An outer collagenous layer begins development during the tenth and twelfth days. Collagenous fibrils average 37 nm in diameter and display axial periodicity measuring 46 nm between major periods. These measurements increase with age as do the number of collagenous fibrils. Only isolated patches of basal lamina are observed in association with the choriocapillary endothelium by the twentieth day.


Increased pressure after paracentesis of the rabbit eye is completely accounted for by prostaglandin synthesis and release plus pupillary block. Paracentesis of the anterior chamber of the rabbit eye results in hyperemia, increased protein in the aqueous, elevated intraocular pressure, and miosis. Aspirin does not affect miosis but attenuates the pressure and protein response by about 60%. Pupillary block resulting from miosis aggravates the rise in intraocular pressure (as does mydriasis). Pretreatment with aspirin plus iridectomy virtually eliminates the elevation of intraocular pressure consequent to paracentesis.


Effect of high-power density microwave irradiation on the soluble proteins of the rabbit lens. New Zealand rabbits were irradiated on the left side of the head by microwaves (2.45 GHz) at 300 mw/cm2 for 20 min on each of 2 consecutive days. Lens changes in irradiated animals, observed by biomicroscopy, ranged from no changes to small posterior subcapsular opacities. Pore-gradient electrophoresis was used to examine the distribution of soluble lens proteins. A marked difference in soluble protein distribution of the lens cortex and nucleus was observed. Comparison of irradiated and control lenses revealed an apparent shift toward higher-molecular-weight components in the cortex samples of the microwave-irradiated lenses.


Tear flow under hydrogel contact lenses. The tear replenishment rate under three different hydrogel lenses was determined with a slit lamp modified to serve as a fluorophotometer. Fractional tear volume replenishment rates under these lenses averaged 0.011 per blink, which is significantly lower than the 0.10 to 0.20 per blink reported for rigid lenses. These data suggest that the amount of oxygen delivered to the cornea by tear pumping for gel lenses is relatively small and that oxygen received by the cornea covered by a gel lens comes principally by diffusion through the material.


Ophthalmic applications of infrared lasers -- thermal considerations. An analysis of the thermal response of clear ocular media to infrared laser radiation is presented. It is shown that from a thermodynamic viewpoint, it should be feasible to use infrared lasers in both vitrectomy and thermokeratoplasty. In vitrectomy, temperature elevations from vitreous vaporization with an intraocular CO2 laser probe would be well below retinal damage threshold levels at distances greater than 2 mm from the center of the beam. In thermokeratoplasty, peak temperature elevations could be moved from the corneal epithelium back into the corneal stroma where collagen shrinkage is desired. Other potential applications for infrared lasers are presented, and the value of accurate measurement of the infrared optical properties of ocular media is emphasized.


Spatial periodicities of periodic complex cells in the visual cortex cluster at one-half octave intervals. Within individual penetrations in the visual cortex, spatial periodicities of periodic complex cells differ by either one-half or one octave. When data are pooled from neurons subserving the central visual area in many cats, the results indicate that spatial periodicities cluster at one-half octave intervals over a 2 1/2-octave range (0.95 to 5.4 cyc/deg). Thus a relatively small number of such channels spaced at regular intervals along a logarithmic scale within each orientation column may suffice for this stage of spatial processing.


Cryoprecipitate: its use and effects in canine coagulum pyelolithotomy. A fibrin clot forming an extractable cast or "coagulum" of the pyelocalyceal system was developed and characterized using a blood product not previously described--single donor type specific cryoprecipitate. The physical properties of the cryoprecipitate coagulum were investigated and compared with other described formulations. Simulated coagulum pyelolithotomy was performed in vivo in 11 canine kidneys with no adverse effect upon creatinine clearance or anatomic integrity. The advantages of the cryoprecipitate are detailed and a new, simplified operative technique is described.


Low molecular weight urinary proteins and renal lithiasis. Twenty-four hour urine specimens were obtained from 20 active calcium oxalate stone formers, 20 inactive calcium oxalate stone formers, 8 struvite stone formers, and 9 non-stone forming controls. Proteins with molecular weights less than 50,000 daltons were concentrated by ultrafiltration and separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Fourteen of the 17 active calcium oxalate stone formers had low molecular weight urinary proteins (less than 35,000 daltons) present in their urine whereas none of the inactive stone formers or struvite stone formers had similar patterns. Only one of the nine control patients had similar proteins present.


Unimpaired sexual behavior of male rats after complete removal of the prostate and seminal vesicles. The ventral and dorsolateral prostate, the coagulating glands, and the seminal vesicles were removed in nine male rats. The rats were tested for sexual behavior 3 to 4 weeks after surgery. The sexual performance of the operated rats was quantitatively and qualitatively equal to that of sham-operated control rats. At autopsy 6 weeks after surgery, no prostatic or seminal vesicle tissue could be found. These studies show that the sexual performance of male rats does not depend on the presence of the prostatic lobes and seminal vesicles.


FSH and LH elevation after radiation for treatment of cancer of the prostate. Regional radiation treatment of prostatic carcinoma produced significant increases in serum follicle-stimulating hormones at 3 and 12 months posttreatment from 6.5 +/- 0.5 to 15.9 +/- 0.9 mIU per ml and 19.5 +/- 1.2 mIU per ml (X +/- SE) respectively. Serum luteinizing hormone also increased at 3 months from 4.5 +/- 0.4 to 6.1 +/- 0.5 mIU per ml (X +/- SE). There were no changes in sex steroid-binding globulin, testosterone, or prolactin. The data indicate damage to the testes as a result of scatter from radiation treatment to the prostate.


The effect of sympathectomy on the urethral pressure profile in the experimental animal. The effect of sympathectomy and various pharmacologic agents on the dog urethral pressure profile (UPP) was assessed. Succinylcholine was used to subtract the effect of the external urethral sphincter from the total UPP. In the presence of succinylcholine effect, sympathectomy caused a decrease in the UPP in 12 of 13 experiments. In addition, an attempt was made to elicit a denervation sensitivity response to phenylephrine after sympathectomy; none could be shown. Measurements were made of UPP's after administration of both succinylcholine and phenylephrine. Seven of the 13 dogs showed a significant decrease in UPP after succinylcholine administration. Nine of 12 dogs showed a marked increase in UPP after phenylephrine was given.


Levamisole immunotherapy of experimental transitional cell carcinoma. Levamisole, in doses comparable to those under clinical investigation, was shown to significantly (P less than 0.02) delay the onset of transplanted transitional cell carcinoma of C3H mice. The growth of transplanted tumors was inhibited and animal survival prolonged with Levamisole treatment. Further progress in the immunotherapy of transitional cell carcinoma may be aided by such models.


Corynebacterium pseudogenitalium sp. nov. Commensals of the human male and female urogenital tracts. Antisera to Corynebacterium genitalium Types C-1 to C-6 were prepared in rabbits and the titers of complement fixing antibodies to the homologous strains, to the heterologous strains, to C. genitalium Types I to V, and to the reference species Corynebacterium xerosis and Corynebacterium minutissimum ascertained. Five Types stimulated low levels of cross-reacting antibodies to all corynebacteria tested including Type C-3. In contrast the antiserum to Type C-3 had antibodies to only two heterologous strains suggesting that these corynebacteria usually shared more than one minor cell wall antigen. The biologic reactions and serotypes of C. genitalium Types C-1 to C-6 have been compared with those of Types I to V. It is considered that C. genitalium should be retained for corynebacteria having the properties of Types I to V whereas corynebacteria having the characteristics of Types C-1 to C-6 that are commensals of the male and female urogenital tracts should be incorporated in a new species Corynebacteria pseudogenitalium sp. nov. The differences in the biologic characteristics of the two species have been discussed and summarized.


On the possible role of glycosaminoglycans as natural inhibitors of calcium oxalate stones. An extract of glycosaminoglycans was prepared from normal urine and components fractionated by electrophoresis on Vinylite support medium. Several fractions displayed an ability to inhibit formation of calcium oxalate crystals in vitro. Inasmuch as well recognized urinary glycosaminoglycans such as chondroitin sulfates and hyaluronic acid must contribute to the urine inhibitory power, an unknown material was isolated with potent inhibitory properties. The material contained little detectable uronic acid of hexosamine and had a molecular weight greater than 10,000.


Urinary bladder and sphincter responses to stimulation of dorsal and ventral sacral roots. The sacral spinal roots have a long intraspinal yet extradural pathway that makes them ideal for electrode implantation for the control of micturition. In the hope of identifying a specific motor pathway to the bladder within these roots, a study of 10 mongrel female dogs was undertaken: bladder and sphincter responses to stimulation of individual sacral roots, and to stimulation of the dorsal and ventral components of each root, were recorded urodynamically. The root producing greatest detrusor response was then divided into its motor and sensory components, and the central and peripheral ends of the latter were stimulated. We found that sphincter resistance to bladder emptying was diminished by removing the afferent dorsal roots from the stimulus field. The physiologic implications of this finding are discussed.


A study of the phase transformation of calcium oxalate trihydrate-monohydrate. The precipitation of calcium oxalates may involve transformation from a metastable hydrate such as calcium oxalate trihydrate, COT, to the thermodynamically stable monohydrate, COM. A highly reproducible seeded crystal growth method has been used to study this transformation reaction over a range of temperatures and in ionic media such as the chlorides of sodium, potassium, and magnesium. After the initial dissolution of COT, the calcium concentration remains constant for prolonged periods while appreciable nucleation and growth of COM takes place concomitantly with COT dissolution. The transformation is markedly dependent on temperature, composition, and concentration of ionic media. In urines, the hydrate conversion is appreciably slower and the rate depends upon the method of pretreatment. In these cases, evidence is advanced for the formation of other phases such as the calcium phosphates.


Studies of the nonspecific cellular immune response in patients with urinary bladder carcinoma. I. PHA-induced lymphocyte transformation. The nonspecific cellular immune response, as measured by phytohemagglutinin (PHA)-induced blastoid transformation of peripheral lymphocytes in autologous serum, was evaluated in 119 patients with bladder carcinoma and in 21 control subjects. Blastoid transformation was determined by quantifying 3H-thymidine incorporation (counts per minute). The rate of blastogenesis of lymphocytes was shown as the stimulation index which was calculated by dividing the number of counts per minute with PHA by that without PHA. The stimulation index of the control subjects was 29.9 +/- 6.6 (+/- SD); that of the experimental group was 13.3 +/- 7 (significantly lower reactivity). There was a converse correlation between the stimulation index and the grade and stage of tumor. In some cases the change in cellular immunity was compared before and after surgery.


Studies of the nonspecific cellular immune response in patients with urinary bladder carcinoma. II. Immunodepressive effect of sera from bladder carcinoma. In vitro reactivity of normal lymphocytes in various sera was determined by quantitation of phytohemagglutinin (PHA)-induced tritiated thymidine incorporation rate (counts per minute). Sera were obtained from normal subjects, fetal calf, and patients with bladder carcinoma. The rate of lymphocyte blastogenesis was expressed as a stimulation index (SI) that was calculated by dividing the number of counts per minute with PHA by that without PHA. The effect of sera on blastogenesis of normal lymphocytes was expressed as percent change (%SI) per SI with fetal calf serum. The SI of normal lymphocytes was similar in autologous serum (26.7 +/- 11.6), fetal calf serum (25.4 +/- 11.8), and heat-inactivated homologous normal AB serum (28.8 +/- 11.4). The SI of normal lymphocytes in sera from patients with bladder carcinoma was significantly lower than in the other two sera (14.0 +/- 7.9). The serum inhibitory effect was significantly associated with the stage and grade of tumor and was diminished after removal of the tumor. The SI of lymphocytes from patients with certain other malignant diseases was significantly lower in autologous serum than in fetal calf serum or homologous normal AB serum. The SI of the lymphocytes from patients with prostatic carcinoma and embryonal cell carcinoma was also low in sera from patients with bladder carcinoma as well as in autologous sera. It is likely that the depressive effect of sera from patients with bladder carcinoma was not specific to bladder carcinoma.


The synthesis and release of prostaglandins by human urinary bladder muscle in vitro. Using the technique of bioassay the presence, production, and importance of prostaglandins (PG) in human bladder muscle have been investigated in vitro. Low basal tissue levels of PG were shown. E series PGs were released by isolated bladder muscle strips in organ bath experiments. The spontaneous activity and PG release of these strips could be markedly reduced by the addition of indomethacin. Incubation of bladder muscle with the PG precursor, arachidonic acid, resulted in the synthesis of substantial quantities of PGs.


Human prostatic acid phosphatases: purification of a minor enzyme and comparisons of the enzymes. The minor enzyme of human prostatic acid phosphatases (pI 5.5) with high specific activity (orthophosphoric monoester phosphohydrolase, acid optimum, EC 3.1.3.2) has been purified for the first time as a pure enzyme protein. The enzyme was a single protein when examined by polyacrylamide gel electrophoresis and isotachophoresis. The specific activity was 1080 micromole per (min X mg) for hydrolysis of 5.5 mmole per liter of p-nitrophenylphosphate at pH 4.8 and 37 C. The purification coefficient was 540 and the recovery of enzyme activity was 2 per cent. The molecular weight of the enzyme subunit when measured by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate was 54,000. The Km of the purified enzyme was 3 X 10(-4) mole per liter for p-nitrophenylphosphate. An antiserum to this enzyme was prepared. The enzyme was cross-reactive with the main enzyme (pI 4.9) of human prostatic acid phosphatases in immunoelectrophoresis. No precipitin arc with the acid phosphatase in the serum of a prostatic carcinoma patient could be shown. Antiserum to the main enzyme caused a precipitin line with the same serum sample.