Size of arteriovenous anastomoses in the dog femoral circulation.

Radioactive plastic microspheres 50 and 200 micra in diameter labeled with Ytterbium169 were used to study distribution in the femoral circulation of living dogs under general anaesthesia. Shunting was demonstrated because radioactivity was detected in the lungs after intraarterial injection of 50 micra microspheres. When the size of the microspheres injected was 200 micra no radioactivity was detected over the lungs. This indicates that the arteriovenous anastomoses are smaller than 200 micra, they are probably located in the skin because there was less radioactivity in the skin after intrafemoral injection of the 50 micra microspheres than when the injected microspheres were 200 micra in diameter.


The sympatho-adrenal system and sulfhydryl groups in the heart in experimental myocardial infarction.

In 59 sexually mature male chinchilla rabbits, and in control sham-operated animals, there were compared the indicators characterizing the functional state of the heart and the levels of catecholamines and of SH groups in experimental myocardial infarction induced by ligating the descending branch of the left coronary artery. Phasic shifts were found in the heart adrenergic regulation, dependent on the stage of infarction. In all animals in the acute stage of myocardial infarction the activity of the sympatho-adrenal system was enhanced. In an extensive transmural infarction and in cases with a lethal outcome the levels of total and protein-bound noradrenaline were lowered. The course and prognosis of experimental myocardial infarction were dependent on the degree of disturbance of formation of complexes of noradrenaline with adrenoreceptor structures, caused by decreases in the levels of noradrenaline and sulphydryl groups.


Stereotypes of mental illness: a comparison with ethnic stereotypes.

This paper draws on empirical and theoretical studies to argue that popular and professional conceptions of mental illness share specific traits with ethnic stereotypes: (1) they are exaggerated and serve to erect a qualitative boundary where none objectively exists: (2) they are maintained through selective perception, rationalization, and sanctions; (3) they help to erect the "thresholds,' i.e., the criteria, for crossing or recrossing the boundary; (4) they serve to define relations, including those of power, between groups; (5) because they perform these important cognitive and conative functions, they persist despite a flow of personnel across them and despite repeated demonstrations of their inaccuracy. They cannot be expected to change until the actual relations between groups change.


Taijin Kyofusho: diagnostic and cultural issues in Japanese psychiatry.

Taijin Kyofusho or 'anthrophobia' is a Japanese culture-specific disgnostic label for the presenting problems of various fear reactions in interpersonal situations. The starting point of the present study was accumulating studies on Japanese cases of Taijin Kyofusho and the assertion in Japanese psychiatry that the symptom complex called Taijin kyofusho is Japanese culture-bound. In light of previous works on culture-bound disorders, the present study examines whether or not American mental health professionals could diagnose Japanese case descriptions of Taijin Kyofusho and what kinds of labels they applied to these Japanese cases. The results showed that American judges were able to diagnose Japanese cases nearly as well as American cases. However, there were considerable variability and inconsistency in their judgments of both the Japanese and American cases. The rate of disgnostic agreement dropped considerable as judges were asked to proceed from broad categories to specific categories. American judges grouped the Japanese cases of Taijin Kyofusho into a number of heterogeneous categories using labels such as paranoid schizophrenia, paranoid personality, phobic neurosis, and anxiety neurosis, among others. These results are discussed in terms of psychopathological diagnostic criteria and present conceptualization of culture-bound disorders, value judgments of mental health professionals, and the social contexts in which Taijin Kyofusho reactions occur.


Hutterite belief in evil eye: beyond paranoia and towards a general theory of invidia.

Most studies of 'evil eye' link economic and political inequality to the fear of appropriation of property while tying envy (invidia) to paranoia. In both psychiatric and anthropological studies of evil eye, explanation of the phenomenon is problematic because the data are retroductive - involving a rationalization of the part of the patient or informant in terms of either delusions or world-view respectively. In this paper the connection between invidia and paranoia is questioned by grounding the analysis of Hutterian beliefs in evil eye in social interaction rather than retroductive explanation. In the case of the Hutterities it is envy itself which is feared and linked to high anxiety levels and sometimes to anxiety attacks or even depression.


An explication of 'wind illness' in northern Thailand.

'Wind illness' is a very common complaint among the Northern Thai, yet is rarely recognized by Thai physicians trained in biomedicine. Persons most susceptible to 'wind illness' are adult women who have ever borne a child. Consequently, data were obtained from 415 everparous women, 43% of whom reported ever having had 'wind illness' and 57%. never having had it. In addition, 20 individuals who had ever had the syndrome were followed for case study, and 13 indigenous healers who traditionally treat clients suffering 'wind illness' were interviewed. Their perceptions of the etiology, symptomatology and treatment of 'wind illness' are reported in Part I. Part II is an attempt to define 'wind illness' in terms of biomedicine and as a consequence of fertility. Part III synthesized the emic and etic accounts with explanations for the perdurance of 'wind illness' despite the advances of biomedicine and the recent fertility decline in Northern Thailand.


Folk concepts of mental disorder among the Lao: continuities with similar concepts in other cultures and in psychiatry.

Folk concepts for mental disorder were studied among rural Lao people. While predominatly inferring etiology (e.g. spirit-caused disorder), certain terms also emphasized particular descriptive psychopathology or behavioral abnormality. Preventive strategies were stressed for insanity due to "excessive worry' or "broken taboo'. These broad folk categories of disorder bore considerable similarity to some psychiatric and neurologic categories within medicine. These includes psychosis, mania, neurosis, organic brain syndrome, mental retardation, cerebral palsy, epilepsy, and childhood autism. Lao folk terms for mental disorder also closely resembled those of other southern Asian cultures, although illiterate tribal peoples appeared to have fewer terms than literate peasant peoples. Folk terms from more distant regions had broad similarity to those of southeast Asia, but lacked the specificity found within the region.


Clonidine in hypertension: a 6-year review.

A study of the use of clonidine in the treatment of patients with hypertension, both in hospital and in the community, during a period of 6 years is reported. Seventy-eight patients (42 males and 36 females) with hypertension were studied during this period both in terms of their immediate response to introduction of clonidine and also the effect of maintenance treatment for periods varying between 2 and 6 years. During the period of study, the hypertension was well controlled in 51 (65.4%) patients. In the remaining 27 patients, clonidine treatment was stopped for a variety of reasons but, despite this, the drug provided effective treatment for period of up to 4 years. Nineteen patients died in the course of the study, but in all these cases the blood pressure remained under adequate control. The clinical response to treatment and the incidence of side-effects are described.


Use of a povidone-iodine alcoholic solution in the treatment of herpes genitalis: a preliminary study.

A preliminary evaluation was carried out in 23 patients with herpes genitalis to assess the effectiveness of a 10% alcoholic povidone-iodine solution applied twice daily for up to 14 days. Clinical diagnosis was supported by positive herpes simplex virus culture in 14 patients. The lesions cleared after an average of 8.9 days' treatment in 8 males presenting with herpes genitalis for the first time, and in 6.1 days in 9 males with recurrent infection, 6 of whom had shown no apparent improvement on other therapies. The 4 female patients presenting with herpes genitalis for the first time all showed substantial improvement or complete remission within 7 days, and the lesions in the 2 women with recurrent infection cleared within the same period. In view of these satisfactory findings, a double-blind controlled study of povidone-iodine is now being undertaken.


Two-years' study with a combination of pindolol and clopamide ('Viskaldix') in patients with moderate hypertension.

A study was carried out to evaluate the long-term effects and side-effects of a combination product containing the beta-blocker pindolol (10 mg) and the diuretic clopamide (5 mg) in 15 patients with moderate hypertension. All patients completed the 2-years' study. The dose of the combination was increased until blood pressure normalized or a maximum dose of 3 tablets (equivalent to 30 mg pindolol and 15 mg clopamide) daily was reached. Blood pressure and heart rate were recorded monthly and detailed medical examinations were done regularly throughout the study. A mean dose of 2 tablets of the combination product (20 mg pindolol and 10 mg clopamide) produced a significant reduction in blood pressure. In all but 1 patient, blood pressure control was achieved and maintained. No tolerance developed. Heart volume showed a marked decrease. No side-effects of clinical importance were noted.


Stopping phenformin treatment in a diabetic clinic.

Phenformin was stopped in 35 patients attending a diabetic clinic. In 4 patients where phenformin alone had been used, subsequent diabetic control was easily maintained with diet or a sulphonylurea. Thirty-one patients had been taking phenformin with a sulphonylurea and 17 (55%) later required insulin. Larger doses of a sulphonylurea were usually needed in the other patients. It is suggested that metformin is probably the biguanide of choice now and should be considered in carefully selected diabetics.


Intra-incisional cephaloridine: a comparison of two methods of administration.

Serum cephaloridine concentrations were measured in the immediate post-operative period in 23 patients who had received a prophylactic dose of 1 g of the drug into the wound at the end of operation. Eleven patients received the antibiotic as a powder and 12 as a solution. The serum concentrations were higher, though not significantly so, in the group receiving powder, and this is thought to be due to the lesser amount of spillage and loss into dressings when the antibiotic is given in this form.


Raynaud's phenomenon in hypertensive dialysis patients taking a sustained-release propranolol formulation.

Five dialysis patients with residual hypertension were treated with a new sustained-release formulation of propranolol (160 mg per capsule) in a dosage of 1 to 2 capsules per day. Four of these patients developed persistent cold, numb, blue and clumsy fingers. The symptoms resolved when the drug was withdrawn.


Cefuroxime in post-operative chest infections.

Forty patients with post-operative chest infection were treated with cefuroxime, the majority receiving 750 mg intramuscularly 3-times daily for a mean period of 6.5 days. The results showed that 36 (90%) responded successfully and required no further antibiotic therapy. The mean time to improvement or cure was 3.6 days, and treatment was generally well tolerated.


The effect of chlormethiazole on serum gonadotrophins and testosterone in chronic alcoholics.

Serum gonadotrophins (LH and FSH) and testosterone concentrations were estimated by radioimmunoassay in 7 male chronic alcoholics on admission and following treatment with chlormethiazole for 6 days. Individual and mean values of serum LH and FSH were within normal limits both before and after treatment, but serum testosterone concentrations were found to be slightly higher than normal on both occasions. Chlormethiazole does not seem to have any effect on serum gonadotrophins or testosterone. It is further suggested that chlormethiazole does not interfere with the hypothalamic releasing factors for pituitary gonadotrophins and that it has no direct effect on testicular endocrine functions.


Cowden's disease.

Cowden's disease, a rare genodermatosis, is associated with characteristic cutaneous and oral lesions: papillomas, verrucous papules, and acral keratoses. Various internal anomalies involving the breast, thyroid, and gastrointestinal, reproductive, and skeletal systems are also seen in patients with this syndrome complex. Twelve of the thirty-two reported patients have been subject to cancers, most commonly of the breast. The characteristic skin and oral lesions make possible an early diagnosis of this disease and permit close follow-up of these patients for the development of any internal disease.


Topical chemotherapy of mycosis fungoides.

Mycosis fungoides is a T-cell lymphoma which is often localized to the skin in the early stages. Untreated, the process eventually progresses through eczematous, plaque, and tumor stages to systemic involvement. Its course, however, is unpredictable. Topical chemotherapy is effective in early stages of mycosis fungoides. Possibly prognostic benefits can occur from the early use of these agents. Nitrogen mustard and BCNU, both alkylating agents, have been used topically to control the disease. A dermatitis may develop in persons treated with nitrogen mustard but systemic side-effects are rare. However, BCNU may rarely lead to marrow depression when used topically. The use of these agents in mycosis fungoides is discussed herein.


Scleromyxedema.

Scleromyxedema (also known as lichen myxedematosus or papular mucinosis) is a rare cutaneous disorder characterized by lichenoid waxy papules, sclerosis, and a characteristic paraproteinemia. Rarely, if ever, is there systemic involvement. The cause and pathogenesis remain a mystery, however, a recent report has linked a serum factor with fibroblast proliferation in the skin. Treatment is often ineffective, although systemic melphalan may lead to improvement in 50 to 60 percent of patients. Morbidity and mortality due to melphalan used in the treatment of scleromyxedema have been reported, therefore, this therapy should be reserved for only the most extreme cases, if at all.


Cutaneous manifestations of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic illness defined and classified according to strict criteria of the American Rheumatism Association. Cutaneous disease may complicate RA or the drugs used in its treatment. Cutaneous vasculitis is potentially a prognostic factor in patients with RA. Controversy exists regarding the role of corticosteroids in the development of rheumatoid vasculitis. Two illustrative cases of RA with cutaneous complications are presented and the joint and cutaneous manifestations are reviewed herein.


Toxic epidermal necrolysis.

Toxic epidermal necrolysis (TEN) is a disorder characterized by the sudden onset of widespread erythema and tenderness of the skin with rapid progression to desquamation of sheets of epidermis, resembling scalding. Although the clinical picture is similar in many instances, toxic epidermal necrolysis is subdivided into two main clinicopathologic types, those due to staphylococcal infections, and the nonstaphylococcal variant. It occurs as the result of a number of causes, including specific exfoliative toxin-producing staphylococci, drugs, vaccines, and the graft vs. host reaction. Differentiation of these types is important, both for therapeutic and prognostic reasons.


Keratoacanthoma of the glans penis.

A patient with a solitary keratoacanthoma of the glans penis is presented. Since this area is devoid of hair, this keratoacanthoma could not have arisen from a hair follicle as has been suggested as the cause of keratoacanthoma. Keratoacanthoma should be included in the differential diagnosis of rapidly growing keratotic tumors of the glans penis. Correct diagnosis of this tumor may save patients from needless mutilating surgery of the penis.


Oligosymptomatic Melkersson-Rosenthal syndrome.

A patient with cheilitis granulomatosa and sialopenia is presented herein as a variant of the oligosymptomatic type of Melkersson-Rosenthal syndrome. Evidence is presented to support its possible neurotrophic origin.


Alcohol availability and alcohol-related casualties in Michigan 1968-1976.

In summary alcohol availability changed throughout the 1969--1976 time period with a particularly major change caused by the 18-year-old legal drinking age (1972) and increases in the numbers and hours-of-operation of on-premise consumption establishments. Eighteen to 20-year-olds experienced increases of at least 4600 additonal traffic crashes associated with alcohol of which at least 89 involved one or more fatalities in the 1972-1975 time period. Associated with the increase in crash involvement, draught beer consumption in Michigan dramatically increased. In the absence of any convincing explanations to the contrary, we consider these conservative analyses to be compelling evidence of the role of alcohol availability in the  social etiology of alcohol-related traffic casualties.


Cephalexin therapy for infections complicated by age and concurrent diseases. A study in general practice.

A broad spectrum antibiotic, cephalexin, was used to treat 64 patients in whom the problems of age, underlying conditions and multiple drug therapy could adversely affect the outcome of antibiotic treatment. The majority of patients were given the antibiotic for a lower respiratory tract infection. Treatment was successful in 50 patients after 5 days, and in a further 3 after 10 days. In 25 patients another antibiotic had been used unsuccessfully to treat infection: 19 of these patients responded to cephalexin therapy. Minor gastro-intestinal side effects were reported in 4 patients.


Curing of typhoid carriers by cholecystectomy combined with amoxycillin plus probenecid treatment.

11 registered thyphoid carriers were treated by cholecystectomy combined with amoxycillin + probenecid in our department. On the basis of our observations (mean observation period was more than 1 year), all our patients can be considered recovered (cure rate = 100%).


[Arteriomesenteric duodenal compression].

Arteriomesenteric obstruction of the duodenum is a rare lesion seen in abdominal surgery. By vascular compression passage is blocked in the lower part of the duodenum. Two forms are described, an inborn and an acquired one, both of which result from a decrease in the aortomesenterial angle. While the acute form of disease causes a complete occlusion, clinically shown as ileus, the chronic intermittent form presents an uncharacteristic upper abdominal complex of symptoms. The diagnostic procedure is an X-ray passage series of the upper gastrointestinal tract. Final diagnostic assurance should be assumed by angiographical determination of the superior mesenteric artery and its angle of branching from the aorta. Retrocolic duodenojejunostomy has proved to be the most satisfactory surgical treatment for this lesion. Our studies demonstrate the value of surgical treatment of arteriomesenteric obstruction of the duodenum in 14 cases.


[Effect of exogenous collagen on the metabolism of burns in rats; the collagen treatment of large superficial excision wounds].

In an animal experiment study the effect of collagen sponge treatment on skin wounds was examined. In a test for defense mechanism, the bandage material was accepted without any disturbance of the surrounding tissue. It could also be removed without any damage to the wound area while renewing the covering bandage. In contrast to the controls, there was a statistically significant difference in the decreasing wound area. No tract formation of the wound edges was observed in the experimental group, and histologically the wounds showed an earlier fiber formation with functional orientation toward the wound surface. The advantages of treatment using collagen instead of inert material include better compatibility, a positive cosmetic effect, and a stimulation of wound healing without the necessity of a two-stage transplantation.


Circadian influence on the immunization of mice with live Bacillus Calmette-Guérin (BCG) and subsequent challenge with Ehrlich ascites carcinoma.

Non-specific immunostimulation with Bacillus Calmette-Guérin (BCG) is of current interest in the treatment of cancer. The main objective of the series of experiments described in this paper was to evaluate the influence the host's circadian system has on a. the stimulation of the immune system with BCG and b. the subsequent efficiency of that stimulated immune system against the Ehrlich Ascites Carcinoma (EAC). There was a circadian rhythm in the length of survival time in non-immunized mice challenged with the EAC. Mice receiving an EAC challenge during the middle of the light period survived significantly longer than those challenged with the EAC around the time of transition from dark to light. Mice immunized with BCG and challenged with EAC also demonstrated a circadian rhythm in the length of survival 30 days after EAC challenge with 86% survivors in the mice treated at 10(00) and 60% survivors in the mice treated at 07(00). The same relationship was also observed 70 and 80 days after EAC challenge. Eighty days after EAC challenge, a circadian rhythm was apparent in the frequency of solid tumors at the site of the initial EAC injection. The highest incidence of solid tumors occurred at 13(00). A circadian rhythm was found in the increase in body weight between the first and second BCG or saline injections. Rectal temperatures recorded on the 8th, 12th and 16th day after EAC challenge were characterized by circadian rhythmicity. In the mice without development of ascites, the peak temperature consistently occurred at 01(00). In the mice with ascites there was a phase advance in the rectal temperature rhythm of 3 h so that the peak in the rhythm consistently occurred at 22(00). In the mice with ascites a further finding was an increasing hypothermia as the ascites continued to develop; however, this hypothermia was not detectable during the time of the peak (10(00)) in the temperature rhythm. The mice which did not die by the 80th day after EAC challenge were challenged again with 5.0 x 10(6) EAC cells, and during the next 46 days circadian variations were observed in the numbers of mice which survived. Similar changes were observed during an additional 46 days after a third EAC challenge of 41.5 x 10(6) cells.


The effects of ibuprofen, indomethacin, aspirin, naproxen, and placebo on the gastric mucosa of normal volunteers: a gastroscopic and photographic study.

The effects of various nonsteroidal antiinflammatory drugs on the gastric mucosa were endoscopically evaluated in 40 normal volunteers. Eight groups, each containing five subjects were designed: aspirin (3600 mg/d); placebo; ibuprofen (1600 mg/d); ibuprofen (2400 mg/d); indomethacin (100 mg/d); indomethacin (150 mg/d); naproxen (500 mg/d); and naproxen (750 mg/d). All volunteers took medication for seven days and gastroscopy was carried out on day one and day eight. All findings were documented by photography. Severe gastric mucosal injury occurred with aspirin (P less than 0.05), both doses of indomethacin, and the higher dose of naproxen. Lesser changes were seen with the lower dose of naproxen, both doses of ibuprofen and placebo. The higher doses of ibuprofen, indomethacin, and naproxen caused a greater degree of gastric mucosal injury, but statistical significance was achieved only with naproxen (P less than 0.01). Subjective gastrointestinal complaints generally correlated with endoscopic pathology; however, nine volunteers had evidence of severe injury to the gastric mucosa with no symptomatology. This was confined to the patients on indomethacin, naproxen, and ibuprofen. Aspirin patients all had some degree of symptomatology but to a lesser degree than expected in view of the endoscopic findings.


The SGOT/SGPT ratio--an indicator of alcoholic liver disease.

The SGOT/SGPT ratio is significantly elevated in patients with alcoholic hepatitis and cirrhosis (2.85 +/- 0.2) compared with patients with postnecrotic cirrhosis (1.74 +/- 0.2), chronic hepatitis (1.3 +/- 0.17), obstructive jaundice (0.81 +/- 0.06) and viral hepatitis (0.74 +/- 0.07). An SGOT/SGPT ratio greater than 2 is highly suggestive of alcoholic hepatitis and cirrhosis. It occurs in 70% of these patients compared with 26% of patients with postnecrotic cirrhosis, 8% with chronic hepatitis, 4% with viral hepatitis and none with obstructive jaundice.


Influence of portacaval anastomosis on serum and biliary unsulfated bile acid composition in patients with liver cirrhosis.

Serum and biliary unsulfated bile acids were studied using a gas chromatographic method in 8 patients before and 2 months after portacaval anastomosis. Total serum bile acids were 21.6 +/- 3.6 mumol/liter before and 68.0 +/- 8.6 mumol/liter after surgery (P less than 0.005). Cholic acid rose from 26.5 +/- 3.4% to 33.8 +/- 4.8% (P less than 0.02) of the total serum bile acids, while chenodeoxycholic acid decreased from 67.9 +/- 4.1% to 60.8 +/- 4.3% (P less than 0.05). The relative concentration of cholic and chenodeoxycholic acids in bile increased slightly but not significantly after surgery, while deoxycholate fell from 8.5 +/- 1.7% to 2.1 +/- 0.6%. (1) in cirrhosis the serum and biliary bile acid composition are markedly different, the cholic-chenodeoxycholic ratio being much lower in serum than in bile; (2) after portacaval anastomosis serum and biliary bile acid patterns tend to become similar; (3) percent biliary deoxycholate decreases significantly after surgery.


An attempt to establish a model for the rhythmic phenomena affecting the growth or sporulation of certain fungi.

A simple two-variable mathematical model is proposed, able to acount for periodic variations relating to growth in Podospora anserina and fructification in Aspergillus niger. This basic model is open to generalization.


Pulmonary aspiration as a consequence of gastroesophageal reflux: a diagnostic approach.

A radioisotope scintiscanning technique that can document pulmonary aspiration of gastric contents in patients with gastroesophageal reflux is described. Six patients with suspected nocturnal aspiration from reflux were studied. Three of the six had positive lung scans 8 hr after intragastric placement of 10 mCi of technetium 99m sulfur colloid. Overnight intraesophageal pH monitoring revealed prolonged episodes of GE reflux in those with positive scans. These preliminary observations suggest that this scintigraphic technique may be an effective method for documenting pulmonary symptoms as a consequence of gastroesophageal reflux.


Chronochemotherapy: L 1210 leukemia and beyond.

In cancer and other therapeutic research, an interpretation of median survival times can and should take cure into account. With this qualification, an analysis of recently published data provides further statistically significant evidence in favor of cancer chronotherapy as compared to homeostatic therapy.


Evaluation of electrofulguration in control of bleeding of experimental gastric ulcers.

The safety and efficacy of electrofulguration for control of bleeding from standard canine experimental gastric ulcers was studied. At settings of 2, 5, and 8 on a Valleylab SSE-3 generator, 0.5-sec applications provided effective hemostasis. However, a setting of 2 required an excessive number of applications. Settings of 5 and 8 showed deep injury to the muscularis externa when examined histologically. In an attempt to reduce the depth of injury, a more easily ionizable gas mixture of 50% argon gas and 50% CO2 was compared to CO2 alone. At a generator setting of 5 with 0.5-sec applications the argon-CO2 mixture produced slightly less deep injury than CO2 alone, but the difference was not significant. Although electrofulguration was effective in stopping bleeding in these experiments, the tissue injury was unpredictable and deep.


Percutaneously placed biliary stents in the management of malignant biliary obstruction.

The management of malignant obstruction of the biliary tree is difficult and often unsuccessful. Advances in the technique of percutaneous transhepatic catheterization have made possible the nonoperative internal drainage of obstructed lesions. We report successful decompression of ten patients with unresectable biliary neoplasms using percutaneously placed internal biliary stents.


Toward a chronopsy: part II. A thermopsy revealing asymmetrical circadian variation in surface temperature of human female breasts and related studies.

A thermorhythmometric analysis was carried out on data from a patient who underwent a prophylactic subcutaneous mastectomy, subsequently to a preoperative mammogram revealing clustered small calcifications in the left breast. The patient self-measured surface temperature of each breast, above and below the nipple, at intervals of 75 +/- 10 min for 59 h while awake. In one location of each breast, the recording thermistor-probe was insulated for 21.5 h while other probe locations remained uninsulated. The overall rhythm-adjusted average surface temperature and the extent of predictable circadian variation differed with statistical significance when the two breasts were compared. The left breast exhibited a higher rhythm-adjusted mean temperature and a lower extent of predictable circadian variation, as compared to the contralateral breast. The interbreast differences of surface temperature also demonstrated a statistically significant rhythm. A review on results of rhythmometry of breast temperature was also carried out. The thermorhythmometric findings here reported must not necessarily be regarded as indicative of cancer; they may be found in non-cancerous subjects and may or may not reflect early pathology. The objective of this publication is to suggest that non-invasive mammary thermorhythmometry may complement clinical histopathology. This subject may exemplify a new principle awaiting scrutiny with much more extensive sampling and much longer follow-up, namely that chronopathology including chronoprotopathology, alongside established diagnostic procedures, may provide an indication for prophylactic intervention.


Clinical and manometric findings in benign peptic strictures of the esophagus.

To determine the possible factors that may contribute to the development of peptic stricture of the esophagus, clinical and manometric features were compared in patients with symptomatic gastroesophageal reflux and those with peptic strictures of the esophagus. Patients with stricture were older and had a longer duration of heartburn than patients without a stricture. Most importantly, patients with stricture had a more marked decrease in lower esophageal sphincter (LES) pressure, 4.9 +/- 0.5 mm Hg, than patients without a stricture, 7.5 +/- 0.6 mm Hg, P less than 0.01. The LES pressure in all patients with stricture was below 8 mm Hg, and did not overlap with normal values. Patients with stricture had either a nonspecific motor abnormality of aperistalsis (64%), compared to patients with symptomatic reflux (32%), P less than 0.05. Thus, peptic stricture of the esophagus is commonly associated with a long duration of reflux symptoms in patients with a very low LES pressure and esophageal motor disorder.


Pancreatic polypeptide response in patients with chronic pancreatitis.

We studied the plasma pancreatic polypeptide (PP) response to a meal in patients with pancreatitis and attempted to correlate the PP increment with the degree of pancreatic exocrine insufficiency. Control subjects and patients with recurrent pancreatitis showed significant mean increase (P less than 0.05) in plasma PP concentration in response to food. By contrast chronic pancreatitis patients had no significant increase in plasma PP. However, some subjects with normal pancreatic had no response and some patients with chronic pancreatitis did show a response. In addition, no correlation was observed between the PP response and pancreatic exocrine secretion. We conclude that the PP response to a meal has only limited value in the detection of pancreatic destruction.


Indium-111-labeled leukocyte imaging in acute pancreatitis with suspected complicating abscess.

Indium-111-labeled leukocyte imaging is described in two cases of acute pancreatitis. The study correctly anticipated the absence in one case, and the presence in the other, of complicating abscesses.


Primary histiocytic lymphoma of the esophagus.

Squamous cell carcinoma represents the most common primary malignant lesion of the esophagus (1). The initial manifestation of lymphosarcoma infrequently occurs in the gastrointestinal tract, and in one large series, there were no lymphosarcomas presenting in the esophagus (2). In the case described below, a primary histiocytic lymphoma (large cell lymphoma) was discovered in the distal esophagus.


Congenital hepatic fibrosis (asymptomatic and latent form) and multiple gastric ulcers.

Congenital hepatic fibrosis (asymptomatic and latent form) was diagnosed in a 67-year-old male during laparotomy for a gastric ulcer. The gastrectomy specimen revealed multiple chronic ulcers with healing in the form of villous mucosal hyperplasia. The pathological diagnosis of congenital hepatic fibrosis and similar hamartomatous lesions is discussed. A possible relationship between congenital hepatic fibrosis and gastroduodenal ulceration is envisaged.


Diabetes and glucose tolerance as risk factors for cardiovascular disease: the Framingham study.

This report examines prospectively, in the Framingham cohort, the relation of diabetes and impaired glucose tolerance to each of the cardiovascular sequelae, taking into account age, sex, and associated cardiovascular risk factors. The incidence of cardiovascular disease, as well as the levels of cardiovascular risk factors, were found to be higher in diabetic than in nondiabetic men and women. The relative impact of diabetes on coronary heart disease, peripheral vascular disease, or stroke incidence was the same in men and women, but for cardiovascular mortality and cardiac failure the impact is greater for women. Present evidence suggests that alleviation of associated cardiovascular risk factors is the most promising course in reducing cardiovascular sequelae in diabetic patients.


Epidemiology of diabetes and its macrovascular manifestations in Pacific populations: the medical effects of social progress.

Worldwide diabetes epidemiology studies have shown quite marked differences in diabetes prevalence rates between ethnic groups. This pattern holds true in the Pacific region and provides unique opportunities for comparative studies. Diabetes is rare in Melanesians, and also in Polynesians, Micronesians, and Australian Aboriginals who retain their traditional life-style. High prevalence rates of insulin-independent diabetes have been demonstrated in Polynesians, Micronesians, and Australian aboriginals who have adopted a Western life-style. Along with the Pima Indians, the Micronesian population of Nauru have the highest diabetes prevalence yet reported--40% of people aged 20 yr and over. As diabetes is rare in traditional living Polynesians and Micronesians, yet high in westernized populations of these ethnic groups, it appears these people may have a "diabetic genotype" that is unmasked by the change in life-style. Obesity, a high caloric Western diet, and reduced physical activity may be the major precipitating factors. Bimodality of glucose tolerance distributions has been demonstrated in both westernized Polynesians and Micronesians. The frequency distributions of both fasting and 2-h postload glucose levels allow separation of these populations into normal and hyperglycemic groups. The optimal cut-off levels between the two groups were a fasting plasma glucose congruent to 140 mg/dl and a 2-h level of congruent 20 mg/dl. These findings provide a valid basis for the diagnosis of diabetes mellitus to be based on the above levels. Only sparse information exists on the prevalence of microvascular and macrovascular complications of diabetes in these populations. However, there is clear evidence that they are occurring and they are similar in nature to the complications seen in Caucasian diabetic patients. Coronary artery disease is not yet a major problem in Pacific Islanders although most of the major risk factors are not present in urbanized communities. However, with increasing westernization, and given more time for the pathologic process of atheroma to develop, it can be expected that coronary artery disease will become a major cause of morbidity and mortality in Polynesians, Micronesians, and the Australian aboriginal.


Coronary heart disease incidence and cardiovascular mortality in Busselton with reference to glucose and insulin concentrations.

In the 1966 study of the population of Busselton, Australia, blood sugar and serum insulin levels were measured one hour after an oral glucose load, in addition to the conventional cardiovascular risk factors. The six-year incidence of coronary heart disease (CHD) and the 12-yr mortality from CHD and from all cardiovascular diseases is described in relation to the initial baseline variables measured using the upper 20th percentile values (age-specific and sex-specific) to define the risk ratios. In younger subjects (ages less than 60 yr), elevated blood pressure levels for both sexes (risk ratios from 2.9 to 5.2) and elevated serum cholesterol concentrations for males (risk ratios from 3.0 to 3.3) were strong predictors of cardiovascular risk. In men aged 60 to 69 yr, those with upper range one-hour serum insulin concentrations showed marked associations with the six-year incidence of CHD, the 12-yr mortality from CHD, and the 12-yr mortality from all cardiovascular diseases (risk ratios were 2.0, 2.3, and 2.4, respectively). The relationship of elevated serum insulin and cardiovascular mortality persisted when males of all ages were analyzed, and it appeared to be independent of the other major risk factors. In females, no association between serum insulin and CHD or cardiovascular disease could be found. Although the age and sex specific upper 20th percentile values for one-hour blood sugar concentrations showed a low grade association in patients with subsequent cardiovascular disease end points, more noticeable risk ratios were demonstrated at the higher blood sugar level of 200 mg/100 ml or greater (in the age group 60 yr and over, risk ratios were 2.2 in males and 2.6 in females.


Epidemiologic studies of insulin-dependent diabetes mellitus.

The incidence of insulin-dependent diabetes mellitus (IDDM) in Denmark in the years 1970--1976 was 13.3 per 100,000 in the age group 0--29 yr. This incidence is almost identical to that found in 1924 in Denmark in the same age group. The prevalence of insulin-consumers is 3.2 per 1,000. Comparison is made with incidence and prevalence data from other studies of Caucasian populations.


Diabetes mellitus and its vascular complications in Japanese migrants on the Island of Hawaii.

Japanese migrants and their offspring on the island of Hawaii and Japanese living in Hiroshima were examined for diabetes mellitus and its vascular complications. the same methods and investigators were used in both locations. Death certificates of Japanese and Caucasians dying on the island during the past 26 yr were analyzed. Diabetes, defined as a venous serum glucose concentration of at least 200 mg/dl 2 h after a 50-g oral glucose load, was significantly more common in the Hawaiian Japanese than in the Hiroshima Japanese subjects. This suggests that diabetes is more prevalent in Japanese in Hawaii than in Japan, although lack of knowledge about the total population of Japanese migrants in Hawaii makes this generalization uncertain. The proportion of deaths attributed to diabetes was much higher in Japanese migrants and their offspring in Hawaii than in Japan. During the 1950s, the proportional death rate from diabetes was about half as large in Japanese Hawaiians as in Caucasian Hawaiians, but it increased to become 1.6 times the Caucasian rate during the 1970s. A nutritional study revealed that the total caloric intake was similar in Japanese in Hawaii and Hiroshima, although the estimated level of physical activity was less in the Hawaiian subjects. Consumption of animal fat and simple carbohydrates (sucrose and fructose) were at least twice as high in Hawaiian as in Hiroshima Japanese. Conversely, Hiroshima Japanese consumed about twice the amount of complex carbohydrate as the Hawaiian Japanese. These observations support the hypothesis that a high fat, high simple carbohydrate, low complex carbohydrate diet and/or reduced levels of physical activity increase risk of diabetes. The proportion of deaths attributed to ischemic heart disease was higher in both diabetic and nondiabetic Japanese Hawaiians than in diabetic subjects in Japan. The rates were similar for Japanese and Caucasians in Hawaii. There was no evidence of an environmental influence on the development of microangiopathy (retinopathy) in diabetes, as the prevalence of diabetic retinopathy (stratified for diabetes duration) was similar in Japanese subjects in Hawaii and in Japan, and it was similar to previous reports from England. On the other hand, diabetes alone did not appear to account for the greater prevalence of macroangiopathy in Hawaiian Japanese than in Hiroshima. Thus environmental factors, possibly including diet, appear to be involved in the development of macrovascular complications of diabetes.


Relationship of glucose tolerance and plasma insulin to the incidence of coronary heart disease: results from two population studies in Finland.

The relationship of glucose tolerance to the incidence of coronary heart disease (CHD) has been investigated in two cohorts of Finnish men: 3267 men ages 40--59 yr from the Social Insurance Institution's (SII) Coronary Heart Disease Study and 1059 men ages 30--59 yr from the Helsinki Policemen Study. The relationship of plasma insulin level to the incidence of CHD was also investigated in the Helsinki Policemen Study. An oral glucose lead of 60, 75, or 90 g according to body surface area was used in both studies. In the SII Study, plasma glucose was determined from venous blood samples taken 1 h after glucose load. In the Helsinki Policemen Study, blood glucose was determined from venous blood samples taken at 0, 1, and 2 h, and at a 5-yr reexamination, plasma insulin was measured during OGTT at 0, 1, 2 h. In the SII Study cohort, the 4-yr mortality from CHD and the 4-yr incidence of nonfatal myocardial infarction (MI) did not show a definite relationship to 1-h postload plasma glucose. In the Helsinki Policemen Study cohort, the 5-yr incidence of "hard criteria" CHD (CHD death and nonfatal MI) was significantly related to high 1-h postload blood glucose level but not to fasting or 2-h postload blood glucose levels. 10-yr mortality from CHD was significantly higher in the top quintile of fasting and 1- and 2-h postload blood glucose levels, as was the incidence of "hard criteria" CHD. However, in multivariate analyses including age, systolic blood pressure, plasma cholesterol, and smoking, the blood glucose variables showed no statistically significant independent contribution in predicted risk of CHD. Univariate analyses by quintiles of plasma insulin levels measured at the 5-yr reexamination showed that the incidence of "hard criteria" CHD during the subsequent 5 yr was significantly higher in the top quintiles of fasting and 1-h and 2-h postload plasma insulin than in the combined lower quintiles. Multivariate analyses showed that the value of high 1-h or 2-h postload plasma insulin level for predicting CHD risk was independent of other risk factors, including blood glucose levels during OGTT.


Prevalence of major vascular complications at the initial visit among Japanese diabetic patients.

The frequencies of retinopathy, proteinuria, hypertension, and electrocardiographic (ECG) abnormalities in 2025 diabetic subjects new to our clinic in Tokyo were analyzed in relation to status at initial visit with respect to age, estimated duration of diabetes, and fasting blood glucose. Frequency and severity of retinopathy increased markedly with duration of diabetes. A relationship was found between retinopathy at first visit and level of blood glucose at that time. Proteinuria also clearly increased with duration; its frequency was generally higher in older age groups. Frequency of hypertension increased with age up to 60 yr, but there was no association between prevalence of hypertension and duration of diabetes. ECG abnormalities also increased with age, although serious abnormalities were rare even in older subjects. Hypertension and ECG abnormalities were not more common in those with higher initial blood glucose values, and the frequencies of these aberrations did not increase with the duration of diabetes. ECG abnormalities were more common among hypertensives, especially in younger age groups. Despite the clear effect of degree and duration of hyperglycemia on microvascular complications, there was no evidence of a direct effect of hyperglycemia on macrovascular abnormalities in this study.


The WHO multinational study of vascular disease in diabetes: 1. General description.

A general description of the multinational study under the auspices of the World Health Organization is presented. The purpose was to compare the prevalence of vascular disease in representative samples of diabetic subjects of different ethnic and cultural habitus. Standardized methods of investigation were devised. Fourteen centers participated, and the data collected so far indicate that the characteristics of the populations studied varied as to age composition, adiposity, cigarette smoking, treatment, age at diagnosis, and duration of diabetes. Thus, taking these factors into consideration and while awaiting completion of the data, conclusions must be drawn with reserve.


The WHO multinational study of vascular disease in diabetes: 2. Macrovascular disease prevalence.

14 national groups have collaborated under WHO auspices to select, from local defined populations of individuals with clinical diabetes, groups of approximately 500 within the age range 35--55 yr stratified by age, sex, and known duration of diabetes. In each center, the selected patients were submitted to a standardized study protocol, which included systematic inquiry (WHO questionnaire) for the presence of symptoms of angina pectoris, history of myocardial infarction, presence of intermittent claudication, and cigarette smoking history. Examination included standard biometry, blood pressure measurement, 12-lead (centrally Minnesota coded) electrocardiography, and central laboratory measurement of serum cholesterol and creatine. Ophthalmoscopic and urinary examinations were also included. The prevalence of arterial disease symptoms and electrocardiographic abnormalities show very large variation between countries, the lowest rates generally being found in the Oriental samples and the highest in the European. "Risk factors" for arterial disease (blood pressure, serum cholesterol, and cigarette smoking) also vary widely between diabetic groups. Although data are not yet complete, these differences appear unlikely to explain the variation in the atherosclerotic morbidity observed. Diabetic women were at least as vulnerable to arterial disease as diabetic men. A high prevalence of nonspecific abnormalities of the repolarization phase of the ECG was found, even in groups where ischemic abnormalities were rare. The origin of these is uncertain; they may represent variable local changes or possibly diabetic cardiomyopathy. This preliminary report confirms and quantifies previous indications that the impact of atherosclerotic disease on persons with diabetes varies considerably between national groups, in broad terms, running parallel with the variations in prevalence in the populations in general and suggesting that cultural and/or ethnic factors are more important determinants of atherosclerosis in diabetic individuals than is the diabetic state per se.


The WHO multinational study of vascular disease in diabetes: 3. Microvascular disease.

A preliminary comparison and analysis of microvascular disease was performed in 14 stratified samples of diabetic subjects. Microvascular disease was assessed by estimating visual disabilities, by standardized examination of the optic fundus by direct ophthalmoscopy, by estimating proteinuria, and by measuring the serum creatinine concentration. Visual impairment by questionnaire positive varied considerably between centers, probably due to cultural differences in interpretation of the questions. Physician-assessed visual disability also yielded considerable differences in frequency; however, the frequency differences were unrelated to those observed for macrovascular disease. Retinopathy--the sum of all components--was related to duration of diabetes in each participating center. The apparent frequency of proteinuria varied considerably between centers. In general, the frequency of retinopathy was related to the level of systolic blood pressure, but there was no systematic association with cigarette smoking.


Studies of the HLA system and insulin-dependent diabetes mellitus.

The relationship between the HLA system and insulin-dependent diabetes mellitus (IDDM) is reviewed. Data compiled by the HLA and Disease Registry reveal that HLA-B8 and/or Dw3 are associated with IDDM in all populations studied so far, but further population studies in non-Caucasian populations should be performed. In Caucasians, HLA-Dw2 renders protection against IDDM while HLA-Dw3 and Dw4 are associated with susceptibility to IDDM. The exact mode of inheritance of susceptibility to IDDM remains to be established. Involvement of at least two genes is likely. Heterogeneity of IDDM is highly possible and should be a matter of major interest in diabetes research.


Standardization of definition, classification, and reporting in diabetes-related epidemiologic studies.

This working paper reviews some advantages and disadvantages of various alternative definitions and classification schemes. Certain of these alternatives were discussed by an international group of experts on the epidemiology of diabetes. It was recommended by the conferees that the following terms not be used as standard descriptors in epidemiologic reports: juvenile diabetes, juvenile-type diabetes, maturity-onset diabetes of youth (MODY), latent diabetes, subclinical diabetes, clinical diabetes, chemical diabetes, and J-type (Jamaica) diabetes. Alternative ways of describing these conditions were offered. Some, but not all, conferees favored abandonment or modification of the terms "secondary diabetes" and "pancreatic diabetes." Two alternate approaches are described in classification. One is designed to classify all types of cases in a single scheme. In this system each case is described by indices that include etiology and special etiologic concomitants, fatness, severity, type of treatment, and, if present, special or peculiar manifestations, and morbidity. This system makes it possible to classify all cases by mutually exclusive categories. A disadvantage of this scheme is that the number of combinations of classifying indices and subindices is great. Another approach is to classify cases by syndromes, using in each class a mixture of indices (e.g., etiology, severity, fatness, etc.). The conferees failed to reach a consensus in the specifics of this approach. There was considerable disagreement on how certain terms should be defined, whether they should be used, and on the degree of need for specific definitions. These designations included the terms "insulin-dependent," "idiopathic," "insulin-requiring," and "ketosis-prone." The conferees agreed that in either of the two approaches to classification, the prime indices should be those that can be ascertained by ordinary clinical methods. Much progress could be accomplished, even in the absence of international standardized definitions and classification systems, provided that authors keep in mind the need to describe the major characteristics of their cases and define the sense in which they use terms such as insulin-dependent, ketosis-prone, obese, etc.


Contrast (modulation) sensitivity functions measured in patients with high refractive error with emphasis on aphakia: I. Theoretical considerations.

Recently, alterations in contrast (modulation) sensitivity functions of patients with high refractive errors have been noted. For example, this seems to be a common finding in aphakia. In some measure the observed alterations are due to the effect of the corrective lens and the optics of the eyes. These optical effects (in addition to blur) must be factored out in order to determine whether residual effects on the visual system remain. The argument is applicable to photographs of sine wave fringes as well as devices designed to produce interference patterns directly on the retina. A simple means for largely correcting these lens effects is discussed.


Prevalence and course of diabetes modified by fasting blood glucose levels: implications for diagnostic criteria.

Data from the epidemiologic survey in Sudbury, Massachusetts, demonstrate that the prevalence of new cases of diabetes, based on the USPHS criteria for the standard 3-h oral glucose tolerance test as originally published, was 0.7%. If a fasting blood sugar greater than or equal to 110 mg/dl had been required for those USPH diagnoses, the prevalence would have fallen to 0.28%. Further, if a peak serum insulin level of less than or greater than 60 microM/ml had been required, the original prevalence rate would have dropped to 0.02%. Data from a prospeh criteria for diabetes indicate by life table analyses that 41% show further deterioration of carbohydrate control over the first 13 yr of the study when the fasting blood sugar was less than 110 mg/dl in the initial diagnostic test and 82% when the fasting blood sugar was greater than or equal to 110 mg/dl. The relationship of fasting blood glucose to later decompensation proved to be a continuous one without evidence of a threshold effect. The implications of both of these studies for diagnostic criteria, particularly recent proposals, is discussed.


Contrast (modulation) sensitivity functions measured in patients with high refractive error with emphasis on aphakia: II. Determinations of patients.

Measurements of Constrast Sensitivity Functions (CSF) were made on normal observers made artificially highly ametropic with spectacle lenses (with high back vertex) distance in order to determine the effect of retinal image size alterations upon CSF measures. While not an exact model for high ametropia per se, this experiment served to familiarize the experimenters with problems associated with the task. Image size alterations occur normally in aphakic patients and highly myopic patients. As a clinical trial, a series of aphakic observers were tested using an interferometric acuity device. CSF measures were made with the patient's spectacle corrections in place and again with correcting contact lenses substituted. The contact lenses reduce induced image size alterations in these cases. The use of contact lenses in such measures allows differentiation between artifactual low frequency fall off in aphakia due to lens effects and possible low frequency fall-off due to other causes.


What is normal binocular vision?

The vergence position of the eyes is determined by the near fixation-accommodation-miosis synkinesis and the fusion mechanism. The contribution of both systems was analysed in 30 normal subjects and 16 subjects with abnormal binocular vision. Prism fixation disparity curves were determined in three different experimental situations: the routine method according to Ogle, a method to stimulate the synkinetic convergence (Experiment I, with one fixation point as sole binocular stimulus) and a method to stimulate the fusion mechanism (Experiment II, with random dot stereograms). Experiment I produced flat curves and Experiment II steep curves. The mean diameter of the horizontal Panum area was 5 minutes of arc in Experiment I and 2 degrees in Experiment II. On the basis of these findings, it was postulated that the synkinetic system operates in the absence of fixation disparity and the fusion system in the presence of fixation disparity. In Experiment II, esodisparities of 100 minutes of arc occur in a number of normal subjects. The dividing line between normal and abnormal binocular vision therefore is blurred. Normal persons can display disparities, the order of magnitude of which is equal to that of the angle of squint in micro-strabismus.


Risk factors other than hyperglycemia in diabetic macrovascular disease.

A five-year prospective follow-up study was done on 10,000 adult males in Israel. The end-points of diabetes mellitus--clinical and unrecognized myocardial infarction, angina pectoris, sudden death, and hypertension--were examined. The incidence rates rise with age and vary significantly by areas of birth, with the Middle Eastern and North African subjects having the highest incidence of diabetes but the lowest cardiovascular rates. A developmental medical model based on a historical-societal perspective is proposed to explain these findings. The major factors found on multivariate analysis in the development of diabetes mellitus are compared with those of the other cardiovascular end-points mentioned above. The similarities and differences between these risk factors are discussed, and I conclude that the prevention or alleviation of diabetic macrovascular disease needs a multifactorial approach against the major risk factors of the macrovascular complications as well as those related to diabetes, in the individual, family, and community.


Oculographic automatic perimetry in glaucoma visual field screening: a clinical study--preliminary results in glaucoma patients.

An automatic method for visual field screening using oculographic potentials have been evaluated on 12 eyes of 65 glaucoma patients. The oculographic perimeter records, plotting the central 22 degrees of the visual field, have been compared with Armaly's manual selective perimetry performed by the Goldman Perimeter. In spite of different testing standards of both methods, equivalent pathological field defects were demonstrated in 72% of the eyes following the first examination. Successive plottings with the automatic method improved the results considerably. The method has proved to be a reliable objective automatic test. Further development is suggested through which the procedure might be useful for glaucoma screening in the future.


[Personality dependence in drug dependence].

Is drug dependence more likely to establish itself in persons whose personality structure is already characterized by a psychological dependence which can be looked at from two aspects: cognitive field dependence and emotional dependence? Three groups of 21 subjects each, multiple drug users, users of cannabis and non-users, are studied with the expectation that the first group is more psychologically dependent than the second one, the latter being in turn more dependent than the group of non-users. The situation is not so simple. Hard-drug users appear to be more active than users of cannabis, whereas non-users are even more dynamic individuals. However, in such a study the duration of consumption exercise an important influence because, in this regard, different personality profiles of the two drug-using groups come into play, the users of cannabis presenting a more incoherent picture. The multiple drug addict selected from his natural environment seems to acquire, through his prolonged consumption, a greater perceptual independence and emotional maturity owing to the clandestine nature of his habit, and a more acute and articulate general way of functioning in order to avoid mishaps.


[Prognosis of alcoholic delirium (author's transl)].

296 cases of delirium tremens treated in 1958-69 were analysed retrospectively. Forty-one patients died in delirium or shortly thereafter. In 72 by now dead patients cirrhosis of the liver was the most common cause of death. Of 68 patients re-examinated, 12 were now teetotallers and six had markedly reduced there intake. Fifty patients had continued drinking and most of them had signs of liver failure, one had hypertension and one also had a polyneuropathy. Those who were abstaining, as well as the patients with a favourable course,and most of them were married. Although the acute death-rate of delirium has been markedly reduced since the introduction of clomethiazole treatment, it remains high after discharge. In almost half of those who were still drinking there had been a slide downwards in their social status. Delirium tremens is almost always precipitated by alcohol withdrawal.


[Liver changes in giant-cell arteritis: temporal arteritis and rheumatic polymyalgia (author's transl)].

Liver changes were demonstrated in six elderly patients with giant-cell arteritis (temporal arteritis, three with polymyalgia). Histologically there was fatty infiltration in four and pericentral congestion in five, star-cell nodules in one and non-specific hepatitis in one. Bromsulphalein test was abnormal in all, but rapidly became normal as the arteritis was successfully treated with corticoids. The pathogenesis of the liver changes is unclear. The authors' observations and published reports suggest that they are typical of giant-cell arteritis; it is of importance in the diagnosis of underlying disease.


[Effect of dihydroergotamine on pulmonary perfusion in acceleration stress (author's transl)].

An orthostatic circulatory load of varying degree (1-4 G) can be simulated by means of a human centrifuge. This results in a partial shifting of the intrathoracic blood volume into the capacity vessels of the lower extremity. In the pulmonary region, this is associated with a decrease in perfusion from the apical to the basal segments, which can be demonstrated by double nuclide perfusion scintigraphy. The degree of change in pulmonary perfusion was determined quantitatively in 26 volunteers by perfusion scintigraphy before and during acceleration, and the influence of dihydroergotamine (Dihydergot) was studied. The results show that the redistribution of the polmonary blood volume into the lower parts of the body can be largely prevented by Dihydergot. Pulmonary perfusion remains almost unchanged, compared with the initial value, up to an acceleration stress of 3 G, following intravenous injection of 0.5 mg dihydroergotamine. After oral administration (6 mg/d over 12 days), this applies to 1 and 2 G. Hence, dihydroergotamine represents, so to say, a "pharmacological anti-G suit".


[Sulprostone, a new prostaglandin E2 derivative (author's transl)].

Sulprostone, a new synthetic prostaglandin E2 derivative, was used for interruption of pregnancy in 479 patients with different lengths of pregnancy. Systemic forms of administration (i.v. and i.m.) were superior to non-systemic ones (intraamnial, extraamnial). In comparison with prostaglandins used up to now this substance is characterised by a higher rate of success and clearly reduced systemic side effects. As a consequence of these results a new clinical concept of artificial abortion with prostaglandins using sulprostone is presented: 1. i.m. application for induction of early abortion before the 6th week of pregnancy and for softening of the cervix up to the 12th week of pregnancy. 2. i.v. drip of termination of intact and disturbed pregnancies beyond the first trimenon.


[Treatment of renal osteopathy with 5,6-trans-25-hydroxycholecalciferol (author's transl)].

The influence of 5,6-trans-25-hydroxycholecalciferol on renal osteopathy was investigated in a total of 132 patients in 26 dialysis centres. Various doses were used, the average being 4000-6000 IU/day. In 32 patients a daily dose of 6000-9000 IU was used. The average individual duration of treatment was 276 days with a maximum of 910 days. Histologically there was an improvement in the renal osteopathy in 55.9% of evaluable cases (n = 34) and in 25.3% there was no deterioration. Radiographically these results were found in 21% and in 70.5% of evaluable cases (n = 105). Serum calcium increased in 46.6% of cases (n = 131), remained the same in 32.8% and decreased in 20.6%. The changes in alkaline phosphatase were similar : it dropped in 42.1% of patients, remained the same in 28.1% and rose in 29.8%. Immunoreactive parathormone which was invariably raised at the beginning of treatment (n = 36), fell in 25.0%, remained the same in 44.4% and rose further in 30.6%. The clinical symptoms of renal osteopathy which had been present in 57 patients improved in 51.0%, remained the same in 46.0% and deteriorated in 3.0%. Signs of intolerance and side effects were rare. Severe hypercalcaemia did not occur.


[Treatment of dopamine-dependent shock with triiodothyronine: prelimary results (author's transl)].

Triiodothyronine (T3) was administered to 11 patients in septic shock. In all there occurred an increase in arterial blood pressure within 24 hours, the rise in systolic pressure being 34 +/- 4.2 mm Hg, of diastolic 14 +/- 8.2 mm Hg, corresponding to a rise in mean arterial pressure of 25 +/- 6.1 mm Hg. Haemodynamic studies in four patients suggest that the action of T3 is mediated via beta-sympathomimetic channels.


[Treatment of myasthenia gravis with plasmapheresis (author's transl)].

Nine out of eleven severely ill patients with myasthenia gravis could be markedly improved by a combination of immunosuppressive drug therapy and plasmapheresis, two patients however suffered grave complications. The effectiveness of plasma exchange underlines the importance of plasma factors in the pathomechanism of myasthenic functional disturbance. Treatment with plasmapheresis may be regarded as a supportive measure of immunosuppressive drug therapy. However, the considerable risk and high technical requirements limit the indication to severe forms of the disease.


[Improvement of growth-hormone stimulation with l-dopa/l-carbidopa by simultaneous administration of propranolol (author's transl)].

The effect of simultaneous administration of 250 mg L-dopa + 25 mg L-carbidopa (Nacom) and 1 mg propranolol/kg body weight (maximal dose 40 mg propranolol) on growth-hormone secretion was tested in 96 children with growth retardation. The results were compared with those in a group of children that had been receiving only L-dopa and L-carbidopa. The additional administration of propranolol reduced the number of children unresponsive to adequate growth-hormone stimulation from 16% to 9.5%. There was no significant difference in mean maximal growth-hormone level between both groups, but the addition of propranolol caused a more long-lasting rise in serum growth hormone levels. Some of the children who previously had failed to have a satisfactory rise in growth-hormone level after L-dopa and L-carbidopa showed satisfactory stimulation when propranolol was added. Since only three blood samples need be taken (0, 45 and 90 minutes) and no significant side effects were noted, the combined treatment is suitable for out-patient use.


[Hypochlorhydria in acute gastritis (author's transl)].

After swallowing a non-sterilised pH electrode a 25-year-old medical student developed an influenza-like illness followed by hypo- and achlorhydria for several weeks, acute leukocyte-gastrititis, and epithelial defects of the antrum. This possibly represents an infectious disease which can be transmitted by contaminated electrodes or probes.


[Paget's osteodystrophia deformans. Occurrence, clinical aspects and complications].

33 monostotic and 27 polyostotic manifestations were found in 60 patients with Paget's disease of bone, 30 of whom were females (mean age 65.7 years) and 30 males (mean age 62.8 years). Pelvis, right tibia, lumbar spine, skull and sacrum were most commonly affected. Alkaline phosphatase activity in serum was raised in 95%, and in 88% hydroxyproline excretion in urine was increased. Due to the variable primary osseous or secondary arthrogenic complaints four groups could be distinguished among the monostotic cases. In polyostotic forms only some of the affected bones caused symptoms, whereas the other locations were only detected radiographically. The indication for calcitonin treatment of Paget's disease can only be made after in-patient investigation and evaluation of skeletal involvement, activity of the disease, complaints and assessment of complications actually present or to be expected according to the pattern of involvement. Under these conditions this form of treatment appeared indicated in 41 of 60 patients.


[The spread of tuberculosis among infants and small children in the G.F.R. (author's transl)].

Due to the interruption of routine BCG immunisation for the first time for 3 decades the current tuberculosis risk for unprotected infants and small children could be assessed locally and nation-wide. Nearly all of the 1,190,714 children born during 2 years between 1975 and 1977 were unprotected. Out of these 469 children had to be admitted up to the beginning of 1978 due to tuberculosis. The number of recognised cases of tuberculosis was thus considerably higher than the expected figures which in this country as a consequence of insufficient notification are used when decisions are necessary. Patients treated on an out-patient basis are not included in these figures and the children were all under 6, maximum age 34 months. In addition no less than 35 generalised and a further 180 more complicated cases of childhood tuberculosis were seen despite unlimited diagnostic possibilities.


[Cimetidine for treatment of stress-induced ulcer haemorrhage (author's transl)].

After gastroscopic demonstration of a definite source of bleeding (gastric or duodenal erosions or ulcers) 56 stress patients were treated with 1,200 mg cimetidine intravenously per day (constant infusion or 200 mg intravenously 4-hourly) in an open prospective study. Not considering 2 false indications because of arterial arrosion 46 patients were treated successfully with cimetidine. Bleeding could not be arrested in 7 cases and 2 of these succumbed, one of them despite repeated operations. In one patient bleeding was arrested; however, operation was necessary in the end due to perforation. Cimetidine has proved to be of value in conservative treatment of stress induced ulcer haemorrhage and is used increasingly prophylactically.


[An attempt to analyze the state of gastric cancer control in the German Democratic Republic (author's transl)].

Starting from the records of the county cancer control offices, an attempt is made to analyze the quality of detection and treatment of gastric cancer in the G.D.R. Possibilities and results of curative treatment strongly depend upon the extent of the disease and the age of the patient at the time of diagnosis. During the period of observation (Berlin 1955--1974, county Königs Wusterhausen 1960--1974), the proportion of elderly patients (65-yrs.) increased, stage distribution remained about the same, the rate of curative operations increased a little. When comparing the situation in the capital Berlin with the district Erfurt, the city of Dresden and the rural county Königs Wusterhausen, it can be demonstrated that the quality of diagnosis and treatment in Berlin is somewhat better then in the other teritories.


[The influence of food-supply to the concentration of blood ammonia (author's transl)].

It has been determined of 70 liver-healthy probands the ammonia concentration of capillary blood after poor on protein respectively rich on proteine food in 30 minutes distances. It comes in both groups to a spontaneous ascent the concentration of ammonia. The highest ammonia concentration depends on the content of protein which has been taken through food and the descent also variable quick. For it amount to the waiting period of food on the determination of blood ammonia after in frontly poor on protein food 90 minutes and after in frontly rich on protein food three hours. The statements have been secured statisticaly by means of U-test.


[Fatty acid metabolism in primary hyperlipoproteinemia (HLP) (author's transl)].

The fatty acid spectra of cholesterol ester and triglyceride fractions separated by thin-layer chromatography were analyzed by gas chromatography in the sera of 252 patients with primary HLP (with 53 cases of type IIa, 48 cases of type IIb, and 151 cases of type IV) and 60 healthy persons. Showing significantly increased values in the cholesterol ester fraction for HLP of types IIa and IIb as well as in the triglyceride fraction for HLP of types IIb and IV were palmitic acid, stearic acid, palmitoleic acid, oleic acid, and eicosatrienic acid. Significantly reduced percentages were obtained for linoleic acid, linolenic acid, arachidonic acid, and eicosapentaenic acid in the same fractions for these types. Possible causes include disturbances of the fatty acid metabolism in the liver, increased selective reesterification of fatty acids of the lipolytic process, and partially altered LCAT activity.


[Pregnanediol and pregnanetriol levels in the urine of rats after thymectomy].

The authors examined arterial blood pressure and excretion of pregnanetriol and pregnanediol in urine of adult male rats of Westar strain under normal conditions and after thymectomy. There was an elevation of arterial blood pressure after 45th day of thymectomy. Excretion of pregnanediol was increased on the 30th day, but that of pregnanetriol on the 60th day after removal of the gland. The increased excretion of both progesterone metabolites was connected with increased renal function, which probably played pathogenic role in postthymectomized hypertensive reaction.


[Pharmacokinetics of the pressor substance, 5,8-dimethoxy-trans-2-(2-hydroxyethyl)-amino-3-hydroxy-1,2,3,4-tetrahydronaphthalene hydrochloride (1b), after intravenous use].

The authors investigated the pharmacokinetics of the pressor substance 5,8-dimetoxy-trans-2-/2-hydroxyethyl/-amino-3-hydroxy-1,2,3,4-tetrahydronaphthaline hydrochloride (1b), which possessed strong pressor action. Blood concentrations after venous administration in a dose of 1 mg/kg of body weight were determined by means of exctration spectrofluorometric method. The data complied with the biexponential equation, meeting the requirements of an open two-compartment model. There was a quick elimination of the substance from the central compartment, which correlated also with the data for quick disappearances of the effect on the arterial pressure.


[Experimental studies of the changes in the wall of the large intestine and in the parenchymatous organs in stasis of the large intestine].

The authors carried out experimental studies on 23 dogs to examine changes, which occurred in the wall of the anastomosed ileum and the large intestine as well as in some organs after performing traversed anastomoses. The results were evaluated on the basis of clinico-experimental observations, on the changes in laboratory indices (complete blood picture, proteinogram, ionogram, blood urea and cholesterol), in microflora and in bioelectrical, activity. They examined ionic absorption in the large intestine excluded from the passage. An analysis was made on the pathologo-histological finding in the colon, anastomised ileum, liver and spleen, kidneys, heart, pancreas. The authors come to conclusions, useful to the physicians performing large intestine surgery.


[New method for the quantitative determination of antidiuretic hormone in the plasma].

Having in mind that ADH affects reapsorption of osmoticaly free water the authors examined urine diuresis together with its osmolality in 85 recipient rats. The animals endured water loading of 5% of their body weight by means of stomach lavages twice at 45 minutes intervals for a period of 3 days. Vena jugularis was cannulated under narcosis with heparinized polyethylene catheter, which was attached to the skull by means of a special socle. The training water loading continued two more days, after which AD activity or a standard solution of ADH was tested. Urine was collected every 15 minutes for a period of 120 minutes and its volume and osmolatily was determined. 0.2 ml of saline, standard or plasma, prepared for removal of nonspecific antidiuretic activity was administered on the 30th minute of the second water loading. There was a linear dependence between osmolality of urine and the administered amount of ADH. A standard curve of the ratio osmolality/microunits of ADH was prepared. The values of osmolality, obtained during administration of plasma were compared with those of the standard curve and the amount of ADH was determined in microunits. The method assures quantitative determination of ADH in values pover 10 microunits, which are obtained in animals after experimental affects and in some diseases of persons.


Inhibition of lipid peroxidation by calcium ions and their protection of steroid hydroxylase activity from peroxidative damage.

Lipid peroxidation of adrenocortical mitochondria and microsomes was greatly stimulated by addition of 1.0 mM or less ferric ions. In the presence of NADPH-yielding system, the formation of corticosterone from endogeneous cholesterol and exogeneous deoxycorticosterone was inhibited as the concentrations of iron increased. Of interest is the fact that 0.5 mM ferric ion-mediated lipid peroxidation was completely abroagated upon addition of 2 mM calcium ions. Accordingly, protected from the peroxidative damage.


Decrease of estrogen receptors induced by 17 beta-estradiol and progesterone in cultured rabbit endometrial cells.

A whole cell technique to measure estradiol receptors in cultured rabbit endometrial cells is described. The estradiol receptors measured appear to be composed of at least two components: one component has high affinity but low capacity, while the other component has low affinity but high capacity. Using the assay, the effects of estradiol and progesterone pretreatment were examined on the estradiol receptor levels. It was found that both of the hormones decreased the number of estrogen receptors in the cultured cells. The finding that estradiol decreased its own receptors was unexpected and its possible relevance is discussed.


A sensitive, convenient radioimmunoassay procedure which demonstrates that serum hTSH is suppressed below the normal range in thyrotoxic patients.

A highly sensitive radioimmunoassay procedures for the measurement of serum hTSH is described which permits delineation of the entire range of values in normal subjects (0.5-4.5 microU/ml). The procedure involves the concentration of hTSH from serum by adsorption to concanavalin A covalently bound to 4B Sepharose, Lactoperoxidase iodination of hTSH, and disequilibrium assay conditions. This method utilizes commonly available radioimmunoassay materials and is convenient to perform. Our results with this assay show that patients with thyrotoxicosis of a variety of etiologies have serum hTSH levels suppressed well below the normal range.


Purification of phosphoenolpyruvate carboxykinase (GTP) by affinity chromatography on agarose-hydrazide-GTP.

The cytosolic form of phosphoenolpyruvate carboxykinase (GTP; EC 4.1.1.32) from rat liver was purified by a procedure involving affinity chromatography on agarose-hydrazide-GTP. Phosphoenolpyruvate carboxykinase is retained quantitatively by the affinity medium in the presence of manganese and can be specifically eluted by a pulse of GTP. On the contrary, no binding to agarose-hydrazide-GTP occurs in the absence of manganese. This suggests that the affinity of the enzyme for GTP is enhanced by prior interaction with manganese. A combination of several conventional purification steps followed by affinity chromatography provides pure phosphoenolpyruvate carboxykinase in good yields. The final specific activity is 19 U/mg protein. The enzyme migrates as a single polypeptide of molecular weight 70,600 during electrophoresis on sodium dodecyl sulfate polyacrylamide gels.


On the mechanism of lactate dehydrogenase release from skeletal muscle in relation to the control of cell volume.

The mechanism of enzyme release from isolated skeletal muscle was illustrated by the study of the release of lactate dehydrogenase (LDH). In hypotonic media of different composition but of same tonicity the increase of LDH permeability was triggered at the same range of relative osmolality R (0.45 less than R less than 0.55), although the swelling in the respective media showed appreciable differences. The kinetics of muscle swelling showed that a deviation from the theoretically computed swelling curve to lower values of swelling was connected with an increased LDH permeability. The reduction of swelling was ATP- and Ca2+ and/or Mg2-dependent. It is concluded that swelling of cells generally precedes the leakage of soluble enzymes, and the cross-linking of filaments at the sarcoplasmic side of the sarcolemma under appropriate conditions can counteract swelling, thereby blebbing off the cell membrane from the filament meshwork. In the course of this process, sufficiently large membrane lesions are produced through which macromolecules may escape into the extracellular space.


Transient 45Ca uptake and release in isolated rat-liver cells during recovery from deenergized states.

1. Aerobic incubation of isolated rat liver cells--after dilution from the anaerobic stock suspension--transiently brings about a state, during which a reversible calcium uptake can be observed on addition of a respiratory substrate. Uptake varies greatly and can reach more than 50 nmol/mg protein, but declines to zero on prolonged preincubation, especially at higher temperature. Repeated additions of succinate or 3-hydroxybutyrate evoke new calcium transients. If ATP is simultaneously added, if greatly potentiates succinate-initiated reversible uptake. 2. If rotenone is present during the preincubation phase, calcium transients are strongly enhanced. Uptake is blocked by uncouplers and respiratory inhibitors, indicating the involvement of mitochondria. 3. Calcium uptake is not accompanied by increased oxygen consumption. The actual respiration cannot account sufficiently for the energy need of calcium uptake. Participation of cytoplasmic ATP is likely, as inhibitors of adenine nucleotide translocase affect uptake. 4. Lanthanum enhances calcium uptake in contrast to its action on mitochondria. 5. Pulse-labeling experiments indicate that the calcium taken up is removed from a rapidly exchangeable calcium pool by withdrawal into the mitochondria as a deep compartment. 6. Calcium uptake is accelerated either by increasing the phosphate level or by high temperature. It is prolonged by low temperature, high pH or high ATP concentration. Calcium release accelerates with increasing temperature, decreasing pH and a further rise in phosphate concentration. 7. The dependency on phosphate and temperature reveals a delicately poised equilibrium of uptake and release. At ambient temperature, phosphate increases uptake up to a concentration of 0.5 mM. Higher concentrations accelerate both uptake and release. At lower temperature, the accelerating effect on uptake predominates. A temperature shift during incubation results in adaptation of the calcium equilibrium to the new temperature, i.e. release of calcium at high temperature, uptake at low temperature. 8. Oxidizing metabolites inhibit succinate-stimulated calcium uptake and promote release of previously accumulated calcium. An increased sensitivity to phosphate is established. 9. With respect to isolated mitochondria, isolated liver cells appear to be a more realistic model for studying the physiological mechanism of mitochondrial calcium release, since compartmental constraints and regulations are maintained.


Thyroid hormones and neurotubule assembly in vitro during brain development.

A new model has been used to evaluate the effects of thyroid hormones on brain development. This model is based on the assumption that the major effect of thyroid hormones is in regulating the rate of neurite growth of the rat brain at early stages of postnatal development. Microtubules were chosen as markers of neurite growth. We tested, therefore, whether the rate of microtubule assembly in vitro is under thyroid hormone control. The following results were obtained: The rate of tubulin assembly into microtubules in vitro seems to be thyroid hormone dependent: (a) in 15-day-old hypothyroid rats the rates of tubulin assembly in vitro are low, comparable to those levels found in normal rats on day 3; (b) normal rates of assembly in vitro are restored upon addition of very small amounts of microtubule fragments which act as nucleating centers in the process of microtubule formation; (c) addition of microtubule-associated proteins to a hypothyroid preparation restores maximal assembly rates; similar results were obtained on adding one of the microtubule-associated proteins (purified tau protein); (d) physiological amounts of thyroid hormones completely restore normal assembly rates provided that they are administered very early after birth; (e) the ability of tubulin to assemble maximally does not seem to be permanently impaired, since normal assembly rates are spontaneously restored when hypothyroidism is maintained until an adult stage; (f) normal microtubule assembly is observed when hypothyroidism is produced at an adult stage. The model which may be constructed from these results implies that thyroid hormones are required briefly after birth to accelerate the rate of microtubule assembly thus allowing intensive neurite growth during the critical period of brain development.


Preferential interstrand cross-linking of DNA rich in guanine and cytosine by cis-dichlorodiammineplatinum(II).

Two native DNAs differing in G + C content were bound equally with the antitumour drug cis-Pt(NH3)2Cl2 at increasing Pt/P ratios. Resulting changes in their ultraviolet absorption spectra show equal fractional decreases in the initially different values of A250/A270 for the two DNAs, and less prominent bathochromic and hyperchromic shifts for DNA richer in G + C. Changes in the absorbance (A260) observed before and after subjecting the DNA samples to the conditions of denaturation (with alkali) and renaturation, indicate the following effects of the platinum binding. Maximum renaturation occurs at 50% lower Pt/P ratio of 0.03 for Micrococcus lysodeikticus DNA (72% G + C) than 0.06 for salmon sperm DNA (41% G + C) and is maintained at higher Pt/P ratios. Interstrand cross-links that facilitate renaturation, cause an incomplete melting of DNA so that the platinum-DNA complex at pH 12.5 has a reduced absorbance. This effect is more evident for the platinum complex with DNA richer in G + C due to more interstrand cross-links. Platinum-induced destabilisation of DNA, shown by its hyperchromicity at the pre-melting state (pH 6--7, 25 degrees C) and also by a lowering of the pH corresponding to the mid-point of its melting, is less evident for DNA richer in G + C.


Characterization of lipids from chloroplast envelopes.

The major neutral, glycolipids and phospholipids from envelopes of spinach chloroplasts were analyzed with respect to proportions, positional distribution and pairing of fatty acids. All specificities in the diacylglycerol portions of lipids known from previous analyses of lipids from whole leaves were also found in envelope lipids. Diacylglycerols and galactolipids share a common diacylglycerol portion. The only exception is digalactosyl diacylglycerol, which contains 18:3/16:0 but lacks 18:3/16:3 species reverting the distribution in other galactolipids. Phosphatidylcholine, phosphatidylglycerol and sulfoquinovosyl diacylglycerol are distinct from the galactolipids, because each one has a unique diacylglycerol profile. The diacylglycerol species present in phosphatidylcholine and galactolipids or free diacylglycerols do not provide evidence for a biogenetic relation between phosphatidylcholine and galactolipids at the level of envelopes.


Induction of interferon in HeLa cells of a protein kinase activated by double-stranded RNA.

Treatment of HeLa cells with human fibroblast interferon results in increased levels of latent protein kinase activity that can be activated by double-stranded RNA (dsRNA). The protein kinase activity in extracts of interferon-treated cells is assayed by two methods: (a) inhibition of protein synthesis in rabbit reticulocyte lysates and (b) phosphorylation of two polypeptides of Mr 72000 (P1) and 38000 (the eIF-2 alpha subunit of initiation factor 2). When extracts of interferon-treated cells are fractionated by centrifugation at 150000 x g, the protein kinase activity is found in the pellet fraction. The kinase is maximally activated by 0.1 micrograms/ml poly(I) . poly(C). An increase in protein kinase activity is detected after 8 h of treatment with 100 units interferon/ml or after a 17-h treatment with 12.5 units/ml or greater interferon concentrations. Therefore, the kinase activity increases as a function of both time of treatment and interferon concentration. Addition of actinomycin D to cells during interferon treatment prevents this increase. The protein kinase activity decreases gradually over three days when interferon-treated cells are subsequently grown in the absence of interferon.


Sequestration and turnover of guinea-pig milk proteins and chicken ovalbumin in Xenopus oocytes.

The stability and distribution of proteins within the living cell can be studied using Xenopus laevis oocytes. Microinjection of messenger RNAs and secretory proteins, followed by cell fractionation, shows that transfer of ovalbumin and milk proteins across intracellular membranes of the oocyte only occurs during their synthesis. Thus milk protein primary translation products, made in the wheat germ cell-free system, when injected into oocytes remain in the cytosol and are not recovered within membrane vesicles. Such miscompartmentalized primary milk proteins are rapidly degraded (t 1/2 0.6 +/- 0.1 h). In contrast, processed milk proteins, extracted from oocytes injected with mammary gland RNA, are relatively stable when introduced into the cytosolic compartment (t 1/2 alpha-lactalbumin 20 +/- 8 h, casein A 6 h, casein B 4 h, casein C 8.3 h). The primary ovalbumin product is also stable (t 1/2 22 +/- 9 h). Indirect evidence that rapid degradation of miscompartmentalized milk protein primary translation products may occur in vivo was obtained by the injection of massive amounts of ovalbumin and milk protein mRNA. Under these conditions there is no accumulation of primary milk protein translation products, but a polypeptide resembling the unglycosylated ovalbium wheat germ primary product can be detected in the cytosol. Only the glyclosylated forms of ovalbumin are found in the oocyte membrane vesicle fraction. We discuss the roles played by the presence of detachable signal sequences and the absence of secondary modifications in determining the rate of degradation of primary translation products within the cytosol.


Glycosulphatase from Pseudomonas carrageenovora. Purification and some properties.

A glycosulphatase present in the soluble fraction of disrupted Pseudomonas carrageenovora has been purified 500-fold by gel filtration on Sephacryl S-200 and ion-exchange chromatography on DEAE-Sepharose CL-6B. By dodecylsulphate/polyacrylamide gel electrophoresis the enzyme is practically homogeneous and has a molecular weight of 55 000. Conditions of optimal sodium chloride concentration and pH at 25 degrees C were 0.25--0.50 mol dm-3 and pH 7.0 respectively. The purified enzyme was inhibited by inorganic phosphate. Preparation is described of neocarrabiose 4-O-[35S]sulphate and neocarratetraose 4-O-[35S]sulphate from labelled Chondrus crispus. The purified glycosulphatase is active against both these substrates although only one of the two sulphate esters in the tetrasaccharide is hydrolysed. Analysis of the reaction products was by gel filtration, electrophoresis and 13C nuclear magnetic resonance spectroscopy. The results are consistent with the products of desulphation being respectively neocarrabiose and neocarratetraose 4-O-monosulphate with the sulphate ester proximal to the reducing end [3,6-anhydro-alpha-D-galactopyranosyl-(1 leads to 3)-beta-D-galactopyranosyl-(1 leads to 4)-3,6-anhydro-alpha-D-galactopyranosyl-(1 leads to 3)-D-galactose 4-O-sulphate].


Differences in the interactions of liver alcohol dehydrogenases with probes binding into the substrate pocket.

The interactions of three groups of probes (berberine alkaloids, tricyclic psychopharmaca and acridine derivatives) with isoenzymes of horse liver alcohol dehydrogenase and with rat liver alcohol dehydrogenase have been examined. These compounds inhibit the activity of the EE isoenzyme of horse liver alcohol dehydrogenase but differ in their behaviour towards the steroid-active enzymes (i.e. the ES isoenzyme of horse liver alcohol dehydrognase and alcohol dehydrogenase from rat liver): psychopharmaca inhibit, acridines activate and berberines do not bind. The ligands differ also in their influence on the modification of the EE isoenzyme by iodoacetate. Polarities (expressed as Kosower's Z values) of the respective binding sites on the EE isoenzyme were estimated from optical properties of bound probes. Berberines bind into a very hydrophobic area of the enzyme molecule, the binding site for psychopharmaca is moderately hydrophobic and that for acridines is rather polar. Steric arrangements of the binding sites are also discussed. The data presented confirm the existence of three distinct binding sites for these ligands in the substrate pocket of liver alcohol dehydrogenase.


Polyamine synthesis in mammalian tissues. Isolation and characterization of spermine synthase from bovine brain.

Spermine synthase, a propylamine transferase, which catalyses the biosynthesis of spermine from S-methyladenosylhomocystemine and spermidine has been purified to an apparent homogeneity (about 6000-fold) from bovine brain using spermine-Sepharose affinity chromatography. The enzyme preparation was free from S-adenosylmethionine decarboxylase and spermidine synthase activities. The molecular Stokes radius of the enzyme was calculated to be 4.16 nm. The enzyme has an apparent molecular weight of approximately 88 000, composing of two subunits of equal size. The enzyme showed a broad pH optimum between 7.0 and 8.0 and an acidic isoelectric point at pH 5.10. The apparent Km values for S-methyladenosylhomocysteamine was 0.6 microM and about 60 microM for spermidine. The enzyme showed strict specificity to spermidine as the propylamine acceptor. Both the reaction products, spermine and 5'-methylthioadenosine inhibited the enzyme activity, methylthioadenosine being a powerful competitive inhibitor with respect to S-methyladenosylhomocysteamine (Ki value of about 0.3 microM). Putrescine also inhibited competitively with respect to spermidine (Ki value of about 1.7 mM). Spermine synthase had no requirements for metal or other cofactors.


X-ray studies of the binding of Cibacron blue F3GA to liver alcohol dehydrogenase.

The binding of Cibacron F3GA to orthorhombic crystals of liver alcohol dehydrogenase has been studied to 0.37-nm resolution. Similarities in the binding of this dye were found for rings B, C and D with the binding of the coenzyme NAD+. However, ring A of the dye and the nicotinamide ribose part of the coenzyme are quite differently bound to the enzyme.


Structure of a new saponin: chrysantellin A from Chrysanthellum procumbens Rich.

A new saponin has been isolated from a tropical plant Chrysantellum procumbens Rich. which is thought to be useful in the therapy of digestive troubles. The structure of this saponin was determined by chemical methods, nuclear magnetic resonance and mass spectrometry. The aglycone moiety is a triterpene, echinocystic acid; D-glucose, D-xylose and L-rhamnose are carbohydrate components. The structure of saponin was established as 3-O-beta-D-glucopyranosyl [L-rhamnopyranosyl-(alpha 1 leads to 3)-D-xylopyranosyl-)beta 1 leads to 4)-L-rhamnopyranosyl-(alpha 1 leads to 2)-D-xylopyranosyl]-(alpha 1 leads to 28)-echinocystyl. The name, chrysantellin A, is proposed for this new saponin.


The specificity of the S1 and S2 subsites of elastase.

Esters of tetrapeptides of the general formula ethoxycarbonyl-prolyl-alanyl-X-Y where either X or Y was an alanine residue were synthesised and their cleavage by elastase studied. It was found that variation of the alcohol moiety between methyl, cyclohexyl and nitrophenyl residues had no effect on the catalytic rate constant for cleavage of ethoxycarbonyl-prolyl-dialanyl-alanine esters demonstrating that acylation is much faster than deacylation for this system and also that non-productive binding is not kinetically significant. The effect of changing the amino acid residue in position X was small compared with that of change in position Y. The presence of valine and serine residues in position Y produced the highest specificity constant but the highest catalytic rate constant was found for a leucine residue in this position. The results are discussed in terms of the binding of the substrate to the enzyme.