[Effect of triterpene glycosides on RNA biosynthesis in a yeast cell culture of Saccharomyces carlsbergensis]. The effect of triterpen glycosides of cauloside C from Caulophyllum robustum, theasaponine from Thea sinensis ahd stichoposide A from Stichopus japonicus on multiplication and biosynthesis of RNA in the cells of a 7-hour culture of Saccharomyces carlsbergensis was studied. It was shown that cauloside C, theasaponine and stichoposide A in concentrations of 7.5 gamma/ml inhibited multiplication of the yeast cells by 65, 10 and 90 per cent respectively. The summation RNA of the yeast cells is divided into 3 zones on Sephadex G-100. The glycosides induced no pronounced changes in the chromotographic profile of RNA. Biosynthesis of the transport and ribosomal RNA were inhibited to the same extent. Triterpen glycosides inhibited the biosynthesis of RNA at the stage of 14C-uridine in corporation into the nucleotide pool of the yeast cells.


[Comparative experimental study of the antileukemia activity of carminomycin and rubomycin]. The antileukemic activity of karminomycin and rubomycin was studied comparatively in parallel experiments with respect to 4 strains of transplantable leukemia, i.e. acute non-differentiated leukemia La, acute lymphoblast leukemia, L-1210 and P-388 and subacute lymphoblast leukemia No. 8 CRIHBT. The doses used were adequate by their toxicity. The tests of the therapeutic effectiveness were: an increase in the life time of the animals treated as compared to the control ones, a decrease in the leukocyte count and the number of the blast cells in the peripheral blood, a decrease in the leukemic infiltration of the organs and tissues of the animals treated. It was shown that karminomycin was more effective in the studied leukemia strains when it was used in the doses with equivalent toxicity. The more pronounced antileukemic activity of karminomycin was especially evident from histological examinations, which showed lower infiltration of the organs and tissues of the mice treated with karminomycin by the leukemic cells as compared to the animals treated with rubomycin.


Effect of monensin on rumen metabolism in vitro. The effect of Monensin (Rumensin, Eli Lilly & Co.) in incubations with mixed rumen microorganisms metabolizing carbohydrate or protein substrates was investigated. Monensin partly inhibited methanogenesis and increased propionate production, although the effect was not always statistically significant. Incubations with substrates specific for methane bacteria suggest that inhibition of methanogenesis by Monensin was not due to a specific toxic action on the methanogenic flora, but rather to an inhibition of hydrogen production from formate. Total and net microbial growth were considerably decreased by addition of Monensin, although the amount of substrate fermented was not altered, resulting in lowered values of microbial growth efficiency. In incubations with casein, Monensin lowered protein degradation in line with a lowered ammonia production, whereas a slight accumulation of alpha-amino nitrogen was observed. The results suggest that besides an influence of Monensin on the rumen carbohydrate fermentation pattern, another reason for the beneficial effects observed in vivo might be decreased food protein degradation in the rumen, altering the final site of protein digestion in the animal. Also, the possibility of a decrease in rumen microbial growth efficiency has to be considered when using Monensin as a food additive.


Effect of coumarin on growth and metabolism of Pythium. Coumarin concentrations that inhibited growth of Pythium sp. rapidly decreased the rate of incorporation of [14C]glucose into the mycelium. Coumarin also reduced drastically the carbohydrate and protein content of the cytoplasm and, to a lesser extent, the amino acid content and cell wall fraction. Enzymes related to the metabolism of cell wall polysaccharides were not affected during early exposure to the inhibitor. The possible mechanism of coumarin action via inhibition of glucose uptake is discussed in the light of the present findings.


Effects of enrichment media and incubation conditions on isolating salmonellae from ground-meat filtrate. Forty-eight combinations of enrichment media, secondary enrichment, incubation times and temperatures, and atmospheres were examined for their efficacy in recovering different serovars of Salmonella that had been inoculated into ground-meat extract. Variations included three selective-enrichment media, two (37 and 43 degrees C) incubation temperatures, two (24 and 48 h) incubation times, two (aerobic and anaerobic) incubation atmospheres, and secondary enrichment to two of the selective-enrichment media. The ratio of Salmonella to other microorganisms was 10: greater than 1,000,000. One-hundred and twenty-four tests were conducted for each enrichment under each condition of incubation. None of the methods recovered Salmonella in more than 60% of the trials. Salmonella typhimurium was recovered most frequently of the serovars tested; S. abortusovis was recovered least frequently. There was considerable variation in the results obtained by the different methods, but there was a statistically significant advantage in the 43 degrees C incubation temperature. Secondary enrichment in tetrathionate broth showed a statistically significant advantage over secondary enrichment in selenite broth. Secondary enrichment into a different medium from the primary enrichment also was advantageous.


Academic manpower in dermatology.

Academic manpower in dermatology. A survey showed that there were 338 strict or geographic full-time dermatologist faculty members in the United States. Ninety-six percent of these 338 faculty members were located at the 72 schools of medicine with residency training programs in dermatology or at the 21 approved residency training programs in dermatology, not affiliated with colleges of medicine. The 42 schools of medicine without approved residency training programs in dermatology reported only 11 full-time dermatologist faculty (3% of the total). Women constituted 7% of the faculty, while foreign medical graduates constituted 9%. More than one third of faculty were trained at the institution in which they currently serve. Approximately one third were likewise trained at four major teaching institutions.


Dermatologists for the nation. Projections of supply and demand. Because inappropriate supply of physician specialists involves unnecessary human suffering or waste of human resources and because free market forces are ineffective in the medical sector, deliberate planning of supply is necessary. A model projecting the future supply of dermatologists was formulated on the basis of current residency capacity, which produces 250 dermatologists annually, and current experience regarding life expectancy and retirement. The model implies that an equilibrium supply of 8,800 dermatologists, or three per 100,000 population, will be realized early in the 21st century. A number of methods were used to estimate the demand for care, and, under conditions of general access, three dermatologists per 100,000 appear to be appropriate. Thus, maintaining current training capacity seems to be prudent, but because of many unknown and unpredictable factors, periodic reassessment is necessary.


Photocontact dermatitis to halogenated salicylanilides and related compounds. Our experience between 1967 and 1975. We evaluated the role of the halogenated salicylanilides and related compounds in the development of photocontact dermatitis between 1967 and 1975 as seen at the University of California, San Francisco clinic. During this period positive photopatch tests to at least one of these chemicals were detected in 98 patients. Prior to 1967, tetrachlorosalicylanilide and the brominated salicylanilides were the most common offenders. Declines occurred in number of patients with positive photopatch tests and patch tests to these agents as well as the number of patients tested to these agents during this period; ie, almost three times as many people were tested and four times as many had positive photopatch tests in the last six months of 1967 as compared to the first nine months of 1975. The most striking reduction in numbers of patients with positive tests occurred after 1968, but the most notable reduction in the total number of positive photopatch tests occurred after 1970. We concluded that these results were most likely due to removal from the market of the more potent photosensitizing chemicals and increased physician familiarity with the disease process.


Staphylococcal infections in patients with atopic dermatitis. Cutaneous staphylococcal infections appear to be relatively infrequent in atopic dermatitis even though patients have broken skin heavily colonized with staphylococcal organsism. We found superficial staphylococcal pustules on the skin of 22 patients with atopic dermatitis. Such lesions were more commonly found with severe exacerbations of atopic dermatitis. They appeared on unbroken skin independent of hair follicles and were associated with considerable pruritus. Such lesions were rapidly removed by excoriation and frequently were overlooked by patients and physicians. Most lesions appeared when polymorphonuclear leukocyte chemotaxis was depressed. Ineffective chemotaxis combined with high-colonization density and inadequate stratum corneum barrier during exacerbations of atopic dermatitis may lead to mild staphylococcal infections. These infections appear to have no systemic effects but possibly the considerable associated pruritus could worsen the atopic dermatitis. Occasional patients may require intermittent or continuous antibiotic therapy.


Topical mechlorethamine. Cutaneous changes in patients with mycosis fungoides after its administration. Six patients with mycosis fungoides were treated with topical mechlorethamine hydrochloride for periods of two to four years. Clinical and histological studies for radiomimetic and radiodermatitis-like effects failed to demonstrate any abnormalities. The only observed changes were generalized hyperpigmentation of the skin and melanin-containing melanophages in the papillary dermis. We consider that the long-term use of topical mechlorethamine may be a safe form of therapy, but that a continuous indefinite follow-up of patients on this medication should be mandatory.


Induction of drug photosensitization in man after parenteral exposure to hematoporphyrin. Two patients had acute phototoxic reactions after intravenous injections of hematoporphyrin (7 mg/kg) and exposure to light. These reactions were characterized by pain, redness, and swelling of affected sites. Controlled clinical studies were instituted using known types and amounts of light to ascertain the degree of photosensitivity at various time intervals after drug administration. In addition, action spectrum studies elicited a peak response at 405 nm (+/- 5 nm). Plasma hematoporphyrin concentration was approximately 520 microgram/100 ml one hour after hematoporphyrin infusion and it gradually declined during a period of 42 days with a biphasic diminution that suggested the existence of at least two pools of hematoporphyrin with half-life decay times of 16 hours and 12 days. beta-carotene was administered to ascertain whether or not the phototoxic response could be modified. It is suggested that a degree of protection was obtained that was insufficient to protect the patient.


Failure of dimethyl sulfoxide in the treatment of scleroderma. Nineteen patients with systemic scleroderma and five with localized scleroderma were treated with topical dimethyl sulfoxide by painting and immersion techniques. Partial control was obtained by using a very low concentration (5%) on one side when involvement was symmetrical. Duration of treatment ranged from 3 to 15 months. Topical dimethyl sulfoxide did not improve the skin induration, range of motion, or Raynaud's phenomenon in the scleroderma patients. No substantial beneficial effect was noted on the healing of ischemic ulcers, and the continuous application of dimethyl sulfoxide did not prevent new ulceratins from developing. Relief of pain was noted in ten of 16 patients, probably due to the local analgesic effect of dimethyl sulfoxide.


Failure to induce tolerance to mechlorethamine hydrochloride. In view of the contradictory results reported in the literature regarding induction of specific immunologic tolerance to mechlorethamine hydrochloride (HN2), the problem was reinvestigated using a "tolerogenic" schedule that had been reported to be effective. Mechlorethamine hydrochloride, 200 microgram, intravenously, was given weekly for five weeks before beginning topical therapy with it. In the test group, five of 13 patients (11 with mycosis fungoides and two with psoriasis) became contact sensitized to mechlorethamine. In another patient, what was probably a contact urticarial reaction developed. In the control group, five of 13 patients (12 with mycosis fungoides, one with parapsoriasis) became contact sensitized to mechlorethamine. Thus, 38% of the patients in both groups became contact sensitized to mechlorethamine. It is concluded that this tolerogenic schedule, just as others previously tried, was not effective in inducing specific tolerance to mechlorethamine.


Trichophytin contact sensitivity in patients with dermatophytosis. Trichophytin contact sensitivity was investigated in patients with dermatophytosis by patch testing with highly concentrated purified trichophytin on partially stripped skin. The lack of primary irritant reactions was confirmed on the skin of children. Positive patch tests were noted in 113 of 178 patients (63.5%). However, there was a great difference in the incidence of trichophytin contact sensitivity between cases with different clinical types. The highest frequency of positive patch tests was obtained in patients with the vesiculobullous type of tinea pedis (83.3%). In contrast, a very low incidence was noted in patients with tinea corporis (37%) and the squamous hyperkeratotic type of tinea pedis (36%). Causative organisms and the age and sex of the patients did not show a relationship with the reactivity. A diminished incidence of positive reactions was noted in atopic individuals and in patients seen in winter. Patients who had persistent or recurrent infections for a long period of time, especially those having inflammatory lesions, had a higher frequency of positive patch tests.


Pterygium inversum unguis-like changes in scleroderma. Report of four cases. During an 18-month period, four patients with scleroderma were found to have nail findings suggestive or pterygium inversum unguis, a recently described condition. In the same time period, two other examples of the disorder were seen. Pterygium inversum unguis-like change may represent an additional nail sign in scleroderma. There are possible mechanisms for its development in patients with Raynaud's phenomenon, connective tissue diseases, or peripheral vascular disease.


Chondrodysplasia punctata. Conradi-Hünermann syndrome. A 10-day-old girl was examined because of a peculiar, patterned hyperkeratosis that was noted at birth. The lesions were distributed over the trunk and limbs and consisted of whorls and streaks of thick, yellow, adherent scales. The salient histologic feature was marked hyperkeratosis with deep invagination of the dilated pilosebaceous ostia nearly to the level of the hair bulb. Additional physical abnormalities included patchy alopecia, bilateral zonular cataracts, a depressed nasal bridge, small stature, and multiple skeletal deformities. Roentgenograms demonstrated widespread stippled epiphyses characteristic of Conradi-Hünermann syndrome.


Acral syringoma.

Acral syringoma. Although syringoma is a relatively common adnexal tumor, syringoma of the hands has not been reported previously. We report a unique case of multiple acral syringomas that appeared as symmetrical grouped erythematous papules limited to the dorsum of the proximal and middle phalanges of both hands in a young man. This condition should be considered in the diagnosis of papular lesions of the hands.


The ultrastructure of granuloma annulare. Nine cases of granuloma annulare at different stages of development were investigated electron microscopically. Special attention was given to collagen changes, to the cellular infiltrate, and to vascular changes. The necrobiotic changes of the collagen were: loosening of the fibers at the borders of the bundles; swelling and loss of cross-striation of the fibrils; and complete degradation of the collagen, with precipitation of mucinous and fibrin material and of glycogen. In 2 cases "cross-banded filamentous aggregations" were present. In later stages new collagen synthesis occurred. In the infiltrate, histiocytes/macrophages were seen developing into epithelioid and giant cells. In addition, numerous active lymphocytes and, at later stages, some neutrophils were found. Vascular changes consisted of endothelial swelling and duplications of the basal lamina. A perivascular infiltrate was present, but no distinct vasculitis was seen. Our results indicate that the necrobiosis of the collagen without primary vasculitis may be an initial event in granuloma annulare. A delayed hypersensitivity mechanism is discussed with regard to pathogenesis.


The influence of synthetic corticoids on the isolated vas deferens of the rat. The influence of corticosteroids on the tone of isolated smooth muscle (vas deferens of the rat) is reported. Corticoids alone are without effect on the muscle tone, but they potentiate the constrictor effect of catecholamines. Fluorinated synthetic steroids exhibit a more pronounced effect than non-halogenated ones.


Absence of arylsulphatases A and B in suction blister fluid interstitial fluid and serum. Suction blisters were raised on human skin. The blister fluid was collected for enzymic assay and the epidermis over the bullae was removed before further suction of interstitial fluid. Preliminary work indicated the presence of arylsulphatases A and B in epidermis, and the same assay procedure with 4-methylumbelliferyl sulphate as substrate was used. There appeared to be no enzymatic activity in blister fluid, interstitial fluid and serum.


Effects of 8-methoxypsoralen (8-MOP) and UVA on human lymphocytes. Peripheral lymphocytes of 37 psoriatic patients are tested before and under PUVA treatment using as parameter the non specific stimulation effect of HgCl2 (10 microgram/ml) in culture, measuring the 3H-thymidine incorporation after the last 16 h of a 5-days culture. Oral 8-MOP in therapeutic doses is decreasing the lymphocyte stimulation as well as 8-MOP together with UVA irradiation during the first week of treatment. After 1 week, the stimulation is, on the contrary, significantly enhanced after irradiation. Lymphocytes isolated by centrifugation over Lymphoprep are submitted to PUVA conditions in petri dishes (Hank's solution 8-MOP 1 microgram/ml, irradiation with 350 nm, 93-372 mJ/cm2). The total cell number, the E-rosette formation (as marker for T-lymphocytes) and the EAC-rosette formation (as marker for B-lymphocytes) are determined. PUVA conditions have an energy dependent decreasing effect on the cell number, while the T- and B-cell proportions remain constant. UVA irradiation alone has such an effect only with high energies. 8-MOP without UVA has no significant influence on the cell number.


Relation between smoking and levels of DDT and dieldrin in human fat. The adipose tissue of humans with known patterns of cigarette smoking was collected during 1973-74 and analyzed for DDT components and dieldrin. Although smokers are exposed to high levels of insecticides from smoke of cigarettes and some of these compounds can be stored in adipose tissue, it could not be demonstrated that a relationship exists between smoking habit and residual levels of DDT found in fat. Smokers seem able, through induction of enzymes by substances in tobacco smoke, to metabolize these insecticides at a rate approximately equal to the rate of their intake in the smoke. Dieldrin residues in black male subjects were found to be linearly related to the number of cigarettes smoked, but the factors governing this relationship were not obvious.


Elevated blood pressure and high sodium levels in the public drinking water. Preliminary results of a study of high school students. High school sophomores residing in a community with elevated levels of sodium in the drinking water (107 mg/1) exhibited a marked upward shift in blood pressure distribution patterns for systolic and diastolic blood pressures in both males and females as compared with a similar group in the control community (8 mg/1). The students group from the high sodium community appears to exhibit a blood pressure distribution characteristic of persons several years older.


Scalp hair as a monitor of community exposure to lead. Lead was measured by photon activation analysis in scalp hair from three population groups with varied types of environmental exposure. Concentrations of lead in hair increased from rural to urban to smelter areas with medians of 9.1, 15.3, and 48.5 ppm, respectively. Boys under 16 residing near smelters showed consistently higher lead levels than girls of the same age group and from the same area. A history of exposure to lead was deduced from the distribution of concentration along the hair length by analyzing 1-or 2-cm segments of hair strands. A reasonably good blood lead-hair lead correlation was obtained for individuals who appeared to be in a steady state with respect to intake and excretion of lead. The analytical method for the photonuclear determination of lead in hair, the hair washing procedure, and the advantages of using hair as an epidemiologic monitor are described.


Severe organophosphate poisoning complicated by alcohol and turpentine ingestion. A 52-year-old comatose white male was admitted to the hospital with what was later learned to be severe poisoning by a turpentine solution of dicrotophos, an organophosphorous insecticide he had ingested while drunk. The patient was treated effectively with atropine and pralidoxime chloride and required the largest doses of both agents reported to data. The case was complicated by difficulty in evaluating the response to therapy because of the effects of alcohol and turpentine. The patient was discharged from the hospital on the thirty-third day with no apparent sequelae.


Respiratory status of surface coal miners in the United States. The United States Public Health Service examined 1,438 surface coal miners to determine the prevalence of coal worker's pneumoconiosis (CWP), chronic bronchitis, and ventilatory impairment among them. Four percent (fifty-nine individuals) showed some roentgenographic evidence of pneumoconiosis, but only seven miners had films interpreted as CWP of category 2 or greater (according to the UICC/Cincinnati classification system). Moreover, most of the affected miners had worked in underground coal mines for prolonged periods. Significant decrements in pulmonary function to increasing exposure to surface mine dust were demonstrated only in the forced vital capacity of smokers. Increased prevalence of chronic bronchitis with increasing exposure was found in all smoking categories. However, significant airway obstruction was an uncommon finding (6.6%) in nonsmoking miners. Employment in surface mining was not likely to cause either the development of CWP or clinically significant respiratory impairment.


Differentiation between Clostridium acidiurici and Clostridium cylindrosporum on the basis of specific metal requirements for formate dehydrogenase formation. The formate dehydrogenases of Clostridium acidiurici and of C. cylindrosporum coupled the oxidation of formate with the reduction of viologen dyes. The basal activity level was about 0.85 mumoles/min X mg of protein for both species. The level of formate dehydrogenase of C. acidiurici increased 12-fold when 10(-7) M tungstate and selenite were present during growth. Molybdate exerted no effect. On the other hand, molybdate and selenite were required to increase the formate dehydrogenase of C. cylindrosporum, and tungstate exhibitedan antagonistic effect in this organism. Growth on hypoxanthine generally depended on the addition of bicarbonate. Supplementation with tungstate and selenite accellerated growth of C. acidiurici and increased again the level of formate dehydrogenase. The addition of both, molybdate and selenite was necessary to initiate growth of C. cyclindrosporum and to form an active formate dehydrogenase. The differences in the requirement for metal ion supplementation to form high levels of formate dehydrogenase and their involvement in hypoxanthine degradation can be used to differentiate between C. acidiurici and C. cylindrosporum.


Fatalities in 2,070 psychiatric outpatients. During a three-year period 28 fatalities, twice the rate in the general population, were found in a sample of 2,070 psychiatric outpatients. Death occurred in these psychiatric patients approximately 20 years earlier than is expected. All three modalities of death: accidents, suicide, and natural causes, were higher than that in the population at large. Three suicides were thought to be preventable by psychiatric approaches. The importance of the patient's initial visits was stressed. At least four, and possibly five, cases of death were avoidable by appropriate medico-surgical means. The rate of physical illnesses in all three groups was more than 80%, of which one third were inadequately diagnosed by their referring physicians. The importance of the physical evaluation of psychiatric patients was emphasized.


Is there a stethoscope in the house (and is it used)? A survey was conducted in Rochester, NY, of the attitudes and practices of psychiatrists (both in private practice and fulltime academic settings), psychiatric residents, internists, and fourth-year medical students concerning physical examinations of psychiatric patients. Thirteen percent of the psychiatrists frequently perform an initial physical examination on their inpatients and 8% frequently do an initial physical examination on their outpatients. These percentages are much larger for the resident groups. A very high percentage of all respondents report that they feel a physical examination of psychiatric patients is important especially when the patient is receiving medication. The largest number of psychiatrists report that they omit the physical examination because the patient has been referred to them after a physical examination by another physician or they refer the patient for such an examination. A notable percentage of psychiatrists in this sample report that they do not feel competent performing a physical examination.


Patterns of death among suicide attempters, a psychiatric population and a general population. This epidemeological study examines patterns of mortality for a population of suicide attempters, a psychiatric population without suicide attempts, and a general population without psychiatric histories in order to clarify earlier reports of differential risks of death associated with these groups. Mortality patterns were investigated over an 11-year period in terms of demographic characteristics and rates of death by various causes. Suicidal deaths were given special attention to identify variables that may have predictive validity for suicide. The results indicate that the suicide attempter group represents a distinctive demographic and mortality entity from either the psychiatric or general populations, and accounts for much of the increased risk of death previously attributed to the psychiatric population. Further, premature deaths due to suicide are strongly associated with the suicide attempter group. The psychiatric and general populations differ in relatively insignificant ways. These results suggest that a profitable approach to the prevention of suicide would be to focus on individuals who were at high risk within the suicide attempter population. Longer-term follow-up of these individuals is necessary if deaths due to suicide are to be prevented. Difficulties associated with implementation of preventive follow-up programs are also discussed.


Increase in suicide attempts by drug ingestion. The Boston experience, 1964-1974. At the Massachusetts General Hospital between 1964 and 1974, there was an estimated 118% increase in emergency ward admissions for drug overdose suicide attempts and an estimated 257% increase in such attempts by individuals in the 20- to 29-year age range. Approximately 67% of overdoses seen in 1972 and 1974 occurred in individuals under age 30. An increase in drug overdose suicide attempts by males was noted. By 1972, males were making approximately as many attempts as females. Based on extrapolations from the Massachusetts General Hospital drug overdose data, and not including an estimate of non-hospital-treated suicide attempts, an estimated annual (1972) suicide attempt rate of 337/100,000 (0.38%) was obtained for Boston. The estimated suicide attempt-completed suicide ratio for the Boston area was 39:1. These estimates should be interpreted as giving an approximate order of magnitude and not as specifying precise rates.


Bereavement and psychiatric hospitalization. Two hundred forty-nine psychiatric inpatients were compared with 249 matched controls and with a psychiatric hospital survey group of 95 patients for incidence of recent bereavement. There were no significant differences between the groups for loss of a first-degree relative in six months and one year prior to admission. There was a preponderance of affective disorder among the psychiatric patients with recent loss. Severe subjective grief reactions were found in the four patients who had lost a spouse or a child and in some patients who had lost a parent, while loss of a sibling usually evoked a mild reaction. Patients with alcoholism tended to increase their drinking during the bereavement period, resulting in incapacitation and hospitalization or, in the case of a control patient, in severe trauma.


Naltrexone and cyclazocine. A controlled treatment study. The induction side effects of cyclazocine and naltrexone were compared in double-blind placebo-controlled studies involving 40 patients (20 for each drug). These studies were carried out with a twice-a-day dosage regimen. Naltrexone produced fewer side effects than cyclazocine. Naltrexone side effects fell to levels indistinguishable from those of placebo in the "induction after placebo" phase. In contrast, cyclazocine "induction after placebo" produced an even higher level of side effects than found in its induction. In no case was naltrexone discontinued because of side effects. On the other hand, three of 20 cyclazocine-treated patients discontinued the drug because of distressing side effects. No toxicity was noted with either agent. The controlled data reported supports the clinical impression that naltrexone produces fewer induction side effects than cyclazocine.


A neuroendocrine study of supersensitivity in tardive dyskinesia. A study of the tuberoinfundibular dopamine tract was undertaken in chronic schizophrenic patients with and without tardive dyskinesia. Biochemical evidence of the purported dopamine receptor supersensitivity in tardive dyskinesia was sought by demonstrating a hyperresponse of growth hormone and prolactin to dopamine agonists. Contrary to this prediction, no endocrine supersensitivity occurred in the tardive dyskinesia patients. Rather, a significantly decreased response to dopaminergic stimulation was demonstrated in the total chronic schizophrenic group.


The assessment of tardive dyskinesia.

The assessment of tardive dyskinesia. Available assessment methods for tardive dyskinesia were reviewed under three headings: instrumentation, frequency counts, and rating scales. The more objective methods have better reliability but less certain validity, while for the clinical assessment techniques the converse tends to be true. The optimat assessment method for a given study depends on the research question asked. For most studies, the combination of one of the objective techniques with a rating method may be ideal. Research on prevalence and etiological factors would benefit from one of the multi-item rating scales, while in treatment studies a global scale may be necessary. Videotapes are invaluable for educational purposes and for training raters.


Catatonia. Prevalence and importance in the manic phase of manic-depressive illness. Of 123 acutely ill patients with bipolar affective disease, 28% exhibited clinical signs of catatonia. We were unable to differentiate manics with catatonic signs from manics without catatonic signs with regard to demographic characteristics, psychopathology, and the prevalence and pattern of psychiatric illness in their first-degree relatives. Our sample was similar to previously studied groups of manics. Although generally held to be associated with schizophrenia and of poor prognostic import, catatonic signs did not predict a poor treatment response in our manic patients. These data support the growing body of evidence demonstrating that catatonic signs are nonspecific and may be highly prevalent among patients with bipolar affective disease.


The family history method using diagnostic criteria. Reliability and validity. Data concerning familial history of psychiatric disorders are often used to assist in diagnosis, to examine the role of genetic or nongenetic familial factors in etiology, or to develop new methods of classification. Information concerning familial prevalence may be collected by two different methods: the family history method (obtaining information from the patinet or a relative concerning all family members), and the family study method (interviewing directly as many relatives as possible concerning their own present or past symptomatology). This study compares these two methods. In general, the family study method is preferred since information is likely to be more accurate. The family history method leads to significant underreporting, but this can be minimized through the use of diagnostic criteria. This study reports on an instrument that has been developed for collecting information concerning family history and that provides criteria for 12 diagnoses--the Family History-Research Diagnostic Criteria. Using diagnostic criteria leads to greater sensitivity, but underreporting remains a major problem of the family history method.


Life events and schizophrenia. II. Impact of life events and symptom configuration. This study investigates the impact of life events on symptom configuration in a group of 132 posthospitalized schizophrenics living in the community. Multivariate techniques were used to isolate specific dimensions of symptoms and to study the influence of life events, viewed in terms of number, the psychological control dimension, and qualitative nature, in contrast to other factors thought to determine symptoms. Life events exert their greatest influence on nonpsychotic symptoms such as anxiety, depression, and somatic concerns. Aspects of psychotic behavior such as gradiosity, delusions, and looseness of associations appear to be somewhat vulnerable to the impact of life events, particularly those events that are undesirable, social losses, and beyond individual psychological control. We discuss the findings in relation to the issue of causal effect in the study of life events and psychiatric impairment.


Measurement of cerebral blood flow with microspheres. Labeled microspheres have been used recently to measure cerebral blood flow in experimental animals. The technique allows repeated measurements of regional, as well as total, blood flow to the brain. The microsphere technique has been used to study physiological regulation of cerebral blood flow, and can be used to examine regional cerebral blood flow in experimental models of disease states.


Cerebral microembolization. I. Pathophysiological studies. Unilateral embolization of the brain was performed in cats by intracarotid injection of 10.5 million carbonized microspheres (15 +/- 5 mu). Intracranial pressure increased from 6.1 +/- 1.5 to 14 +/- 2.3 mm Hg within two minutes and continued to rise more slowly to 24 +/- 18.3 mm Hg within four hours. Embolization caused a nonhomogenous distribution of microflow, but initially had no effect on global cerebral blood flow, nor on cortical oxygen tension. Yet, a functional suppression of cortical electrical and metabolic activity occurred. The ipsilateral EEG flattened irreversibly after 15 seconds; the contralateral EEG was transiently suppressed shortly thereafter. Arteriovenous difference of oxygen fell from 10.5 +/- 0.7 to 5.3 +/- 0.6 vol%, and the arteriovenous difference of glucose fell from 11.7 +/- 3.9 to 2.6 +/- 2.1 mg/100 ml as a consequence of reduced oxygen and glucose extraction. Subsequently, severe vasogenic brain edema, secondary ischemia, and severe functional suppression developed between two and four hours.


Subclinical optic neuropathy in multiple sclerosis. Optic neuropathy in multiple sclerosis is often not detectable by conventional clinical assessment. Temporal resolution of vision was measured at localized retinal sites by a simple perceptual test of double light-flash discrimination. Nine of 11 multiple sclerosis patients with normal fundi and no prior history of optic neuritis displayed abnormal temporal resolution. Double-flash discrimination was consistently more sensitive than any of the clinical variables measured and in some cases complementary to them. The more advanced the disease, the more spatially widespread was the double-flash impairment in the central visual field. There was a significantly increased level of double-flash impairment in advanced multiple sclerosis patients compared with patients with spinal forms of the disease and with unilateral retrobulbar neuritis.


Long-term prognosis in stroke related to cerebral blood flow. In 180 patients, cerebral blood flow was measured between one and six weeks after acute cerebrovascular ischemia. Patients were grouped according to their clinical deficits at the time of blood flow study. Statistical analysis revealed highly significant differences among the flow values of the groups. The patients were followed up for a period of up to 6 years (mean, 34 months) after the attack, and then regrouped. In these groups, the statistical significances of differences among the flow values was even higher. Patients also were grouped according to changes in neurologic status, and again the flow values differed significantly among the groups. The results show significant relationships among flow values after cerebrovascular ischemia and neurologic deficits, change in status, and the final functional state. Cerebral blood flow measurement together with other clinical signs permits an estimation of a patient's chance for functional recovery after a stroke.


The effects of epileptogenic activity on auditory evoked potentials in cats. Epileptogenic foci were produced by application of penicillin to the auditory cortex of cats. A gradual modification of the evoked potentials to clicks and of the recovery cycle to paired clicks was noted following the application of penicillin. With the onset of interictal spikes, responses were initially depressed. The depression gradually changed till every click triggered a reflex epileptogenic spike. Areas surrounding the primary focus and areas at the mirror focus had depressed evoked potentials, while at the primary focus a click elicited reflex spikes. Progressive recruitment of cortical regions farther away from the primary focus was noted with increased epileptogenicity. The recovery cycle was also affected with prolongation of the absolute refractory period. These complex modifications of sensory input were closely related to the intensity of the epileptogenic disturbance, the distance of the area processing the information from the primary epileptogenic focus, and the time of arrival of the signal to be processed in relation to the interictal and ictal discharges.


Reversible paralysis of automatic respiration in multiple sclerosis. On a background of acute bulbar dysfunction, a patient experienced the simultaneous onset of severe proprioceptive loss and paralysis of automatic respiration that rapidly reverted to normal. Subsequent progressive neurological deterioration over several months ended in death, and neuropathological examination revealed demyelination in discrete distribution. The anatomical and diagnostic implications of this are briefly discussed.


'Silent' brain metastasis from lung carcinoma determined by computerized tomography. Computerized tomography (CT) was utilized as a preoperative screening procedure in a series of 50 patients with lung carcinoma who were neurologically asymptomatic and whose radionuclide brain scans and skull roentgenograms were normal. Three patients (6%) were discovered to have metastasis (cerebellum, occipital, corpus callosum). The metastatic lesions were only directly visualized after administration of contrast substance. The CT findings greatly influenced the therapeutic planning in these patients, and surgery was avoided in two. When feasible, patients with lung carcinoma should have CT examinations (with contrast administration) prior to thoracic surgery even if they do not have neurologic symtoms.


Neuroparalytic accidents of antirabies vaccination with suckling mouse brain vaccine. Clinical and pathologic study of 21 cases. Twenty-one cases of neuroparalytic accidents of rabies vaccination (with suckling mouse brain vaccine), 11 of them fatal, were observed, occurring predominantly in men; the mean age of the patients was 29 years. On the average, 13 doses of the vaccine were used. Only three patients received less than seven doses. The mean latent period was 14 days (range, 4 to 24 days). In 16 patients (76%), a Guillain-Barré syndrome occurred that was moderate in three, severe in seven, and fatal in six. Pathologically, this was shown to be a typical polyradiculoneuritis. Five patients had fatal involvement of the central nervous system. Three had an acute disseminated perivenous leukoencephalopathy, with concurrent rabies encephalitis in one case. One patient had a perivenous myeloradiculopathy and one a chronic encephalomyelopathy of six years' duration with demyelinating plaques in the periventricular white matter, cerebellum, and spinal cord. Since the reduction of postexposure rabies vaccination to seven doses, no new cases have been observed in Colombia.


Neuropsychological correlates of hypertension. Twenty newly diagnosed, untreated hypertensive men (diastolic blood pressure greater than 105 mm Hg) and 20 normotensive controls were given a neuropsychological battery, including tests of generalized, more global functions (eg, reaction time and full-scale IQ) and of specific functions (eg, language and visual-spatial abilities) sensitive to focal damage. Tests of specific abilities yielded no differences between the two groups. In contrast, tests of general neuropsychological functioning revealed a deficit among hypertensives, who were significantly slower on the reaction time test and had a shorter span for digits in forward order. Results suggest that arterial hypertension is associated with impairment of vigilance and attention span. Future research will determine whether this impairment is associated with the diffuse pathological changes seen in the brain of hypertensive subjects, or with a more "functional" change (eg, reduced cerebral blood flow).


Prognosis in hereditary amyotrophic lateral sclerosis. Two different forms of hereditary amyotrophic lateral sclerosis (ALS) has been separated according to duration of illness. A rapid course with short survival as seen in sporadic ALS is usual, but a comparatively benign type with a mean survival of 12 years has been reported in some families. Four patients from an ALS-afflicted family with five affected members in three generations were examined and then followed up. A conspicuous variability in progression among the patients was observed, with death occurring from 26 months to 12 years after onset; one patient is alive 13 years after onset. Wide differences were also found with respect to initial site of involvement and pyramidal tract signs. Three other families with this mixed pattern of prognosis have been reported previously. Affected individuals within involved families had either short or long duration of the disease, rather than displaying a continuum. However, in view of the existence of a type of hereditary ALS with marked intrafamilial variability, prognosis, even in the presence of previous benign cases, should be cautiously given.


Screening tests in acute porphyria.

Screening tests in acute porphyria. Two recognized screening procedures for rapid evaluation of urinary porphobilinogen (PBG) concentrations are compared with quantitative PBG determinations (expressed as mg/24 hours and as a concentration in urine, mg/liter). One hundred ninety-one 24-hour urine specimens from 74 patients with suspected or documented acute type porphyria are included in this investigation. The two screening tests are compared with regard to sensitivity and method of performance. In this study, the Watson-Schwartz and Hoesch tests are positive at PBG concentrations in urine greater than 9 mg/liter. Both methods produced the characteristic pink color only once at a concentration below 3 mg/liter. Both methods are useful in detecting the abnormal concentration of urinary PBG observed during an acute porphyric attack. The Hoesch procedure provides a simple and rapid evaluation of urinary PBG. Positive results from either screening test demand quantitative urinary PBG determinations to confirm the suspected abnormality.


Anatomic considerations for computed tomography of the optic chiasm. When the clinical distinction between lesions of the optic nerves or the chiasm is not apparent, computed tomographic scans should be performed at both 0 degrees and 25 degrees or 35 degrees to the orbital-meatal line (Reid's baseline). The former plane is preferable for the demonstration of the optic nerves or orbital structures, while the latter allows superior visualization of perichiasmatic structures.


A reversible ocular manifestation of thalamic hemorrhage. A case report. A patient had a thalamic hemorrhage and periodic downward and medial tonic deviation of the eyes. The ocular findings remitted with ventricular drainage. We discuss the possible contribution of increased intracranial pressure to this ocular syndrome.


Control of emotional expression in pseudobulbar palsy. A personal experience. This report is based on the recorded experience of a patient with lability of emotional expression and other features of the syndrome of pseudobulbar palsy. We describe severe emotional overflow despite an underlying affective tone that is normal. In this context, emotional lability is a misnomer. "Hyperactive emotional reflexes" would be a more appropriate descriptive term, as the underlying mood appears normal, and only the degree of emotional expression is pathological.


Rhegmatogenous retinal detachment in infancy. A 5-week-old male infant had small stature, microphthalmia, bilateral rhegmatogenous retinal detachments, ventricular septal defect, and fundus lesions suggestive of previous chorioretinitis. Diagnostic workup failed to disclose a cause of the intraocular disorder. Bilateral retinal detachment surgery, performed when the boy was 2 and 3 months of age, has appeared successful 12 months postoperatively. This may be a description of the youngest patient with rhegmatogenous retinal detachments that were subsequently repaired.


The fishmouth phenomenon. I. Clinical characteristics and surgical options. A typical fishmouth retinal break is a large horseshoe-shaped tear, located near the equator, with an associated bullous retinal detachment. During scleral buckling and drainage of subretinal fluid, the break tends to open more widely, making its closure difficult. Clinical characteristics that permit preoperative anticipation of the fishmouth phenomenon and several surgical methods that were previously suggested for its management are reviewed. The surgical methods include: an equatorial implant with a meridional addition, a two-band procedure, broad scleral buckling, and episcleral silicone sponge. A radial, intrascleral, solid-silicone implant (wedge) with an encircling element is recommended, as are other technical maneuvers that may be helpful in troublesome cases.


The fishmouth phenomenon. II. Wedge scleral buckling. Radial retinal folding, associated with equatorial scleral buckling, contributes to the difficulty in repairing a retinal detachment due to a fishmouth break. To minimize this effect, a wedge-shaped implant was designed to approximate more closely the same relative reduction in  the circumference of the circles of the globe along the meridian of the break. The surgical details of use of the implant are described. In a consecutive series of 56 eyes in which the fishmouth phenomenon was expected, 49 (88%) were successfully managed at first encounter using a wedge buckling device. Revised scleral bucklings and open-sky vitrectomies, in early failures and delayed recurrences, salvaged additional eyes for final success in 52 (93%) of the eyes.


Ocular involvement in wound botulism.

Ocular involvement in wound botulism. A 7-year-old girl developed bilateral ptosis, total ophthalmoplegia, and fixed, dilated pupils associated with bulbar paralysis and generalized weakness six days after she sustained a compound supracondylar fracture of the right humerus. Nerve conduction studies showed a facilitated muscle action potential after repetitive nerve stimulation. Blood cultures were negative. Although the wound site appeared noninfected, the wound was explored. Clostridium botulinum, type B, grew from cultures taken from the depths of the wound. The patient recovered fully with supportive care, and EEG abnormalities present during the acute phase of the illness disappeared.


Ophthalmoplegia and Ondine's curse.

Ophthalmoplegia and Ondine's curse. Ocular abnormalities and psychomotor difficulties were prominent in two unrelated children; in addition, the older child had respiratory irregularity during sleep. The pathologic findings included lesions of the optic nerve in the case with available material and established the diagnosis of Leigh's subacute necrotizing encephalopathy. This disorder is thought to result from inhibition of a thiamine-dependent enzymatic process and may be modified by greatly increased thiamine intake. Suspicion of the diagnosis in a child with ophthalmoplegia or other ocular abnormalities may lead to earlier recognition and more successful treatment of the disease.


Herpes simplex retinitis and encephalitis in an adult. A 17-year-old girl developed a viral encephalitis that was followed by massive exudative retinal detachments in both eyes. A diagnosis of herpes simplex encephalitis and retinitis was made as a result of finding rising herpes simplex viral titers. An examination of the patient's cell-mediated immune system showed it to be grossly intact.


Visually evoked response testing with a stimulator-ophthalmoscope. Macular scars, hereditary macular degenerations, and retinitis pigmentosa. Visually evoked responses (VERs) were recorded from 47 patients under age 60 years with macular scars, hereditary macular degenerations, or retinitis pigmentosa. A hand-held, two-channel stimulator-ophthalmoscope was used to present to the central fovea a 1.5 degrees flickering stimulus centrally superimposed on a steady 10 degrees background. All 31 patients with visual acuity (VA) 20/50 or less had abnormal VERs; among patients with VA 20/25 to 20/40, all six with macular degenerations and five of ten with retinitis pigmentosa also showed abnormal VERs. Abnormal VERs were either out of phase or indistinguishable from noise. Sensitivity of the technique depended on a low ratio of stimulus to background retinal illuminance and the fact that the stimulus could be visualized by the examiner through the ophthalmoscope and maintained on the central fovea througout testing.


The ocular manifestations of Behçet's disease. Of 32 patients with Behçet's disease, 21 had uveitis. The uveitis was seldom the initial manifestation of systemic disease, but once established, it tended to become chronic and bilateral, involving the anterior and posterior segments. Hypopyon was a relatively uncommon occurrence in this series. All patients with uveal inflammation had obvious cellular reactions within the vitreous body. Other posterior segment manifestations of the disease included localized retinal edema, macular edema, disc edema, retinal pigmentary changes, and accumulation of exudative material in the deep retina. One patient developed a necrotizing retinitis with deep retinal exudation and subsequent retinal detachment. Occlusions of retinal vessels were common. Neuro-ophthalmologic manifestations of Behçet's disease included cranial nerve palsies, a homonymous hemianopic field defect, and papillitis.


Nevus of Ota with contralateral cerebral melanoma. A case of unilateral nevus of Ota was associated with ipsilateral ocular melanocytosis and contralateral malignant melanoma of the CNS. The malignant neoplasm may have arisen from an area of bilateral leptomeningeal melanosis associated with unilateral nevus of Ota.


Choroidal melanoma and retinal tear.

Choroidal melanoma and retinal tear. The patient's eye contained a choroidal melanoma and a horseshoe retinal tear. Clinical recognition of the tumor led to the correct diagnosis and enucleation, avoiding unnecessary and potentially detrimental retinal detachment operations.


Management of persistent filtering cicatrix following cataract extraction. We used a safe and simple surgical technique in the management of persistent filtering cicatrices after cataract extraction. The edematous, friable filtering cicatrix was excised entirely and a healthy fornix-based conjunctival flap was sutured over the fistula. Invariably, the fistula was very small, usually only large enough to admit a 27-gauge needle. Of the 27 eyes treated with this technique, there were two failures, but no other complications.


Repair of occluded lower canaliculus.

Repair of occluded lower canaliculus. Epiphora resulting from traumatic occlusion of the inferior canaliculus has long been a vexing problem. A simple operation to cure some of these cases consists of unroofing the proximal portion of the canaliculus with use of a smooth-tipped pigtail probe passed from above as a guide. Prerequisites for the operation are a patent superior canaliculus, sac, and proximal segment of the inferior canaliculus. Epiphora was corrected in five of seven eyes with this surgery.


A hand-held, two-channel stimulator-ophthalmoscope. A hand-held optical system for presenting focused stimuli on known retinal areas by direct ophthalmoscopy is described. The optical system provides a time-modulated stimulus beam of variable dimension, retinal illuminance, wave-length, and polarization, and a steady background beam of variable retinal illuminance and wavelength. Both beams enter the patient's eye in maxwellian-view for precise control of the ratio of stimulus to background retinal illuminance. The stimulator-ophthalmoscope allows the examiner to compensate easily for variable fixation.


Industrial lead poisoning and the family physician. According to Health Department Regulations, lead workers are required to undergo periodical medical examinations to determine their fitness for work. These examinations are supervised by the Industrial Hygiene Division which can assist any practitioner with a patient thought to have had excessive exposure to lead.


The general practitioner's identification and management of emotional disorders. In summary, a systematic survey of Sydney metropolitan general practice consultations revealed an appreciable level of emotional disorder in one sixth of the patients. Doctors noted a similar number of patients in whom emotional and social factors were important in that day's consultation. There was concordance of assessment in only one third of the patients and as there are reasons for believing that the questionnaire is valid, inspection of the age and sex differences suggests that the doctors' perception of emotional problmes may be affected by cultural stereotypes of who is likely to be emotionally ill. In contrast, once cases are recognized, the provision of appropriate treatment such as counselling and drugs appears to be prudently and rationally prescribed.


Investigation of hypertension in general practice. The responsibility for identifying the hypertensive patients in the community and supervising their long term management is clearly the domain of the general practitioner. Having once decided that a patient's blood pressure warrants lowering, it is necessary that some form of routine investigation be carried out before treatment is started. A simplified approach to the investigation, collection and recording of the relevant data in these patients is outlined.


Home care in myocardial infarction.

Home care in myocardial infarction. Details are given of a prospective study of 131 patients with definite acute myocardial infarction, seen by general practitioners in Victoria from 1972 to 1974. This number was divided into 91 who were treated initially at home and subsequently referred to hospital, and 40 who were treated totally at home; this decision being made by the doctor after the infarct was diagnosed. There was no statistical difference between these two groups with regard to age or sex. The group treated totally at home had a lesser incidence of past history of myocardial disease, was seen later by the doctor of first contact, and had a lesser incidence of arrhythmias when first seen. With regard to mortality and morbidity, those selected patients kept at home fared no worse.


Patient compliance in general practice. Factors contributing to poor compliance and suggestions for improvement. Patients from a solo general practice were followed up to determine what factors were common to those who were poor compliers. A multiple treatment programme where oral antibiotics were a part of the programme was the most frequent feature of poorly complying patients, especially amongst 0-9 and 30-39-year-olds, and ENT patients of any age. Improvement may be gained by establishing good rapport with patients, ordering a simple treatment programme and avoiding overprescribing for all patients, but especially for those groups of patients who are particularly poor compliers.


Brain damage by extracts of parasitised annual ryegrass (Lolium rigidum) in nursling rats. Extracts of annual ryegrass (Lolium rigidum) infected with Anguina sp. and Corynebacterium sp., and associated with an outbreak of annual ryegrass toxicity in sheep, were administered to 2-week-old rats by a single intraperitoneal injection. Rats that received a lethal dose of toxin developed neurological signs including incoordination and convulsions from the second day and most died between 2 and 7 days after injection. Histologically, the brains showed widespread lesions of focal necrosis consistent with anoxia. Peripheral circulation rate was greatly reduced after 3 days and gangrene of the tail and hind legs developed in some rats. Evidence of restricted blood flow was also seen in kidneys, lungs and brain. It was concluded that the toxin contains a long-acting vasoconstrictor.


The physicochemical properties of erythrocyte derived activity which enhances murine bone marrow colony growth in agar culture. A stable preparation which retains enhancement activity for the growth of murine granulocyte-macrophage colonies in agar culture has been extracted from human and rat erythrocytes by osmotic lysis and high speed centrifugation. Trypsin digestion followed by Sephadex G-25 column chromatography has resulted in the removal of haemoglobin and the isolation of an active fraction with an apparent molecular weight of 900 to 1000 daltons. Enhancement activity was abolished by n-ethylmaleimide (NEM) treatment, suggesting that the enhancement is dependent on the presence of free sulphydryl groups.


A pneumatically driven pump for constant perfusion manometry. Syringe pumps are almost universally used for constant perfusion oesophageal manometry, despite important technical limitations. A pneumatically driven perfusion pump has been designed specifically for oesophageal manometry. This pump requires less than one third the flow setting of a syringe pump to achieve a given rate of pressure rise. It is simple to operate and needs infrequent refilling. Nearly two years' practical experience with this pump has confirmed its superiority over the syringe pump for constant perfusion manometry.


Plasmids mediating resistance to gentamicin and other antibiotics in Enterobacteriaceae from four hospitals in Melbourne. In twenty-nine gentamicin-resistant strains (mostly Klebsiella species) isolated from four Melbourne hospitals over a six month period, the genes for gentamicin resistance were carried on conjugative plasmids belonging to the rare incompatibility group L. These plasmids conferred resistance to gentamicin and sisomycin but not to amikacin or tobramycin, and were inferred to specify the enzyme aminoglycoside 3-N-acetyltransferase (AAC(3)I or GAT I). In addition, they specified resistance to a number of other antibiotics, including ampicillin and carbenicillin, chloramphenicol, kanamycin and neomycin, spectinomycin and streptomycin, sulphonamides and tetracyclines. Although they had a wide host range amongst the Enterobacteriaceae, none of these plasmids appeared able to transfer to Pseudomonas.


Genetic similarities and differences between sublines of certain inbred strains of mice held within Australia. Inbred mice  of the strains C57B1/6, CBA, C3H, Balb/c and DBA/2 from a total of 17 different sources within Australia were compared, utilizing 12 different blood proteins and a morphometric analysis of a series of lower jaws. Evidence for genetic differentiation between sublines was found in only two cases. Evidence for the recent contamination of an inbred strain with another stock was found in one case.


The simulation of the urea cycle: correlation of effects due to inborn errors in the catalytic properties of the enzymes with clinical-biochemical observations. Steady-state rate equations are written on the basis of information obtained from the literature describing the kinetics of the four enzyme-catalysed reactions comprising the urea cycle. These equations are formulated into a set which also accounts for fluxes of input and output compounds external to the cycle. Numerical integration of this set of equations is performed employing parameters selected to approximate those pertaining to the operation of the urea cycle in normal liver. The result is a pattern of intermediate metabolite concentrations, which forms a basis for the comparison of patterns reflecting the effects of inborn errors of metabolism. The latter are calculated by varying specified kinetic parameters in the numerical integration. Each of the observed clinical syndromes. Hyperammonemia Types I and II, Hyperarginemia, Citrullinemia and Argininosuccinicaciduria, is discussed.


Importance of luminal lecithin in intestinal absorption and transport of lipid in the rat. Feeding a gastric test meal, the absorption and transport of fat was studied in control and bile fistula rats with bile salts replaced but with and without egg lecithin supplemented. No evidence was found that luminal lecithin played an important role in the transport of absorbed fat as chylomicrons.


[Experimental infection of horses with Fasciola hepatica]. Ten pony foals were infected with Fasciola hepatica; five animals received up to 1000 metacercariae orally, the remaining animals received up to 80 specimens of 24 hours old adulescariae intraperitoneally. The rate of development of the parasites varied in a wide range between 0,2 and 41%. Most of the liverflukes were found in animals severely infected with strongyles in the same time. Only 22 weeks after oral infection, the flukes had reached a length of 20 mm and sexual maturity. Fasciola-eggs could not be detected in the feces.


[Fracture of the 1st phalanx in the horse]. Of 28 fractures of the first phalanx 21 were treated with osteosynthesis; one was treated conservatively. 2 to 4 compression screws have been applied, while the distal part of the limb was immobilized by a light cast bandage for 8 days. The implants were removed 2 to 3 months post operationem. All patients are again used in sports.


[Occurrence of Coxiella burneti in foodstuffs in animal origin]. Some of the organs and secretions from Q fever infected cattle originally intended for human consumption were tested for their Coxiella content. In the cows, the udder and udder lymph nodes were found to contain over 75% of the exciters; the exciters were also found to a large extent in the milk, reaching levels of between 10(1) and 10(5) Inf. E/ml milk. On the other hand, other parts of the animal used as meat were less infected. Lymph nodes in the body contained 28%, liver, kidney, pancreas and lungs 25% and musculature (meat) 8%. Udder infections in cows can last for months or even years, but they persist only for a few weeks in sheep. Treatment and preservation methods used on the meat after the animals is slaughtered also decimate the exciters, thus decreasing any risk to the consumer. Infected milk also loses its capacity for infection when sufficiently pasteurised, though the problem of oral infection in fresh milk still exists. Tests on guinea pigs show that when they are fed fresh milk containing Coxiella the formation of blood antibodies can take place, and also infestation of the organs. Essential conditions for this can be found in the exciter content, the virulence of the exciters and a weak defence mechanism in the organism.


[Microbiological and epidemiological problems in the feeding of animal excrements]. Tests were made to determine the minimal hygiene demands necessary when animal excrement is used as fodder. Research to date give only limited information, as it has been undertaken almost entirely on slamonella. The minimal demands must include guaranteed destruction of vegetative forms of disease exciters and viruses. However, the risk of infection must remain where spores can form and endanger health.


[The elimination of the sense of smell and its effect on the suckling behavior in young rabbits]. In the experiments described the ability to smell was eliminated in rabbits aged 1-7 days with two different methods: destruction of the nasal mucous membranes with 2% ZnSO4 solution administered in 2 doses of 100 microliter with a time interval of 12 hours between the two applications and destruction of the olfactory bulbs with high-frequency coagulation (20 V, 80 mA for 12 se.). Both treatments disturbed the suckling behavior, as the young rabbits failed to find the mammary gland. These results suggest that a releaser phenomon is secreted in the mammary gland region, which enables the rabbit to find the test and thus to initiate suckling behavior.


Consumption of fat as an important part of the food and nutrition policy in developed countries. In developed countries, the excess consumption of some nutritive factors and foodstuffs becomes a major problem. The consumption of fat is included here due to its contribution to the high energy intake and its potential health risks. The consumption of fat as a nutrient is characterized by a steady increase. The physiological requirements of fat intake are not included in many dietary allowances and requirements of other indicators, such as linoleic acid, fatty acids, and cholesterol, are formulated in scientific papers only. The confrontation of existing fat allowances with the effective consumption indicates a tremendous excess. The same is true of some other indicators. The findings about the consumption of fat commodities complete these considerations. The indicated problems of fat consumption reveal the important position of this nutrient and of fat commodities in the food and nutrition situation. But opinions about these important factors are not sufficiently formulated what causes difficulties in food and nutrition planning and therefore in elaborating of the food and nutrition policy. For this reason, the international unification of opinions is urgently needed.


Specific protein synthesis in isolated epithelium of guinea-pig seminal vesicle. General features. Four intrinsic soluble proteins are synthesized and secreted by sexually mature guinea-pig seminal-vesicle mucosa, which comprises a monolayer of a homogeneous columnar epithelial cell. All four proteins can be extracted readily in 154mm-NaCl from the organ's luminal constituents in which they are present in high concentration. They are referred to as proteins 1, 2, 3 and 4 in order of their elution during DEAE-cellulose column chromatography. Specific primary antibodies were harvested from goats that had been inoculated with the purified vesicular proteins; secondary antibodies were obtained from a donkey inoculated with goat gamma-globulins. Double-antibody-immunoprecipitation techniques were developed to precipitate the vesicular proteins. Thus proteins newly synthesized from (14)C-labelled amino acids could be precipitated and the incorporated radioactivity assessed. Isolated seminal-vesicle mucosa, incubated in only a buffered salt solution containing glucose, readily synthesized the soluble secreted proteins from added [(14)C]lysine plus [(14)C]glycine, [(14)C]histidine plus [(14)C]glutamate, [(14)C]glutamine alone and [(14)C]arginine alone. The rates of incorporation (d.p.m./mg of total soluble protein) of labelled lysine and glycine and of labelled arginine were linear with time over 180min. With the other labelled precursors, rates diminished between 60 and 180min. Labelled protein could be detected after only 10-15min of incubation. Only 4-9% of the newly synthesized protein remained associated with the mucosa; the remainder was found in the cell-free incubation medium. The isolated seminal-vesicle mucosal preparation will provide a unique opportunity to study the synthesis and secretion of abundant cell-specific proteins by this androgen-dependent tissue.


Specific protein synthesis in isolated epithelium of guinea-pig seminal vesicle. Effects of castration and androgen replacement. Four intrinsic soluble secretory proteins are synthesized in vitro by isolated seminal-vesicle mucosa from sexually mature guinea pigs. Newly synthesized specific proteins labelled with [(14)C]glycine and [(14)C]lysine were precipitated by using double-antibody immunoprecipitation techniques and their radioactivity was assessed. Rates of synthesis were determined on each of 5 days after castration. By 5 days after castration the wet weight of the epithelium decreased to 42% of intact control values; the absolute amount of specific protein synthesized in vitro after 60min incubation decreased to 28% and the 27500g cytoplasmic protein content decreased to 31%. Thus androgen deprivation leads to a decrease in general protein synthesis in vivo, as well as to a decrease in specific protein synthesis in vitro. Specific protein synthesis comprised 76% of the total protein formed in isolated tissue from animals 5 days after castration as compared with 99-100% in tissue from intact animals. At 72h after an injection of testosterone or dihydrotestosterone, seminal-vesicle epithelium wet weight, cytoplasmic protein content and capability for synthesizing specific proteins in vitro were restored to approx. 70% of normal values. At 72h after onset of therapy with 3alpha-androstanediol, both epithelium wet weight and cytoplasmic protein content had increased significantly, but without a corresponding increase in the capability of the isolated tissue to synthesize specific proteins. The soluble labelled proteins synthesized in vitro by isolated epithelium from intact animals during 60 or 120min incubation were essentially entirely immunoprecipitable, i.e. specific. In contrast, approx. 29% of all soluble protein newly synthesized by isolated epithelium from animals 5 days after castration was acid-precipitable, but not immunoprecipitable, i.e. ;non-specific'. The injection of testosterone into castrated animals inhibited the synthesis of the non-specific fraction by isolated tissue. The effects of castration on the ultrastructure of guinea-pig seminal-vesicle epithelium are also presented.


Preferential utilization in vitro of iron bound to diferric transferrin by rabbit reticulocytes. 59Fe uptake by rabbit reticulocytes from human transferrin-bound iron was studied by using transferrin solutions (35, 50, 65, 80 and 100% saturated with iron) whose only common characteristic was their content of diferric transferrin. During the early incubation period, 59Fe uptake from each preparation by reticulocytes was identical despite wide variations in amounts of total transferrin, total iron, monoferric transferrin and apotransferrin in solution. During the later phase of incubation, rate of uptake declined and was proportional to each solution's monoferric transferrin content. Uptake was also studied in a comparative experiment which used two identical, partially saturated transferrin preparations, one uniformly 59Fe-labelled and the other tracer-labelled with [59Fe]diferric transferrin. In both experiments, iron uptake by reticulocytes corresponded to utilization of a ferric ion from diferric transferrin before utilization of iron from monoferric transferrin.


Induction of peroxidase in corpora lutea of rat ovary by lutropin. The lutropin-induced depletion of ascorbate in corpora lutea of albino-rat ovary is shown to be associated with the induction of peroxidase in corpora lutea. An inverse relationship between ascorbate depletion and peroxidase activity was established in a time-course study with lutropin. Analyses made at different phases of the reproductive cycle are in accord with this relationship. It is suggested that ascorbate, which is a well-established donor in peroxidase reactions, undergoes rapid oxidation in the presence of this enzyme, producing an intermediate free radical which, if coupled with pregnenolone, might produce progesterone in the corpora lutea. The exact role of peroxidase in steroidogenesis, however, remains to be elucidated and established.


Bacterial catabolism of threonine. Threonine degradation initiated by L-threonine acetaldehyde-lyase (aldolase) in species of Pseudomonas. 1. The route of l-threonine degradation was studied in four strains of the genus Pseudomonas able to grow on the amino acid and selected because of their high l-threonine aldolase activity. Growth and manometric results were consistent with the cleavage of l-threonine to acetaldehyde+glycine and their metabolism via acetate and serine respectively. 2. l-Threonine aldolases in these bacteria exhibited pH optima in the range 8.0-8.7 and K(m) values for the substrate of 5-10mm. Extracts exhibited comparable allo-l-threonine aldolase activities, K(m) values for this substrate being 14.5-38.5mm depending on the bacterium. Both activities were essentially constitutive. Similar activity ratios in extracts, independent of growth conditions, suggested a single enzyme. The isolate Pseudomonas D2 (N.C.I.B. 11097) represents the best source of the enzyme known. 3. Extracts of all the l-threonine-grown pseudomonads also possessed a CoA-independent aldehyde dehydrogenase, the synthesis of which was induced, and a reversible alcohol dehydrogenase. The high acetaldehyde reductase activity of most extracts possibly resulted in the underestimation of acetaldehyde dehydrogenase. 4. l-Serine dehydratase formation was induced by growth on l-threonine or acetate+glycine. Constitutively synthesized l-serine hydroxymethyltransferase was detected in extracts of Pseudomonas strains D2 and F10. The enzyme could not be detected in strains A1 and N3, probably because of a highly active ;formaldehyde-utilizing' system. 5. Ion-exchange and molecular exclusion chromatography supported other evidence that l-threonine aldolase and allo-l-threonine aldolase activities were catalysed by the same enzyme but that l-serine hydroxymethyltransferase was distinct and different. These results contrast with the specificities of some analogous enzymes of mammalian origin.


The degradation and turnover of fucosylated glycoproteins in the plasma membrane of a neuroblastoma-cell line. When monolayer cultures of neuroblastoma N2a cells were prelabelled with [(3)H]fucose to steady state, and then reincubated in complete medium in the presence of unlabelled 40mm-l-fucose, there was a rapid metabolism of fucosylated cellular macromolecules and the specific radioactivity of the acid-insoluble material decreased by 22% within 2h. After this period of time the remaining radioactive glycoproteins appeared to be more stable and the rate of loss of specific radioactivity markedly decreased. Since fucose is known to be associated predominantly with plasma-membrane components, the analysis of fucosylated glycoproteins was characterized in plasma-membrane fractions by polyacrylamide-gel electrophoresis. Two experimental approaches were used to measure glycoprotein degradation and turnover in the cell-surface membranes. In one set of experiments, with a similar incubation procedure to that used with intact cells, three membrane components were rapidly degraded (150000, 130000 and 48000 daltons), but another surface glycoprotein (68000 daltons) appeared to be more slowly metabolized than the mean rate of glycoprotein degradation. The relationship of the degradation of membrane glycoproteins to their turnover was analysed by dual-label experiments that used both [(14)C]fucose and [(3)H]fucose. Glycoproteins of the surface membrane of neuroblastoma cells were found to turn over at heterogeneous rates. The components mentioned above that exhibited significantly rapid rates of degradation, were also shown to turn over more rapidly than the average surface component. In addition to the membrane components detected by the use of only [(3)H]fucose, dual-label experiments illustrated that numerous surface glycoproteins were metabolized more rapidly or slowly than most of the cell-surface constituents.


Induction of human choriogonadotropin in heLa-cell cultures by aliphatic monocarboxylates and inhibitors of deoxyribonucleic acid synthesis. The ectopic production of the glycopeptide hormone human placental choriogonadotropin by HeLa(65) cells was measured by radioimmunoassay with antiserum against the beta-subunit of choriogonadotropin and with the (125)I-labelled beta-subunit as a tracer antigen. Choriogonadotropin synthesis was markedly (500-fold) stimulated by sodium butyrate. Kinetic studies and the use of an inhibitor of protein synthesis, cycloheximide, indicated that protein synthesis was required for this induction. Investigation of the efficiency of 22 aliphatic short-chain fatty acids and derivatives in causing increased choriogonadotropin synthesis by HeLa cells showed stringent structural requirements. Induction of choriogonadotropin synthesis in HeLa cells was not restricted to butyrate. Other aliphatic acids (propionate, isobutyrate, valerate and hexanoate) were also capable of inducing choriogonadotropin synthesis at 10-50% of the efficiency of butyrate. Hydroxy derivatives of monocarboxylate inducers, related mono- and di-carboxylic acids, alcohols, amines, ketones, esters and sulphoxide were ineffective in increasing choriogonadotropin production by HeLa cells. A saturated C(4) straight-chain acid without substituent hydroxyl groups but with a methyl group at one end and a carboxyl moiety at the other appeared to be most efficient in activating choriogonadotropin production. A second clonal line of HeLa cells, HeLa(71), showed a higher constitutive synthesis of choriogonadotropin than HeLa(65) cells, which was also markedly increased by butyrate. Butyrate and other aliphatic monocarboxylate inducers of choriogonadotropin synthesis inhibited HeLa-cell growth and DNA synthesis. This inhibition of DNA replication may be related to the mechanism of choriogonadotropin synthesis, since two well-characterized anti-neoplastic inhibitors of DNA synthesis, hydroxyurea and 1-beta-d-arabinofuranosylcytosine, also stimulated a 300-fold increase in choriogonadotropin synthesis in HeLa cells and were synergistic with butyrate in promoting choriogonadotropin synthesis. Thus activation in tumour cells of genes normally expressed by foetal tissue and the consequent ectopic synthesis of polypeptide hormones may require neither cell division nor DNA synthesis.


Effect of endotoxin on tryptophan pyrrolase and delta-aminolaevulinate synthase: evidence for an endogenous regulatory haem fraction in rat liver. Endotoxin was administered to rats at a dose shown previously to stimulate hepatic haem oxygenase activity and to block induction of delta-aminolaevulinate synthase, apparently by causing redistribution of haem from cytochrome P-450 to a regulatory haem pool in the liver. Within 5h of the administration of endotoxin (at a time when the effect of the compound on cytochrome P-450 is maximal) the relative saturation of tryptophan pyrrolase with intrinsic haem rose, from a basal value of 50% to 90%, indicating that 'free' haem had become available. Concurrently, the activity of delta-aminolaevulinate synthase was decreased to 25% of its basal value. Haem oxygenase reached peak activity 13h after endotoxin administration. These findings provide new evidence for the existence of an 'unassigned' hepatic haem fraction, which exchanges with cytochrome P-450 haem and regulates these three enzyme functions.


Experimental radiation synovectomy by 165Dy ferric hydroxide macroaggregate. The short half-life beta emitter 165Dy coprecipitated as a macroaggregate with ferric hydroxide (FHMA) has been shown to destroy knee synovium in the antigen-induced arthritic rabbit. Using 153Gd as a gamma tracer for leakage studies revealed that the leakage of this system from rabbit knee joints never exceeded 1.2% over 24 hours. This is such less than the leakage rates reported from any human studies or our rabbit studies using 198Au.


The activating effect of synovial fluid and washings of synovial membrane on autologous lymphocytes in rheumatoid arthritis. The effect of synovial fluid and washings of synovial membrane on autologous lymphocytes from patients with rheumatoid arthritis and other diseases has been studied using a rapid method based upon the increase in intranuclear birefringence occurring in the early stages of lymphocyte activation. Retardation of polarized light indicating increased lymphocyte activation was seen in lymphocytes from patients with rheumatoid arthritis but not in lymphocytes from patients with other diseases.


Failure of proteoglycans to form aggregates in morphologically normal aged human hip cartilage. The macromolecular organization of proteoglycans in morphologically and histochemically normal hip cartilage from aged humans has been studied. In contrast to findings in articular and nonarticular cartilage from other sources, most of the proteoglycans in these tissues did not exist in large aggregates. Treatment with hyaluronic acid beta1 leads to 3 hydrolase failed to diminish the size of proteoglycans prepared under conditions favoring aggregation, a finding suggesting that they were not complexed with hyaluronic acid. Polyacrylamide gel electrophoresis failed to demonstrate the presence of link glycoproteins associated with the proteoglycans. After incubation in vitro with hyaluronic acid, minimal augmentation of hydrodynamic size of the preparation occurred, an indication that hyaluronate-proteoglycan interaction had not taken place. These results suggest that proteoglycan aggregation was diminished because of a defect in the core protein of the proteoglycans resulting in an impaired ability of these molecules to interact with hyaluronic acid.


Polyclonal hyperviscosity syndrome.

Polyclonal hyperviscosity syndrome. The clinical course of two patients who presented with polyclonal hyperviscosity syndrome is described. Polymerizing IgG rheumatoid factors were isolated from the serum of both patients. The presence of these polymers with their extraordinary rheologic properties was the principal determinant of the abnormal rheological properties of the plasma. Neither patient had a discrete rheumatic disease. In both, a lymphoproliferative syndrome was present with features suggestive of the "pseudolymphoma" of Sjögren's syndrome.


The effect of synovial tissue on the breakdown of articular cartilage in organ culture. Living (pig) cartilage in contact with synovium lost both proteoglycan and collagen and sometimes became reduced to a mass of fibroblast-like chondrocytes without matrix; dead cartilage lost proteoglycan but less collagen. Similar changes appeared in living cartilage grown at a distance from the synovium but in the same dish; dead cartilage was unaffected. the synovium has a) a direct, presumably enzymatic action on cartilage matrix and b) an indirect effect mediated through the chondrocytes.


Interaction of D-penicillamine with gold salts: in vivo studies on gold chelation and in vitro studies on protein binding. Serum and urinary gold levels were monitored in 18 patients previously treated with gold salts for rheumatoid arthritis and the effects of D-penicillamine studied. There was no statistically significant change in urinary gold levels on D-penicillamine therapy although there were some individual variations. Serum gold levels fell during D-penicillamine therapy but the rates of fall did not differ from those seen in patients not treated. In vitro studies on protein binding of gold salts suggest that a high affinity exists between gold salts and albumin with low levels of unbound gold even at concentrations far exceeding those seen in vivo. These preliminary results suggest that at therapeutic levels only small amounts of gold are available for chelation by penicillamine. It is concluded that penicillamine at low dosage is an unreliable chelator of gold salts in vivo and its use in the management of gold toxicity remains speculative.


Zymosan-induced arthritis: a model of chronic proliferative arthritis following activation of the alternative pathway of complement. Zymosan particles, which are able to activate complement by the alternative pathway and to induce enzyme secretion from macrophages, were injected into knee joints of mice. After various time intervals, synovia were assessed histologically for various markers of inflammation. Within 7 days after intraarticular injection of zymosan, a chronic inflammatory arthritis with mononuclear cell infiltration, synovial hypertrophy and pannus formation was observed. Latex particles, which do not activate complement or macrophages, produced only mild, transient inflammatory reactions.


Use of a hapten-carrier system in experimental immune arthritis in the rabbit. Animals immunized systemically with dinitrophenylated-bovine serum albumin (DNP-BSA) in complete Freund's adjuvant, show delayed hypersensitivity skin responses to DNP-BSA and to BSA, but not to other DNP-conjugates. These animals show high levels of antibodies to BSA and to DNP to radioimmunoassay. When injected with the carrier (BSA), the right knee joint develops a chronic arthritis. The left knee, when injected with the DNP hapten conjugated to another carrier (human serum albumin), shows an acute arthus response of the same magnitude as the right knee, but fails to develop a chronic synovitis. It appears that in this model, chronicity is not mediated primarily by a humoral mechanism to the initiator.


Fibrous long spacing collagen in aortic explants of normal rabbit cultured in hypercholesterolemic serum. Aortic tissues consisting of all three tunics were removed from normal adult rabbits and cultured in a semisynthetic gelosed medium supplemented by 10% serum obtained either from normal or hypercholesterolemic rabbits. Fibrillar cross-striated aggregates appeared with a high frequency (50%) in the extracellular space of explants cultured from four to eight days in medium supplemented by serum from hypercholesterolemic rabbits, but did not appear in explants cultured in serum from control animals (3%). The electron-dense segment was ruthenium red positive and digested by testicular hyaluronidase. The electron-lucent segment, composed of ruthenium red negative thin filaments, was not modified after hyaluronidase treatment but was strongly digested after collagenase treatment. It is believed that this material was fibrous long spacing collagen synthetized under culture conditions, as shown after tritiated proline incorporation.


Patellar whiskers and acute calcific quadriceps tendinitis in a general hospital population. Described is a case of acute calcific quadriceps tendinitis which presented as monoarticular arthritis. A survey of general hospital patients revealed a 7% incidence of calcification of the superior patellar tendon. The most common concurrent abnormality was degenerative joint disease (94%); concomitant chondrocalcinosis was not seen. The "patellar whisker" is a relatively common x-ray finding that may be the clue to an uncommon cause of acute arthritis.


Effects of chronic ethanol consumption on the catabolism of chylomicron triacylglycerol and cholesteryl ester in the rat. Rats were fed for 24 days a liquid diet with ethanol as 36% of calories to produce hyperlipemia and hepatic steatosis. The catabolism of chylomicrons doubly-labeled in the triacylglycerol and cholesteryl ester moieties was studied in conscious rats after ingestion of their usual liquid diets with or without ethanol. A constant intravenous infusion of chylomicrons revealed a defect in chylomicron catabolism after chronic treatment with ethanol. The plasma clearance of chylomicron cholesteryl ester was impaired to a greater extent than clearance of chylomicron triacylglycerol. These findings are consistent with defective catabolism of chylomicron remnants, and suggest that the accumulation of chylomicron remnants in the plasma contributes to the development of increased post-prandial hyperlipemia and chronic hyperlipemia in association with excessive ethanol consumption.


Reduction of myocardial reinfarction by the combined treatment with clofibrate and nicotinic acid. In an ongoing study 558 consecutive survivors of myocardial infarction below 70 years, mean age 59 years, were randomly allocated 4 months after the acute episode into a control group or a chemotherapy group from December 1972 to April 1976. Both groups were given moderate advice about diet and the chemotherapy group was prescribed clofibrate, 1 g twice daily, and nicotinic acid 1 g three times daily. Serum cholesterol and triglycerides were lowered around 15-20% and 30% respectively in the chemotherapy group while only insignificant reductions were observed in the control group. Until December 1976 total mortality and mortality from IHD has been the same in the two groups. The number of non-fatal myocardial infarctions has been 38 in the control and 19 in the chemotherapy group, a statistically significant reduction (P less than 0.01).


The fatty acid composition of triglycerides in arteries, depot fat and serum of amputated diabetics. The triglyceride fatty acid pattern (TFAP) in arterial wall, adipose tissue and serum in vivo has been estimated in amputated diabetic subjects by gas-liquid chromatography simultaneously. Besides, in some probands the fatty acid pattern of cholesterol esters of vessel walls has been obtained. In arterial wall the percental content of lauric, myristic, myristoleic, palmitoleic, stearic, oleic and linolenic acid was high and that of palmitic and linoleic acid was low, when compared to serum, whereas eicosatrienoic, arachidonic and eicosapentaenoic acid were of similar magnitude. In comparison to adipose tissue myristic, palmitic and nervonic acid were decreased and eicosatrienoic, arachidonic and eicosapentaenoic acid were increased in arterial wall. In view of the results the speculation is obvious that certain fatty acids have distinct metabolic positions in several tissues, such as depot fatty acids and precursors of prostaglandins, for example.


Time dependence of [131I]albumin uptake following removal of an experimental aortic stenosis. The uptake of trypan blue and [131I]human serum albumin (HSA) has been studied in the dog's abdominal aorta between 1 and 42 days after removal of an experimental stenosis (approximately 90%) applied 1 week previously. Previous work has shown that when the stenosis was present during circulation of these markers, their uptake was increased immediately proximal to the stenosis decreasing to normal by the renal artery level. Distal to the stenosis uptake was reduced apart from small areas of high uptake probably due to turbulent jet impacts. Within the stenosed section the uptake was normal. In this present study it was found that, after removal of the stenosis, proximal uptake initially remained elevated, returning to normal after approximately 15 days whilst the distal uptake returned to normal after approximately 10 days. In the previously stenosed section uptake was increased markedly following the release of the stenosis but returned to normal within approximately 20 days. The relationship of these findings to alterations in the local haemodynamic state and to possible changes in endothelial morphology are discussed.


Effect of selective depletion of fibrinogen on the evolution of cholesterol-induced atherosclerosis in rabbits. Atherosclerosis was produced by induced alimentary hyperlipaemia in four groups of rabbits. Animals of groups II and III received cholesterol feeds daily for 2 months while in groups IV and V this was followed by another 3 months of intermittent feeding. Group I comprised normal control rabbits. Selective fibrinogen depletion was produced in groups III and V with Arvin so as to maintain the plasma fibrinogen around 100 mg/dl over the last 2 months of cholesterol feeding. Serum lipids, blood coagulation and euglobulin clot lysis as well as the post mortem histopathology of aorta, heart, kidneys, liver and lungs did not reveal any significant differences between corresponding groups of hyperlipaemic animals treated with (groups III and V) or without (groups II and IV) Arvin. It appears that fibrinogen or fibrin incorporation does not play a significant role in the pathogenesis of atherosclerotic lesions induced in rabbits by cholesterol feeding.


Hypocholesterolemic action of a novel delta8-dihydroabietamide derivative, THD-341, in rats. The hypocholesterolemic properties of THD-341, N-(2,6-dimethylphenyl)-delta8-dihydroabietamide, were studied in rats. THD-341 reduced serum cholesterol levels in cholesterol-cholate-fed rats at a concentration of less than 0.001% in the diet or an oral dose of less than 3 mg/kg, once a day. When compared in terms of the 50% inhibitory dose for serum cholesterol elevation (ID 50%, % in diet), THD-341 (0.0008%) was comparable to D-thyroxine (0.0005%), more potent than estradiol (0.003%), and far more potent than clofibrate (0.2%), beta-sitosterol (0.8%), cholestyramine (2%), or nicotinic acid (3%). A daily intravenous injection of THD-341 was also effective (ID 50%: 7 mg/kg). THD-341 reduced serum and liver cholesterol in rats made hypercholesterolemic by 0.3% dietary thiouracil or 0.25% dietary cholate. Liver cholesteriol was more profoundly affected than the serum cholesterol. In normal rats, cholesterol was reduced in liver but not in serum. Its mechanism of action is unknown but the results suggest that THD-341 inhibits cholesterol absorption or re-absorption.


Appointment-keeping behavior re-evaluated. Many of the traditional approaches to the problem of appointment-keeping behavior have ignored the organizational factors that may be implicated in differentially high broken appointment rates leading to an implicit assumption that low-income and ethnic minority patients will be more likely to break appointments. A case study at a Model Cities Health Center which maintains a kept appointment rate of 85 per cent examined the relationship of broken appointments to age, sex, ethnic background, and payment mechanisms. The results suggest alternative explanations for differentially high broken appointments centering on the role of the institution in reinforcing appointment-keeping behavior.


Experimental studies on myocardial metabolism of carbohydrate and lipid in surface-induced deep hypothermia. In surface-induced deep hypothermia, metabolic acidosis resulting from lactacidemia was observed. In the aspect of myocardial metabolism, the rate of reduction in coronary A-V difference ratio of lactate, pyruvate and NEFA was less than that of coronary flow and myocardial oxygen consumption in the hypothermic heart. Namely, it seems  that lactate, pyruvate and NEFA play an important role as energy fuel in the hypothermic heart. On the other hand, myocardial metabolism of glucose was reduced in the hypothermic heart. Moreover, it seems that exogenous corticosteroid and ATP do not influence on the myocardial metabolism of carbohydrate and lipid in the hypothermic heart.


Perceived exertion and stimulus intensity modulation. Perceptual augmentation and reduction were considered contrasting styles of Stimulus Intensity Modulation. Differences in perceived exertion between augmenters and reducers were determined for three cycle ergometer work loads. Subjects were 20 males having similar physiological characteristics. Stimulus Intensity Modulation was determined by kinesthetic figural aftereffect. Augmenters rated their perceptions of physical exertion to be more intense than reducers at 450, 750 and 1050 kpm/min. Differences in physiological responses between augmenters and reducers were not significant at the three work loads. Style of Stimulus Intensity Modulation appeared differentially to influence perceived exertion at the work levels studied.