Changes in plasma norepinephrine, blood pressure and heart rate during physical activity in hypertensive man. We have investigated the changes in plasma norepinephrine and blood pressure and heart rate during a range of physical activities in eight hypertensive subjects in order to determine whether changes in plasma norepinephrine reflect changes in sympathetic activity. Blood pressure was recorded over 24 hours from an intra-arterial cannula. Plasma norepinephrine, measured by a sensitive radioenzymatic method, increased progressively with increasing levels of physical activity. In each subject a statistically significant linear relationship was observed between the logarithm of plasma norepinephrine and systolic blood pressure. Analysis of variance showed that 66% of the variance of plasma norepinephrine was associated with changes in blood pressure and heart rate. These observations support the hypothesis that plasma norepinephrine reflects short-term changes in sympathetic activity. Use of the quantitative relationship described, in conjunction with measurements of norepinephrine metabolism, may help to determine the significance of increased levels of plasma norepinephrine observed in some hypertensive patients.


Pathophysiology of hypertension in blacks and whites. A review of the basis of racial blood pressure differences. Differences in blood pressure between blacks and whites in the United States are now well documented. The causes of these differences remain speculative. Genetic factors, personal characteristics, renal physiology, endocrine factors, autonomic nervous system function, cardiac function and various environmental factors are examined in the present review as potential determinants of racial blood pressure differences. Racial differences in renal physiology and environmental influences such as socioeconomic status seem to be likely candidates for important contributions to blood pressure differences. Further research aimed specifically at black-white blood pressure differences is of great importance to a fundamental understanding of the etiology and prevention of essential hypertension.


Clonidine and carotid baroreflex in essential hypertension. Clonidine is believed to reduce blood pressure by a neural action and animal experiments suggest that this consists in potentiation of baroreflexes. In 16 patients with essential hypertension we studied the effects of alterations in carotid sinus baroreceptor activity (neck chamber technique) on arterial blood pressure (catheter measurements) and heart rate, before and after intravenous administration of 150 microgram and 300 microgram of clonidine. The magnitude of the reflex responses was assessed by the slope of the linear regressions relating applied increase and decrease in tissue pressure at the carotid sinus (and therefore applied decrease and increase in carotid sinus transmural pressure) and resulting changes in mean arterial pressure and R-R interval. Clonidine caused a marked reduction in mean arterial pressure (-26 +/- 3 mm Hg) and a slight but significant reduction in heart rate (-5 +/- 1 b/min). There was no evidence for a potentiation of the baroreceptor influence on blood pressure, although a slight potentiation of the baroreceptor influence on heart rate was observed in few instances. We conclude that in man clonidine can exert a pronounced hypotensive effect without potentiating baroreceptor influence on blood pressure. Therefore this mechanism does not play a prominent role in the clinical antihypertensive action of the drug.


Central hemodynamics in the developmental stage of spontaneous hypertension in the unanesthetized rat. The hemodynamic alterations associated with the developmental phase of high blood pressure were investigated in the spontaneously hypertensive rat (SHR). All hemodynamic measurements were made in unanesthetized, unrestrained SHR and Wistar-Kyoto (WKY) rats instrumented with chronic electromagnetic flow probes on the ascending aorta and arterial pressure catheters. Rats were studied at 30-41 days, 80 days, and 120 days of age. Hemodynamics of SHRs and WKYs in the 30-41 day group were monitored daily. Spontaneously hypertensive rats demonstrated a higher cardiac index than WKYs (p less than 0.05) from 32 through 41 days of age. Total peripheral resistance (TPR) was not elevated in SHRs at this time. Heart rate and stroke index were elevated in SHRs (p less than 0.05) from 34 through 41 days, however, stroke volume was not. At 80 and 120 days SHRs had higher mean arterial pressure (MAP) and TPR than WKYs (p less than 0.05), although cardiac index was not significantly different. This hemodynamic pattern of a hyperkinetic circulation prior to the development of hypertension supports the theory of total body autoregulation. A transient increase in cardiac index precedes an increase in TPR, which then normalizes cardiac index while elevating MAP.


Chronic hypothalamic stimulation in awake rats fails to induce hypertension. Daily electrical stimulation of the posterior hypotalamus for 12 weeks in awake rats caused persistent cardioacceleration but barely increased systolic pressure. Subsequent postmortem examination showed extensive fibrosis at sites of electrode implantation in both stimulated and unstimulated rats. Because Folkow and Rubinstein had succeeded in elevating blood pressure progressively by stimulating the "hypothalamic defence area," chronic stimulation was repeated following their stereotaxic coordinates. Systolic pressure rose but the elevation was significant only on Weeks 8 and 10. To maintain behavioral effects during chronic stimulation, current strengths had to be increased periodically, and stimulated rats gained weight more rapidly than unstimulated controls. Both these findings indicated that electrical stimulation had damaged the brain, but since local fibrosis made histologic verification difficult, additional experiments were done to determine if functional deficits could be detected. Upon further hypothalamic stimulation, electrical thresholds were higher and pressor and sympathetic nerve responses were smaller in rats that had been stimulated chronically than in those that had not. Although our results do not disprove the hypothesis that centrally-induced sympathetic hyperactivity initiates hypertension, they show that blood pressure cannot be elevated by hypothalamic stimulation alone when the brain has been injured.


Estimating compliance with diuretic therapy: urinary hydrochlorothiazide-creatinine ratios in normal subjects. We gave 21 healthy young men 100 mg of hydrochlorothiazide daily to determine whether or not urinary detection of the drug was feasible as a measure of compliance on a standard antihypertensive regimen. All subjects took the drug daily for 6 days, after which they were divided into four groups with differing patterns of medication administration. Urine hydrochlorothiazide and creatinine measurements were obtained to validate the urinary hydrochlorothiazide-creatinine ratio (UHCR) as an accurate quantitative index of compliance. The subjects achieved a constant level of UHCR of 13 +/- 3.0 within 48 hours of hydrochlorothiazide administration. The UHCR levels decreased to 5.0 +/- 0.8 48 hours after discontinuation of the drug (p less than 0.001). UHCR values in the range of  13 +/- 6 indicate that the subject has ingested hydrochlorothiazide 24 hours previously. The UHCR is a potentially useful means of assessing compliance in hypertensive patients taking hydrochlorothiazide.


Symptomatic sick sinus syndrome due to guanethidine. Case report. A patient is described who developed symptomatic sinus bradycardia as low as 20 beats per minute and sinus arrest of up to 4.4 seconds while receiving guanethidine, 75 mg daily. The bradycardia resolved following discontinuation of the drug and reappeared upon challenge with it. Intrinsic disease of the sinoatrial and atrioventricular nodes was evidenced 3 weeks following discontinuation of the guanethidine by a borderline abnormally prolonged sinus node recovery time of 1500 msec and a PR interval of 0.28 seconds. Although sinus bradycardia is a known and not infrequent side effect of guanethidine, such an extreme form as seen in our patient appears to be quite rare, and may be related to the pre-existing disease of the conduction system.


Hemodynamic responses to DOCA in young pigs. Hemodynamic variables were measured in 20 young pigs; thirteen received subcutaneous implantations of desoxycorticosterone acetate (DOCA) impregnated in Silastic strips, seven received implants of Silastic strips alone and served as controls. No salt was added to the standard diet of either group. Mean arterial pressure (MAP) rose in a regular pattern in the DOCA-treated pigs, reaching on the average a level significantly greater than that of the control group 48 hours after the implantation. Pressure continued to rise, reaching a plateau 38% above that of the preimplant value 2 weeks later. In some pigs the MAP elevation was caused by an increase in cardiac output (CO); in others it was caused by an increase in total peripheral resistance (TPR). An increase in central venous pressure occurred in many DOCA-treated pigs regardless of whether the increase in MAP was caused by an increase in CO or in TPR. The results indicate that it is arterial pressure per se that is the regulated variable in this model of mineralocorticoid hypertension. The regulating system, whether it resides in the kidney or in the central nervous system, elevates pressure by effecting increases in either CO or TPR.


Can overnight urine replace 24-hour urine collection to asses salt intake? Are overnight urine specimens adequate for characterizing the daily salt intake of individuals, i.e., can the overnight specimen replace the 24-hour specimen? Data from 142 male participants of an ongoing trial on the primary prevention of hypertension were used to examine this question with correlation analysis and quantile classification. Estimated correlation between the true mean 24-hour and the true mean overnight sodium excretion was 0.72. Furthermore, 67% of the individuals in the upper third of the distribution of true mean overnight urine sodium were also in the upper third of the distribution of true mean 24-hour sodium. Thus, these data are promising in regard to the use of overnight urine specimens for characterizing the salt intake of individuals. The number of overnight urine collections required to estimate accurately the correlation between an individual's true mean overnight urine sodium and a variable of interest (e.g., blood pressure) was calculated. Given the observed intra- and inter-individual variation, the data indicate that 14 measurements are needed to limit the diminution of the correlation coefficient to 10%.


Blood pressure in childhood. The National Health Examination Survey. Data were analyzed from the U.S. Health Examination Survey (Cycle II) to determine relationships between blood pressure and other characteristics. This survey examined a national probability sample of children aged 6-11 years. Significant relationships were found for blood pressure and the following variables: chronological and skeletal age, skinfold thickness (adiposity) and other anthropometric measurements, pulse rate, and systolic murmurs. These relationships may be interpreted as indicating important relationships between blood pressure and growth, adiposity, and hemodynamic manifestations of cardiac output. Data from this representative population portray blood pressure relationships in childhood.


Blood pressure in adolescence. The United States Health Examination survey. A nationally representative sample of adolescents 12-17 years of age were examined in the U.S. Health Examination Survey and relationships between blood pressure and other variables were explored. During adolescence, blood pressure increases more rapidly in males than in females and only small racial differences are present. Weight has the strongest relationship to both systolic and diastolic pressure. Physiological maturation assessed by skeletal age and adiposity (skinfold thickness) are components of weight and each is also related to blood pressure. Although systolic murmurs are related to blood pressure at the time of examination, the murmurs are transitory and not predictive of future pressures. All factors were equally influential in each race-sex group. No significant relationships were found between geographic or demographic variables and blood pressure. These observations indicate the important relationships of physiological maturation and adiposity to adolescent blood pressure.


Sympathetic nerve activity and blood pressure in normotensive backcross rats genetically related to the spontaneously hypertensive rat. The genetic basis of hyperactivity of the sympathetic nervous system (SNA) in spontaneously hypertensive rats (SHR) was assessed by measuring SNA in animals derived from a backcross (BC) breeding program designed to isolate single gene differences causing changes in blood pressure. Selective breeding of the male hypertensive rats with inbred normotensive female Wistar/Lewis rats yielded progeny with a range of blood pressures, but whose group mean pressures were lower than the group mean pressures of the original SHR. Progressive generations had progressively lower group mean pressures. There was a positive correlation between SNA and mean arterial pressure in BC rats. These results indicate that the genetic defect in SHR may be abnormality in SNA, and the hypertension in these animals is a secondary result of this primary defect. Baroreceptor function was also assessed in SHR and in BC rats. In young (8 to 24 weeks old) SHR, baroreceptor function was similar to that in BC rats, whereas SNA was markedly increased. Only in older (24 to 40 weeks old) SHR was there an abnormality in the gain of baroreceptors. The development of hypertension in SHR therefore appears to be due to increased SNA resulting from a defect in the central nervous system. Changes in baroreceptor function are secondary to the hypertension and occur after the hypertension is established.


Arterial baroreceptor reflex control of sympathetic nerve activity in the spontaneously hypertensive rat. The combined and individual carotid sinus and aortic baroreceptor control of sympathetic nerve activity (SNA) and mean arterial pressure (MAP) were studied by direct measurement in groups of spontaneously hypertensive rats (SHR) and normotensive Kyoto Wistar rats (WKY) of 5 to 40 weeks of age. The SHR showed a significantly greater SNA and resultant MAP increase as a function of age compared to that of the WKY rats. Both SHR and WKY rats showed a significant rise in SNA and MAP with ablation of all four major baroreceptors. The proportionate change of SNA and MAP after ablation was greater in the younger SHR than in the younger WKY groups and the change in these decreased as a function of age in the SHR. The reflex inhibition of SNA via baroreceptor stimulation also decreased as a function of age in the SHR, due to a 43% loss of aortic inhibitory function; no significant loss of carotid sinus function was found in either the SHR or WKY. The decrement in aortic function occurred after the rapid phase of blood pressure development; therefore baroreceptor dysfunction cannot be the cause of the high SNA and MAP observed in young SHR. An upward resetting of central sympathetic centers was evaluated via the baroreceptor deafferentation; and it appears that the hyperactive sympathetic nervous system and resultant hypertension in the SHR is due to central resetting of sympathetic centers rather than baroreceptor dysfunction.


Evidence for enhanced sodium transport in the tail artery of the spontaneously hypertensive rat. Transmembrane Na+ and K+ gradients in the rat tail artery were dissipated by overnight incubation in K-free PSS at 10 degrees C and then allowed to recover in normal physiologic salt solution (PSS) at 37 degrees C. The active extrusion of Na+ and uptake of K+ during the recovery period was monitored with Na+ and K+ selective glass electrodes. Passive exchanges were differentiated by re-admitting K+ at 3 degrees C, or in the presence of 1 mM ouabain at both 3 degrees C and 37 degrees C. Active exchange was switched on by an abrupt transfer of the tissue from 3 degrees C to 37 degrees C. Active exchange, measured in perfused, superfused, or sequentially incubated arteries, was distinctly enhanced in young (16-, 20- and 26-week-old) spontaneously hypertensive rats (SHR) of the Okamoto strain compared with age-matched Wistar-Kyoto normotensive (WKY) controls. No such difference was observed in rats with hypertension of 7 or 12 weeks' duration and equal severity induced by unilateral constriction of the renal artery. Steady-state Nai and Ki were measured after washing the tissues for 45 minutes at 3 degrees C in lithium-substituted medium to exchange extracellular sodium with lithium. Cell sodium in these tissues was further partitioned into a free component proportional to [Na]0 and an independent, constrained component. Cell potassium was found to be distinctly elevated in 2- and 4-month-old SHR, while free cell sodium remained normal, despite increased cell permeability demonstrable in a significant exchange of lithium for cell potassium and sodium even at 3 degrees C.


Serum immunoglobulins in hypertension.

Serum immunoglobulins in hypertension. We measured serum immunoglobulins in 52 persons whose blood pressure was higher than 140/90 mm Hg, and 52 normotensive controls matched for age, sex and race. All were selected from a population of actively employed persons undergoing a routine health evaluation. Contrary to previous reports, the hypertensive subjects did not have higher levels of IgG or IgA than the controls. Sixteen hypertensive subjects with mean blood pressure higher than 115 mm Hg did not have elevated IgG or IgA levels when analyzed separately. Serum IgM was significantly lower in the 52 hypertensive subjects (125 +/- 67 mg/dl vs 171 +/- 85 mg/dl, p less than 0.01). Our subjects failed to show the increase in immunoglobulins reported by others. The most likely reasons for this is the mildness of their blood pressure elevation, although the absence of immunoglobulin elevation in the small number with more marked hypertension does not support this explanation.


Phenomenological structuring of the adult lifespan as a function of age and sex. The hypothesis that increasing differentiation in the phenomenological structure of the lifespan can be expected to occur during adolescence and early adulthood, stabilization during adulthood and a process of de-differentiation in the later part of life, was tested on eighty Israeli participants, age sixteen to seventy-eight. They were asked to divide the course of life into periods, starting at age eleven, and to mark the range of each period. As hypothesized the younger people perceived the lifespan as more differentiated (divided into more periods) whereas older people perceived it in a less differentiated way. There was consensus among the different age groups in their perception of the different stages of development. The earlier stages were viewed as more differentiated whereas the later periods were viewed in a more global way. In addition, women tended to perceive the lifespan as somewhat more differentiated than men; they also tended to perceive the pace of life as more rapid.


Individual differences in cognitive functioning in the elderly - phenomena and interpretation. Residents (N = 27) of a Jewish home for the aged were given a battery of twenty-five tests of cognitive abilities. Participants included people carrying a diagnosis of organic brain syndrome. Subsets of tests were designed to measure immediate sequential memory, ability to handle categories, and ability to execute motor patterns. There were marked individual differences among participants. Poorer performance was associated with carrying a diagnosis of organic brain syndrome and with a number of other background variables. There was empirical evidence that immediate sequential memory and ability to handle categories can be discriminatively measured. A wide variety of qualitative behavioral phenomena was described. The findings were interpreted in terms of an information-processing model.


Safety on the streets: cohort changes in fear. Using data from two national surveys, cohort changes in fear for one's safety on the streets are examined over an eleven year period. Fear of walking alone at night has increased among all cohorts, but the greatest increases have taken place among the older cohorts. These results are consistent with interpretations that stress characteristics of the aging process to account for the elderly's greater fear of vulnerability to criminal victimization.


The impact on mood of verbal reminiscing in later adulthood. The impact on mood of verbal reminiscing was compared with that of talking about the present or future in a group of thirty-six female participants between the ages of forty-six and eighty-five. Self reports of mood showed a relatively more positive effect of reminiscing and thus support the hypothesis that reminiscence may serve an adaptive function in later life. Participants over sixty-five years of age, however, did not report a different impact on mood than the younger participants, calling into question the age-specific nature of this phenomenon. Potential theoretical explanations and clinical implications of these findings are discussed.


Delivery of care for severely retarded children: a follow-up study. The study progress in the move from institutional toward community care a study was made of all children below 16 years of age for whom application for residential care had been made between 1970 and 1974. These children were followed-up in 1975 to (1) compare services needed with services obtained for those residing in hospitals compared to those living in the community, and (2) ascertain factors determining placement. Among those who applied, level of functioning was associated to a greater extent with age than degree of retardation. Two thirds of the youngest group was non-ambulant, at age 11-15 only 5% were still non-ambulant. Similar improvements with age occured in speech development and ability to follow simple instructions. Children living in the community in 1975 failed to obtain needed services more than those institutionalized although both groups did not differ in regard to service needs. Especially scarce for parents of children living at home at follow-up were supportive services as counselling for parents, home-maker or baby sitters needed by most. It was expected that placement would be related to level of functioning of the retarded, behavior problems, proportion of broken families. Yet no relationship was found between these variables and placement. Placement was determined solely by social class and ethnic background of the patients. In contrast to an earlier study more parents came from ethnic minorities and the lower classes. These parents may be more tolerant, more accepting of having a retarded child that middle class parents. Progress was noted in the proportion of retarded placed into the community and regionalization.


Espousing melodic intonation therapy in aphasia rehabilitation: a case study. A program of Melodic Intonation Therapy (MIT) was adapted as a home training procedure to enable a severely affected aphasic adult to respond to 52 simple questions bearing relevance to his daily life. MIT involves embedding short phrases or sentences in a simple, non-distinct melody pattern. As the patient progresses through the program, the melodic aspect is faded and the program eventually leads to production of the target phrase or sentence in normal speech prosody. The present procedure consisted of three levels of training designed to advance the subject from an initial level of intoning responses in a simple melody to producing the responses in normal speech prosody. The subject's wife was trained to administer MIT both in the clinical and home settings. Considerable improvement was obtained in imitation and in context related responses to questions. These findings lend support to the proposal that the music dominance to the right hemisphere assists, and perhaps diminishes the language dominance of, the damaged left hemisphere. The limitations of use of Melodic Intonation Therapy were discussed.


Horticultural therapy--aspects of land use for the mentally handicapped. A system of planning for the requirements of the mentally handicapped gardener. An increasing number of facilities for the mentally handicapped use horticulture, agriculture and gardening in their training programmes. This paper contains a review of: (1) some aspects of land use as a medium for leisure, rehabilitation, therapy and training for the mentally handicapped, (2) employment, both sheltered and open, in land use as reflected in a recent survey, (3) the variety of knowledge available through the medium of land use. The main emphasis of the paper deals with: (1) the need for planning, (2) a suggested planning system that assists the instructor in understanding the requirements of the mentally handicapped gardener when he approaches a given job, (3) some problems peculiar to land use work with the mentally handicapped. In conclusion the authors briefly examine: (1) the need for assessment, (2) the need to distinguish between production and training, (3) suggestions towards an expansion of the planning system to take in other areas of the horticultural unit than were originally described, (4) social activities connected with the horticultural activities described, (5) the hierarchy identified through the use of a particular planning system.


Time trends in colo-rectal cancer mortality in relation to food and alcohol consumption: United States, United Kingdom, Australia and New Zealand. Recent epidemiologically and experimental research has implicated dietary factors, including alcoholic drinks, in cancers of the colon and rectum. Analysis of time trends in cancer mortality since 1921, in the United States, England and Wales, Australia, and New Zealand, in relation to changes in per capita consumption of foodstuffs and alcohol reveals some support for the protective effect of fibre, but an inconsistent role for fat and meat in colon cancer. For rectal cancer, and to a lesser extent colon cancer, the most consistent correlate in comparisons across time, and between place, sex, and age-group, is beer consumption. Possible reasons for this correlation within this data set are discussed.


Isoniazid exposure in relation to cancer incidence and mortality in a cohort of tuberculosis patients. 41 226 isoniazid exposed and 22 811 non-exposed patients admitted to Canadian institutions for the treatment of tuberculosis from 1952 to 1960 were followed to 1973 by computerised record linkage to the National Death Index and, for 1969 to 1973, to the National Cancer Incidence Reporting System; The mortality for the total cohort compared to that expected from the mortality in the Canadian population, was greater than expected for tuberculosis, other chest diseases and certain cancer sites associated with cigarette smoking (except bladder cancer). There was, however, no difference between the isoniazid-exposed and non-exposed in mortality from all cancer and individual cancer sites, except for oesophageal cancer in males. Cancer incidence from 1969 to 1973 was also similar for the isoniazid- exposed and non-exposed groups. An elevated standardised incidence ratio was seen only for buccal cavity and pharynx in male exposed subjects. It is concluded that this study provides additional negative evidence on the carcinogenicity of isoniazid in man.


Quantity and variation in morbidity: THAID-analysis of the occurrence of gastroenteritis among Ethiopan children. Morbidity figures from a one-year longitudinal child health study comprising 749 children in an urban area in Ethiopia are reported. Aggregated morbidity measures, based on frequency distributions according to morbidity level, demonstrate gastroenteritis among infants and young preschool children as a quantitatively important morbidity problem. Variation in the occurrence of gastroenteritis is studied among 390 children under 5 years by means of a multi-variate method, THAID-analysis, designed for a categorical or, as in this study, a categorized criterion variable. The results indicate that variables expressing nutrition, housing, hygiene and sanitation are dominating predictors of childhood diarrhoeal disease.


The relation between respiratory illness in primary schoolchildren and the use of gas for cooking--II. Factors affecting nitrogen dioxide levels in the home. The study was designed to determine whether there was an association between indoor levels of nitrogen dioxide (NO2) and respiratory illness and lung function in schoolchildren. NO2 was measured for one week in the winter outside and inside the homes of children aged 6-7 years living and attending primary schools in a defined 4 square km area in Middlesbrough, Cleveland, UK. Outdoor levels of NO2 measured at 75 points within the area ranged from 14-24 ppb weekly average. Measurements were also made in 428 kitchens with gas cookers, range 5-317 ppb, mean 112.2 ppb, and in 87 kitchens with electric cookers, range 6-188 ppb, mean 18.0 ppb. In a random subsample of homes the range of NO2 levels in 107 children's bedrooms in homes where gas was used for cooking was 4-169 ppb, mean 30.5 ppb, in 18 bedrooms in electric cooking homes the range was 3-37 ppb, mean 13.9 ppb. NO2 levels in the gas cooking kitchens were positively related to the presence of pilot lights, use of gas fires for main heating, number of regular smokers, and the number of people in the home. Information from 29 homes with the highest kitchen NO2 levels paired with 29 low NO2 gas cooking homes showed that the daily number of meals eaten and the frequency with which the cooker was used for heating and drying clothes were significantly greater in the high NO2 homes.


The relation between respiratory illness in primary schoolchildren and the use of gas for cooking--III. Nitrogen dioxide, respiratory illness and lung infection. We examined the relation between lung function and respiratory illness in a population of 808 primary school children aged 6-7 years and the levels of nitrogen dioxide (NO2) in the kitchens and bedrooms in their homes. Complete data were collected on about 66% of the population. The children lived in a defined 4 square km area in Middlesbrough, Cleveland, UK. One week average outdoor levels of NO2 varied little over the area (14-24 ppb); The prevalence of respiratory illness was higher in children from gas than electric cooking homes (p approximately or equal to 0.1). Although prevalence was not related to kitchen NO2 levels (range 5-317 ppb) it increased with increasing levels of NO2 in the children's bedrooms in gas cooking homes (range 4-169 ppb, p approximately or equal to 0.1). Symptoms in siblings and parents were not related to kitchen NO2 levels. Lung function was not related to NO2 levels in the kitchen or bedroom. Because of the very low levels of NO2 at which an association with illness was observed and the inconsistency between our results in the UK and those from several studies in the US, it is possible that the NO2 levels were a proxy for some other factor more directly related to respiratory disease such as temperature or humidity.


The relationship of symptoms and blood pressure in a population sample. The relationships of symptoms and blood pressure were studied in a population sample of 1926 individuals. Analysis of covariance showed that none of the 13 symptoms was significantly related to systolic or diastolic BP. Symptoms were more strongly associated with confounding variables.


Impact of changing age and parity distributions of mothers on perinatal mortality in Sweden, 1953-1975. A study was made on how the shift in the age and parity distribution of mothers affected the perinatal mortality in Sweden between 1953-55 and 1973-75. During these years the overall perinatal mortality rate fell from 29 to 13 per 1 000 births. The authors used the specific perinatal mortality rates by the mother's age and infant's birth order in 1973-75 to calculate what the overall perinatal mortality rate would have been with the age and parity distributions of mothers in 1953-55 and 1963-65. They conclude that only 1.4 of the 16 per 1 000 decline in perinatal mortality could be attributed to the shift in the mother's age and parity distribution.


Mortality in chromium chemical production workers: a prospective study. Mortality among male employees was studied in a chromium chemical production plant, part of which was rebuilt in 1950-51 and the remainder in 1960, to reduce exposure to chromium bearing dusts. Of 2 101 employees initially employed between 1945 and 1974 and having worked at least 90 days, the vital status of 88% was ascertained, as of mid-1977. Lung cancer mortality for hourly workers initially employed between 1945 and 1959 was significantly higher than in the comparison Baltimore City population (SMR = 2.0), yet it was lower than that reported in previous studies of this industry. A dose response effect was evident from the relationship between duration of employment and mortality. The lung cancer mortality among those employed for three or more years exclusively in the new facility was similar to that observed for such long-term workers in other parts of the plant. Specific job positions were examined. A history of employment in the Bichromate and Special Products Department (production of chromic acid and other products), known as the 'wet end', was associated with the increased lung cancer mortality in contrast to the Mill and Roast Department, known as the 'dry end'. Because of the long latency period associated with chromium exposure and cancer, it was not possible to adequately assess the risk of cancer for workers initially employed after 1960. Methodological issues related to these findings are discussed.


A follow-up study of non-retired and retired members of the Danish Carpenter/Cabinet Makers' Trade Union. A 6 years follow-up study of mortality among Danish carpenters and cabinet makers (40 000 persons) shows an SMR of 82 in the group of non-retired and an SMR of 70 in the group of retired union members. No major causes of death except nasal cancer were significantly above the national average. Problems of methodology in using retired workers in the occupational mortality studies are discussed.


Potential-years-life-lost from motor vehicle crashes in Israel: an epidemiologic analysis. Motor Vehicle Crashes (MVC) were the 7th ranking specific cause of mortality (Israel 1975) after ischaemic heart disease (ISHD), cerebrovascular disease, respiratory disease, various types of cancer, and accidents other than MVC, but were the top ranking single cause (in males, next to accidents of all kinds) of Potential-Years-Life-Lost (PYLL) ages 1-65 among men and women and men 1-70 and 2nd ranking cause of PYLL age 1-75 among men. Many young male deaths from MVC and few from non-traumatic causes below age 40 account for these high PYLL rankings for MVC. Israeli age-specific death rates from MVC below age 40 were lower than those of USA, but higher among the elderly (reason: pedestrian deaths). Both Israel's PYLL rate (PYLL per 100 000 persons) from MVC and crude mortality rates are only slightly lower than those of USA. Trends in Israel point to a growing number of drivers among young and poorer groupings, who have been shown elsewhere to be at high-risk for MVC mortality. PYLL from MVC in Israel can be expected to increase, even if crude death rates remain stable or decline. Swift low-cost preventive measures could arrest or reverse these predicted trends.


Immersion and distance: two varieties of experience of psychiatric hospitalization. In this paper we describe an inquiry into the experience of short-term hospitalization. Sixty-seven patients were interviewed shortly before discharge with the goal of obtaining a picture of their subjective impressions--satisfactions, criticisms, hopes for the future--growing out of their hospitalization. Two broad types of experiences were noted, which we label 'immersion' and 'distance'. We illustrate some of the clinical manifestations of these two divergent hospital experiences, discuss their relations to traditional diagnostic categories, and speculate on their implications for clinical management.


Multiple primary malignant tumors: a rare combination in the stomach. We have reported one case of a rare combination of multiple primary malignancies in the stomach, a leiomyosarcoma and an adenocarcinoma in a 72-year-old male. He also had a leiomyoma of the stomach and a cavernous hemangioma of the spleen. Since he has had two malignant and two benign tumors, it would appear that this patient has a tendency to develop neoplasia.


Peptic ulcer in Rwanda, Africa: influence of geography and dietary habits. There are areas of Africa with an extremely high incidence of peptic ulcer disease, while most of Africa has a low incidence of ulcer disease. The reason for this variation is unknown. Thirty-three patients with peptic ulcer disease in Rwanda, Africa, were studied in an attempt to determine why they had ulcer disease. High basal acid studies (mean of 10.3 mq per hour) were found in the patients with duodenal peptic ulcers. The males predominated over the females and the Batutsi predominated over the Bahutu in having much more peptic ulcer disease. The male population and patients with ulcers had the custom of eating only one large meal per day. There is a definite correlation between the incidence of peptic ulcers among certain tribes and going for long periods without eating.


Hemobilia: an unusual complication of the intrahepatic intubation of the biliary ducts. Hemobilia, occurring as a complication in the intrahepatic intubation of biliary digestive anastomosis, carried out according to the Saypol and Kurian technique, is reported. It is postulated that this complication can occur when anatomic variations of the artery related to the biliary duct in either the anterior or posterior position are present.


Intraoperative transcystic extraction of common bile duct stones by a Dormia-Pironneau catheter. During cholecystectomy 21 patients were subjected to transcystic extraction of common bile duct stones by a Dormia-Pironneau catheter; this was the only treatment used for lithiasis of the common bile duct, in the absence of papillary lesions. Of these patients, 14 were followed up from one to three years after surgery. Clinical and radiological controls revealed the patients' complete recovery from the biliary disease. Our late results thus warrant the method. We suggest that is should be employed in all cases in which the presence of minute stones in the gallbladder, a wide cystic duct, and the absence of papillary lesions suggest migration of gallstones from the gallbladder to the common bile duct.


Aneurysm of pancreaticoduodenal artery: report of a case and review of the literature. Aneurysms of the pancreaticoduodenal artery are uncommon. Only 24 cases have so far been reported. A case of clinically unsuspected, fatally ruptured pancreaticoduodenal artery aneurysm in a 64-year-old man with a five-day history of mild epigastric pain is reported. A review of the literature and brief discussion of etiologic factors and clinical presentations are also included.


Pancreatic abscess: a case report.

Pancreatic abscess: a case report. The case history of an 81-year-old man who developed a large pancreatic abscess following pancreatitis is presented in depth. The underlying cause was biliary tract disease, and the patient successfully underwent cholecystectomy, choledocholithotomy, and drainage of the pancreatic abscess. Several important points in the management of this problem are emphasized.


Colon and anorectal neoplasms in a tropical African population. At the University College Hospital, Ibadan, Nigeria, over a 30-month period (January 1975 to June 1977) more than 29 cases were fully studied. Nine patients presented with acute large bowel obstruction. In five cases, colonic neoplasms were palpated abdominally before surgery, and four of the patients were initially being treated for "hemorrhoids". All the patients presented at late stages. There was neither socio-economic nor sexual bias in this affliction. Sixty-nine percent of all the tumors occurred in the anorectal area well within the reach of the index finger, and 27.5% occurred in the right colon. Differential diagnosis included ameboma, rectal schistosomiasis, rectal tubercolosis, anal fistula and adult chronic intermittent intussusception. The treatment administered depended on the nature, location and stage of the disease. There was a case of metastatic squamous cell carcinoma of the hepatic flexure causing obstruction. The metastasis was from carcinoma of the cervix which had been treated with cesium insertions about three years previously. It is now known that colon and anorectal neoplasms, once regarded as rare among Africans living in tropical Africa, is not that rare. With the Africans boycotting native "doctors" in favor of medical institutions, many of the diseases once thought to be rare in Africans will unfortunately become less rare.


Mechanical problems in the use of the intra-aortic balloon. Although there are many complications in the use of the intraortic balloon (IAB) support device, they are relatively benign compared to the benefits of the device. The purpose of this paper is, firstly, to review a protocol in the safe use of this device, and secondly to remind enthusiastic users of the IAB that the use of this method is not always as benign as we would like it to be. Rarely reported findings at postmortem examination in two patients who died in cardiogenic shock are described. The aorta of one of the two cases in this report had a longitudinal tear which involved only the intima and extended from the common femoral artery to well above the renal arteries. In the second case, the balloon tip had entered at the bifurcation of the aorta in a subintimal manner and had re-entered well below the renal arteries, to be relocated in the proper site in the descending aorta.


Priapism and pudendal arteriovenous fistula. The authors report a case of recurrent priapism treated by saphenocavernous bypass and accompanied by a congenital internal pudendal arteriovenous fistula. In the light of this case and the literature, they discuss the physiopathology of priapism and the sound basis of the various therapeutic methods proposed.


Staging laparotomy in Hodgkin's disease. In a series of 34 consecutive staging laparotomies for Hodgkin's disease, unsuspected disease was discovered below the diaphragm in four cases (11,8%). The clinical staging was changed in 11 cases (32,4%). These data correspond to the results in most large series. Since staging laparotomy can be performed with minimal morbidity and gives the clinician the information essential to a rational plan of therapy, it is suggested that staging be performed prior to initiation of treatment in all patients with Hodgkin's disease not clinically proven to be disseminated.


Birth injury to the spinal cord.

Birth injury to the spinal cord. 11 cases of children with birth injury to the spinal cord born between 1960 and 1970 are presented in review and compared to about 200 previously published cases. 8 children presented at delivery with one or both feet and 2 with breech. 9 of these infants were born by difficult extraction and needed resuscitation due to primary asphyxia. One child had an easy vertex delivery without evident risk. Diagnosis was established within the first days of life, based on flaccid motor and sensory paralysis below a defined level, mostly in the cervical or upper thoracic spine, with bladder and bowel paralysis, and confirmed by autopsy or by follow-up study. One child with disruption of the spinal cord above C4 survived only a few hours despite artificial ventilation. 4 children died within the first three years of life, 3 of them due to acute pneumonia. 5 of 6 surviving children were followed regularly and are now 10 to 18 years old. They are ambulant with crutches and are well integrated in their families. 4 children attend normal school, and one girl gets special training for mentally retarded children.


Posttraumatic anterior pituitary insufficiency in childhood. 5 patients are presented in whom cerebral trauma of varying intensity during childhood was followed by pituitary insufficiency. There was no correlation between the severity of injury and subsequent hormonal defects. Among other anterior pituitary hormone defects, growth retardation secondary to growth hormone deficiency is a predominant feature in the pediatric age group. Only one patient requires treatment of neurohormonal diabetes insipidus. The prevalence of traumatic origin among the hypopituitary dwarfs observed in our departement is 3.7%.


[Serum IgE levels in atopic diseases in childhood]. The serum IgE levels were determined according to the radioimmunosorbent technique (RIST), in 208 children aged between 1 and 14 years, with atopic diseases alone or in combination. Geometric mean IgE levels were significantly increased and rose progressively from the atopic dermatitis "alone" to the allergic rhinitis, the allergic asthma and the combination of asthma with rhinitis, with the highest values in patients where atopic dermatitis was combined with respiratory allergy. IgE levels rose slowly with age. For the atopy diagnosis in vitro, two criteria were chosen and compared: a fixed IgE-level of 100 U/ml, and one standard deviation below the geometric mean of the atopic children.


[Bacterial meningitis in newborn infants. A retrospective study from a pediatric clinic 1967-1978]. A total of 22 newborn infants (14 boys, 8 girls) have been admitted and treated for bacterial meningitis in the University Pediatric Service of Geneva over a period of 11 years (May 1967 to May 1978). The three most common infectious agents were: Group B beta-hemolytic Streptococcus (6/22 cases), Escherichia coli (6/22 cases), and Listeria monocytogenes (4/22 cases). Thirteen of the 22 infants died (a 59% mortality, in keeping with that observed in other centers). Follow-up of the nine survivors showed a relatively favorable course from a developmental and neurological point of view. Only two of the infants have significant sequelae. Factors predisposing toward the occurrence of neonatal meningitis are a small birth weight, premature rupture of the membranes, and perinatal maternal infection. Prevention of neonatal meningitis is therefore very much dependent upon good perinatal care of the mother. Treatment of neonatal meningitis is impaired by the poor diffusion of antibiotics through the blood-brain barrier. Intrathecal antibiotics were used in 4 cases in this series, and three of these 4 patients died: intrathecal antibiotherapy is obviously not a good solution. Molecules with a better diffusion such as chloramphenicol should be considered with renewed interest.


Nonsurgical treatment of interhemispheric subdural empyemas. Interhemispheric subdural empyema complicating sinusitis was diagnosed in two children by CAT scan. One of them presented with intracranial hypertension and paresis of one foot (syndrome of the falx cerebri). Antibiotic treatment alone without surgery (in one case with brief initial steroid therapy) brought rapid and complete clinical and radiological cure. A nonsurgical approach can now be considered in certain cases of intracranial local suppurations, given the possibility of earlier and more precise initial diagnosis and follow-up with CAT scan.


Subdural interhemispheric empyema in a 7-year-old boy. Subdural interhemispheric empyema was diagnosed by angiography and computerized tomography (CT) in a 7-year-old boy suffering from acute left hemiparesis. After neurosurgical intervention his condition improved. Peptostreptococcus intermedius was cultured from the empyema. One year after hospitalisation the boy is in good condition. The importance of the CT-scanning for diagnosis and management of brain abscess or empyema is stressed.


Strychnine treatment attempted in newborn twins with severe nonketotic hyperglycinemia. Strychnine, a potent antagonist of glycine was given to twins suffering from nonketotic hyperglycinemia at age 73 hours. Within hours of the onset of treatment favorable effects were observed such as improvements of muscle tone, movements, defense reactions, and probably breathing. Pyridoxine, N5-formyl-tetrahydrofolate and lipoic acid were given concomitantly with strychnine but failed to alter glycine levels in plasma and cerebrospinal fluid. The therapeutic trial was terminated after 2 1/2 days because success, though considerable, was judged inadequate.


Amniotic cells in fetal Fallopian tubes. In a dizygotic 25-week-old twin fetus the histologic examination of the Fallopian tubes disclosed an unusual finding: the bilateral salpingeal lumen was filled with amniotic cells. The latter were especially numerous in the ampulla which still had few folds and which therefore had a comparatively wide  lumen. Amniotic cells and numerous granulocytes were present in stomach and duodenum, but no focus of perforation could be demonstrated. The clinical significance of the so far unknown resorptive potential of the Fallopian tubes and the possible late complications of prenatal intraperitoneal blood transfusions are discussed.


Disorders of candidacidal activity and other neutrophil functions in three cases of chronic candidiasis. Three unrelated cases of recurrent and untreatable candidiasis have been followed for about one year. A persistent in vitro defect of neutrophil candidacidal activity characterized the three cases, while other neutrophil functions were shown to be only transiently impaired during the period of observation. None of the three cases could be identified with previously described granulocytopathies.


Unilateral galactocoele in a male infant. An otherwise healthy 1 1/2-year-old boy slowly developed a marked enlargement of his right breast during several months. The lesion was soft, round, fluctuant and translucent. Aspiration revealed the presence of a milk-like fluid. Surgical extirpation was performed. Histologically the cyst showed areas of actively secreting acinar mammary cells.


[What can be expected of the endolaryngeal use of the neodymium-YAG laser as a treatment method?]. A short review of experiences in animal usage is made, and the first clinical experiences with the endolaryngeal application of the Neodymium: YAG laser MediLas in the treatment of benign vocal cord lesions are reported. The initial results are favourable, but final judgement of this microsurgical technique must be based upon a larger number of patients and a longer follow-up.


[The behavior of the facial nerve in vitamin A and thalidomide induced atresia auris congenita. A microsurgical and histological animal study (author's transl)]. Atresia auris congenita may include either a complete or incomplete paralysis of the facial nerve as well as a possible abnormal course of its tympanic segment. Pregnant Wistar rats were given high doses (50,000, 80,000 or 100,000 USP units) of vitamin A and (10,15 or 20 mg) Thalidomide on the 8th, 9th, 10th and 11th days of gestation. The animals were then sacrificed, and the temporal bones and the medulla oblongatas of the fetuses and the adult rats were examined microsurgically and histologically. In contrast to previous reports in the literature, no significantly abnormal courses of the nerve could be found. These findings corresponded to those of 62 endaurally operated human ear malformations. The paralysis of the facial nerve in these patients seems due to a reduced diameter of the nerve and not to a malformation of its nucleus.


[Psychopathology in patients with presumed nasal deformities (author's transl)]. If a patient with a "normal" nose desires rhinoplastic surgery, psychopathologic behavior should be recognized. In such patients, surgery is contra-indicated and the origin for the neurosis should be investigated. Two patients are presented in whom psychoanalysis was useful in correcting complex neurotic fixations on the nose with their attendant psychic dysharmonias. Therapy provided each patient with a more satisfying personal image. Each patient's desire for corrective nasal surgery was eliminated and patients were better able to accept their nasal features as well as gain positive social adjustments in their future lives.


[Experiences with osteosynthesis for maxillofacial fractures (author's transl)]. Over the past few years a number of methods, including the miniplate system for the osteosynthesis of facial fractures have been developed. These and the instruments used are described with examples.


Nodular fasciitis and proliferative myositis as variants of one disease entity. The concept of nodular fasciitis and proliferative myositis as variants of the same fibroblastic disorder is supported by intermediary cases, showing simultaneous features thought to be typical of either nodular fasciitis or proliferative myositis. Various other anatomical, pathological and clinical similarities found in this study of 100 cases support such conclusions. 'Ganglion-like' cells were a distinct, but not exclusive, feature of all cases with sole, or only partial, muscle involvement.


[Septoplasty without postoperative nasal packing. Mucosal repair of the upper airway with human biologica glue (author's transl)]. With the use of human biological adhesives in nasal septal surgery with or without extensive dissection, nasal packing can be avoided or at least its use essentially shortened. As a result, nasal breathing is not interrupted and mucociliary clearance resumes at an earlier stage of healing. In addition, infections of the sinsuses or the deep airway are prevented. The provisional high costs of the adhesive can be justified by the lessened patient morbidity. Similar favorable experiences with the adhesive were also found in various other reconstructive procedures of the head and neck, including tympanoplasty, aural atresia, skin transplantation, etc.


Metrical analysis of growth changes in the jaws and teeth of normal, protein deficient and calorie deficient pigs. Weanling pigs were separated into three groups: control animals were allowed unlimited food; protein deficient animals were allowed unlimited carbohydrate or fat but restricted in protein intake; calorie deficient animals were restricted in total food intake. The skulls and teeth of animals killed at one year and at two years of age were measured from radiographs, and from the results were derived the following conclusions: (1) Pigs fed on protein and on calorie deficient diets all showed considerable retardation of the growth of jaws and teeth, consistently more severe in the calorie deficient than in the protein deficient animals. (2) The shape of the mandible was altered by both types of malnutrition, the height of the ascending ramus being reduced to a greater extent than either its anteroposterior width or the length of the body of the mandible. The labial alveolar process became more proclined with increasingly severe malnutrition. (3) The upper and lower jaws were retarded to a similar extent in both groups of experimentally malnourished animals. (4) Retardation of tooth growth was less severe than that of jaw growth. (5) Contralateral asymmetry of molar crown size in the protein deficient animals was initally quite marked, but when the teeth were approaching their final size the asymmetry was no greater than in control animals.


Morphological observations on the metanephros in the postnatal opossum, Didelphis virginiana. The metanephros of the newborn opossum is very immature, consisting only of collecting tubules and a few immature nephrons. Development during the postnatal period can be divided into two distinct phases. The initial phase occurs during the first 60 days of postnatal life and is concerned with nephronogenesis and the differentiation of nephrons that have formed during this period. The second phase lasts through the remainder of the postnatal period and is concerned with further differentiation and growth of established nephrons. During this latter period the tubular portion of the nephron increases in length and the renal corpuscle increases in diameter. Ultrastructural observations suggest that metanephric nephrons are not functional during the first 4 days of postnatal life, while the mesonephros reaches the height of its development during this period: there may be some functional overlap between the mesonephros and metanephros during the latter part of the first week of postnatal life. The pattern of nephron induction and differentiation in the opossum is discussed.


Ultrastruct and origin of epiplexus cells in the telencephalic choroid plexus of postnatal rats studied by intravenous injection of carbon particles. Epiplexus cells in the telencephalic choroid plexus of postnatal rats were shown with the electron microscope to be of two kinds, one with monocyte features including an indented nucleus with coarse chromatin, numerous polyribosomes, long profiles of rough endoplasmic reticulum, a well-developed Golgi apparatus, lysosomes, microtubules and coated vesicles, long cytoplasmic process and filopodia; the other with the addition of highly vacuolated cytoplasm. In order to clarify the origin of these cells, rats were given two intravenous injections of carbon particles. Shortly after the second carbon injection (1-4 days) none of the epiplexus cells were tagged with carbon. Five and six days after the second carbon injection, however, a variable number of epiplexus cells were labelled with intracytoplasmic carbon. Their number decreased later and by 9 days hardly any were seen. The present evidence suggests that the carbon-labelled epiplexus cells are derived from circulating monocytes which have ingested the carbon particles while in the blood. The labelled cells then cross the walls of subependymal blood vessels, penetrate the multilayered subspendyma and ependymal lining and enter the lumen of the lateral ventricle.


The role of cartilage canals in the formation of secondary centres of ossification. The present studies indicate that in the growth of cartilage canals the cartilage is removed by chondroclasts which stem from the primitive connective tissue cells of the perichondrium. Besides fusing to form multinucleated chondroclasts, these cells also provide the osteoblasts which establish the secondary centre of ossification. The growing tips of the blood vessels within the canals are also fashioned from these primitive connective tissue cells as they invade the microhaemorrhages at the ends of the canals. This is an identical procedure to that found in the vascular invasion of the primary growth plate. The cartilage canals are clearly useful sites in which to study the development of osteoclasts and chondroclasts from more primitive (osteoprogenitor) cells.


Age-related degenerative changes in the mouse mandibular joint. The mandibular joints of ageing male ICR mice were studied by light and electron microscopy. A high incidence of degenerative joint disease was found relatively early in adult life, osteoarthrosis being evident by the seventh month. Initially the pathological changes were those of chondromalacia confined to isolated foci on the articular surface of the condylar cartilage. Later, characteristic signs of osteoarthrosis were noted, namely fibrillation, fibrous ankylosis, lipping and subchondral osteosclerosis. Ultrastructural examination indicated a marked heterogeneity in the articular lesions. Deep fissures and extensive cracks spread to the underlying matrix, and these were associated with severe alterations in its macromolecular structure. It is proposed that ageing chondrocytes produce a matrix which is increasingly incapable of withstanding normal mechanical forces, and this leads to the morphological changes recognized first as chondromalacia and then as osteoarthrosis.


A scanning electron microscope study of the pineal recess of the adult brush-tailed possum (Trichosurus vulpecula). The ventricular surface features of the pineal recess of 35 adult brush-tailed possums (Trichosurus vulpecula) were studied, mainly with the scanning microscope. The complex and interesting details observed have not been reported before. The pineal recess shows three distinct zones, and it is suggested that these be called: central, paracentral, and peripheral. The surface cells of the central zone show neither cilia nor microvilli, the paracentral zone shows microvilli (in a polygonal and homogeneous array), supraependymal cells and CSF-contacting nerve processes, while the peripheral zone is heavily ciliated. These features are consistent with the hypothesis that, in certain physiological states, the CSF from the pineal recess carrying pineal secretion is momentarily 'swept' forward in the direction of the median eminence to influence hypothalamic functions directly.


Experimental induction of premature movement of rat palatal shelves in vivo. In order to enhance further knowledge of palatal shelf movement and the factors involved in palate closure, a method was developed for prematurely elevating palatal shelves in utero. Approximately 7 hours before expected shelf elevation, pregnant Sprague-Dawley rats were laparotomized and two medially directed squeezes were applied to the face of some of the embryos through the intact uterine wall. Palates from control (unsqueezed) and experimental animals were obtained immediately after the procedure and 2, 4, 7, 12 and 24 hours later. In the 0, 2 and 4 hours groups, 82% of experimental palates were elevated, whereas only 6% of control palates were elevated. At 0 hours only the hard palate in the experimental group had elevated, but at 2 and 4 hours almost half this group showed elevation of the soft palate as well, and, in addition, contact had been made between the elevated shelves.


Demonstration of circadian rhythm in granular vesicle number in pinealocytes of mice and the effect of light: semi-quantitative electron microscopic study. Adult (70-100 days) male dd-mice were killed at 7 a.m., 1 p.m., 7 p.m. and 1 a.m. under controlled daily photoperiods (L: 7 a.m.-7 p.m.) and temperature, and at 6, 12 and 18 hours after exposure to continuous lighting which started at 7 p.m. Montage photographs were made from electron micrographs at x8200 based on mesh hole areas, using either 150 or 300 meshes. The number of granular vesicles per unit area was counted (GV Score). The GV Score in distal, mid and proximal portions of the body of the pineal gland showed marked 24 hour change, with high values in the late light period and low values in the dark period. The GV Score in the Golgi region showed a 24 hour change with a smaller amplitude. A peak level was attained at mid-light period and low values during a dark period. Additional lighting inhibited the nocturnal decrease in the GV Score in both the whole cytoplasm and the Golgi region, resulting in a slight increase. It is concluded that the number of granular vesicles in mouse pinealocytes (and in their Golgi regions) follows a 24 hour rhythm, and that the nocturnal decrease in the vesicle number depends upon darkness.


The chick embryo late primitive streak and head process studied by scanning electron microscopy. Changes in cell shape during the formation of the head process and regression of Hensen's node have been examined by scanning electron microscopy in a series of chick embryos from stage -5 to stage -8. The endoderm was removed from embryos mounted for New culture so that the mesoderm could be viewed from the ventral surface. As the primitive streak shortens its cells flatten and lose the flap-like processes characteristic of earlier stages. The notochord differentiates and its cells become transversely orientated, then re-align along the embryonic axis between stage 6 and stage -8. At the same time a split or cleft appears between notochord and head mesoderm, and extracellular fibrils are formed which are the first sign of the formation of a notochordal sheath.


The ventricular surface of the subcommissural organ: a scanning and transmission electron microscopic study. The subcommissural organ of the rat has been studied by a combination of light, scanning and transmission electron microscopy. Special attention has been paid to the appearance of the ventricular surface of the organ. The ependyma-derived cells on the surface of the organ are extremely long with a width which diminishes steadily from the base, where the nucleus is situated, to the ventricular surface. This results in a fan-shaped arrangement of cells, the cytoplasm of each cell reaching the surface of the ventricular system. The apical surface of the cell has small ciliated extensions 1-1.5 micrometers in diameter protruding into the ventricular lumen. With conspicuous rough endoplasmic reticulum and Golgi apparatus, and microtubules in profusion, the subcommissural organ cells possess the hallmarks of active secreting cells. The surface of the cells shows pinocytic vesicles-suggesting exchange of materials with the cerebrospinal fluid.


The structure of the excurrent ducts of the testis of the guinea-fowl (Numida meleagris). The epididymal region of the guinea-fowl was studied in sexually mature birds. The structure of the epididymal region was generally similar to that already described for the domestic fowl, turkey and Japanese quail. Well formed, intratesticular tubuli recti was seen connecting the seminiferous tubules with the rete testis. The latter consists of both intracapsular and extracapsular portions. Six main cell types were recognised in the region: the rete testis was lined by squamous cells, the proximal efferent ductules by ciliated and non-ciliated Type I cells, the distal efferent ductule by ciliated and non-ciliated Type II cells, and the connecting ductules, ductus epididymidis and ductus deferens were lined by non-ciliated Type III and basal cells. The cell classification adopted in this study is discussed.


Aortic aneurysm in Marfan's syndrome: changes in the ultrastructure and composition of collagen. Aneurysmal aortic tissue and the mitral valve of a patient with Marfan's syndrome were examined. Biochemical analysis of the tissue showed a qualitative and quantitative defect in alpha 2 chain production of Type I collagen. On polyacrylamide gel electrophoresis of the aortic extract, two separate bands in the alpha 2 region and an increase of the alpha 1 to alpha 2 ratio were found. Examination by electron microscopy revealed elastic fibre degeneration, helical collagen fibres, and metabolically active modified smooth muscle cells. The formation of helical collagen fibres is attributed to a defect in the development of chains and cross-links of collagen precursors produced by the hypertrophic smooth muscle cells. Elastic fibre disintegration is believed to be due to a lack of support by Type I collagen fibres, which have decreased tensile strength. A scheme for the pathogenesis of aortic aneurysm and other connective tissue abnormalities in Marfan's syndrome is proposed as follows. Type I collagen fibres have decreased tensile strength because of a defect in the alpha 2 chain biosynthesis and decreased cross-linking. Over many years the wall of the ascending aorta is subjected to cyclic stresses and it dilates. Elastic fibres disintegrate. The attempt at repair by metabolically activated modified smooth muscle cells is abortive, and rupture is likely to occur.


Regeneration of peritoneum: a fibrinolytic study. The healing of peritoneal wounds has been studied using a fibrin slide technique. Normal peritoneal mesothelium shows fibrinolytic activity. During the first 48 hours of healing fibrinolytic activity is absent from the wound surface but thereafter gradually increases until 8 days, when peritoneal regeneration is complete. At this time the activity is much greater than that in normal mesothelium. The results suggest that fibrinolytic activity of regenerating mesothelial cells will allow them to penetrate into and lyse fibrinous adhesions before fibroplasia occurs, thus preventing the formation of permanent fibrous adhesions.


Hydroheptin: a water-soluble polyene macrolide. I. Taxonomy, fermentation and isolation. A soil isolate of Streptomyces, which has been deposited in the culture collection of the Waksman Institute of Microbiology, Rutgers University as IMRU 3962, produces a new heptaene macrolide antifungal antibiotic, hydroheptin. The producing microorganism, which co-produces the antibiotic, chartreusin, has been identified as a strain of Streptomyces chartreusis. Fermentation and bioassay procedures were developed for the production and analysis of hydroheptin and chartreusin. Isolation and purification procedures based on solvent extraction and precipitation of an organic acid yielded a relatively pure product of hydroheptin.


Hydroheptin: a water-soluble polyene macrolide. II. Chemical and biological properties. Hydroheptin, a new polyene macrolide antifungal antibiotic, is co-produced with the antibiotic, chartreusin, by a strain of Streptomyces chartreusis designated as IMRU 3962 isolated in our laboratory. The unique water-solubility of this antibiotic at neutrality, revealing in aqueous solution molecular dispersion and an ultraviolet-visible absorption spectrum characteristic of an all-trans heptaene chromophore, clearly distinguishes it from all previously-described and naturally-occurring heptaene macrolides. The isolation and identification of the amino sugar, mycosamine (3-amino-3,6-dideoxy-D-mannose), in acid hydrolysates of hydroheptin and the absence of an aromatic amine upon retrograde alkaline dealdolization of the molecule certainly characterize the antibiotic as a member of the non-aromatic heptaene macrolide group. Chromatographic and countercurrent distribution studies likewise support its novelty. With little or no demonstrable activity against bacteria, hydroheptin as compared to other non-aromatic heptaene macrolides exhibits excellent but somewhat less activity against a wide variety of yeasts and fungi. Likewise, its parenteral toxicity appears to be less than that of other heptaene macrolides.


Staphcoccomycin, a new basic macrolide antibiotic. Staphcoccomycin (SCM) is a new member of the basic macrolide family of antibiotics which was isolated from the fermentation broth of Streptomyces sp. AS-NG 16. The production, purification and determination of physical and chemical properties of this novel metabolite have been completed. Comparison of the mass fragmentation patterns of SCM and its peracetate with those of angolamycin peracetate suggested a des-mycarosyl derivative of angolamycin. Moreover, the molecular ion peak (m/e 771) corresponded to C39H65NO14 and the 1H-NMR of SCM was also consistent with the proposed structure.


Biosynthetic relationships among the secalonic acids. Isolation of emodin, endocrocin and secalonic acids from Pyrenochaeta terrestris and Aspergillus aculeatus. Cynodontin, emodin, endocrocin and secalonic acids A, E and G have been isolated from five strains of Pyrenochaeta terrestis. Aspergillus aculeatus produces emodin, endocrocin and secalonic acids B, D and F. No cynodontin was detected. Isolation of emodin in small amounts supports previous evidence that it is an intermediate in secalonic acid biosynthesis. Isolation of cynodontin and endocrocin, which are co-produced with secalonic acids in other organisms, suggests that these compounds are formed by a common branching pathway. A natural isolate of P. terrestris contained variant strains which produced different relative amounts of secalonic acids A, E and G. From the combinations of secalonic acids produced in organisms so far examined it is concluded that precursor tetrahydroxanthone units or formed in pairs differing in stereo-chemistry only at C-5 or at the trans-invariant C-6 : C-10a positions. A possible biosynthetic pathway is discussed.


The structures of fortimicins C, D, and KE. Fortimicins C, D, and KE are new aminocyclitol antibiotics produced by a mutant of fortimicin-producing organisms. Their structures have been determined by 1H and 13C NMR and mass spectra and chemical degradations. Fortimicin C is 4-N-hydantoylfortimicin B, fortimicin KE is 6'-demethylfortimicin B, and fortimicin D is 4-N-glycylfortimicin KE. The last two antibiotics have purpurosamine C instead of 6-epi-purpurosamine B.


Chloramphenicol resistance of three different flavobacteria. The chloramphenicol resistance of some flavobacteria was investigated comparatively. This resistance can be explained either by acetylation of chloramphenicol to O-acetylchloramphenicol via constitutively formed acetyltransferases, followed by cometabolic degradation (strain CB 60), or by limited uptake and total degradation (strain CB 6) by inducible enzymes or by other mechanisms (F. devorans). The mechanisms of resistance, CM-acetylation, CM-degradation and limited uptake are discussed.


Semisynthetic beta-lactam antibiotics. II Cephalosporin derivatives in the naphthalene series. Chemical and microbiological properties. A seris of new 7-acylamidocephalosporins, containing a substituted naphthalene moiety in the side chain, has been prepared and tested for their in vitro antibacterial activity. Some observations are made on the structure-activity relationships.


Pamamycin: a new antibiotic and stimulator of aerial mycelia formation. Pamamycin is a new antibiotic isolated from Streptomyces alboniger ATCC 12461. The antibiotic is active in vitro against Gram-positive bacteria, Neurospora, and Mycobacteria. The compound also acts as a streptomycete differentiation effector. It stimulates aerial mycelia formation in the producing organism. The new antibiotic of elemental composition C36H63NO7 is completely different from puromycin, also produced by this strain. The present communication deals with the isolation, properties, and preliminary characterization of pamamycin.


New antibiotic pigments related to fusarubin from Fusarium solani (Mart.) Sacc. I. Fermentation, isolation, and antimicrobial activities. A cholesterol-decomposing fungus, Fusarium solani (Mart.) SACC. strain PP 96, was found to produce several different naphthaquinone pigments in a glycerol-mineral salts medium. Three novel compounds structurally related to fusarubin were isolated by chloroform extration followed by silicic acid column chromatography and preparative thin-layer chromatography. The purified compounds were found to have relatively low activity against bacteria, yeasts and filamentous fungi.


New antibiotic pigments related to fusarubin from Fusarium solani (Mart.) Sacc. II. Structure elucidations. Three antibiotic pigments isolated from Fusarium solani and related to fusarubin (4) were shown to be O-ethylfusarubin (2), hydroxidihydrofusarubin (3) and O-ethylhydroxydihydrofusarubin (1).


Semisynthetic bicyclomycin derivatives: preparation and antibacterial evaluation. A number of semisynthetic bicyclomycin derivatives have been prepared by modifications at various sites of the molecule. The preparation, characterization and antimicrobial evaluation of the new compounds is described. In contrast to bicyclomycin itself, the new derivatives 48 and 58 are also active against Proteus species. Otherwise, the antibacterial potency of the bicyclomycin molecule was found to be very sensitive to structural changes.


Bactericidal activity of cefadroxil, cephalexin, and cephradine in an in vitro pharmacokinetic model. Cefadroxil (Duricef, Mead Johnson and Company), resembles cephalexin and cephradine in spectrum of antibacterial activity but differs in human pharmacokinetic properties. Whether the latter are likely to affect activity in vivo was assessed by determining bactericidal activity against clinical isolates under conditions simulating the variation of drug concentration in the blood stream after an oral dose of 500 mg to adults. In this kinetic model, cefadroxil was more active than cephalexin or cephradine against Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae, Proteus mirabilis, Haemophilus influenzae and one of two strains of Escherichia coli. The other strain of E. coli was virtually unaffected by the cephalosporins. S. pyogenes was equally susceptible to all three cephalosporins. Analysis of the results suggest that the pharmocokinetic properties of an antibiotic affect its activity in the blood stream, provided the susceptibility of the infecting organism is concentration-dependent within the range of drug concentration occurring in serum.


In vitro actions of some antibiotics on phospholipases. The effects of some antibiotics on activities of phospholipase A2, B and C were investigated in vitro. Tetracyclines, macrolides, chloramphenicol and carbenicillin inhibited the activity of Crotalus adamanteus phospholipase A2 towards phospholipids of egg-yolk emulsions. When the ability to inhibit the activity of Penicillium notatum phospholipase B towards mixed micelles of phosphatidylcholine and Triton X-100 was investigated, polymyxin B was found to be inhibitory while chloramphenicol and carbenicillin were found to stimulate the activity of the phospholipase. The activity of Bacillus cereus phospholipase C towards the mixed micelles was inhibited by bleomycin, oleandomycin and chloramphenicol.


Comparative effects of ionophores grisorixin, alborixin and two derivatives on K+ glutamate efflux in rat liver mitochondria. The alkali cations discrimination on a liquid membrane electrodes system, was determined for the carboxylic ionophores grisorixin, alborixin and two derivatives, dihydrogrisorixin and hexahydroalborixin. The two antibiotics exhibited a great perference for K+. Dihydrogrisorixin again showed the selectivity curve of a carboxylic ionophore, but with a discrimination power lowered compared with grisorixin. Hexahydroalborixin had lost all the complexing properties of the natural molecule. The selectivity scales measured for cations, were directly correlated with the K+ and glutamate effluxes measured in rat liver mitochondria. The chemical modifications of the natural structures of grisorixin and alborixin resulted in a drastic reduction of their ionophoric properties. The loss of K+-glutamate might occur in two steps, the efflux of K+ catalysed by the ionophores then causing a loss of negative charges in the form of glutamate.


Selecting interspecific human-mouse and Chinese hamster-mouse hybrids using a new half-selection technique with a polyene antibiotic. Interspecific human-mouse and Chinese hamster-mouse hybrids were isolated from polyethylene glycol fused cells by a new half-selection technique employing a structurally modified polyene macrolide antibiotic, amphotericin B methyl ester (AME), and HAT media. Unfused parental cells were killed as a result of innate sensitivity to AME or their genetic deficiency, absence of thymidine kinase (TK-) or hypoxanthine guanine-phosphoribosyl transferase (HGPRT-). In contrast, hybrid colonies were isolated after two to three weeks growth in three or four changes of HAT-AME media and subsequent growth in HAT media alone. The ability of hybrid cells to proliferate using this selective protocol indicates that genetic complementation resulted, and polyene antibiotic resistance was expressed as a dominant phenotypic property in the hybrids. Hybrid selection was dependent on: (1) the number of cells of each parental cell type co-cultivated; (2) the level of polyene antibiotic administered; and (3) the time interval before selection was initiated. The half-selection technique described in this report is simple to use, very effective in eliminating unfused parental cells and increases the potential types of hybrids which can be formed. Only one parental cell type need contain a biochemical defect, whereas the second parental type can be genetically normal.


Different behaviour of quadratic and cubic difference tones. Level and phase of the cubic and quadratic difference tone were measured as a function of the primary tones' level, frequency separation, frequency region as well as of the frequency of an additional simultaneous masker. The results lead to the conclusion that quadratic and cubic difference tones are produced in different nonlinearities although both result in the same kind of adequate stimulus.


Scaling of pitch strength.

Scaling of pitch strength. Pitch strength of the following equally loud sounds was scaled by magnitude estimation procedures: pure and complex tones, band-pass filtered complex tones, AM-tones, low-pass, high-pass and band-pass noise, comb-filtered noise. AM-noise and Zwicker-tone. At the test frequencies 125, 250 and 500 Hz pure tones were assigned a pitch strength of 100%. Relative to this value spectral pitches reach 100--75%, virtual pitches 50% and noise pitches 25--0% pitch strength. At 125 Hz no consistent data were found for the Zwicker-tone, while at 500 Hz it elicits on the average the same pitch strength as a pure tone (100%). Implications concerning pitch mechanisms would seem to suggest a prevalence of the 'place principle' in comparison to the 'time principle'.


Frequency selectivity in bird and man: a comparison among critical ratios, critical bands and psychophysical tuning curves. The relative frequency selectivity of the internal auditory filters, as measured by critical bands or critical ratios, and psychophysical tuning curves, was compared in an avian species (parakeet) and human listeners. The results indicate that the critical band predicts the frequency selectivity of psychophysical tuning curves and vice versa. These findings suggest that there are similar mechanisms which contribute to the frequency selectivity measured by these two procedures and that these mechanisms operate in both the human and avian ear.


Effects of exposure to noise on ion movement in guinea pig cochlea. Healthy guinea pigs were exposed to broad band noise at levels between 95 and 115 dBA for 7 days. A significant decrease of the sound-induced cochlear responses, together with a substantial increase of the endocochlear potential, was observed in guinea pigs exposed to noise at 105 or 115 dBA. Microsamples of the endolymph obtained from these guinea pigs showed a significant increase of K+ and Cl- concentrations and a decrease of Na+ concentration, when compared with those from control animals. The K+, Na+ and Cl- concentrations in the perilymph were not markedly affected by noise exposure. When the perilymphatic space was perfused with artificial perilymph containing 43K, 22Na or 36 Cl, the uptake of radiotracers into the endolymph showed a single exponential function of the perfusion time. When compared with rate constants in normal animals, the value of rate constant for K+ was significantly decreased in animals exposed to noise. These results indicate that ionic permeability changes of the endolymph-perilymph barrier are a significant factor in the physiological mechanisms underlying noise-induced hearing loss.


Effects of noise on cochlear potentials and endolymph potassium concentration recorded with potassium-selective electrodes. Guinea pig cochleas were exposed to either broad-band noise at intensities between 95 and 115 dBA or octave-band noise centered at 380 Hz or 4.2 kHz at intensities between 115 and 125 dB SPL. Cochlear microphonics (CM), summating potentials (SP) and action potentials (AP) were recorded from differential electrodes in the perilymphatic scalae between successive 20-min periods of noise exposure. The endocochlear potential (EP) and endolymph potassium concentration [Kendo+] were recorded continuously from scala media using double-barreled potassium-sensitive electrodes. It was found that the initial exposure to noise at 115 dBA produced considerable suppression of the CM and AP, while the EP and [Kendo+] were elevated above their normal values. When animals previously treated with kanamycin were subjected to the same level of noise exposure no systematic increase in either EP ro [Kendo+] was observed. After prolonged exposure to 380 Hz octave-band noise at 125 dB SPL, a slow decline of EP and [Kendo+] was observed. The relationships between the changes in EP, [Kendo+] and CM are discussed.


The functions of assessment: implications for selection and development of devices for assessing repertoires in clinical, educational, and other settings. An attempt is made to identify the many different functions that assessment of an individual's repertoire can serve. Implications of these functions for the character of and evidence about assessment devices are suggested. The functions fall into two general groups, those which influence decisions regarding an individual learner, and those which influence policy, program development, and scientific knowledge. The first group of functions is presented in a rough chronological sequence such that they form a "behavioral assessment funnel," beginning with functions involving broad-band assessment to identify likely persons and skill areas, and narrowing to the precise pinpointing, monitoring, and follow-up functions. The contribution of behavior analysis and behavior therapy to assessment methodology in this sequence is identified as well as the areas where more traditionally conceived methods are still useful. The second group of functions and behavioral contributions to it are then discussed.


Social validation: the evolution of standards of competency for target behaviors. The use of social validation procedures has become widespread in recent years. Although most researchers have used social validation procedures to select target behaviors and to evaluate whether the changes produced by a treatment program should be considered socially useful, little attention has been focused upon using the social validation process to determine the optimal levels for target behaviors. This paper suggests several ways in which social validation procedures can be employed in order to select when and how much to change target behaviors.


Assessment of smoking behavior.

Assessment of smoking behavior. The nature of smoking risk is first reviewed and a classification of procedures for assessing smoking behavior is presented. Areas requiring assessment include not only the traditionally measured smoking rate, but also the substance used and topography of consumption. Each of these areas may be assessed through a variety of self-report, observational, or indirect techniques. These techniques as well as some of their advantages and disadvantages are presented. Recently published (1975 to mid-1978) data-based smoking research appearing in four journals (Addictive Behaviors, Behavior Therapy, Journal of Applied Behavior Analysis, and Journal of Consulting and Clinical Psychology) is then reviewed with respect to measurement reliability and the use of multiple measures. Results show a strong tendency to assess only the risk area of smoking rate and a low frequency of appropriate measurement reliability checks, especially during baseline and treatment phases. Some of the implications of these results are discussed.


Multivariate assessment of conflict in distressed and nondistressed mother-adolescent dyads. A battery of measures was used to assess conflict between mothers and young adolescents (females and males, 11 to 15 years of age). Two groups of families, one composed of a distressed clinical sample (N = 38), the other a nondistressed normative sample (N = 40), participated. The assessment battery included retrospective judgments, frequency estimates, self-monitored home recording, and tape-recorded discussion of a home problem. Content of assessment measures tapped aspects of parental control, decision-making, self-reported interaction behavior, arguments, interaction behavior rated by independent "blind" observers, frequency and anger-intensity of specific problematic issues, and perceptions of positive and negative behaviors of the other family member. Based on univariate analyses, 21 of the 26 defined variables discriminated significantly in the predicted direction. Maternal and adolescent reports of behavior and independent ratings of tape-recorded interaction emerged as strong and consistent discriminators. Stepwise multivariate discriminant analysis provided successful classification of 100% of the families based on the inclusion of nine variables. In a cross-validation sample, 84% of the families were correctly classified. Implications for systematic outcome research as well as clinical application are discussed.


Analysis of the consistency of objective measures of sexual arousal in women. Eight adult women volunteers viewed the same erotic film in two different sessions. Their resulting genital responses were recorded simultaneously by three different measures: vaginal pressure pulse, vaginal blood volume, and labial temperature change. During the erotic stimulation, the vaginal pressure pulse and labial responses always increased, and the vaginal blood volume response increased on all but two occasions. Although there was considerable intersubject variability in each genital measure, all three measures were found to have some intrasubject consistency over sessions with respect to either their response amplitudes or patterns, with labial temperature being the most consistent on both parameters. The relationship between the response patterns of the three measures during the film was also relatively consistent across sessions, as was the correspondence between subjective ratings of arousal and both vaginal pressure pulse and labial responses but not vaginal blood volume response. To overcome the problem of considerable intrasubject variability of response amplitudes, it was suggested that the inclusion in the data analysis of several parameters of response patterns, which were relatively stable over sessions, might facilitate the evaluation of a treatment.


Isolation and characterization of tunicamycin resistant mutants from Chinese hamster ovary cells. Stable clones selected for resistance to tunicamycin (TM) have been isolated from Chinese Hamster Ovary (CHO) cells. The TMR phenotype is stable for more than nine months in the absence of the drug. The morphology of TMR mutant varies from epitheloid to abnormally elongate. The mutants do not display cross-resistance for ConA but are slightly cross-resistant to PHA. Biochemically labeled membrane proteins and glycoprotein of Vesicular stomatitis virus (VSV) grown in the TMR mutants revealed that the incorporation of radioactive glucosamine was markedly reduced in the mutants. The results indicate that TMR cells are a novel type of membrane mutant.


Concanavalin A is mitogenic for resident peritoneal macrophages. Con A, a known T-cell mitogen, is also mitogenic for resident peritoneal macrophages. The stimulated cells morphologically resemble macrophages and are actively phagocytic. The concentration of con A (30 micrograms/ml) required to stimulate 3H-TdR incorporation is ten times that required for T-cell activation. Con A must be present throughout the entire culture period to produce the maximum effect, and con A-depleted supernatant fluids from con A-stimulated cells cannot replace the con A requirement. Stimulation of 3H-TdR incorporation occurs after a 48-hour lag period and is maximal on the fifth to seventh day of culture. At the peak of the response, 20-30% of the macrophages can be stimulated to incorporate 3H-TdR, but little or no increase in the total number of cells present in the culture occurs. This and pulse-chase experiments indicate that only a single cycle of replication occurs in the stimulated cells. Con A-responsive peritoneal macrophages appear to be a distinct subpopulation and might play a different role in the interaction with T cells and B cells in the immune response than the con A-non-responsive cells.


Effect of cytosine arabinoside triphosphate on the incorporation of 3H-thymidine in mitochondria isolated from HeLa cells. HeLa cell mitochondria were allowed to incorporate 3H-thymidine in a cell free system and the effect of ethidium bromide, cytosine arabinoside and cytosine arabinoside triphosphate on the labeling of mitochondrial DNA was studied. The labeled products, isolated by sedimentation velocity in CsCl-ethidium bromide two-step gradients, showed similar sedimentation profiles as in vivo labeled mtDNA. Cytosine arabinoside triphosphate and ethidium bromide strongly inhibited the labeling of mitochondrial DNA, whereas cytosine arabinoside appeared to be much less effective. Tritiated deoxycytidine was found to be incorporated by isolated mitochondria, whereas cytosine arabinoside was shown to enter the mitochondrial acid-soluble pool but not to be incorporated in acid-insoluble form. These results are in agreement with the previously reported findings of in vivo experiments.


Spontaneous, mutagen-induced and adenovirus-induced anchorage independent tumorigenic variants of mouse cells. Normal C57 Black mouse embryo cells did not form colonies in agarose, but rare variant (ar+) cells able to grow in agarose were detected. Fluctuation analysis showed that ar+ variants arose by spontaneous mutation in the cultured cells. The frequency of ar+ variants was increased by treating cells with N-methyl-N'nitro-N-nitrosoguanidine or ethyl methane sulphonate, or by abortive infection by human adenovirus type 5. Induced ar+ cells were fibroblastic; most grew slowly and had slightly reduced saturation density and increased serum requirement, but formed colonies in agarose. Fourteen of twenty ar+ clones induced by Ad5 were T antigen negative and two of these were also negative when tested for viral DNA. Six clones contained a few cells that were T antigen positive when first tested, but were negative when retested later. The ar+ variants were tumorigenic in athymic and in normal syngeneic mice. The results suggest that the ar+ phenotype can arise by spontaneous or chemically-induced mutation, and can be induced by adenovirus by a process different from classical transformation.


Trace element uptake by L-cells as a function of trace elements in a synthetic growth medium. The concentration of trace elements in L-cells has been studied as a function of the trace metal content of the growth medium. Cells were cultured in synthetic media which contained varying trace amounts of the elements manganese, iron, cobalt, copper, zinc and molybdenum. The cellular concentration of the of the elements potassium, iron, copper and zinc were then determined. It was found that the cell accumulates trace metals at a different rate than they are made available. Deficiencies in zinc could be "induced" in the cell by increasing the concentration of iron, manganese and cobalt; cellular iron deficiencies were observed at larger medium concentrations of zinc, manganese, copper and cobalt. Trace metal uptake by the cell was seen to parallel the utilization by multicellular organisms.


On the adaptation of cultured chick embryo cells to growth in the presence of chloramphenicol. We have found that tryptose phosphate broth (TPB) prevents the inhibitory effect of chloramphenicol (CAM) on the cell proliferation of chick embryo fibroblasts. Study of growth parameters indicated that no lag or adaptation period appeared necessary for TPB-exposed chick cell populations to grow in the presence of CAM suggesting that a particular cell type was not selected. TPB did not prevent the inhibitory effect of CAM on the mitochondrial protein-synthesizing system. This was supported by cytochrome oxidase activity measurements, studies on the incorporation of 35S-metionine into mitochondrial proteins, electron microscopic observation of alterations in mitochondrial structure. Oxygen consumption was reduced by 95% and cyanide, 2-4-dinitrophenol, and salicylhydroxamic acid do not significantly affect the residual respiration. Analyses of reduced-minus-oxidized-cytochrome spectra of CAM-treated chick cells demonstrate the disappearance of the absorption bands of cytochromes aa3, b559, c1, and c. The presence of a type b cytochrome with maxima at 552 and 557 nm was observed. The results obtained indicate that long-term cultures of CAM-treated chick embryo cells cultivated in the presence of TPB grow with mitochondria devoid of a functional respiratory chain.


[Biliary abscess and fistula. Three cases associated with cholelithiasis (author's transl)]. These three cases illustrate the course of biliary abscess (abscess formation, tumour with a chronic course, fistula formation) and the problems of diagnosis and treatment of this complication of cholelithiasis, which has been known for sometime but which has become rare.


[Reflexion on thirty eight cases of Monteggia fracture of children (author's transl)]. The authors report thirty eight cases of Monteggia fractures, seven of which being old dislocations of the head of the radius. They insist on early diagnosis and treatment of recent fractures, with a successful result if the ulnar hache become rightly alined. In late untreated luxations of the head of the radius, they occasionally use fascia lata transplant to repair the annular ligament, after correction of ulnar hache. However, early diagnosis and immediate full treatment are the best for successful result.


[The lymphatic drainage of the stomach (author's transl)]. The authors became interested in the lymphatic drainage of the stomach in order to attempt to determine for each region the type of drainage and the risk of cancer spread. They studied 132 dissections including 97 injections, 210 cases records of gastric carcinoma, 8 lymphographies by ultrafluid Lipiodol and 17 peroperative injections of vital staining. The system of drainage proposed by Rouvière was on the whole confirmed; however, one should emphasise the doubling of the hepatic chain, the existence of long collectors which bypass a relay in the left gastric artery, the importance of the posterior gastric artery which transmits the lymphatics of the splenic chain. Finally, the authors emphasise the existence of 3 longitudinal areas on the stomach where the presence or agsence of valvules in the subserous collectors orients the lymph towards the lesser or greater curvature of the stomach, which easily explains the onset of isolated carcinomatous adenopathy, situated on the curvature opposite the neoplasm.