Hepatic conversion of 1-(tetrahydro-2-furanyl)-5-fluorouracil into 5-fluorouracil in patients with hepatocellular carcinoma

The pharmacokinetics of 1-(tetrahydro-2-furanyl)-5-fluorouracil (FT) and its conversion into 5-fluorouracil (FUra) in liver tissue were studied in ten patients with hepatocellular carcinoma (HCC). The plasma concentration of FT after its intravenous injection (dosage: 800 mg) was computerfitted to a bi-exponential function (C = Ae-alpha t + Be-beta t), indicating a two-compartment disposition. The pharmacokinetic parameters did not significantly differ between the five patients with, and the five without cirrhosis of the liver. The plasma concentrations of FUra likewise showed no significant difference between the two groups. The rates of FT degradation in the liver tissue homogenate were similar for four of the patients with cirrhosis (0.10 +/- 0.05 mumol/g liver protein/30 min) and four of those without it (0.13 +/- 0.05). The rates of cytochrome P-450-dependent FUra formation in the microsomal fraction of liver tissue from two patients (1.1 and 1.3 nmol/mg microsomal protein/30 min) were dramatically reduced to less than half of those of two control subjects (2.4 and 2.7). The estimated rates of FUra formation in the soluble fraction (105,000 X g supernatant fraction) from the two patients (0.1 and 0.13 nmol/mg protein/30 min) were almost identical to those from the controls (0.12 and 0.14), suggesting that the rate in the soluble fraction from HCC patients may not be as strongly affected as the rate in the microsomal fraction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Left ventricle in Noonan's syndrome. Electro-vecto-echo and angiocardiographic aspects

The electrocardiographic features of Noonan's syndrome have been known for several years, but the discordance between these electrical findings and the underlying haemodynamic disorders remains unexplained. In an attempt to elucidate the genesis of electrical abnormalities, we present here a retrospective study of 14 children with Noonan's disease, aged from a few days to 16 years and evaluated by electrocardiography, vectography, one- or two-dimensional echocardiography, angiography and His bundle electrophysiology. The electrocardiographic abnormalities observed concerned ventricular depolarization and intracardiac electric conduction with, notably, a QRS axis directed towards the right upper part of the electric field and a first degree infra-hisian atrioventricular block (His bundle potentials). Vectography showed in some cases an image of inferior pseudo-necrosis due to the absence of initial inferior forces; this image is highly characteristic. In other cases the QRS loop showed an image of left segmental block which is unusual in this type or cardiac pathology (pulmonary stenosis with or without atrial septal defect of the ostium secundum type).     

The effects of caffeine on various body systems: a review

Caffeine is the most widely consumed drug in Western society. The intake of caffeine-containing beverages in many adults and children often reaches levels that can induce pharmacological effects. Ninety-nine percent of ingested caffeine is absorbed and distributed to all tissues and organs. The effects of caffeine intake differ greatly according to acute or chronic intake, level of intake, and the development of tolerance. Caffeine administered acutely to non-users or recent abstainers can induce hypertension, arrhythmias, altered myocardial function, increased plasma catecholamine levels, plasma renin activity, serum cholesterol levels, increased production of urine, gastric acid secretion, and alterations in mood and sleep patterns. Tolerance to chronic caffeine intake develops in most individuals, with the cessation of its effects on the renal system, the cardiovascular system, the gastrointestinal system and, to some extent, the central nervous system. Moderate caffeine consumers probably need to have little concern for the effect of caffeine intake on their health if their other life-style habits are also moderate.     

Smoking behavior among participants in the nurses' health study.

We analyzed smoking behavior of 91,651 married female nurses, aged 30-55 years in 1976. The prevalence of smoking was similar among all birth cohorts. The largest percentage increase in starting to smoke occurred between ages 15 and 25 years; by age 25, 50 per cent had started smoking. The cessation rate was lowest in earlier birth cohorts and among nurses starting to smoke at earlier ages. The cessation rate increased substantially between 1963-73 compared with the period 1948-58.     

Diagnoses of the relatives of schizotypal outpatients

Relatives of 22 schizotypal probands were evaluated for lifetime psychiatric diagnoses. Forty-four (N = 44) of the 97 available relatives were interviewed directly using the Diagnostic Interview Schedule. The rates of psychiatric diagnoses were compared with those of sixty-six (N = 66) of 140 relatives of 30 depressed patients. Family history of mental illness was ascertained by the informant method on the remainder of relatives of both proband groups. The rate of depression found in the relatives of schizotypal patients was 52% in those directly interviewed and 25.7% when informants' reports on unavailable relatives are pooled with direct interview data. These rates were not significantly higher than those found for the relatives of depressed probands (34.8% by direct interview and 21% including reports from informants). The high rates of depression in the relatives of schizotypal probands may indicate that schizotypal personality is associated with affective disorder and not only with schizophrenia. However, the high rates may be due to the presence of depressive character traits in relatives, which inflate the rates of dysthymic disorder and other chronic depressive disorders in the relatives of borderline patients.     

Temporal arteritis-like presentation of carotid atherosclerosis

A 68 year-old woman presented with a two-week history of amaurosis fugax, ipsilateral fronto-temporal headache and jaw claudication suggesting carotid giant cell arteritis. However, this syndrome proved to be due to atherosclerosis causing complete occlusion of the external carotid artery at its origin and narrowing of the internal carotid artery. Combined external and internal carotid endarterectomy relieved the symptoms. The symptom complex of temporal arteritis may be rarely mimicked by carotid atherosclerotic occlusive disease.     

Intra-urban variations of neonatal and post-neonatal mortality in a developing city

Numerous surveys at the national and regional level have demonstrated that large inequalities in infant health status exist in Southern Africa. Few studies have assessed infant mortality at the intra-urban scale of geographic analysis. Comparisons between infant mortality rates from different areas are made even more meaningful if the data are divided into two primary categories based on period-of-death; these being the neonatal and post-neonatal components. This study presents the results of a survey undertaken in Metropolitan Cape Town (population 1.6 million) during 1982. The aim was to determine the spatial variation of neonatal and post-neonatal mortality at the suburb (or community) level within the city. Overall, a total of 36,789 live births and 928 infant deaths were recorded; 53.4% in the neonatal period and 46.6% in the post-neonatal period. The mean infant mortality rate was 25.2 per 1000 live births; the neonatal mortality rate and post-neonatal mortality rate being 13.5/1000 and 11.7/1000, respectively. A marked range in death rates was evident for both components. For the neonatal category it was 0.0-49.9/1000 and 0.0-40.0/1000 for the post-neonatal period. The generally low post-neonatal mortality rate among the 69 suburbs studied has made the neonatal component the dominant contributor to the infant mortality rate. However, in the lowest socio-economic areas the post-neonatal mortality rate was responsible for over 60% of infant deaths.(ABSTRACT TRUNCATED AT 250 WORDS)     

Health risks among submarine personnel in the U.S. Navy, 1974-1979

This study evaluated health risks associated with U.S. Navy submarine duty by comparing hospitalization rates of submariners with surface ship personnel. The groups were compared using age-adjusted hospitalization rates for 16 major diagnostic categories and several specific diagnoses postulated to be submarine associated. Submarine personnel did not have significantly higher hospitalization rates for any diagnostic categories nor for any of the submarine-associated illnesses. Submariner relative risk of hospital admissions was greater for a few selected diagnoses but statistical significance was not attained. Submarine personnel had lower hospitalization rates for nearly all of the diagnostic categories examined. Reasons for these lower rates may be stringent screening of submariners, higher levels of education among submariners, difficulty of evacuation from a submarine, and the healthy-worker effect. The health status of U.S. Navy personnel does not seem to be adversely affected by submarine duty.