Increased susceptibility to liver disease in relation to alcohol consumption in women

Sex-related differences were prospectively studied in patients with the first presentation of alcoholic liver disease. Among 42 patients the diagnosis was cirrhosis in 8 women and 15 men, alcoholic hepatitis in 4 women and 1 man, steatosis in 6 women and 6 men, and no histologic changes were found in the liver biopsy specimens from 2 men (p greater than 0.1). The median (range) antipyrine clearance was 14.6 (1.0-64) versus 17.2 (3.0-83) ml/min and the clinical score in accordance with the Pugh modification of the Child-Turcotte classification was 8 (5-13) versus 8 (5-11) in the women and men, respectively (p greater than 0.05). In 5 women and only 1 man the antipyrine clearance was less than 5 ml/min, indicating an almost total loss of functional liver mass (p less than 0.05), whereas the Pugh score was above 11 in 6 women, but not in any of the men (p less than 0.05). On an average, the men estimated their total lifetime consumption of alcohol to be 2.1 times greater and the number of days they had consumed more than 5 drinks 2.9 times higher than the women (p less than 0.05). These ratios are reduced to 1.4 and 1.7, respectively (p greater than 0.05), if the female alcohol intake is adjusted to the average male volume of distribution. The results support the concept that women may develop similar, and sometimes even more severe, liver disease after consumption of less alcohol than men. The apparent difference in susceptibility to alcohol may be partly explained by differences in volume of distribution.     

Primary care physicians and their HIV prevention practices

A national random-sample survey of 4011 primary care physicians was conducted to determine the extent to which they are providing HIV prevention and clinical services, and to learn what characteristics and attitudes might impede the provision of such services. Physicians were asked about their history-taking practices for new adult and adolescent patients, including asking about the use of illicit drugs (injection and noninjection), the number of sexual partners, use of condoms and contraceptives, past episodes of sexually transmitted diseases (STDs), sexual orientation, and sexual contact with partner(s) at high risk for HIV. A preliminary analysis was conducted and reported earlier by the Centers for Disease Control and Prevention (CDC), focusing on the HIV-prevention services being provided by primary care physicians. This report provides additional analyses from this study, focusing on characteristics and attitudes that may prevent physicians from providing these services. Male physicians and the physicians' belief that patients would be offended if asked questions about their sex behaviors were strongly predictive of not asking new patients about their sex and drug behaviors. The physician's specialty was also a strong predictor-OB/GYNs were predictive of asking these questions and GP/FPs were predictive of not asking the questions. Physicians who indicated that a majority of their patients were white were less likely to report asking patients about their sex and drug behaviors. The authors conclude that a substantial number of primary care physicians are missing important opportunities to prevent HIV transmission by not adequately assessing patients' risks and not providing necessary risk-reduction counseling during their physician-patient encounters. Physician's attitudes and beliefs about their patients, as well as their level of experience with HIV, may help to explain these observations.     

The diagnostic and prognostic value of 18F-FDG PET/CT in the initial assessment of high-grade bone and soft tissue sarcoma. A retrospective study of 89 patients

Purpose

To evaluate the feasibility of ¹⁸F-FDG PET/CT for initial assessment in high-grade bone sarcomas (BS) and soft tissue sarcomas (STS).

Methods

During the years 2001–2010, 89 patients (30 BS, 59 STS) referred for further evaluation and surgical treatment of a high-grade BS or STS also had a PET/CT scan performed for staging preoperatively (n?=?68) or within 1?month of surgery (n?=?21). Metastatic lesions suggested on the PET/CT scan were confirmed or rejected by histological evaluation, by additional imaging or by follow-up. In 68 patients (28 BS, 40 STS) the relationship between the maximal standardized uptake value (SUVmax) of the primary tumour and survival was examined.

Results

The PET/CT scan suggested the presence of 13 metastatic lesions in BS patients (5 lymph node, 8 distant) and 21 metastatic lesions (6 lymph node, 15 distant) in STS patients. The calculated sensitivity (SE) and specificity (SP) were 95?% and 96?% for detection of distant metastases, and the predictive value (PV) of a positive or a negative test was 87?% and 98?%, respectively. SE and SP were 100?% and 90?% for detection of lymph node metastases, and the PV of a positive or a negative test was 27?% and 100?%, respectively. The 5-year survival was 81?% among patients with SUVmax below the median value (≤10), but was 33?% among those with SUVmax >10.

Conclusion

FDG PET/CT for the initial assessment of patients with high-grade BS or STS was feasible with high SE and SP, but in those with lymph node metastases the PV of a positive test was low. The SUVmax of the primary tumour was a strong prognostic factor for survival.     

Stimulation of histamine synthesis from tumour cells by concanavalin A and A23187

In the present study the amount of histamine synthesized by two experimental tumour cell lines, the Yoshida ascites sarcoma cells and SEWA cells, was measured after stimulation in vitro with the calcium ionophore A23187 and the plant lectin Concanavalin A (Con A). After 7 hrs of incubation with the two stimulators, histamine could be measured and the amount was still increasing up to 15 hrs of incubation with a maximal net histamine production of approximately 1.0 ng histamine per 10(6) tumour cells per ml sample. In addition, the tumour promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) was found to enhance the synthesis of histamine in the presence of Con A or A23187, except in high concentrations, i.e. 50 ng/ml TPA, where an inhibitory effect was seen. TPA alone could not induce detectable histamine synthesis. In order to measure the histamine, the tumour cells were incubated in glass microfibre-based microtiter plates, which have been shown to bind histamine with high affinity and selectivity. The aim has been to develop a functional in vitro tumour assay which can detect histamine from tumour cells and which can be used to measure pharmacological interaction of the tumour cell function as well as histamine production from different tumour cell types.     

Paracetamol-Induced Spindle Disturbances in V79 Cells with and without Expression of Human CYP1A2

Abstract: Spindle disturbing effects in terms of c-mitosis and cytotoxicity of paracetamol were investigated in two Chinese hamster V79 cell lines, one of which (V79MZh1A2) was transfected with human CYP1A2. This enzyme catalyses the oxidative formation of the reactive paracetamol metabolite, NAPQI, believed to initiate hepatoxicity by covalent binding to proteins after overdose. In the native V79 cell line paracetamol increased c-mitosis frequency in a concentration dependent manner from 8.7±3.5% (control) to 66±18% at 20 mM. A significant increase to 13.3±3.5% was first seen at 2.5 mM in the native cell line (P<0.05). In the V79MZh1A2 cells the concentration-effect curve was slightly shifted to the left (P<0.05) with c-mitosis frequency increased to 12.1±2.6% (P<0.05) at 1 mM paracetamol. At 5 mM paracetamol the c-mitosis frequency was 14.4±5.0% and 19.0±3.8% in the native and CYP1A2 expressing cell lines, respectively (P<0.05). At 20 mM paracetamol the c-mitosis frequency was 61±10% in the V79MZhlA2 cells. Cell survival was reduced to approximately 50% at 5-10 mM paracetamol in both cell lines. At 20 mM paracetamol survival was further decreased to 39±9% in V79MZh1A2 cells only (P<0.05). The present study demonstrated that paracetamol may disturb the spindle of dividing cells conveying a risk of aneuploidy. The spindle disturbind effect was only slightly enhanced by expression of CYP1A2, suggesting that metabolic activation plays only a minor role in this genotoxic effect. The reduction of survival mirrored the increase in c-mitosis frequency.     

Oxidative DNA damage estimated by oxo8dG in the liver of guinea-pigs supplemented with graded dietary doses of ascorbic acid and alpha- tocopherol

Dietary antioxidants may influence cancer risk and aging by modifying oxidative damage. The effect of graded dietary doses of the antioxidant vitamins C and E on oxidative DNA damage was studied in the liver of guinea-pigs under normal conditions. Like human beings, guinea-pigs cannot synthesize ascorbate and alpha-tocopherol. In one experiment, three groups of 6-8 guinea-pigs were fed diets containing 15 mg of vitamin E/kg chow and three different amounts of vitamin C (33,660 or 13,200 mg/kg) for 5 weeks. In a second experiment, three groups of seven guinea-pigs were fed diets containing 660 mg of vitamin C/kg and three different amounts of vitamin E (15, 150 or 1500 mg/kg) for 5 weeks. The three graded levels of each vitamin respectively represent marginal deficiency, an optimum supplementation and a megadose. Oxidative damage to liver DNA was estimated by measuring 8-oxo-7,8- dihydro-2'-deoxyguanosine (oxo8dG) referred to deoxyguanosine (dG) by means of high-performance liquid chromatography with simultaneous electrochemical-coulometric and ultraviolet detection. The level of ascorbate in the liver was 0.034 +/- 0.051, 1.63 +/- 1.06 and 1.99 +/- 0.44 micromol/g in the low, medium and high dose ascorbate groups (59- fold variation). The liver concentration of alpha-tocopherol was 28 +/- 11, 63 +/- 18 and 187 +/- 34 nmol/g in the low, medium and high dose alpha-tocopherol groups (7-fold variation). The level of oxo8dG in the liver DNA was 1.89 +/- 0.32, 1.94 +/- 0.78 and 1.93 +/- 0.65 per 10(5) dG in the low, medium and high dose ascorbate groups (no effect: P > 0.05). In the low, medium and high dose alpha-tocopherol groups oxo8dG level in the liver DNA was 2.85 +/- 0.70, 2.74 +/- 0.66 and 2.61 +/- 0.92 per 10(5) dG (no effect: P > 0.05). It is concluded that even very large variations in the content of the antioxidant vitamins C and E in the diet and liver have no influence on the steady-state level of oxidative damage to guanine in the liver DNA of normal unstressed guinea-pigs.      

Clinical decision making and health care policy: what is the link?

The relationship between clinical decision making and health care policy is here considered in different ways. First, it is suggested at the most simple level that a key link between the two is that both are concerned with health. Second, the need for accepting the presence of uncertainty at both levels is highlighted: uncertainty related to inputs and outputs; to assessing weights for various outcomes; to attitudes to risk; etc. Third, the paper emphasises the desirability of looking beyond only the output 'health' at the two levels of decision making. Not that the relationship between clinical and health service decision making is taken to be constant across all health care systems in all countries. The paper suggests rather that just how clinical decision making is affected by the health care environment in which it finds itself needs more investigation than it has received to date. The authors indicate that the recent growth in the formal analysis of medical decision making is to be welcomed but stress the need to extend such analysis to consider the impact on clinical decision making of health care policy making.     

Antipyrine clearance in pneumonia

Antipyrine clearance was estimated by a one-sample technique in 14 patients with acute fever and clinical pneumonia. Antipyrine clearance during the acute illness was 31.4 +/- 7.6 ml/min (X +/- SD). Fourteen and 28 days later during convalescence, clearance values were higher (47.8 +/- 18.9 and 49.2 +/- 15.0 ml/min, respectively). We conclude that microsomal hepatic drug metabolism in adults is impaired during pneumonia.     

Autoimmune Haemolytic Anaemia with Positive Ham and Crosby's Test and Scleroderma: A Case Report

A report is given on a case of scleroderma with a fulminant, autoimmune haemolytic anaemia with positive Ham's and Crosby's tests as the first symptom. The scleroderma was localized to the skin. The haemolytic anaemia was treated effectively with corticosteroids.