Nutrition-related alterations in liver microsomal testosterone hydroxylases

The oxidation products of testosterone formed by liver microsomes from normal-fed and protein-energy malnourished male rats have been analysed by HPLC. Microsomes from normal-fed rats oxidized testosterone at a rate of 4.52 nmol/min/mg protein. The major products formed were: 6 beta-, 7 alpha- and 16-alpha-hydroxytestosterone; these three metabolites represented 65% of the total testosterone metabolism. Microsomes from protein-energy malnourished rats oxidized testosterone at a reduced rate of 2.03 nmol/min/mg protein. The major product formed was 7 alpha-hydroxytestosterone, which accounted for 43% of total testosterone oxidation. Microsomes from protein-energy malnourished rats showed a CO-reduced cytochrome P-450 spectra with a maxima at 452 nm, and a 38% decrease in the total content of cytochrome P-450. Some testosterone hydroxylases were drastically affected by protein-energy malnutrition but others, such as 7 alpha-hydroxylase, remained unchanged. The present results suggest that nutritional status can modify the relative amounts of individual cytochrome P-450 isozymes, thus explaining the observed changes in several testosterone hydroxylases. Protein-energy malnutrition seems to be an excellent tool with which to obtain a microsomal fraction containing predominantly P-450 isozymes, which are probably involved in key mono-oxygenations of physiological substrates.     

Sex steroid hormone concentrations in preterm labour and the outcome of treatment with ritodrine

Summary. Peripheral plasma concentrations of unconjugated oestradiol-17β, progesterone and total oestriol were measured in patients presenting with uncomplicated preterm labour. Control samples were obtained from normal healthy women matched for maternal age, parity and duration of pregnancy. Oestrogen concentrations were often higher and progesterone concentrations often lower in patients presenting in preterm labour, and in particular, in those presenting in advanced labour and those failing to respond to treatment with ritodrine, but the differences were not statistically significant.     

DISTRIBUTION OF α1(IV) AND α3(IV) CHAINS OF TYPE IV COLLAGEN IN LUNG TUMOURS

Tumour invasion is associated with strong remodelling of the extracellular matrix, including the basement membrane (BM). The major structural component of BMs is type IV collagen, which is composed of an association of three α chains. In this study, the distribution of the α1 and α3 chains in both normal and neoplastic lung tissues has been examined by immunohistochemistry, using specific monoclonal antibodies. In normal tissues, the α1(IV) chain was found in all BMs, whereas the α3(IV) chain was only found in alveolar BMs. In 36 lung tumours, the α1(IV) chain was detected in all cases, with irregular positivity around tumour clusters and in the stroma. It was noteworthy that this stromal distribution was particularly associated with the presence of cancer cells, whatever their invasive properties. In contrast, in 22 tumours out of 36, the α3(IV) chain was only found at the interface between invasive tumour clusters and stroma, with a linear and disrupted pattern. These data show a distinctive distribution of type IV collagen chains in lung tumours, with expression of α1(IV) chain and likely neosynthesis of the α3(IV) chain around some invasive tumour clusters. The results suggest the involvement of these BM components in the process of tumour invasion. © 1997 John Wiley & Sons, Ltd.     

Issues in primary health care development in Vanuatu

The primary health care (PHC) approach has been adopted as ameans of achieving health for all in Vanuatu since 1984. Thishas proved remarkably successful as a guiding force for primarycare especially at the national level. It has, however, provedmore difficult than at first anticipated to devolve planningand management to the regional and district levels. A task force,which was set up in 1989, appears to have been successful, atleast initially, in developing concrete plans for greater co-ordinationat the regional level. This article reviews some of the issuesinvolved in implementing the objectives of PHC in Vanuatu, withparticular reference to a regional review and planning processbegun in 1989. Problems and future directions in the practicalapplication of the principles of PHC are discussed.     

Annual direct medical cost and contributing factors to total cost of epilepsy in Oman

OBJECTIVES: To describe the pharmaceutical use, health care resource utilisation patterns, and annual direct medical cost of epilepsy as well as determining the impact of various demographic and clinical characteristics on total costs of epilepsy in Oman. METHODS: Medical and pharmacy data were collected for 6 months on all patients aged > or =13 years attending the Sultan Qaboos University Hospital. Unit pharmacy and medical costs were retrieved for each patient, and multiple linear regression was utilised to analyse the impact of various demographic and clinical characteristics on total cost. RESULTS: A total of 486 patients were seen over the study period. Annual direct medical costs of epilepsy amounted to 1,426 US dollars. In-patient care, the antiepileptic drug (AED) lamotrigine and specialist visits, respectively, were the first, second and third most significant predictors of total cost. Age was associated positively, and was the most significant predictor of total costs among demographic and clinical parameters. CONCLUSIONS: This analysis, the first economic study of epilepsy in Oman, could assist in health care allocation of scarce resources and in pharmacoeconomic analysis of AEDs. Besides in-patient admission, our findings demonstrate that the newer drugs are significant predictors of total cost, and hence any incremental benefits derived from them must be rigorously assessed for their cost-effectiveness.     

Angiotensin II levels in hypertensive and normotensive pregnancies

Summary. We measured circulating angiotension II by radioimmunoassay in women with pregnancy-induced hypertension (  n = 54  ), and compared these values with those obtained in women with normal pregnancy (  n = 18  ) and in non pregnant women (  n = 20  ). Pregnant women had statistically significantly higher plasma angiotensin II [mean (SD): 41.3 (12.6) pg/ml] than non-pregnant women [  29.2 (11.3) pg/ml; P < 0.004  ]. Angiotensin II concentrations in women with pregnancy- induced hypertension [mean (SD): 31.7 (16.2) pg/ml] were, on average, 25% lower than in normal pregnancy (   P < 0.003  ) and resembled those obtained in non-pregnant women. The lowest angiotensin II levels were found in women with more severe forms of pregnancy-induced hypertension, such as proteinuric or superimposed pregnancy-induced hypertension. Review of the published studies on angiotensin II and our data suggest that the conflict among studies on angiotensin II levels in pregnancy-induced hypertension is largely due to the heterogeneity of the study populations in the various reports.     

Changes in plasma steroid hormones during treatment of preterm labour with ritodrine-HC1

Summary. Peripheral plasma concentrations of unconjugated oestradiol 17-β, progesterone and total oestriol were measured in 21 patients presenting with 'uncomplicated' preterm labour. Serial measurements were made during intravenous treatment with ritodrine over a period of 24 h. Mean levels of unconjugated oestradiol 17-β fell significantly during infusion with ritodrine. Changes in progesterone levels remained within the range of diurnal fluctuations normally found in uncomplicated late pregnancy. Mean total oestriol levels fell significantly, but the changes did not exceed normal variations. No correlation was found between the magnitude, the rate or the timing of changes in any of the hormones measured and the short or long term effects of ritodrine on uterine activity. Although alterations in the peripheral oestrogen concentrations may be a direct effect of β-mimetics, it is unlikely that this mechanism is important in the inhibition of uterine activity.     

VIMENTIN EXPRESSION IN CERVICAL CARCINOMAS: ASSOCIATION WITH INVASIVE AND MIGRATORY POTENTIAL

Vimentin is an intermediate filament protein normally expressed in mesenchymal cells, but evidence is accumulating in the literature which suggests that the aberrant expression of vimentin in epithelial cancer cells might be related to local invasiveness and metastatic potential. Vimentin expression has previously been associated with invasive properties in an in vitro model consisting of a set of HPV-33-transformed cervical keratinocyte cell lines.^1,2 In the present study, in order to emphasize those in vitro findings, the expression of vimentin has been investigated in cervical neoplasms of different grades, using immunohistochemistry. A clear association is reported between vimentin expression and metastatic progression, since vimentin was detected in all invasive carcinomas and lymph node metastases, but not in CIN III lesions. These in vivo results are compared with present and previous data obtained in vitro on cervical keratinocyte cell lines, where vimentin expression also correlated with in vitro invasiveness.     

Controlled Comparison of Tianeptine,Alprazolam and Mianserin in the Treatment of Adjustment Disorders with Anxiety and Depression

A multicentre study compared tianeptine (37·5 mg/day), an original psychotropic compound characterized by both antidepressant and anxiolytic potentials, with a reference antidepressant, mianserin (60 mg/day) and a reference anxiolytic, alprazolam (1·5 mg/day), in the treatment of 152 patients fulfilling DSM-III-R criteria for adjustment disorder with mixed emotional features (anxiety and depression). The study used a double-blind parallel design over a 6-week period. Clinical assessments included the Clinical Global Impressions (CGI), the Montgomery and Asberg depression rating scale (MADRS), the Hamilton anxiety rating scale, a visual analogue scale, and the somatic scale of the system developed by the Association for the Methodology and Documentation in Psychiatry (AMDP). Results showed very similar improvement in the three treatment groups on all rating instruments. Moreover, the number of patients exhibiting adverse events did not differ among the three groups. Therefore, these results show similar antidepressant and anxiolytic activity for tianeptine, mianserin and alprazolam in patients suffering from adjustment disorder with mixed emotional features. These promising findings should however be confirmed in a placebo-controlled trial.