Expression of cytochrome P450 enzymes in the cervix. An immunohistochemical study

The expression of cytochrome P450 isoenzymes (subfamilies) CYP1A, CYP2B, CYP2C, CYP3A and CYP4A in the histologically normal cervix was explored using a panel of polyclonal antibodies. There was variation in the intensity of immunohistochemical reaction between the isoenzymes and between the various components of the cervix. Half the subjects tested were smokers and had increased urinary cotinine levels. Statistical analysis revealed no significant differences between smokers and nonsmokers in the expression of these isoenzymes. The implications of these observations in relation to cervical carcinogenesis are discussed.     

Detection and measurement of DNA adducts in the cervix of smokers and non-smokers

Smoking has been associated, on epidemiologic grounds, with an increased risk of cervical neoplasia. We have investigated this association, using laboratory-based methods. A ³²P post-labeling assay was performed on 97 cervical biopsies to detect and measure DNA adducts (additional products formed by the covalent binding of potential chemical carcinogens to nuclear DNA). The specimens were taken from both normal cervices as well as the histologically normal regions of cervices with invasive and intraepithelial neoplasia. A detailed smoking history was obtained from each patient and correlated with an assay of cotinine level in urine. Characteristic smoking-related DNA adducts were found, and a significant difference in their levels was detected between current and non-current smokers ( P = 0.017, Mann-Whitney test). There was also a highly significant trend in median adduct levels between the three tissue types ( P < 0.002). We conclude that the finding of smoking-related cervical DNA damage is suggestive of a causal association between smoking and cervical neoplasia.     

The Presentation and Outcome of HIV-related Disease in Nairobi

The range of clinical presentations of HIV-related disease inAfrica has not been adequately described, despite the fact thatmany hospitals have to rely heavily on clinical diagnosis. Sixhundred adult medical patients seen in the Casualty Departmentof the main Government hospital in Nairobi were enrolled ina study of the presentation and outcome of HIV-related disease:506 of these patients were admitted, of whom 19 per cent (95)were HIV seropositive. The remaining 94 were dealt with as outpatients:11 percent (10) of these were seropositive. A history of priortreatment for sexually transmitted disease and, if male, beinguncircumcised, were associated with being seropositive. Threepresentations were strongly associated with HIV infection: acutefever with no focus except the gastrointestinal tract (entericfever-like illness), acute cough with fever (community-acquiredpneumonia) and chronic diarrhoea with wasting. The WHO clinicalcase definition (CCD) for AIDS missed a substantial amount ofHIV-related morbidity (sensitivity 39 per cent) and misidentifiedmany seronegative patients (positive predictive value 59 percent). In comparison with the Centers for Disease Control surveillancedefinition for AIDS, the CCD was specific (91 per cent) andsensitive (79 per cent) but only had a positive predictive valuesof 30 per cent: the CCD may therefore be a poor surveillancetool for AIDS. Seropositive patients were much more likely todie than were seronegative patients (39 per cent vs. 15 percent mortality). Enteric fever-like illness was the presentationwhich most commonly proved fatal. A wider spectrum of diseaseis associated with underlying HIV immunosuppression than haspreviously been described in Africa.     

Localized neural control of blood flow in the renal cortex of the anaesthetized baboon

Localized neural control of renal cortical blood flow was observed in five chloralose-anaesthetized baboons. Renal artery blood flow was measured with an electromagnetic flowmeter, while superficial renal cortical blood flow was measured with a laser Doppler flowmeter. Stimulation of all renal nerve bundles isolated produced significant reductions in total renal blood flow, but reduced the superficial renal cortical blood flow only in localized areas. Systemic arterial blood pressure did not vary significantly, which suggests that the changes in renal cortical blood flow were neurally mediated and not the result of autoregulation. The renal cortical blood flow response was delayed 1-4 s with respect to the total renal blood flow response. The localization of flow control is consistent with the neuroanatomy of the kidney, and the delayed renal cortical blood flow response is consistent with the vascular anatomy of the kidney and with previous measurements of red cell transit times through the renal cortex.