The incidence of lower mid-trunk hyperpigmentation (linea nigra) is affected by sex hormone levels

The incidence of linea nigra was studied in 1,550 Nigerians of both sexes and of different age groups and among pregnant women and men with benign and malignant prostatic diseases over a nine-month period. From the study, it would appear that linea nigra increases in incidence from the age group 0-15 years (31.4%) to the age group 16-30 years (47.3%) before starting to fall in clinically normal individuals >30 years to 19.2%. For age groups 0-5 years, 6-10 years and 16-30 years, females more often than males have a linea nigra. For age group 11-15, males are equally as likely as females to have a linea nigra. The results suggest that women over 30 are more likely to have a linea nigra than men, but there are too few patients to make a definite statement, given the number of statistical tests performed. Pregnant women far more often have a linea nigra than nonpregnant women of the same age. The findings suggest that the likelihood of having a linea nigra depends on the level of sex hormones. This means that changes in the levels of hormones, either due to disease or drugs, may be reflected in changes in the incidence of a linea nigra. If this finding is confirmed, the linea nigra may serve as a convenient, noninvasive, free marker of alterations in sex hormones.     

Inhibition of serum and transforming growth factor beta (TGF-β1)-induced DNA synthesis in confluent airway smooth muscle by heparin

1. Airway remodelling occurs in asthma and involves an increase in airway smooth muscle mass through cell proliferation and hypertrophy. Increased eosinophil density in the airways is a feature of asthma. Eosinophils exhibiting activation in the airways of asthmatics also exhibit increased expression of transforming growth factor beta (TGF-β1). We have examined the capacity of TGF-β1 and epidermal growth factor (EGF) to influence airway smooth muscle division and the effect of heparin on TGF-β1, EGF and serum-induced smooth muscle DNA synthesis in confluent airway smooth muscle cells (ASMC) as an indication of entry into S phase preceding mitogenesis.
2. ASMC were obtained from cell populations growing out from explanted bovine trachealis muscle sections. Cell division was monitored in sparse plated cells by direct cell counting following nuclear staining. Cell DNA synthesis in confluent cells was monitored by uptake of [³H]-thymidine.
3. TGF-β1 (100 pM) inhibited FBS (10%)-induced smooth muscle division in sparsely plated cells (40%). TGF-β1 (100 pM) increased cell DNA synthesis (200%) in confluent cells in the presence of bovine serum albumin (BSA, 0.25%). EGF (0.7 nM) also increased airway smooth muscle DNA synthesis (69%) in the presence of BSA (0.25%). The facilitatory effect of TGF-β1 was observed between 1–100 pM, while that of EGF was observed between 20–200 pM.
4. Heparin inhibited serum and TGF-β1-induced DNA synthesis in confluent ASMC (55%), consistent with our previous observation of inhibition of division in sparsely populated ASMC (Kilfeather et al., 1995a). This action of heparin was observed between concentrations of 1–100 μg ml⁻¹. Heparin did not inhibit DNA synthesis in response to EGF. An anti-mitogenic effect of heparin was also observed against responses to combined exposure to TGF-β1 and EGF.
5. There was a clear inhibitory effect of heparin in absolute terms against serum-induced division in cells plated at 10, 20 and 45×10³ cells cm⁻². The inhibitory effect of heparin was also observed at a plating density of 45,000 cells cm⁻² when responses to serum were expressed as fold-stimulation of basal DNA synthesis.
6. These findings demonstrate a potential role of TGF-β1, EGF and heparin-related molecules in regulation of airway smooth muscle division.

     

Elevated cardiac troponin measurements in critically ill patients

BACKGROUND: The clinical significance of elevated cardiac troponin (cTn) level in patients in the intensive care unit (ICU) is uncertain. We reviewed the frequency of cTn elevation and its association with mortality and length of ICU stay in these patients. METHODS: Studies were identified using MEDLINE, EMBASE, and reference list review. We included observational studies of critically ill patients that measured cTn at least once and reported the frequency of elevated cTn or outcome (mortality and length of ICU or hospital stay). We pooled the odds ratios (ORs) using the inverse variance method in studies that conducted multivariable analysis to examine the relationship between elevated cTn and mortality (adjusted analysis). We calculated the weighted mean difference in length of stay between patients with and without elevated cTn and pooled the results using the inverse variance method (unadjusted analysis). RESULTS: A total of 23 studies involving 4492 critically ill patients were included. In 20 studies, elevated cTn was found in a median of 43% (interquartile range, 21% to 59%) of 3278 patients. In adjusted analysis (6 studies comprising 1706 patients), elevated cTn was associated with an increased risk of death (OR, 2.5; 95% confidence interval [CI], 1.9 to 3.4; P < .001). In the unadjusted analysis (8 studies comprising 1019 patients), elevated cTn was associated with an increased length of ICU stay of 3.0 days (95% CI, 1.0 to 5.1 days; P = .004) and an increased length of hospital stay of 2.2 days (95% CI, -0.6 to 4.9; P = .12). CONCLUSIONS: Elevated cTn measurements among critically ill patients are associated with increased mortality and ICU length of stay. Research is needed to clarify the underlying causes of elevated cTn in this population and to examine their clinical significance.     

Correlation of serum PSA and Gleason score in Nigerian men with prostate cancer

Objective  Prostate cancer is an important cause of morbidity and mortality worldwide. While the predisposing factors are not fully understood, African descent is an important risk factor, and prostate cancer has become the number-one cancer in Nigerian men. This was a retrospective study of the correlation between serum prostate specific antigen (PSA) and Gleason grade and score in patients of Nigerian descent. Patients and Methods  The University College Hospital (UCH) Ibadan Cancer Registry was used to identify and quantify the incidence of prostate cancers occurring between 1998 and 2000. The histological slides of appropriate cases were reviewed to confirm the Gleason grade and score. The serum PSA values were retrieved from the patients' case notes and laboratory files. The data obtained were subjected to statistical analysis to look for associations and correlations. Results  The study included 67 men with prostate adenocarcinoma and PSA measurements who were diagnosed and treated at the UCH Ibadan between January 1998 and December 2000. There was a positive correlation between serum PSA and Gleason grade, as well as between serum PSA and Gleason score in our cohort of Nigerian African men with prostate cancer. PSA levels were significantly lower in patients with stage B disease than in patients with stage D disease. Conclusion  Serum PSA is significantly higher in metastatic than in localized disease. Further studies are necessary to determine biomarkers that complement serum PSA and the Gleason grading system in the prognostication of prostate cancer in African patients.     

Efficacy of Artemisinin-Based Combination Treatments of Uncomplicated Falciparum Malaria in Under-Five-Year-Old Nigerian Children

The efficacy of 3-day regimens of artemether-lumefantrine and artesunate-amodiaquine were evaluated in 747 children < 5 years of age with uncomplicated malaria from six geographical areas of Nigeria. Fever clearance was significantly faster (P = 0.006) and the proportion of children with parasitemia 1 day after treatment began was significantly lower (P = 0.016) in artesunate-amodiaquine—compared with artemether-lumefantrine-treated children. Parasite clearance times were similar with both treatments. Overall efficacy was 96.3% (95% confidence interval [CI] 94.5–97.6%), and was similar for both regimens. Polymerase chain reaction-corrected parasitologic cure rates on Day 28 were 96.9% (95% CI 93.9–98.2%) and 98.3% (95% CI 96.1–99.3%) for artemether-lumefantrine and artesunate-amodiaquine, respectively. Gametocyte carriage post treatment was significantly lower than pretreatment (P < 0.0001). In anemic children, mean time to recovery from anemia was 10 days (95% CI 9.04–10.9) and was similar for both regimens. Both treatments were well tolerated and are safe and efficacious treatments of uncomplicated falciparum malaria in young Nigerian children.     

Statistical issues in the design and analysis of expertise-based randomized clinical trials

In order to avoid certain difficulties with the conventional randomized clinical trial design, the expertise-based design has been proposed as an alternative. In the expertise-based design, patients are randomized to clinicians (e.g. surgeons), who then treat all their patients with their preferred intervention. This design recognizes individual clinical preferences and so may reduce the rates of procedural crossovers compared with the conventional design. It may also facilitate recruitment of clinicians, because they are always allowed to deliver their therapy of choice, a feature that may also be attractive to patients.The expertise-based design avoids the possibility of so-called differential expertise bias. If a standard treatment is generally more familiar to clinicians than a new experimental treatment, then in the conventional design, more patients randomized to the standard treatment will have an expert clinician, compared with patients randomized to the experimental treatment. If expertise affects the study outcome, then a biased comparison of the treatment groups will occur.We examined the relative efficiency of estimating the treatment effect in the expertise-based and conventional designs. We recognize that expected patient outcomes may be better in the expertise-based design, which in turn may modify the estimated treatment effect. In particular, a larger treatment effect in the expertise-based design can sometimes offset a higher standard error arising from the confounding of clinician effects with treatments.These concepts are illustrated with data taken from a randomized trial of two alternative surgical techniques for tibial fractures.