To determine the impact of treatment of tuberculosis on plasma HIV-1 load in African subjects and to correlate viral load with response to treatment and changes in immune activation.
Clinical and ...microbiological responses, immune activation parameters and plasma HIV-1 load were determined in 20 patients with pulmonary tuberculosis and HIV-1 coinfection in Ghana, West Africa during the first 3 months of anti-tuberculosis treatment.
Plasma HIV-1 load and markers of immune activation were determined by commercially available assays. Human leukocyte antigen (HLA)-DR incorporation into the HIV-1 envelope was measured by using an immunomagnetic capture technique.
Treatment of tuberculosis resulted in significant improvements in weight and haemoglobin, a high sputum smear conversion rate and marked reductions in mean plasma tumour necrosis factor (TNF) receptor-1, interleukin-6 and C-reactive protein. Furthermore, incorporation of host HLA-DR into the HIV-1 envelope decreased; this also suggested a reduction in immune activation of the cells supporting viral replication. However, of importance with regard to AIDS pathogenesis, neither mean plasma TNF-alpha nor HIV-1 load decreased significantly.
The failure of HIV-1 plasma load to decline significantly during the initial months of anti-tuberculosis treatment is associated with high, sustained systemic levels of TNF-alpha. The dissociation between the sustained levels of plasma TNF-alpha and the major reductions in other, diverse immune activation parameters may represent dysregulation of cytokine production in these African patients.
Our objective was to determine whether a strategy of intended incomplete percutaneous transluminal coronary angioplasty revascularization (IR) compromises long-term patient outcome.
Complete ...angioplasty revascularization (CR) is often not planned nor attempted in patients with multivessel coronary disease, and the extent to which this influences outcome is unclear.
Before randomization, in the Bypass Angioplasty Revascularization Investigation, all angiograms were assessed for intended CR or IR via angioplasty. Outcomes were compared among patients with IR intended if assigned to angioplasty, randomized to coronary artery bypass graft surgery (CABG) versus angioplasty; and within angioplasty patients only, among patients with IR versus CR intended.
At 5 years, there was a trend for higher overall (88.6% vs. 84.0%) and cardiac survival (94.5% vs. 92.1%) in CABG versus angioplasty patients with IR intended. The excess mortality in angioplasty patients occurred solely in diabetic subjects; overall and cardiac survival were similar among nondiabetic CABG and angioplasty patients. Freedom from myocardial infarction (MI) at 5 years was higher in nondiabetic CABG versus angioplasty patients (92.4% vs. 85.2%, p = 0.02), vet was similar to the rate observed (85%) in nondiabetic CABG and angioplasty patients with CR intended. Five-year rates of death, cardiac death, repeat revascularization and angina were similar in all angioplasty patients with IR versus CR intended. However, a trend for greater freedom from subsequent CABG was seen in CR patients (70.3% vs. 64.0%, p = 0.08).
Intended incomplete angioplasty revascularization in nondiabetic patients with multivessel disease who are candidates for both angioplasty and CABG does not compromise long-term survival; however, subsequent need for CABG may be increased with this strategy. Whether the risk of long-term MI is also increased remains uncertain.
We performed a systematic review to determine the overall efficacy of serotonin (5-HT3) receptor antagonists for the prevention and treatment of pruritus, nausea, and vomiting in women receiving ...spinal anesthesia with intrathecal morphine for cesarean delivery.
Reports of randomized, controlled trials that compared prophylaxis or treatment of pruritus and/or nausea, and vomiting using one of the 5-HT3 receptor antagonists or placebo in women undergoing cesarean delivery were reviewed. The articles were scored for validity and data were extracted by the authors independently and summarized using relative risks (RR) with 95% confidence intervals (CI).
Nine randomized, controlled trials were included in the systematic review. The nine trials had a total of 1152 patients enrolled; 539 received 5-HT3 receptor antagonists, 413 received placebo, and 200 received other antiemetics and were not included in the analysis. The incidence of pruritus was not reduced with 5-HT3 receptor antagonists prophylaxis compared with placebo (80.7% vs 85.8%, RR 95% CI = 0.94 0.81-1.09). However, their use reduced the incidence of severe pruritus and the need for treatment of pruritus (number-needed-to-treat = 12 and 15, respectively). Their use for the treatment of established pruritus showed improved efficacy compared with placebo with a number-needed-to-treat of three. There was a significant reduction in the incidence of postoperative nausea (22.0% vs 33.6%, RR 95% CI = 0.750.58-0.96) and vomiting (7.7% vs 16.8%, RR 95% CI = 0.49 0.30-0.81), and the need for postoperative rescue antiemetic treatment with the use of 5-HT(3) receptor antagonists when compared with placebo (9% vs 23%, RR 95% CI = 0.38 0.21-0.68).
Although prophylactic 5-HT(3) receptor antagonists were ineffective in reducing the incidence of pruritus, they significantly reduced the severity and the need for treatment of pruritus, the incidence of postoperative nausea and vomiting, and the need for rescue antiemetic therapy in parturients who received intrathecal morphine for cesarean delivery. They were also effective for the treatment of established pruritus. Although more studies are warranted, the current data suggest that the routine prophylactic use of those drugs should be considered in this patient population.
Inflammation of the retinal vasculature without an infectious etiology, systemic disease association, or concomitant ocular disease is termed primary retinal vasculitis, and can result in severe and ...permanent vision loss. Patients with primary retinal vasculitis usually are subjected to an extensive but unrewarding diagnostic evaluation. This study was undertaken to determine the value of such a diagnostic workup, and to determine whether systemic diseases develop in these patients during the course of their illness.
The clinical records of 25 patients seen between 1984 and 1994 with the referring diagnosis of primary retinal vasculitis were reviewed retrospectively. Recorded data included patient age, sex, race, medical history, medications, visual acuity, extent of retinal disease, and the results of their diagnostic evaluations.
On presentation, none of the patients had an underlying systemic disease attributable as the cause of their retinal vasculitis. Review of systems was suggestive of an underlying systemic disease in 1 of 25 patients. Diagnostic evaluation in this patient showed a positive antinuclear antibody value and a double-stranded DNA, suggestive of systemic lupus erythematosus. Subsequently, systemic lupus erythematosus was diagnosed based on the development of other diagnostic criteria. The review of systems was not suggestive of an underlying systemic disease in 24 of 25 patients. False-positive diagnostic test results were obtained in 5 (20.8%) of these 24 patients. No underlying systemic disease associated with the patients' retinal vasculitis subsequently developed in any of these five patients (mean follow-up, 4 years).
Few diagnostic tests should be ordered in patients with retinal vasculitis in the absence of a medical history suggestive of underlying systemic disease.
Background: The efficacy and safety of mometasone furoate aqueous nasal spray (MFNS; Nasonex) 200 μg once daily for the treatment and prophylaxis of seasonal allergic rhinitis (SAR) and treatment of ...perennial rhinitis have been demonstrated in adults. However, the dose response of MFNS in pediatric patients has not yet been characterized.
Objective: This study was conducted to determine the dose-response relationship of 3 different doses of MFNS in a pediatric population.
Methods: This was a multicenter, double-blind, active- and placebo-controlled study of 679 children 6 to 11 years of age with histories of SAR and documented positive skin test responses. Patients were randomized to one of the following treatment groups for 4 weeks: MFNS 25 μg once daily, MFNS 100 μg once daily, MFNS 200 μg once daily, beclomethasone dipropionate 84 μg twice daily (168 μg/day), or placebo. Physician evaluations were performed at days 4, 8, 15, and 29, and patient evaluations were analyzed for days 1 to 15 and 16 to 29.
Results: The mean reduction from baseline in physician-evaluated total nasal symptom scores at day 8 (the primary efficacy variable) was significantly greater in the MFNS and beclomethasone dipropionate groups than in the placebo group (
P ≤ .02). No significant differences were observed among the 3 MFNS groups. However, as treatment continued, symptoms in patients treated with MFNS 100 or 200 μg once daily continued to improve, whereas those treated with MFNS 25 μg once daily demonstrated little further improvement. By day 29, MFNS 100 and 200 μg once daily both were significantly more effective than MFNS 25 μg once daily in relieving symptoms of SAR, but MFNS 200 μg provided no additional benefit over MFNS 100 μg. All doses of MFNS were well tolerated, and cosyntropin stimulation tests performed before and after treatment found no evidence of hypothalamic-pituitary-adrenal axis suppression.
Conclusion: These results indicate that the most appropriate therapeutic dosage of MFNS in the treatment of SAR in children 6 to 11 years of age is 100 μg once daily. In addition, MFNS at doses up to 200 μg once daily for 4 weeks was well tolerated and had no detectable effects on hypothalamic-pituitary-adrenal axis function. (J Allergy Clin Immunol 1999;104:107-14.)
Obesity is a genetically heterogeneous disorder. Using targeted and whole-exome sequencing, we studied 32 human and 87 rodent obesity genes in 2,548 severely obese children and 1,117 controls. We ...identified 52 variants contributing to obesity in 2% of cases including multiple novel variants in GNAS, which were sometimes found with accelerated growth rather than short stature as described previously. Nominally significant associations were found for rare functional variants in BBS1, BBS9, GNAS, MKKS, CLOCK and ANGPTL6. The p.S284X variant in ANGPTL6 drives the association signal (rs201622589, MAF~0.1%, odds ratio = 10.13, p-value = 0.042) and results in complete loss of secretion in cells. Further analysis including additional case-control studies and population controls (N = 260,642) did not support association of this variant with obesity (odds ratio = 2.34, p-value = 2.59 × 10
), highlighting the challenges of testing rare variant associations and the need for very large sample sizes. Further validation in cohorts with severe obesity and engineering the variants in model organisms will be needed to explore whether human variants in ANGPTL6 and other genes that lead to obesity when deleted in mice, do contribute to obesity. Such studies may yield druggable targets for weight loss therapies.
To discuss interdisciplinary research and education in the context of informatics and medicine by commenting on the paper of Kuhn et al. "Informatics and Medicine: From Molecules to Populations".
...Inviting an international group of experts in biomedical and health informatics and related disciplines to comment on this paper.
The commentaries include a wide range of reasoned arguments and original position statements which, while strongly endorsing the educational needs identified by Kuhn et al., also point out fundamental challenges that are very specific to the unusual combination of scientific, technological, personal and social problems characterizing biomedical informatics. They point to the ultimate objectives of managing difficult human health problems, which are unlikely to yield to technological solutions alone. The psychological, societal, and environmental components of health and disease are emphasized by several of the commentators, setting the stage for further debate and constructive suggestions.
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