Risk factors for HIV infection among circumcised men in Uganda: a case-control study

Introduction

Male circumcision (MC) reduces the risk of HIV infection. However, the risk reduction effect of MC can be modified by type of circumcision (medical, traditional and religious) and sexual risk behaviours post-circumcision. Understanding the risk behaviours associated with HIV infection among circumcised men (regardless of form of circumcision) is critical to the design of comprehensive risk reduction interventions. This study assessed risk factors for HIV infection among men circumcised through various circumcision approaches.

Methods

This was a case-control study which enrolled 155 cases (HIV-infected) and 155 controls (HIV-uninfected), all of whom were men aged 18–35 years presenting at the AIDS Information Center for HIV testing and care. The outcome variable was HIV sero-status. Using SPSS version 17, multivariable logistic regression was performed to identify factors independently associated with HIV infection.

Results

Overall, 83.9% among cases and 56.8% among controls were traditionally circumcised; 7.7% of cases and 21.3% of controls were religiously circumcised while 8.4% of cases and 21.9% of controls were medically circumcised. A higher proportion of cases than controls reported resuming sexual intercourse before complete wound healing (36.9% vs. 14.1%; p<0.01). Risk factors for HIV infection prior to circumcision were:being in a polygamous marriage (AOR: 6.6, CI: 2.3–18.8) and belonging to the Bagisu ethnic group (AOR: 6.1, CI: 2.6–14.0). After circumcision, HIV infection was associated with: being circumcised at >18 years (AOR: 5.0, CI: 2.4–10.2); resuming sexual intercourse before wound healing (AOR: 3.4, CI: 1.6–7.3); inconsistent use of condoms (AOR: 2.7, CI: 1.5–5.1); and having sexual intercourse under the influence of peers (AOR: 2.9, CI: 1.5–5.5). Men who had religious circumcision were less likely to have HIV infection (AOR: 0.4, 95% CI: 0.2–0.9) than the traditionally circumcised but there was no statistically significant difference between those who were traditionally circumcised and those who were medically circumcised (AOR: 0.40, 95% CI: 0.1–1.1).

Conclusions

Being circumcised at adulthood, resumption of sexual intercourse before wound healing, inconsistent condom use and having sex under the influence of peers were significant risk factors for HIV infection. Risk reduction messages should address these risk factors, especially among traditionally circumcised men.     

A systematic review of interventions to reduce psychological distress in pediatric patients receiving radiation therapy

Objective

Radiation therapy (RT) is a cornerstone for management of pediatric cancer. For younger patients, unintended radiation to critical organs is a concern and children need to remain immobile. Distress in children is common so many centres sedate pediatric patients. Children often are unable to remain still, due to anxiety. Interventions to reduce distress could also reduce sedation rates. The objectives of this systematic review were to: review the interventions used to address pediatric RT patients' distress and anxiety and assess their effectiveness.

Cyclic guanosine monophosphate-dependent protein kinase is targeted to intermediate filaments and phosphorylates vimentin in A23187-stimulated human neutrophils

The effects of the calcium ionophore, A23187, on human neutrophil activation were studied in relation to the signaling mechanism of cyclic guanosine monophosphate (cGMP)-dependent protein kinase (G- kinase). Immunocytochemistry demonstrated that G-kinase translocated from a diffuse localization in the cytoplasm to the cytoskeleton after stimulation with A23187. Over a period of 5 minutes, G-kinase was transiently colocalized with the intermediate filament protein, vimentin. At 3 minutes' stimulation with A23187, colocalization of G- kinase and vimentin was predominantly confined to filaments that extended into the uropod. The time of colocalization of G-kinase and vimentin was reduced in the A23187-stimulated cell from 3 minutes to 1 minute by 8-Br-cGMP. Coincident with colocalization was an increase in cGMP levels and transient phosphorylation of vimentin in adhered A23187- stimulated cells. Phosphorylation of vimentin was maximal after 3 minutes with A23187, and was essentially over at 5 minutes. The time of phosphorylation of vimentin was also reduced from 3 minutes to 1 minute when cells were preincubated with 8-Br-cGMP and then stimulated with A23187, which suggests that cyclic adenosine monophosphate (cAMP)- dependent protein kinase does not phosphorylate vimentin in A23187- treated neutrophils. Phosphorylation of vimentin was not observed in nonactivated cells treated only with 8-Br-cGMP. The presence of the protein kinase C inhibitors, staurosporine or H-7, did not inhibit vimentin phosphorylation in A23187-treated cells, which provides supportive data that protein kinase C is not the phosphorylating enzyme. These results suggest that vimentin and G-kinase are colocalized in a Ca(2+)-dependent manner in neutrophils, and that vimentin is transiently phosphorylated by G-kinase in response to the colocalization of the two proteins. The transient redistribution of compartmentalized G-kinase represents one type of neutrophil activation mechanism.     

HLA DRB1* typing and cartilage oligomeric matrix protein (COMP) as predictors of joint destruction in recent-onset rheumatoid arthritis

The carriage of a characteristic sequence of amino acids at position 67- 72 in the third hypervariable region of the HLA DRB1 chain has been linked to susceptibility to rheumatoid arthritis (RA). Whether this epitope is also a predictor of more severe disease remains controversial. Cartilage oligomeric matrix protein (COMP) is a protein, the serum levels of which have been found to correlate with large joint destructive disease in previous work. In this paper, we compare DRB1* typing and serum COMP levels in a prospectively observed group of RA patients with or without early hip joint destruction. The COMP levels at study inclusion, median 11 months from onset of symptoms, were significantly higher in the patients with early hip joint destruction compared to the patients in the more benign group. There was no difference in the number of disease susceptibility-related epitopes between the groups. DRB1*04, in contrast, was found among 8/8 patients with hip destruction, but also in 5/8 more benign cases. We conclude that in this type of RA patient, COMP serum levels are more informative predictors of aggressive disease than HLA DRB1* typing.      

Thiotepa, busulfan, and cyclophosphamide: a new preparative regimen for autologous marrow or blood stem cell transplantation in high-risk multiple myeloma

Forty patients with multiple myeloma received thiotepa (750 mg/m2), busulfan (10 mg/kg), and cyclophosphamide (120 mg/kg) (TBC) followed by autologous bone marrow or blood stem cell support. Granulocyte-Colony stimulating factor (G-CSF) was administered to accelerate hematopoietic recovery. Sixty-five percent of all patients responded to this treatment. Eighty-eight percent of patients transplanted in partial remission had a further reduction of the myeloma and 53% achieved a complete remission. Forty-eight percent of patients with refractory myeloma responded. All responding patients transplanted during partial remission or with primary refractory myeloma remain free of progression for a period of 4 to 24 months post-transplant, but the remission duration of patients treated in refractory relapse was short (4 months). Five of 24 patients transplanted with marrow and none of 16 receiving blood stem cells died of treatment-related complications. Use of blood stem cells resulted in more rapid granulocyte and platelet recovery. We conclude that TBC is an effective, relatively well tolerated, preparative regimen for patients with multiple myeloma.     

Pediatric urography: comparison of metrizamide and methylglucamine diatrizoate

A non-ionic contrast medium (metrizamide) was compared to an ionic agent (methylglucamine diatrizoate) for pediatric urography. Fifty children were divided into two age groups: under 5, and 5 to 10. In younger children, metrizamide gave more excellent images (19% vs. 0%) and fewer inadequate images (0% vs. 18%) than methylglucamine diatrizoate (p = 0.06). In older children, metrizamide likewise gave more excellent images (44% vs. 14%) and fewer inadequate images (0% vs. 7%). The same pattern was seen when the two groups were combined (excellent, 28% vs. 8%; inadequate, 0% vs. 12%) (p = 0.05). Differences with respect to changes in hematocrit, serum osmolality, serum sodium, and SGOT were statistically significant, but not adverse reactions. In terms of both efficacy and safety, the authors conclude that metrizamide is preferred for pediatric urography.     

Effect of a short-term in vitro exposure to the marine toxin domoic acid on viability, tumor necrosis factor-alpha, matrix metalloproteinase-9 and superoxide anion release by rat neonatal microglia

Background

The excitatory amino acid domoic acid, a glutamate and kainic acid analog, is the causative agent of amnesic shellfish poisoning in humans. No studies to our knowledge have investigated the potential contribution to short-term neurotoxicity of the brain microglia, a cell type that constitutes circa 10% of the total glial population in the brain. We tested the hypothesis that a short-term in vitro exposure to domoic acid, might lead to the activation of rat neonatal microglia and the concomitant release of the putative neurotoxic mediators tumor necrosis factor-α (TNF-α), matrix metalloproteinases-2 and-9 (MMP-2 and -9) and superoxide anion (O₂-).

Results

In vitro, domoic acid [10 μM-1 mM] was significantly neurotoxic to primary cerebellar granule neurons. Although neonatal rat microglia expressed ionotropic glutamate GluR4 receptors, exposure during 6 hours to domoic acid [10 μM-1 mM] had no significant effect on viability. By four hours, LPS (10 ng/mL) stimulated an increase in TNF-α mRNA and a 2,233 % increase in TNF-α protein In contrast, domoic acid (1 mM) induced a slight rise in TNF-α expression and a 53 % increase (p < 0.01) of immunoreactive TNF-α protein. Furthermore, though less potent than LPS, a 4-hour treatment with domoic acid (1 mM) yielded a 757% (p < 0.01) increase in MMP-9 release, but had no effect on MMP-2. Finally, while PMA (phorbol 12-myristate 13-acetate) stimulated O₂- generation was elevated in 6 hour LPS-primed microglia, a similar pretreatment with domoic acid (1 mM) did not prime O₂- release.

Conclusions

To our knowledge this is the first experimental evidence that domoic acid, at in vitro concentrations that are toxic to neuronal cells, can trigger a release of statistically significant amounts of TNF-α and MMP-9 by brain microglia. These observations are of considerable pathophysiological significance because domoic acid activates rat microglia several days after in vivo administration.