Usefulness of a rapid human immunodeficiency virus-1 antibody test for the management of occupational exposure to blood and body fluid.

OBJECTIVE: To describe the usefulness of the OraQuick Rapid HIV-1 Antibody Test (OraSure Technologies, Bethlehem, PA) in cases of occupational exposure regarding its use with source-patient sera, effects on post-exposure prophylaxis (PEP) use, potential cost savings, and effects on healthcare worker (HCW) stress reaction symptoms. DESIGN: Before-and-after analysis. SETTING: A 269-bed, tertiary-care medical center with adjacent clinics. PARTICIPANTS: All source-patients and HCWs experiencing an occupational exposure during the study period. METHODS: Use of the OraQuick test with patient sera was validated prior to its use for occupational exposures. Exposures from January 1 through July 10, 2003 (enzyme immunoassay [EIA] group) and July 11 through December 31, 2003 (OraQuick group) were retrospectively reviewed and the use and cost of PEP was compared for each group. Randomly selected HCWs from both groups completed a survey to assess their stress reaction symptoms. RESULTS: After exclusion, there were 71 exposures in the EIA group and 79 in the OraQuick group. OraQuick results were 100% concordant with the reference standard of EIA and Western blot using patient sera. The mean number of doses ingested per course of PEP was significantly higher for HCWs in the EIA group (3.8; range, 0 to 6) compared with the OraQuick group (1.2; range, 0 to 3; P = .016). Cost analysis revealed a mean savings of dollar 6.62 with the OraQuick test per occupational exposure. Although the survey failed to detect an overall reduction in HCW stress reaction symptoms using OraQuick for source-patient testing, 11 HCWs in the EIA group had repetitive thoughts of the exposure compared with 5 in the OraQuick group (P = .049). CONCLUSION: Because of the reduction in ingested doses of unnecessary PEP and reduced cost of occupational exposure management with their use, rapid HIV-antibody tests should be the preferred method for source-patient testing following an occupational exposure.     

Bioluminescent Imaging Reveals Novel Patterns of Colonization and Invasion in Systemic Escherichia coli K1 Experimental Infection in the Neonatal Rat

Key features of Escherichia coli K1-mediated neonatal sepsis and meningitis, such as a strong age dependency and development along the gut-mesentery-blood-brain course of infection, can be replicated in the newborn rat. We examined temporal and spatial aspects of E. coli K1 infection following initiation of gastrointestinal colonization in 2-day-old (P2) rats after oral administration of E. coli K1 strain A192PP and a virulent bioluminescent derivative, E. coli A192PP-lux2. A combination of bacterial enumeration in the major organs, two-dimensional bioluminescence imaging, and three-dimensional diffuse light imaging tomography with integrated micro-computed tomography indicated multiple sites of colonization within the alimentary canal; these included the tongue, esophagus, and stomach in addition to the small intestine and colon. After invasion of the blood compartment, the bacteria entered the central nervous system, with restricted colonization of the brain, and also invaded the major organs, in line with increases in the severity of symptoms of infection. Both keratinized and nonkeratinized surfaces of esophagi were colonized to a considerably greater extent in susceptible P2 neonates than in corresponding tissues from infection-resistant 9-day-old rat pups; the bacteria appeared to damage and penetrate the nonkeratinized esophageal epithelium of infection-susceptible P2 animals, suggesting the esophagus represents a portal of entry for E. coli K1 into the systemic circulation. Thus, multimodality imaging of experimental systemic infections in real time indicates complex dynamic patterns of colonization and dissemination that provide new insights into the E. coli K1 infection of the neonatal rat.     

Quality of abortion care in the Unified Health System of Northeastern Brazil: what do women say?

Abortion is a serious health problem in Brazil and complications can be avoided by adequate and timely care. The article evaluates the quality of care given to women admitted for abortion in hospitals operated by the Unified Health System, in Salvador, Recife and S?o Luis, the benchmarks being Ministry of Health norms and user satisfaction. The article analyzes 2804 women admitted to hospital for abortion complications in 19 hospitals, between August and December 2010. Four dimensions were defined: reception and guidance; inputs and physical environment; technical quality and continuity of care. There was a closer fit to norms on reception and guidance. Social support and the right to information were not well rated in all three cities. The technical quality of care was rated poor. With respect to inputs and physical environment, cleanliness was the least adequate criterion. Continuity of care was the most critical situation in all three cities, due to the lack of scheduled follow-up appointments, information about care available after hospital discharge, the risk of further pregnancy and family planning. Abortion care falls short of that advocated under Brazilian norms and by international agencies.     

Coenzyme Q(10), vitamin E, selenium, and methionine in the treatment of chronic recurrent viral mucocutaneous infections

ObjectiveHost defense and latency determinants in viral recurrent dermatologic infections are not entirely understood, as conventional protocols are inadequate to achieve fast healing and relapse prevention. Endogenously produced oxygen/nitrogen reactive species (ROS/RNS) are essential for antiviral immune defense, while their excess may aggravate skin inflammation. Here, we sought a nutritional approach capable of controlling ROS/RNS balance to accelerate recovery and inhibit recurrences of two mucocutaneous chronic DNA-virus infections.MethodsTwo controlled clinical trials evaluated the feasibility of ROS/RNS-modulating nutriceutical dosages of coenzyme Q₁₀, RRR-α-tocopherol, selenium aspartate, and L-methionine associated with established therapies. Clinical trial 1 evaluated 68 patients with relapsing human papillomavirus skin warts treated with cryotherapy followed by 180 d of nutriceutical/placebo administration. Clinical trial 2 compared the combination of acyclovir followed by 90 d of nutriceutical administration versus acyclovir alone in patients with recurrences of herpes simplex genitalis (n = 60) or herpes zoster (n = 29). Viral DNA levels were assessed by polymer chain reaction, biomarkers of antiviral defense (peroxynitrite and IFNα/γ) and antioxidant capacity (lipophilic antioxidants and glutathione) were assayed by biochemical/enzyme-linked immunosorbent assay techniques in blood fractions.ResultsIn both trials, the nutriceutical induced significantly faster healing (P < 0.01-0.05) with reduced incidence of relapses (P < 0.05) as compared to control groups, which was confirmed by decreased viral load and increased antiviral cytokine and peroxynitrite plasma levels. Plasma antioxidant capacity was higher (P < 0.01) in the experimental versus control groups.ConclusionsResults document positive clinical outcomes of the selected nutriceutical associated with conventional protocols in the management of relapsing mucocutaneous human papillomavirus and herpes infections.     

Validation of the human activity profile in stroke: A comparison of observed,proxy and self-reported scores

Purpose. To assess the concurrent validity of the Human Activity Profile (HAP) with stroke and healthy control individuals, when reported by the subject or a proxy and compared to observed performance, used as gold standard; factors related to discrepancies; as well as to determine variables that could best predict physical activity levels.

Methods. A total of 24 stroke and 23 healthy control subjects took part in the study. Functional outcome measures included personal/demographic factors, HAP, the 10-meter walk, and cognition.

Results. Strong relationships were found between self-reported and observed scores for both groups (r = 0.89 – 0.99). The relationships between proxy and observed scores were acceptable for stroke (r = 0.80 – 0.87) but lower for control subjects (r = 0.65 – 0.75), with intraclass correlation coefficients (ICCs) ranging from 0.69 – 0.89. Significant differences were found between proxy and observed scores for stroke, but not for control subjects. Discrepancies between scores showed little predictability from selected variables. For stroke subjects, the strongest variable explaining physical activity levels was walking speed (r² = 43%) and the best combination of variables was walking speed plus cognition (r² = 55%).

Conclusions. Self-reported HAP was an excellent measure both for stroke and control subjects and related well to observed performance. Proxy reports appear to be valid for stroke subjects. HAP was significantly related to measures of walking speed.     

In vitro and in vivo evaluation of pyridinium oximes: mode of interaction with acetylcholinesterase, effect on tabun- and soman-poisoned mice and their cytotoxicity

The increased concern about terrorist use of nerve agents prompted us to search for new more effective oximes against tabun and soman poisoning. We investigated the interactions of five bispyridinium oximes: K027 [1-(4-hydroxyiminomethylpyridinium)-3-(4-carbamoylpyridinium) propane dibromide], K048 [1-(4-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium) butane dibromide], K033 [1,4-bis(2-hydroxyiminomethylpyridinium) butane dibromide], TMB-4 [1,3-bis(4-hydroxyiminomethylpyridinium) propane dibromide] and HI-6 [(1-(2-hydroxyiminomethylpyridinium)-3-(4-carbamoylpyridinium)-2-oxapropane dichloride)] with human erythrocyte acetylcholinesterase (AChE; E.C. 3.1.1.7) and their effects on tabun- and soman-poisoned mice. All the oximes reversibly inhibited AChE, and the enzyme-oxime dissociation constants were between 17 and 180 microM. Tabun-inhibited AChE was completely reactivated by TMB-4, K027 and K048, with the overall reactivation rate constants of 306, 376 and 673 min(-1)M(-1), respectively. The reactivation of tabun-inhibited AChE by K033 reached 50% after 24h, while HI-6 failed to reactivate any AChE at all. Soman-inhibited AChE was resistant to reactivation by 1mM oximes. All studied oximes protected AChE from phosphorylation with both soman and tabun. In vivo experiments showed that the studied oximes were relatively toxic to mice; K033 was the most toxic (LD50=33.4 mg/kg), while K027 was the least toxic (LD50=672.8 mg/kg). The best antidotal efficacy was obtained with K048, K027 and TMB-4 for tabun poisoning, and HI-6 for soman poisoning. Moreover, all tested oximes showed no cytotoxic effect on several cell lines in concentrations up to 0.8mM. The potency of the oximes K048 and K027 to protect mice from five-fold LD50 of tabun and their low toxicity make these compounds leading in the therapy of tabun poisoning. The combination of HI-6 and atropine is the therapy of choice for soman poisoning.     

Osteopontin inhibits macrophage nitric oxide synthesis to enhance tumor proliferation

BACKGROUND: Interactions between tumor cells and their host environment can play a major role in regulating survival programs required for tumor progression. Osteopontin (OPN) is a glycophosphoprotein overexpressed by tumors, and is a key molecule for tumor progression and metastasis. OPN also inhibits expression of autocrine and paracrine inducible nitric oxide synthase (iNOS). Given the cytotoxic effects of macrophage NO expression, we hypothesized that tumor-derived OPN inhibits expression of local macrophage iNOS to potentiate tumor survival. METHODS: We used a coculture system of murine CT26 colorectal cancer cells with RAW264.7 murine macrophage cells. CT26 expresses OPN at high levels. RNA interference was utilized to produce long-term specific silencing of OPN in CT26. RESULTS: Inhibition of constitutive OPN synthesis in CT26 upregulates local NO production with inhibition of CT26 proliferation and promotion of CT26 apoptosis. Macrophage iNOS expression is accompanied by increased binding activity of nuclear factor-kappaB DNA. When the CT26 culture media were examined for a panel of proinflammatory cytokines, elevated concentrations of granulocyte colony-stimulating factor (G-CSF) were found. Subsequently, in CT26 cells treated with antisense-G-CSF, NO levels in CT26-RAW cocultures were significantly decreased. CONCLUSION: In our system of CT26-RAW264.7 coculture, we conclude that inhibition of OPN synthesis in CT26 results in G-CSF-mediated induction of macrophage iNOS expression with resultant inhibition of CT26 proliferation via increased apoptosis. Our results suggest that tumor-derived OPN may enhance tumor survival by down regulating expression of NO in the local microenvironment. This is one mechanism by which OPN may potentiate cancer survival and progression.     

Differential diagnosis and therapy of nephrogenic hemorrhagic diathesis]

For the development of nephrogenic haemorrhagic diatheses in the first place a decreased function of the thrombocytes and a thrombocytopenia are responsible. An inhibition in the intrinsic system may be referred to a lesion of the thrombocytic factor 3. Up to now defects in the extrinsic system do not allow a systematic classification. The best causal therapy are an effective haemodialysis and a renal transplantation. The detection of defects in the coagulation system is of importance for the dosed heparinisation and the control of the treatment with cytostatics for the immune suppression. Among 33 patients undergoing dialysis only 3 patients the Quick-value was reduced to 50% in 9 patients the thrombocyte values were below 150,000 mm3 and in 2 patients below 100,000 mm3. Among 28 carriers with renal graft only in 1 case the Quick-value was reduced to about 50%. In 12 patients the thrombocyte values were decreased below 150,000 mm3 and in 4 patients below 100,000 mm3. A correlation between the two global tests was not to be proved.