2D-fluoroscopic navigated percutaneous screw fixation of pelvic ring injuries - a case series

Background  

Screw fixation of pelvic ring fractures is a common, but demanding procedure and navigation techniques were introduced to increase the precision of screw placement. The purpose of this case series was the evaluation of screw misplacement rate and functional outcome of percutaneous screw fixation of pelvic ring disruptions using a 2D navigation system.     

Novel CYP2B6 Enzyme Variants in a Rwandese Population: Functional Characterization and Assessment of In Silico Prediction Tools

Cytochrome P450 CYP2B6 is a highly polymorphic enzyme that metabolizes numerous drugs, pesticides, and environmental toxins. Sequence analysis of a Rwandese population identified eight functionally uncharacterized nonsynonymous variants c.329G>T (p.G110V), c.341T>C (p.I114T), c.444G>T (p.E148D), c.548T>G (p.V183G), c.637T>C (p.F213L), c.758G>A (p.R253H), c.835G>C (p.A279P), and c.1459C>A (p.R487S), and five novel alleles termed CYP2B6*33 to CYP2B6*37 were assigned. Recombinant expression in COS‐1 cells and functional characterization using the antidepressant bupropion and the antiretroviral efavirenz (EFV) as substrates demonstrated complete or almost complete loss‐of‐function for variants p.G110V, p.I114T, p.V183G, and p.F213L, whereas p.E148D, p.R253H, p.A279P, and p.R487S variants were functional. The data were used to assess the predictive power of eight online available functional prediction programs for amino‐acid changes. Although none of the programs correctly predicted the functionality of all variants, substrate docking simulation analyses indicated similar conformational changes by all four deleterious mutations within the enzyme's active site, thus explaining lack of enzymatic function for both substrates. Because low‐activity alleles of CYP2B6 are associated with impaired EFV metabolism and adverse drug response, these results are of potential utility for personalized treatment strategies in HIV/AIDS therapy.     

CD4 cell counts of 800 cells/mm3 or greater after 7 years of highly active antiretroviral therapy are feasible in most patients starting with 350 cells/mm3 or greater

OBJECTIVE: CD4 cell count changes in therapy-naive patients were investigated during 7 years of highly active antiretroviral therapy (HAART) in an observational cohort. METHODS: Three endpoints were studied: (1) time to >or=800 CD4 cells/mm in 5299 therapy-naive patients starting HAART, (2) CD4 cell count changes during 7 years of uninterrupted HAART in a subset of 544 patients, and (3) reaching a plateau in CD4 cell restoration after 5 years of HAART in 366 virologically suppressed patients. RESULTS: Among patients with <50, 50 to 200, 200 to 350, 350 to 500, and >or=500 CD4 cells/mm at baseline, respectively, 20%, 26%, 46%, 73%, and 87% reached >or=800 CD4 cells/mm within 7 years of starting HAART. Periods with HIV RNA levels >500 copies/mL and age >or=50 years were associated with lesser increases in CD4 cell counts between 6 months and 7 years. Having reached >or=800 CD4 cells/mm at 5 years, age >or=50 years, and >or=1 HIV RNA measurement >1000 copies/mL between 5 and 7 years were associated with a plateau in CD4 cell restoration. CONCLUSIONS: Restoration to CD4 cell counts >or=800 cells/mm is feasible within 7 years of HAART in most HIV-infected patients starting with >or=350 cells/mm and achieving sufficient suppression of viral replication. Particularly in patients >or=50 years of age, it may be beneficial to start earlier than current guidelines recommend.     

Bactericidal effect of pefloxacin and fosfomycin againstPseudomonas aeruginosa in a rabbit endocarditis model with pharmacokinetics of pefloxacin in humans simulated in vivo

The bactericidal activity of pefloxacin and fosfomycin alone and in combination againstPseudomonas aeruginosa was evaluated in an experimental rabbit endocarditis model after 24 h of treatment. Two strains with intermediate susceptibility to pefloxacin and good susceptibility to fosfomycin were tested. The serum kinetics obtained during administration of 400 mg every 12 h in humans were simulated in the animals using computer-controlled variable-flow infusion. Fosfomycin was administered as a continuous infusion at a constant flow, allowing a steady-state concentration of 47.4±11.9 mg/ml to be reached in serum. In valvular vegetations, pefloxacin was less bactericidal than fosfomycin, and in combination treatment, it reduced (but did not abolish) the bactericidal effect of fosfomycin. The duration of the pretreatment interval (12–48 h) had a negative effect on the bactericidal activity of both drugs, especially that of fosfomycin.     

All infiltrating T-lymphocytes in Hodgkin's disease express immunohistochemically detectable T-cell receptor zeta-chains in situ

Aim: We studied the expression of TCR zeta-chain on tumour-infiltrating lymphocytes in EBV-positive and EBV-negative cases of Hodgkin's disease (HD), to assess whether downregulation of TCR zeta-chain on tumour-infiltrating lymphocytes might be a mechanism for immune escape of the neoplastic cells. METHODS AND RESULTS: By immunohistochemistry we investigated tissue of 27 cases of primary HD, both paraffin embedded and frozen, for the presence of T-cell receptor complex zeta-chain and other T-cell markers on the reactive cells. Strong membranous staining of TCR zeta-chain was present in all cases in frozen tissue. In contrast, in paraffin-embedded material substantial loss of TCR zeta-chain was detected in old (> 6 years) tissues. However, no differences in either the number of positive cells or their staining intensity were observed in EBV-positive and negative cases of HD as detected in frozen tissue. Storage of paraffin-embedded tissue leads to a rapid and substantial loss of TCR zeta-chain reactivity compared to frozen material of the same HD cases. Staining reactivity of other T-cell markers (CD3, CD4 and CD8) on paraffin-embedded material remained unaffected. Immunofluorescent double-staining confirmed colocalization and coexpression of TCR zeta-chain and CD3. CONCLUSIONS: In frozen biopsies of primary HD TCR zeta-chain was expressed on all reactive CD3-positive cells, both in EBV-positive and EBV-negative cases. This suggests that zeta-chain downregulation is not a likely mechanism whereby neoplastic cells of HD can escape immune surveillance.     

Hopefulness predicts resilience after hereditary colorectal cancer genetic testing: a prospective outcome trajectories study

Background -  

Genetic testing for hereditary colorectal cancer (HCRC) had significant psychological consequences for test recipients. This prospective longitudinal study investigated the factors that predict psychological resilience in adults undergoing genetic testing for HCRC.     

Determinants of high-risk sexual behavior among immigrant groups in Amsterdam: implications for interventions

OBJECTIVES: To determine predictors for sexual risk behavior among immigrant men in Amsterdam. METHODS: From May 1997 to July 1998, 650 men from Surinam, the Antilles, and Ghana were recruited by convenience sampling. Multivariate logistic regression was used to find independent predictors for 1) multiple sex partners (>sexual 1 partner in the past year), 2) unprotected sex with casual partners in The Netherlands, 3) sexual activity in country of origin, and 4) unprotected sex in country of origin. RESULTS: 1) Multiple sex partners were reported by 50% of respondents. Independent predictors were a recent infection with a sexually transmitted disease (STD), youth, low educational level, Afro-Surinamese origin, lack of a long-term relationship and history of commercial sex contact. 2) Unprotected sex occurred in 24% of casual partnerships. Independent predictors were a recent STD infection, low educational level, use of hard drugs, age between 20 and 29, few sexual partners, unprotected sex in country of origin, and a partner from the respondent's ethnic group. 3) During the past 5 years, 24% were sexually active in country of origin. Independent predictors were Ghanaian origin, age over 20, a relatively high income, and multiple partners. 4) Unprotected sex occurred in 39% of the partnerships in country of origin. Independent predictors were low educational level, history of STDs, lack of health insurance, Ghanaian origin, frequent visits to home country, few sexual partners, and unprotected sex with casual partners in The Netherlands. CONCLUSION: Among immigrant men in Holland, important target groups for AIDS prevention programs have been identified. Men who visit their country of origin should be made aware of the risk of sexual contact with local women. Furthermore, it should be taken into account that immigrant men use condoms less frequently with women of their own ethnic group than with Dutch women.     

BK virus genotypes and humoral response in kidney transplant recipients with BKV associated nephropathy

Background

Among kidney transplant recipients (KTR) with BK virus associated nephropathy (BKVN), BKV genotypes’ evolution and anti-BKV humoral response are not well established. We aim to analyze BKV replication and genetic evolution following transplantation, and characterize concomitant anti-BKV-VP1 humoral response.

Methods

We retrospectively analyzed 32 cases of biopsy-proven BKVN. Stored plasma and kidney biopsies were tested for BKV viral load, and VP1 sequencing performed on positive samples. BKV–VP1 genotype-specific neutralizing antibodies (NAbs) titers were determined at transplantation and BKVN.

Results

At the time of BKVN diagnosis, BKV viral load was 8.2 log₁₀IU/10⁶ cells and 5.4 log₁₀IU/mL in kidney and plasma, respectively. VP1 sequencing identified the same BKV-subtype in both compartments in 31/32 cases. At the time of transplantation, 8/20 (40%) of biopsies tested positive for BKV detection, whereas concomitant BKV viremia was negative. VP1 sequencing identified a different subtype compared to BKVN in 5/6 of these samples. This was confirmed following transplantation: 8 patients had a BKV+ biopsy before BKV viremia, and VP1 sequencing identified a different subtype compared to BKVN in all of them. After the onset of BKV viremia and prior to BKVN diagnosis, the BKV subtype in BKV+ plasma and kidney biopsy was the same as the one isolated at BKVN. BKV–VP1 NAbs titers were significantly higher at the time of BKVN compared to transplantation (p = .0031), with similar titers across genotypes.

Conclusion

Altogether, our data suggest that among some KTR with BKVN, the BKV genotype from the donor may not be responsible for BKVN pathogenesis.