The presence of anti-LPS antibodies and human serum activity against Proteus mirabilis S/R forms in correlation with TLR4 (Thr399Ile) gene polymorphism in rheumatoid arthritis

ObjectivesProteus mirabilis strains are human pathogens responsible for urinary tract infections, which may also be involved in rheumatoid arthritis (RA).Design and methodsWe determined whether the binding site of anti-LPS antibodies on the O-polysaccharide part of P. mirabilis LPS correlates with the level of TLR4 (Thr399Ile) gene polymorphism in the sera of RA patients. We investigated the deposition of C3d and C5b complement components on the P. mirabilis LPS. The ELISA method used in this study was optimized with LAL test and laser interferometry.ResultsDepending on LPS P. mirabilis used in these studies, the amount of antibodies in RA patients sera varied. We did not observe a correlation between anti-LPS antibodies binding and the level of TLR4 (Thr399Ile) gene polymorphism. We found that the lower complement components deposition by O49 in contrast to O9 LPS correlates with its reduced sensitivities to human complement-mediated killing.ConclusionThe immunological response against P. mirabilis LPS might play a role in rheumatoid arthritis.     

AbetaPP-overexpression and proteasome inhibition increase alphaB-crystallin in cultured human muscle: relevance to inclusion-body myositis

Amyloid-beta precursor protein (AbetaPP) and its fragment amyloid-beta (Abeta) are increased in s-IBM muscle fibers and appear to play an important role in the pathogenic cascade. alphaB-Crystallin (alphaBC) was shown immunohistochemically to be accumulated in s-IBM muscle fibers, but the stressor(s) influencing alphaBC accumulation was not identified. We now demonstrate, using our experimental IBM model based on genetic overexpression of AbetaPP into cultured normal human muscle fibers, that: (1) AbetaPP overexpression increased alphaBC 3.7-fold (p=0.025); (2) additional inhibition of proteasome with epoxomicin increased alphaBC 7-fold (p=0.002); and (3) alphaBC physically associated with AbetaPP and Abeta oligomers. We also show that in biopsied s-IBM muscle fibers, alphaBC was similarly increased 3-fold (p=0.025) and physically associated with AbetaPP and Abeta oligomers. We propose that increased AbetaPP is a stressor increasing alphaBC expression in s-IBM muscle fibers. Determining the consequences of alphaBC association with Abeta oligomers could have clinical therapeutic relevance.     

Epidemiological features of patients infected with HCV genotype 4 in Poland: Epidemiology of HCV genotype 4 in Poland

Background

Hepatitis C genotype 4 (HCV-4) is considered to be rare outside northern Africa and southern Europe.

Objectives

To describe the epidemiological characteristics of patients infected with HCV-4 in Poland.

Patients and Methods

The study group included 290 patients with HCV-related chronic liver disease and intravenous drug users with HCV infection recruited in years 2002-2006 in Podlaskie region, north-eastern Poland. In all cases, HCV infection was confirmed by HCV-RNA detection by qualitative nested RT-PCR. HCV genotype was determined by 5''UTR sequencing and comparison with known genotype-specific sequences.

Results

HCV 4 was found in 45 (15.5%) of 290 HCV-infected and HCV RNA-positive individuals. 60% of HCV 4 infections occurred in intravenous drug users; 51% of HCV 4-infected patients were also HIV-positive. Among 119 patients whose source of infection was other than drug use, there were 16 (10.5%) HCV 4 cases. Seven (46%) of 13 HCV 4-positive and HIV-negative patients who received combined antiviral treatment had sustained viral response.

Conclusions

HCV 4 exists in eastern Poland, and the infection is frequently related to intravenous drug use and accompanied by HIV infection. HCV 4 also causes a proportion of non-drug-related HCV infections.     

Incisional hernia, midline versus low transverse incision: what is the ideal incision for specimen extraction and hand-assisted laparoscopy?

Background  

Minimally invasive surgery is associated with smaller surgical incisions than those of traditional midline laparotomy. However, most colorectal resections and all hand-assisted procedures require an incision either for specimen retrieval or insertion of the hand-assist device. The ideal site of this incision has not been evaluated with respect to the incidence of incisional hernia. This study compares the rates of incisional hernia associated with a standard midline laparotomy, a midline incision of reduced length, and a Pfannenstiel incision.     

Tolerability and efficacy of GM-CSF [Leucomax] in patients with small cell lung cancer treated with intensive chemotherapy

The aim of this study was to evaluate tolerability and efficacy of Leucomax (Sandoz/Schering Plough) used for neutropenia in patients with small cell lung cancer (SCLC) treated with etoposide and cisplatin. The potential influence of granulocyte-macrophage colony stimulating factor (GM-CSF) on chemotherapy relative dose intensity (RDI) was also evaluated. The chemotherapy used was the following, cisplatin 50 mg m^-2 i.v. 1 and 7 day, etoposide 170 mg m^-2 i.v. 3-5 days, q 3-4 weeks. Patients received a median of six cycles (range 2-8) over 4-36 weeks (median: 20). Thirty-two consecutive patients were treated, six were excluded. Eleven patients received GM-CSF 5 /zg kg"1 s.c. due to absolute neutrophil count (ANC), 1000/mm3 until recovery (ANC > 2000 mm3) or during 7 days, and thereafter prophylactically 24 hours post subsequent chemotherapy cycles for 7 days. Four patients received single GM-CSF course during the terminal disease phase. In 11 patients, there was no neutropenia requiring GM-CSF during the whole treatment course. Toxicity of chemotherapy was high, including thrombocytopenia, neutropenia, anaemia, mucositis, fever and hypotension. GM-CSF toxicity was the following, first dose reaction - one patient, local erythema - two patients, arthralgia - one patient, hypotension, chills, fever requiring GM-CSF discontinuation one patient RDI of cisplatin/etoposide was 0.77/0.62 in GM-CSF group, and 0.90/ 0.80 in patients who didn’t receive Leucomax. Overall objective response rate to chemotherapy and complete response rate were 80% (21/26), 26% (7/26) and median survival of all patients was 10 months. Median disease free survival was 8 months. Four patients are alive, two patients lost during progression, 20 died. Administration of GM-CSF did not appear to improve RDI of chemotherapy, overall response rate (RR) nor survival in this phase I/II clinical study. RDI of chemotherapy was reduced in patients receiving GM-CSF due to thrombocytopenia and/or extrahaematologic toxicity of chemotherapy.     

A comparison of the efficacy of oral fluconazole, 150 mg/week versus 50 mg/day, in the treatment of tinea corporis, tinea cruris, tinea pedis, and cutaneous candidosis

Two hundred and forty five patients with dermatophytoses and cutaneous candidosis were enrolled in the study; 122 were randomized to the once-weekly regimen and 123 to the once-daily regimen. Subjects included both men and women; the average age was 42 years. There were no statistically significant differences between the two groups with regard to age, sex, race, and body weight distributions. In the group receiving once-weekly fluconazole, there were 58 tinea pedis infections and 77 nonpedis infections (tinea corporis, tinea cruris, and cutaneous candidosis). In the group receiving once-daily fluconazole, there were 56 tinea pedis infections and 76 nonpedis infections. The duration of infection and total score of signs and symptoms did not differ significantly between the two groups. Patients received treatment until clinically cured or up to a maximum of 6 weeks for tinea pedis and 4 weeks for tinea corporis, tinea cruris, or cutaneous candidosis. Medical history, physical and laboratory examinations, and the clinical diagnosis were recorded. Clinical and mycologic examinations and laboratory testing were performed at baseline and 2 weeks after treatment initiation, and then weekly until clinically cured or the maximum duration of treatment allowed was reached. Safety analysis was performed for all patients. Follow-up clinical and mycologic examinations were performed 1 month after the therapy ended. The clinical efficacy was based on cure (disappearance of all baseline signs and symptoms of infection), marked improvement, moderate improvement, failure (no change or worsening of the signs and symptoms), or unevaluable (most commonly due to protocol evaluations or the absence of an identified pathogen). Mycologic efficacy was based on eradication (absence of pathogen on microscopy and/or culture), persistence (presence of pathogen on microscopy and/or culture), superinfection (absence of pathogen, but with a different fungal pathogen on microscopy and culture associated with clinical disease), or unevaluable. Long-term follow-up evaluation included the category relapse, defined as the absence of pathogen at the end of treatment, with the reappearance of that pathogen on microscopy and/or culture at follow-up visit. The culture result determined the efficacy where discrepancies between microscopy and culture findings occurred.     

Linkage studies exclude the AT-V gene(s) from the translocation breakpoints in an AT-V patient

An 8-year-old girl with severe microcephaly of prenatal onset, borderline intelligence, defects of skin pigmentation, deficiency of both humoral and cellular immunity, a normal serum α-fetoprotein level and hypersensitivity to ionizing irradiation is described. Spontaneous chromosomal breakage in lymphocytes together with the clinical presentation led to the diagnosis of ataxia telangiectasia variant (AT-V). In addition, the patient carried a constitutional translocation of paternal origin: 46,XX,t(3;7)(q12;q31.3) pat. In subsequent linkage and haplotype studies in 12 AT-V families with microsatellite markers from each of the translocation breakpoint regions, we could clearly exclude the localization of an AT-V gene to these regions.