Unilateral blindness following septoplasty

Visual loss following routine nasal surgery is an extremely rare and devastating complication. We report a case of unilateral blindness due to orbital apex syndrome following septoplasty. We also review the literature and discuss probable causes. To the best of our knowledge, this is only the second published report of this complication.     

Recombinant PorA,the Major Outer Membrane Protein of Campylobacter jejuni,Provides Heterologous Protection in an Adult Mouse Intestinal Colonization Model

Immunity against Campylobacter jejuni, a major food-borne pathogen causing diarrhea, is largely serotype specific. The major outer membrane protein (MOMP) of C. jejuni, PorA, is a common antigen with the potential to provide broad protection. Adult BALB/c mice were orally immunized with a recombinant glutathione S-transferase (GST) fused to PorA prepared from Campylobacter jejuni C31 (O:6,7) (GST-PorA) combined with a modified heat-labile enterotoxin of Escherichia coli as an adjuvant and later orally challenged with C31 strain or three heterologous strains: 48 (O:19), 75 (O:3), and 111 (O:1,44). Protection from colonization with the challenge organism was studied by fecal screening daily for 9 days. Serum and intestinal lavage fluid antibodies against the vaccine and Sarkosyl-purified MOMP from C31 were measured by using an enzyme-linked immunosorbent assay. The vaccine produced robust antibody responses against both antigens in serum and secretion. Since strain C31 was a poor colonizer, homologous protection could not be studied. The protective efficacies of heterologous strains were 43% (for strain 48, P < 0.001), 29% (for strain 75, P < 0.005), and 42% (for strain 111, P < 0.001) for the 9-day period compared to control mice given phosphate-buffered saline. Thus, PorA provided appreciable protection against colonization with heterologous serotypes.Campylobacter jejuni is a food-borne pathogen and a leading cause of diarrhea worldwide (19, 33, 34). Campylobacteriosis is associated with a number of important sequelae, including Guillain-Barre syndrome, Reiter''s syndrome, reactive arthritis, and irritable bowel syndrome (10, 37). C. jejuni also contributes to significant mortality of children in developing countries (18). In view of significant morbidity, mortality, and economic burden associated with C. jejuni infection, the control and prevention of campylobacteriosis are a priority. One possible tool for the prevention of campylobacteriosis is vaccination. It has been observed that C. jejuni infection results in the acquisition of immunity. However, immunity in humans seems to be serotype (Penner serotype) specific (13, 36). There are numerous serotypes of C. jejuni according to the Penner serotyping scheme, which is based on the lipopolysaccharide capsule (25). Therefore, vaccines based on common antigens that are shared by all serotypes seem attractive for broad protection. One such antigen is the major outer membrane protein (MOMP) of C. jejuni, PorA, which is present in abundant quantity in the organism. There are three conformational forms of MOMP: folded monomer (35 kDa), denatured monomer (45 kDa), and the native trimer (120 to 140 kDa). Only the folded monomer and the native trimer have pore-forming activities (44). The MOMP is involved in ion transport across the bacterial cell wall and adhesion of the bacterium to the intestinal mucosa (30, 41). It consists of 18 β-strands connected by short periplasmic turns and nine external loops. The external loops are antigenically variable (44). This is evident in the extreme genetic diversity of the porA gene encoding the MOMP (17, 44). However, the β-strands representing the conserved regions have common antigenic epitopes for different strains (16, 44). The sera of patients recovering from C. jejuni infection (8, 12, 35), as well as those of animals immunized with C. jejuni (21), possess antibodies to MOMP. Therefore, PorA seems to be an appropriate antigen that could be investigated as a possible subunit vaccine.There are no easily handled, widely available, and inexpensive natural animal models of C. jejuni diarrhea. Laboratory mice are widely available, inexpensive, and easy to handle. Oral feeding of the adult mouse with C. jejuni does not result in diarrhea in the animal. However, the organism colonizes the intestine, with shedding of the organism for several days in the stool. The organism can be isolated from the blood as well (7, 9). Thus, the adult mouse can be used as a colonization model of C. jejuni infection.Since the PorA of C. jejuni has never been investigated as a vaccine candidate, we studied a recombinant PorA in the form of a fusion protein in the adult mouse colonization model for broad protection against colonization. We studied fecal excretion of the challenge organisms and serum and intestinal antibody responses to the vaccine.     

Direct observation of DNA bending/unbending kinetics in complex with DNA-bending protein IHF

Regulation of gene expression involves formation of specific protein-DNA complexes in which the DNA is often bent or sharply kinked. Kinetics measurements of DNA bending when in complex with the protein are essential for understanding the molecular mechanism that leads to precise recognition of specific DNA-binding sites. Previous kinetics measurements on several DNA-bending proteins used stopped-flow techniques that have limited time resolution of few milliseconds. Here we use a nanosecond laser temperature-jump apparatus to probe, with submillisecond time resolution, the kinetics of bending/unbending of a DNA substrate bound to integration host factor (IHF), an architectural protein from Escherichia coli. The kinetics are monitored with time-resolved FRET, with the DNA substrates end-labeled with a FRET pair. The temperature-jump measurements, in combination with stopped-flow measurements, demonstrate that the binding of IHF to its cognate DNA site involves an intermediate state with straight or, possibly, partially bent DNA. The DNA bending rates range from approximately 2 ms(-1) at approximately 37 degrees C to approximately 40 ms(-1) at approximately 10 degrees C and correspond to an activation energy of approximately 14 +/- 3 kcal/mol. These rates and activation energy are similar to those of a single A:T base pair opening inside duplex DNA. Thus, our results suggest that spontaneous thermal disruption in base-paring, nucleated at an A:T site, may be sufficient to overcome the free energy barrier needed to partially bend/kink DNA before forming a tight complex with IHF.     

Use of miniaturized protein arrays for Escherichia coli O serotyping

Serological typing of Escherichia coli O antigens is a well-established method used for differentiation and identification of O serotypes commonly associated with disease. In this feasibility study, we have developed a novel somatic antibody-based miniaturized microarray chip, using 17 antisera, which can be used to detect bound whole-cell E. coli antigen with its corresponding immobilized antibody, to assess the feasibility of this approach. The chip was tested using the related 17 control strains, and the O types found by the microarray chip showed 100% correlation with the O types found by conventional typing. A blind trial was performed in which 100 E. coli isolates that had been O serotyped previously by the conventional assay were tested by the array approach. Overall, the O serotypes of 88% of isolates were correctly identified by the microarray method. For several isolates, ambiguity of O-type designation by microarray arose due to increased sensitivity of this method, allowing signal intensities of cross-reactions to be quantified. Investigation of discrepancies between conventional and microarray O serotyping indicated that some isolates upon storage had become untypeable and, therefore, gave poor signal intensity when tested by the microarray or retested by conventional means. For all 20 serotype O26 and O157 isolates, the apparent discrepancy in O serotyping was analyzed further by a third independent test, which confirmed the microarray results. Therefore, the use of miniaturized protein arrays increases the speed and efficiency of O serotyping in a cost-effective manner, and these preliminary findings suggest the microarray approach may have a higher accuracy than those of traditional O-serotyping methods.     

Trends in cancer prevalence in Quebec

Cancer prevalence is of prime interest in public health because of its use in estimating the disease's burden on the heath care system. This study's objective was to estimate five-year prevalence of tumours from 1989 to 1999 and ten-year prevalence of tumours from 1994 to 1999 in the Province of Quebec (Canada). Five-year prevalence was used to represent tumours for which people are more likely to obtain primary treatment; ten-year prevalence included those tumours in addition to tumours that can be considered cured but still need follow-up. Information was extracted from the Quebec Cancer Registry. Prostate cancer was the most prevalent malignancy among males (25 percent, five-year prevalent tumours), while breast cancer was most prevalent among females (38 percent, five-year prevalent tumours). For both sexes, the greatest observed prevalence increase was for endocrine glands. On average, five-year prevalence proportions were 16 percent higher in men than in women; those of ten year were 14 percent higher in men. Furthermore, the largest differences were observed for bladder and lung cancer. The change in cancer prevalence in Quebec was dependent on the tumour site.     

Vaccine Related Reactogenicity for Primary Immunization: A Randomized Controlled Trial of 23(Wider) vs. 25(Narrower) Gauge Needles with Same Lengths

Objectives  

To compare vaccine related reactogenicity during primary immunization in healthy infants using 23 vs. 25 gauge needles.     

Individual outcome prediction for myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia from MDS after allogeneic hematopoietic cell transplantation

We integrated molecular data with available prognostic factors in patients undergoing allogeneic hematopoietic cell transplantation (alloHCT) for myelodysplastic syndrome (MDS) or secondary acute myeloid leukemia (sAML) from MDS to evaluate their impact on prognosis. Three hundred four patients were sequenced for mutations in 54 genes. We used a Cox multivariate model and competing risk analysis with internal and cross validation to identify factors prognostic of overall survival (OS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM). In multivariate analysis, mutated NRAS, U2AF1, IDH2, and TP53 and/or a complex karyotype were significant prognostic markers for OS besides age above 60 years, remission status, IPSS-R cytogenetic risk, HCT-CI > 2 and female donor sex. Mutated NRAS, IDH1, EZH2, and TP53 and/or a complex karyotype were genetic aberrations with prognostic impact on CIR. No molecular markers were associated with the risk of NRM. The inclusion of molecular information results in better risk prediction models for OS and CIR when assessed by the Akaike information criterion. Internal cross validation confirmed the robustness of our comprehensive risk model. In summary, we propose to combine molecular, cytogenetic, and patient- and transplantation-associated risk factors into a comprehensive risk model to provide personalized predictions of outcome after alloHCT.     

Prevalence and factors associated with HCV (hepatitis C virus) seropositivity in Islamabad, Pakistan

An estimated 150-200 million people worldwide are infected with hepatitis C. Prevalence is higher in some countries in Asia and Africa. Only limited information about the epidemiology of Hepatitis C Virus (HCV) infection especially in females is available. The aim of this study is to determine the prevalence of anti-HCV antibodies and the possible factors for transmission in the female population of a largely urban city Islamabad. A cross sectional study was conducted from May 2006 to August 2006 in Islamabad. We select 252 female households (n=252) following the selection criteria. The primary outcome variables were HCV seropositivity and factors like history of major surgical procedure, blood transfusion, Intravenous drug use etc. The results showed mean age of the sample was 33.21 (±9.95) years and HCV seropositivity was present in 62 (24.6%) females. Final Forward Stepwise multiple logistic regression showed blood transfusion [OR, 10.094 95% CI 1.950-52.257], dental procedure [OR, 5.381 95% CI 2.315-12.507] and dilation and curettage [OR, 3.869 95% 1.867-8.015] were significantly associated with HCV seropositivity in females. The study highlights poor quality of care provided and a massive need to educate general population including patients as well as health professionals and allied health workers.