Injurious effect of the eosinophil peroxide-hydrogen peroxide-halide system and major basic protein on human nasal epithelium in vitro

Tissue injury is observed in allergic and nonallergic eosinophilic rhinitis, but the mechanism of this injury is unclear. Because eosinophils are prominent in biopsy specimens in these conditions, we hypothesized that they may participate in the injury process. Initially, we developed techniques to isolate and purify human nasal epithelial cells from turbinate biopsies to use as target cells for eosinophil granule products. Primary cultures from explants were characterized by electron microscopy and indirect immunofluorescence with a panel of primary monoclonal and polyclonal antibodies. These studies revealed the homogeneity of the cells and confirmed their epithelial nature. Cultured nasal epithelial cells were then exposed to either purified human eosinophil peroxidase, bromide, and glucose plus glucose oxidase, as a continuous source of hydrogen peroxide, or eosinophil major basic protein. Neither eosinophil peroxidase alone nor glucose plus glucose oxidase in the absence of eosinophil peroxidase were injurious, but the combined addition of eosinophil peroxidase, glucose/glucose oxidase, and bromide produced marked target cell lysis. This effect was time- and eosinophil peroxidase dose-dependent. Catalase and azide significantly inhibited the lysis of these cells, suggesting the eosinophil peroxidase-catalyzed products of halide oxidation mediated this form of injury. The addition of purified human eosinophil major basic protein also caused dose- and time-dependent lysis of the nasal epithelial cells but required longer incubation periods to effect injury. We hypothesize that the eosinophil peroxidase-hydrogen peroxide-halide system and major basic protein may injure the nasal epithelium in inflammatory conditions such as allergic and nonallergic eosinophilic rhinitis.     

Outcome of hepatitis B virus infection in homosexual men and its relation to prior human immunodeficiency virus infection.

To investigate the effect of human immunodeficiency virus type 1 (HIV-1) infection on subsequent hepatitis B virus (HBV) infection, HIV antibody was sought in homosexual men who developed HBV infection during a hepatitis B vaccine trial. Among 134 unvaccinated HIV-1-negative men, 7% became HBV carriers, 64% had viremia, and 42% had clinical illness. Among vaccinated HIV-1-negative men, HBV infection severity decreased with number of vaccine doses administered. When adjusted for prior hepatitis B vaccination status, persons with HIV-1 infection preceding HBV infection had a significantly higher risk of developing HBV carriage, viremia, prolonged ALT elevation, and clinical illness. Among HIV-1-infected men, the risk of HBV carriage was increased in unvaccinated persons (21%) and those who failed to respond to vaccination (31%) and further increased in those who received vaccine doses at the time they developed new HBV infection (56%-80%), suggesting inactivated hepatitis B vaccine may temporarily impair the immune response to HBV infection in HIV-1-infected persons. HIV-1 infection was also associated with reduced alanine aminotransferase elevations during the first 36 months of follow-up of men who became HBV carriers.     

Protein-protein interactions with subunits of human nuclear RNase P

A yeast two-hybrid system was used to analyze interactions among the protein subunits of human nuclear RNase P themselves and with other interacting partners encoded in a HeLa cell cDNA library. Subunits hpop1, Rpp21, Rpp29, Rpp30, Rpp38, and Rpp40 are involved in extensive, but weak, protein-protein interactions in the holoenzyme complex. Rpp14, Rpp20, and Rpp30 were found to have strong interactions with proteins encoded in the cDNA library. The small heat shock protein 27, which interacts with Rpp20 in the two-hybrid assay, binds to Rpp20 during affinity chromatography and can be found to be associated with, and enhances the activity of, highly purified RNase P. RNase P activity in HeLa cell nuclei also increases under the stress of heat shock.     

Evaluation of nursing care during treatment of viral hepatitis C by interferon

OBJECTIVE: Interferon alpha treatment requires parenteral administration and some patients receive injections from nurses. The aim of this study was to evaluate the role of nursing care during ambulatory treatment of hepatitis C by interferon alpha. METHODS: A questionnaire was sent by mail to all nurses who practice ambulatory care in the Val de Marne region (n =545). RESULTS: One hundred fourteen questionnaires were returned (return rate: 20%). Among these nurses, only 42 (37%) were caring for at least 1 patient for the treatment of hepatitis C by interferon. In the 16 months before the survey, these 42 nurses had cared for 135 patients. The nurses cared for the patients throughout the entire treatment in 81% and only to teach them in 19% of cases. The time spent for each injection was 12 min 48 sec, 2 min 42 sec for the injection itself, 3 min 54 sec to answer to patient's questions, 3 min 30 sec for psychological support, and 2 min 48 sec for unspecific time. In relation to hepatitis C and interferon treatment, 74% and 64% of the nurses felt that patients asked questions they did not ask their physician. Seventy seven of the nurses felt they were did not have enough training to answer the questions. Psychological support for the patient was noted as important or very important by 38 % of nurses. CONCLUSIONS: The role of nurses during interferon treatment is not limited to injecting the drug. Advice and psychological support takes up most of the time spent with patients. Specific training and better collaboration with the physician who prescribes the treatment are needed.     

Long-term follow-up of therapy with intermittent etidronate disodium in Paget's disease of bone

A long-term trial of etidronate disodium therapy in 93 patients with Paget's disease of bone yielded generally favorable results. Treatment or retreatment was initiated for symptomatic Paget's disease with elevated serum alkaline phosphatase and urinary hydroxyproline values. Improvement occurred in 60 percent of patients even in the presence of secondary osteoarthritis. There appeared to be three types of responses: (1) Patients with prolonged clinical and chemical improvement after a single course of therapy (40 percent); these patients tended to have less active disease on the basis of initial alkaline phosphatase and hydroxyproline values, with suppression to normal in 76 percent of patients after etidronate disodium therapy. (2) Patients with response to retreatment (45 percent); these patients had modest disease on the basis of alkaline phosphatase and hydroxyproline values and required retreatment less often than once a year. (3) Patients with response to retreatment but eventual development of resistance to etidronate disodium (15 percent); these patients had the most severe disease clinically and on the basis of alkaline phosphatase and hydroxyproline values. In this last group, resistance to etidronate disodium (5 mg/kg per day) was common and early, and patients received etidronate disodium more often than one course per year; alkaline phosphatase response was transient, often of less than three months' duration.     

Therapeutic treatment of canine osteoarthritis with glycosaminoglycan polysulfuric acid ester

The therapeutic effect of glycosaminoglycan polysulfuric acid ester (GAGPS) was studied using the Pond-Nuki model of canine osteoarthritis. The clinical setting was simulated by permitting 4 weeks ambulation without treatment, following anterior cruciate transection. Animals were then injected with GAGPS, 4 mg/kg intramuscularly, twice weekly during weeks 4-8. Control animals received intramuscular saline. The study was terminated 4 weeks after completion of the GAGPS or saline regimen (i.e., 12 weeks postoperatively). Cartilage from the medial femoral condyle was analyzed for collagen integrity (swelling properties), hydroxyproline, uronic acid, active and total proteoglycan (PG)-degrading metalloproteinase, PG-degrading serine proteinase, and histopathology (Mankin score). Condylar cartilage from animals treated with GAGPS demonstrated less cartilage swelling, less total and active metalloproteinase, and lower histopathologic scores than were found in cartilage from saline-treated animals. GAGPS was able to suppress PG-degrading enzyme activity and maintain a more normal-appearing cartilage. It is proposed that GAGPS suppressed PG breakdown by decreasing synthesis of metalloproteinase or by directly inhibiting metalloproteinase in cartilage, rather than by increasing synthesis of PG by chondrocytes.     

Identifying patients with undetected pancreatic cancer in primary care: an independent and external validation of QCancer? (Pancreas)

Background

Despite its rarity, the prognosis of pancreatic cancer is very poor and it is a major cause of cancer mortality; being ranked fourth in the world, it has one of the worst survival rates of any cancer.

Aim

To evaluate the performance of QCancer^® (Pancreas) for predicting the absolute risk of pancreatic cancer in an independent UK cohort of patients, from general practice records.

Design and setting

Prospective cohort study to evaluate the performance QCancer (Pancreas) prediction models in 364 practices from the UK, contributing to The Health Improvement Network (THIN) database.

Method

Records were extracted from the THIN database for 2.15 million patients registered with a general practice surgery between 1 January 2000 and 30 June 2008, aged 30–84 years (3.74 million person-years), with 618 pancreatic cancer cases. Pancreatic cancer was defined as incident diagnosis of pancreatic cancer during the 2 years after study entry.

Results

The results from this independent and external validation of QCancer (Pancreas) demonstrated good performance data on a large cohort of general practice patients. QCancer (Pancreas) had very good discrimination properties, with areas under the receiver operating characteristic curve of 0.89 and 0.92 for females and males respectively. QCancer (Pancreas) explained 60% and 67% of the variation in females and males respectively. QCancer (Pancreas) over-predicted risk in both females and males, notably in older patients.

Conclusion

QCancer (Pancreas) is potentially useful for identifying undetected cases of pancreatic cancer in primary care in the UK.