An NMR approach to structural proteomics

The influx of genomic sequence information has led to the concept of structural proteomics, the determination of protein structures on a genome-wide scale. Here we describe an approach to structural proteomics of small proteins using NMR spectroscopy. Over 500 small proteins from several organisms were cloned, expressed, purified, and evaluated by NMR. Although there was variability among proteomes, overall 20% of these proteins were found to be readily amenable to NMR structure determination. NMR sample preparation was centralized in one facility, and a distributive approach was used for NMR data collection and analysis. Twelve structures are reported here as part of this approach, which allowed us to infer putative functions for several conserved hypothetical proteins.     

A detailed genetic map of the chromosome 7 bronchial hyper-responsiveness locus

Non-specific bronchial hyper-responsiveness to various inhaled stimuli is a characteristic of asthma. We have previously shown linkage of bronchial responsiveness to methacholine (measured as dose-response slope (DRS)) and the peripheral blood eosinophil count (EOS) to chromosome 7. We have now further investigated these linkages by genotyping 49 microsatellite markers across the DRS locus on chromosome 7. The markers were spaced on average 2.6 cM apart and spanned a sex averaged cumulative genetic distance of 129 cM. Multipoint linkage to DRS was bimodal and dipped at the centromere. The two peaks of linkage were close to markers D7S484 (P=0.0003) and D7S669 (P=0.006) respectively. Separate testing for linkage to paternally and maternally derived alleles showed that the linkage near D7S484 was paternally derived (P<0.00001): maternally derived alleles did not exhibit significant linkage. The results indicate that two disparate loci may be influencing asthma from chromosome 7.     

Paediatric immunisation: special emphasis on measles and MMR vaccinations

The dictum, 'prevention is better than cure', is applicable to all ailments but it can be most easily followed for infectious diseases, increasing numbers of which are being contained by specific vaccinations since the first discovery of smallpox vaccine by Edward Jenner in 1796. Advances in immunology and laboratory techniques including cell culture, genetic engineering and animal experiments have contributed significantly to the production of more and more vaccines, used successfully in preventive programmes. Infectious diseases are widely prevalent in the developing countries. The child population is specially vulnerable to many of them. These infections contribute to high morbidity and mortality and immunisation programmes have been undertaken as preventive measures against them at the national level. Paediatricians and experts are actively engaged in formulating and improving these programmes as problems are faced in their implementation. Much new information is continuously being available in the literature, mostly in specialised journals. The general practitioners, particularly those serving in the remote and vast rural areas, are not likely to have access to these recent developments which they need for self-motivation in initiating the parents with confident advice to have their children properly immunised and also for tackling effectively any problem arising out of immunisation. This paper attempts to discuss the subject of paediatric immunisation with special emphasis being laid on measles and MMR vaccinations.     

Factors predicting survival for cancer of the ethmoid sinus

OBJECTIVE: The aim of this study was to determine survival and prognostic factors for ethmoid sinus cancer. METHODS: From the Surveillance, Epidemiology, and End Results database for the time period 1988-1998, all cases of ethmoid sinus malignancy were extracted. Demographic, staging, treatment, and survival data were computed. Survival analysis was conducted with the Kaplan-Meier method. Clinical factors influencing survival were determined with the Cox proportional hazards model. RESULTS: After excluding patients with metastatic disease on presentation (8.9%) and patients with missing data for T stage, a total of 180 cases were identified. Average age was 60.2 years. Squamous cell carcinoma was the most common tumor (27.8%), followed by adenocarcinoma (12.8%). Overall mean survival was 57 months (median, 38 months) with a 5-year survival of 40.3%. The percentage of patients presenting with T4 lesions was 45.6%, which had a notably lower mean survival of 38 months (median, 18 months). Only 2.3% of patients had positive nodal disease. Increasing age, T stage, and absence of radiation therapy predicted poorer survival in the multivariate model Adenocarcinoma, adenoid cystic carcinoma, esthesioneuroblastoma, and melanoma showed more favorable survival than other tumor types. CONCLUSIONS: T stage and tumor histology are the most important prognostic factors in ethmoid sinus carcinoma. Survival for T4 lesions is markedly worse than survivalfor T1-T3 lesions. Radiation therapy offers a survival benefit in ethmoid sinus malignancy.     

Management pitfalls in the use of embolization for the treatment of severe epistaxis

Angiographic embolization for the treatment of severe recurrent epistaxis was added to the traditional treatment options--nasal packing, cauterization, and surgical vessel ligation--in 1974. Since then, clinical experience has shown that this procedure is safe and effective. When epistaxis cannot be controlled with cautery, nasal packing is the most common next step. As such, it is often performed by emergency physicians and other clinicians who are not otolaryngologists. We report two cases in which intranasal neoplasms were obscured as a result of a significant distortion of the normal anatomy. This distortion was secondary to emergency-room treatment of severe epistaxis by repeated nasal packing followed by angiographic embolization. Pre-embolization angiographic studies and subsequent postembolization endoscopic evaluations did not reveal the presence of the occult neoplasms because of the presence of inflammation and edema after treatment. Clinicians should be aware that nasal packing and embolization can obscure the underlying source of epistaxis, and follow-up radiologic studies and endoscopic evaluations are essential to avoid delays in diagnosis.     

Rate of and risk factors for acute inpatient mortality after orthopaedic surgery

BACKGROUND: Orthopaedic surgeons operate on a diverse group of patients, and many of these patients have concomitant medical problems. The purpose of this study was to identify the rate of mortality and to evaluate the risk factors associated with mortality after orthopaedic surgery. METHODS: Data from the National Hospital Discharge Survey, a nationwide sample of hospital admissions, were obtained for the years 1995 through 1997. The study was limited to hospital admissions. Univariate and multivariate analyses were performed. RESULTS: The 43,215 inpatient orthopaedic operations that we evaluated were associated with a mortality rate of 0.92%. Seventy-seven percent of all deaths occurred after procedures performed for patients who were more than seventy years old, and 50% of all deaths occurred after operations performed for the treatment of hip fractures. The independent preoperative medical risk factors for death included chronic renal failure, congestive heart failure, metastasis to bone, atrial fibrillation, chronic obstructive pulmonary disease, and osteomyelitis. The risk factors of diabetes, coronary artery disease, peripheral vascular disease, septic arthritis, and rheumatoid arthritis did not achieve significance. Among orthopaedic subspecialty categories, operations for tumors, trauma, and infection were associated with elevated mortality rates. In a predictive model, five critical risk factors were identified as most helpful in identifying patients at risk for death: chronic renal failure, congestive heart failure, chronic obstructive pulmonary disease, hip fracture, and an age of greater than seventy years. The mortality rate was 0.25% for patients with no critical risk factors. A linear increase in mortality was seen with increasing numbers of critical risk factors (p < 0.005). CONCLUSION: Death is rare after orthopaedic operations. In the United States, the rate of acute mortality after inpatient orthopaedic surgical procedures is approximately 1% for all patients, 3.1% for patients with a hip fracture, and 0.5% for patients without a hip fracture. These data will aid orthopaedic surgeons in predicting operative mortality for their patients.