Differential effect of NAT2 on the association between active and passive smoke exposure and breast cancer risk.

BACKGROUND: Polymorphisms in the N-acetyltransferase 2 (NAT2) gene influence the rate of metabolism of aromatic and heterocyclic amines present in tobacco smoke. Because the physicochemical composition of mainstream and sidestream smoke differ, we conducted a case-control study to assess a possible differential effect of NAT2 genotype on the relationship between active/passive smoke exposure and breast cancer risk. METHODS: Breast cancer patients diagnosed by 50 years of age and population-sampled controls were interviewed to obtain detailed lifetime active and passive smoking history. NAT2 genotype was determined in 422 breast cancer patients and 887 controls. Multivariate logistic regression analysis was performed to estimate breast cancer risk in relation to smoking history by acetylator status and interaction effects. RESULTS: Compared with women never regularly exposed to tobacco smoke, odds ratios (ORs) for current smoking and ex-smoking were 1.7 [95% confidence interval (CI): 1.0-2.9] and 1.2 (95% CI, 0.7-2.0) in slow acetylators, and not increased in rapid acetylators. Active smoking variables, such as pack-years, duration of smoking, and time since cessation, showed significant dose-response relationships with breast cancer risk among slow acetylators but not rapid acetylators. In contrast, passive smoking was associated with higher risk in rapid than in slow acetylators, with ORs of 2.0 (95% CI, 1.0-4.1) and 1.2 (95% CI, 0.7-2.0), respectively. CONCLUSIONS: Our results suggest that the NAT2 status has a differential effect on the association of active and passive smoking with breast cancer and demonstrate the need to consider possible different mechanisms associated with exposure to main- and sidestream tobacco smoke.     

Streptococcus pyogenes meningitis: report of a case and review of the literature

Streptococcus pyogenes is a very uncommon cause of bacterial meningitis beyond the neonatal period. A case report and a review of the recent literature is presented. We report on a previously healthy 7-year-old boy who developed S. pyogenes meningitis following a 2-day history of otitis media. A CT scan revealed right-sided mastoiditis as a possible focus of infection. The patient was treated with penicillin G for 14 days. The clinical course was uneventful, and he recovered without sequelae. By means of the polymerase chain reaction, the presence of streptococcal pyrogenic exotoxin (SPE) B and SPE C, but not SPE A genes was discovered from the bacterial DNA. Conclusion Streptococcus pyogenes is a rare cause of bacterial meningitis but has to be considered as the causative pathogen beyond the neonatal period. Received: 17 May 1999 / Accepted: 4 January 2000     

Assisted reproductive technologies in Africa: first results from the African Network and Registry for Assisted Reproductive Technology, 2013

Research question

What were utilization, outcomes and practices in assisted reproductive technology (ART) in Africa in 2013?

Von Hippel-Lindau disease--a rare disease important to recognize

INTRODUCTION: Von Hippel-Lindau disease (VHL) is an autosomal dominant multisystemic cancer syndrome due to a mutation of the VHL tumor suppressor gene on chromosome 3, region p25-26, with an incidence of 1/36,000 in newborns. Patients are at risk of developing cerebellar, spinal and retinal hemangioblastoma, renal cell carcinoma, pheochromocytoma, pancreatic neuroendocrine tumors, pancreatic and renal cysts, and epididymal cystadenoma. The most common causes of death from VHL are metastases from renal cell carcinoma and neurological complications from cerebellar hemangioblastomas. Molecular analysis of the VHL gene is clinically available and indicated in patients with known or suspected VHL. CASE REPORT: A 19-year-old woman was surgically treated for cerebellar hemangioblastoma in 1998 and for renal cell carcinoma of the right side in 2002. Familial VHL was subsequently diagnosed as the patient's mother was found to be affected with bilateral polycystic kidney disease with chronic renal failure as well as hemangioblastoma of the retina and medulla oblongata. The mother underwent surgery for bilateral renal cell carcinoma in 2003. CONCLUSION: The multitude of VHL-associated tumors and intra-familial variability in clinical expressivity render early diagnosis of VHL difficult. We therefore shortly illustrate the spectrum of clinical phenotypes and the VHL screening and surveillance guidelines.     

Periosteal osteosarcoma--a European review of outcome

Periosteal osteosarcoma is a rare primary malignant bone tumour. Treatment is by surgical excision, but controversy remains about the value of chemotherapy. The members of the European Musculo Skeletal Oncology Society (EMSOS) collaborated to produce a dataset of 119 patients. The predominant site for the tumour was the femur, followed by the tibia. All but 2 patients underwent surgery, with 9 requiring amputation and the others having limb salvage. A total of 81 patients had chemotherapy, of whom 50 had neoadjuvant chemotherapy. There was no standard chemotherapy regime, but all patients receiving chemotherapy were given doxorubicin combined with at least one other agent. The overall survival was 89% at 5 years and 83% at 10 years. Eight patients developed local recurrence, of whom 5 died. Survival was related to appearance of local recurrence (P < 0.0001) but no other single factor. The use of chemotherapy was not shown to be a prognostic factor, but was used in two-thirds of the patients in this study.     

Interstitial loss and gain of sequences on chromosome 22 in meningiomas with normal karyotype

In nearly half of sporadic low grade meningiomas no chromosome aberration can be detected. In the majority of the other half chromosome 22 is lost. In higher grade meningiomas this loss is followed by characteristic secondary chromosome aberrations. Regarding the molecular findings in Schwannomas, homozygous loss or mutation of the NF2 gene located on chromosome 22, was supposed also to be the primary event in meningioma development. However, in nearly all high grade but in only a minority of low grade meningiomas the loss of the NF2 protein is observed. Therefore, both the hypothetical combined heterozygous loss of or inactivation of two or more tumour suppressor genes (at least one of them located on chromosome 22) or the homozygous loss of a regulatory gene on chromosome 22 different from NF2 was discussed. In search for microdeletions or/and structural recombinations of chromosome 22 we investigated primary cell cultures of 43 meningiomas by conventional G-banding (26 without, 17 with loss of chromosome 22). Twenty-seven tumours were analysed with spectral karyotyping (SKY) and 16 with fluorescence in situ hybridisation (FISH) with DNA probes for the chromosomal regions of 22q11.2, 22q11.23q12.1, 22q12.1 and 22q13.3. SKY analysis confirmed G-banding data for chromosome 22 and could specify marker chromosomes and translocations containing material from chromosome(s) 22. Confirming our assumption microdeletions on chromosome 22 were detected by FISH in 6/8 cytogenetically non-aberrant meningiomas. Surprisingly, in 2/8 cases we observed gains of the 22q13.3 and in 2/8 gains of the 22q12.1 region. Here we present first evidence for an uncommon mechanism during early meningioma development at least for a meningioma subgroup: i) duplication and translocation of sequences from chromosome 22 to different chromosomes. ii) deletion of the original sequences on chromosome 22, resulting in disomy again (only visible as translocation in metaphase FISH). iii) loss of chromosome 22.     

Are MTT assays the right tool to analyze drug resistance caused by ABC-transporters in patient samples?

Drug resistance can be caused by ATP-binding-cassette (ABC)-transporters which function as outward pumps for chemotherapeutic drugs. The aim of the present study was to analyze the association between eight ABC-transporters (BCRP, MDR1, SMRP, MRP1, MRP2, MRP3, MRP4, and MRP5) and in vitro drug resistance.Leukemic cells from 52 children with previously untreated acute leukemia (ALL: n=37; AML: n=15) were analysed. The expression of the ABC-transporters was measured by TaqMan real-time PCR. In vitro drug resistance to cytarabine, vincristine, tioguanine, daunorubicin, etoposide, dexamethasone, and prednisone was analysed with methyl-thiazol-tetrazolium (MTT) assays.MDR1 was weakly associated with resistance to vincristine (p<0.05) in AML samples. No other correlation between an ABC-transporter and a higher in vitro drug resistance was found. In vitro drug resistance was not associated with the simultaneous expression of a larger number of ABC-transporters.MTT assays are a widely used and validated method to analyse in vitro drug resistance but they may not be a useful tool to detect resistance which is caused by drug efflux in patient samples. If that is the case, MTT assays and the expression of ABC-transporters could provide complementary information on the drug resistance profile of patients with acute leukemia.     

Workplace stress, lifestyle and social factors as correlates of back pain: a representative study of the German working population

OBJECTIVES: To investigate the prevalence of back pain in the German working population and the relationship between back pain and workplace stresses, lifestyle and social factors. METHODS: The first National Health Survey of the Federal Republic of Germany was carried out between October 1997 and March 1999. It comprised a representative epidemiological cross-sectional study of the working population, with a total sample of 3,488 persons between the ages of 18 and 69 years. The participants took part in a medical examination and answered a self-rating questionnaire. The relationship between subjective back pain and workplace stresses and social and lifestyle factors was investigated with bivariate tests and multiple logistical regression analyses. RESULTS: The 7-day prevalence for back pain in the German working population was found to be 34%, and the 1-year prevalence was 60%. The odds ratios were significantly higher in women, persons of lower socioeconomic status, married and depressed persons and non-athletes. Carrying heavy loads or maintaining a single working posture were the most significant work-related correlates of back pain, for members of both the female and male working population, while environmental stress and psychological stress correlated significantly with back pain in men only. CONCLUSIONS: This study reports the first representative epidemiological prevalence data for back pain, and its correlates and potential risk factors, for the German working population. To reduce the negative impact of back pain the most promising behavioural and conditional prevention measures in the workplace would be to reduce carrying stress and to vary working posture. In addition, a more active, athletic lifestyle, plus the avoidance of being overweight, should provide an additional protective or preventive effect.     

Do consultants differ? Inferences drawn from hospital in-patient enquiry (HIPE) discharge coding at an Irish teaching hospital

Objective: To find out if there was a difference between hospital consultants, all trained in acute general medicine, in length of stay (LOS), re-admission rates, resource utilisation, and diagnostic coding, among patients admitted as emergencies to St James'' Hospital (SJH) Dublin. Methods: A retrospective analysis was performed of data on discharges from hospital, recorded in the hospital in-patient enquiry (HIPE) system, relating to 9204 episodes among 6968 emergency medical patients admitted to SJH between 1 January 2002 and 31 October 2003. For comparative analysis, four physician groups were defined consisting of gastroenterology (GI, n = 4), respiratory (n = 3), general internal medicine (GIM, n = 2), or specialty (n = 5). Results: GIM consultants had the shortest LOS (median 5 days); GIM and respiratory consultants were less likely to have long stay patients (> 30 days, p<0.0001). Patients re-admitted under the same consultant had a longer LOS than those re-admitted under a different consultant (p<0.0001). Endoscopy and GI radiology investigations were used most by GI consultants, computed tomography of the thorax by respiratory, ECHO by respiratory and specialty, and computed tomography of brain by GIM and specialty consultants. GI diagnostic codings were more frequent with GI consultants (p<0.0001), respiratory diagnoses and malignancy with respiratory (p<0.0001 for both), diabetes and hypertension with specialty (p = 0.0017), and heart failure more with GIM consultants (p = 0.001). Conclusions: This study found that the HIPE database was very powerful in predicting differences between hospital consultants in LOS, re-admission rates, resource utilisation, and disease coding. It would be of interest to examine the extent to which protocols and guidelines could reduce such variations.