Young age at first pregnancy does protect against early onset breast cancer in <Emphasis Type="Italic">BRCA1</Emphasis> and <Emphasis Type="Italic">BRCA2</Emphasis> mutation carriers

Purpose

Previous research assessing the impact of pregnancy and age at first pregnancy on breast cancer risk in BRCA1 and BRCA2 mutation carriers has produced conflicting results, with some studies showing an increased risk following early first pregnancy in contrast to the reduced risk in the general population of women. The present study addresses these inconsistencies.

Methods

Female BRCA1 and BRCA2 carriers from North West England were assessed for breast cancer incidence prior to 50 years of age comparing those with an early first full-term pregnancy (< 21 years) to those without a full-term pregnancy. Breast cancer incidence per decade from 20 years and Kaplan–Meier analyses were performed.

Results

2424 female mutation carriers (1278 BRCA1; 1146 BRCA2) developed 990 breast cancers under the age of 50 years. Women who had their first term pregnancy prior to age 21 (n = 441) had a lower cancer incidence especially between age 30–39 years. Kaplan–Meier analysis showed an odds ratio of 0.78 for BRCA1 (p = 0.005) and 0.73 for BRCA2 (p = 0.002).

Conclusions

The present study demonstrates a clear protective effect of early first pregnancy on breast cancer risk in both BRCA1 and BRCA2 mutation carriers.

     

Femoral head avascular necrosis: correlation of MR imaging, radiographic staging, radionuclide imaging, and clinical findings

To better correlate the appearance of avascular necrosis (AVN) of the femoral head on magnetic resonance (MR) images with the stage of disease, MR images of 56 proved AVN lesions were compared with staging from corresponding radiographs (n = 56), Tc-99m scans (n = 41), and grade of symptoms (n = 28). Fractures complicating AVN were seen in 28 (50%) of 56 radiographs (radiographic stages III-V). With long repetition (TR) and echo delay (TE) times, a characteristic "double line sign" consisting of high signal intensity inside a low-intensity peripheral rim was seen in 45 lesions (80%). The central region within the rim was isointense with marrow fat on both short and long TR and TE images in 20 (71%) of 28 lesions uncomplicated by fracture (stages I-II) but in only four (14%) of 28 stage III-V lesions (P less than .001). Symptoms were least severe in lesions isointense with fat and most severe in lesions with low-signal central regions at short and long TRs and TEs. The peripheral double line sign on long TR/TE images may add specificity to the diagnosis of AVN by MR imaging. A chronologic pattern of central MR signal features is presented which may allow staging of AVN by MR imaging.     

Demonstration of burst-promoting activity of recombinant human GM-CSF on circulating erythroid progenitors using an assay involving the delayed addition of erythropoietin

We demonstrate through the use of an in vitro assay involving the delayed addition of erythropoietin that human recombinant GM-CSF, cloned from a mature T cell line, Mo, clearly has burst-promoting activity (BPA) on peripheral blood erythroid progenitors at picomolar concentrations. Delay for up to 72 hours of the addition of erythropoietin to semi-solid methylcellulose cultures of concentrated peripheral blood progenitors minimizes or eliminates BPA-independent erythroid colony formation with little loss of BPA-dependent erythroid colony formation. This assay will prove useful in accurately detecting sources of BPA.     

Acute allograft rejection in liver transplant recipients: lack of correlation with loss of hepatic artery diastolic flow

Eighty hepatic artery Doppler ultrasound (US) examinations performed in 49 patients after liver transplantation were retrospectively analyzed to determine if loss of diastolic flow correlated with pathologic evidence of acute allograft rejection. All 80 Doppler examinations were performed within 7 days of hepatic needle biopsy. Forty-three Doppler waveforms from 27 patients showed normal diastolic flow. Seventeen Doppler studies in 17 patients showed complete absence of diastolic flow. Review of biopsy results for each group showed no significant difference in the proportion of acute allograft rejection present (42% for the normal group and 46% for the group lacking diastolic flow). The data from 53 US and biopsy examinations performed 2 days apart in 37 patients confirmed the lack of correlation between absent hepatic artery diastolic blood flow and rejection. The authors conclude that the loss of hepatic artery diastolic flow has no apparent clinical application for the diagnosis of acute hepatic allograft rejection.     

纺织工作环境及其噪声对女工心理健康的影响

目的：评价纺织工作环境及其噪声对纺织女工心理健康的影响,为有关部门制定卫生标准和防护措施提供科学依据。 方法：调查于2006-02/04进行,选取成都市某织布厂接触噪声高于85dB（A）的女工341名作观察组,另选取同厂接触噪声强度低于85dB（A）的女工154名作对照组,检测两组作业环境的噪声强度、风速、气温、气湿,并了解两组受试者的一般情况,采用SCL-90症状自评量表评价调查对象的心理健康状况,包括躯体不适、强迫症状、人际关系敏感、抑郁、焦虑、敌对、恐怖、偏执和精神病性9项因子,得分越高症状越重。 结果：495名受试者的资料进入结果分析。①两组作业环境检测,除观察组接触的噪声强度超过国家噪声卫生限值[85dB（A）]外,两组的其余各项指标均符合国家卫生标准,并且其一般情况的构成相似。②观察组SCL-90量表的9项因子分、总均分、阳性项目数以及阳性症状均分均高于对照组（P〈0.05）,躯体不适和强迫症状两项因子分≥3分的阳性检出率明显高于对照组（P〈0.05）。③观察组各个工龄组SCL-90的9项因子分、总均分和阳性项目数中,除躯体不适和敌对因子以外,其余指标均以1-年工龄组为最高（P〈0.05）。 结论：高强度的纺织噪声对女工心理健康有一定的影响,其中对1-年工龄组的影响最明显。建议采取积极有效的措施,以保护纺织女工的心理健康。     

Post-cimetidine Surveillance for up to Ten Years: Incidence of Carcinoma of the Stomach and Oesophagus

The long-term effects of cimetidine on the occurrence of gastricand oesophageal cancer were assessed in a prospective cohortstudy of 9928 patients who had been prescribed cimetidine. Theywere first identified between 1978 and 1980, and cancer registrationsand deaths were identified among them over a period of up to10 years. One hundred and eleven cancers were identified afterthe start of cimetidine treatment: 71 were adenocarcinomas ofthe stomach, 27 were carcinomas of the cardia and/or oesophagus(22 adenocarcinomas, five unknown histology) and the remaining13 tumours were squamous cell cancers of the oesophagus. Onlysix patients presented with early gastric cancers. Over a periodof eight years the ratio of observed to expected (O/E) gastriccancer deaths has fallen from 10.7 (p<0.001) to 1.2 (NS).The O/E ratio of oesophageal cancer deaths also fell over thefirst six years of study, from 5.4 (p<0.01) to 1.4 (NS) butit has risen slightly in years 7 and 8 to 3.7 (p<0.05). Thesefindings do not suggest that there is an increased risk of developingoesophageal or gastric cancer from cimetidine treatment, andare generally consistent with cimetidine being used inadvertentlyto treat the early symptoms of gastric and oesophageal cancer.The slight rise in oesophageal cancer deaths in years 7 and8 was unexpected and will be the subject of further observation.     

GASTROENTERITIS CAUSING CRITICAL LIMB ISCHAEMIA

SUMMARY Six days after admission to hospital with Salmonella gastroenteritis, this patient presented with a critically ischaemic leg, having developed an iliac occlusion, and a subcutaneous Salmonella abscess in the anterior compartment of the leg. Critical limb ischaemia and abscess formation can be added to infective aortic aneurysm as vascular complications of Salmonella gastroenteritis.     

Recombinant human interleukin-1 receptor antagonist in the treatment of steroid-resistant graft-versus-host disease

Acute graft-versus-host disease (GVHD) that is resistant to therapy is a highly lethal complication of marrow transplantation. Inflammatory cytokines such as interleukin-1 (IL-1) may be critical mediators of this process. If so, specific inhibition of IL-1 activity with recombinant human IL-1 receptor antagonist (IL-1Ra), a naturally occurring competitive inhibitor of IL-1, may ameliorate acute GVHD. We performed an open-label, phase I/II trial to evaluate the safety and efficacy of IL-1Ra in 17 patients with steroid-resistant GVHD. The IL- 1Ra was administered as a 24-hour continuous infusion over 7 days. The dose was escalated in cohorts of patients from 400 to 3,200 mg/d. Acute GVHD was evaluated in each affected organ and as an overall grade. Stage-specific improvement of acute GVHD occurred in the skin (8 of 14, 57%), gut (9 of 11, 82%), and liver (2 of 11, 18%). Overall, acute GVHD improved by at least one grade in 10 of 16 (63%) patients. Response to therapy was associated with a reduction of tumor necrosis factor-alpha (TNF-alpha) mRNA levels in blood mononuclear cells (P = .001). The only toxicity attributable to IL-1Ra was reversible transaminase elevation in two patients. Inhibition of IL-1 activity with IL-1Ra is safe and has demonstrable efficacy in acute GVHD that failed to respond to conventional treatment. These data provide further evidence that IL-1 is a mediator of GVHD.