Chronic treatment of female rhesus monkeys with low doses of the antiprogestin ZK 137 316: establishment of a regimen that permits normal menstrual cyclicity

Large doses of antiprogestin typically disrupt menstrual cyclicity. A chronic low-dose regimen of the potent new antiprogestin ZK 137 316, which permits continued menstrual cyclicity but alters gonadal- reproductive tract activity, was established. Rhesus monkeys received vehicle (n = 6) or 0.01 (n = 8), 0.03 (n = 8) or 0.1 (n = 5) mg ZK 137 316/kg body weight daily for five menstrual cycles (C-1 to C-5). Oestradiol, progesterone and gonadotrophin profiles were normal during cycles involving vehicle and 0.01 and 0.03 mg ZK 137 316/kg body weight. In the 0.1 mg/kg group, mid-cycle oestradiol and gonadotrophin surges, and subsequent progesterone production, were absent in C-3 and C-5. Ovarian cyclicity was accompanied by timely menstruation in the vehicle and 0.01 mg/kg groups. By C-3, half the animals in the 0.03 mg/kg group and all animals in the 0.1 mg/kg group were amenorrhoeic. A corpus luteum was noted during the mid-luteal phase of C-5 in the vehicle, 0.01 mg/kg and 0.03 mg/kg groups. Large antral and cystic follicles were evident in the 0.1 mg/kg group. Thus, a daily treatment with 0.01 mg/kg ZK 136317 permitted normal menstrual cyclicity in macaques. While the daily administration of 0.03 mg/kg ZK 136 317 allowed ovarian cyclicity, menstruation was disrupted in some animals. Increasing the dose to 0.1 mg/kg antagonized pituitary function and resulted in anovulation and amenorrhoea. A chronic low-dose regimen of the antiprogestin ZK 137 316, which permits normal ovarian/menstrual cyclicity, has potential as a contraceptive in women.      

Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung

Lung carcinoids occur sporadically and rarely in association with multiple endocrine neoplasia type 1 (MEN1). There are no well defined genetic abnormalities known to occur in these tumors. We studied 11 sporadic lung carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene were inactivated. All four tumors showed the presence of a MEN1 gene mutation and loss of the other allele. Observed mutations included a 1 bp insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide substitution affecting a donor splice site. Each mutation predicts truncation or potentially complete loss of menin. The remaining seven tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH. The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a complex germline MEN1 gene mutation. The data implicate the MEN1 gene in the pathogenesis of sporadic lung carcinoids, representing the first defined genetic alteration in these tumors.      

Physicians at the roadside: Pre-hospital emergency care in the United Kingdom

In some parts of the United Kingdom (UK), family doctors (or "general practitioners" as they are called in the UK) are routinely called upon by the emergency medical services (EMS) system to attend road accidents. The doctors are volunteers and travel to the scene of the accident in their own cars. Members of one such general practitioner accident service operating in Mid-Anglia complete an accident report form after attending each incident. In 1983, the Mid-Anglia General Practitioner Accident Service (MAGPAS) received 1,715 calls for medical assistance, and in 95% of these a doctor was sent immediately. Of these calls, 57% were passed to the doctor within one minute of the receipt of the call in the MAGPAS control room, and 78% were relayed within two minutes. This rapid call-out, combined with the close proximity of the local doctor to the accident site, resulted in the doctors arriving ahead of the ambulance in 42% of the calls. A total of 54 patients with airway obstruction were treated by the doctors prior to the arrival of the ambulance. Ninety-nine patients required immediate intravenous fluid replacement in the pre-hospital phase of their medical care. This report suggests that general practitioners in rural areas can play a vital role in the early management of trauma patients, especially in the absence of ambulance personnel trained in advanced life support skills.     

Breast cancer in young women: Imaging and clinical course

The purpose of this study was to characterize presenting imaging findings in women younger than 40 diagnosed with invasive breast cancer in the context of pathology and clinical course. Retrospective chart and imaging reviews were performed in patients under 40 diagnosed with breast cancer between July 1, 2004, and December 31, 2013. Patient demographic, imaging, pathology, and clinical data were collected. Overall and recurrence-free survival were estimated using the Kaplan-Meier method. Univariate Cox proportional hazards models were performed to identify factors associated with recurrence-free survival. Our study cohort consisted of 110 patients with invasive mammary carcinoma. One hundred one (91.8%) presented with a palpable mass. The mean size of all lesions on imaging was 3.5 cm ± 2.9 cm. Malignant calcifications were present in 54 (49.1%) cases. Imaging demonstrated multifocal or multicentric disease in 45 (40.9%) cases. Seventy four (67.3%) cancers were high grade. Luminal genomic subtypes were the most common (n = 61, 55.5%). At presentation, 4 (3.6%) patients had bilateral malignancy and 8 (7.3%) patients had distant metastatic disease. Ninety seven (88.2%) underwent neoadjuvant chemotherapy and 67 (60.9%) underwent radiation therapy. Seventy five (68.2%) of the patients underwent mastectomy. The restricted mean time to recurrence was 9.01 years (standard error 3.162 months). ER positivity was associated with compromised recurrence-free survival. The overall survival rate was 0.962 at 10 years. Young patients diagnosed with breast cancer typically present with advanced breast imaging findings and undergo aggressive treatment. Recurrence often occurs >5 years from diagnosis, and ER positive subtypes are at increased risk for recurrence.     

Quality of Life Assessment,of Ileogastrostomy

Twenty of 26 (77%) consecutive patients undergoing ileogastrostomy, performed by the same surgeon (IGMC) between February 1989 and May 1992, responded to a mailed quality of life survey. Average present weight was reported as 50.9 kg less than a mean preoperative weight of 139.7 kg. Mean time of follow-up was 24.75 months. When comparing perceptions before and after surgery, several quality of life improvements were noted in the areas of vocation, relationships, emotional well-being and physical well-being. Post-surgery, jobs were rated more satisfying, eating habits improved, self-image and self-confidence increased and body disparagement declined. Satisfaction with sexual relations increased, as did frequency. In general, relations with partners, co-workers and friends seemed to improve. Exercise also increased significantly. In contrast, foul flatus, bloating, and bowel movements regularly hampered activities or caused embarassment when in public. Despite these physical side-effects, we observed that a large majority of persons undergoing ileogastrostomy noted significant improvements in quality of life.     

下消化道出血221例分析

0　引言　下消化道出血是消化科的常见病 ,是指十二指肠空肠移行部 ,屈氏韧带以下的小肠和大肠疾病引起的肠道出血 .有人认为一般不包括痔和肛裂出血 [1 ] .临床最常见为慢性出血 ,但有时出血量大危及生命 ,需要做紧急处理 ,现将我院1992 - 0 1/ 1999- 0 8门诊及病房收治的 2 2 1例下消化道出血进行分析 ,报告如下 :1　临床资料　男 12 0例 ,女 10 1例 ,年龄 14～ 72 (平均 42 )岁 ,病程 16 h～ 10 a.患者分别以脓血便、暗红色血便、鲜血便或果酱色血便为主诉前来就诊 ,其中有休克症状的大出血者6例 .血 Hb<110 g·L- 1 40例 ,<80 g·L- 1…     

A comparison of perinatal mortality between ethnic Chinese and ethnic whites: Why the Chinese rate was lower

Objectives. To confirm the observation that has been occasionally reported in the literature that perinatal mortality rate is lower in ethnic Chinese than in ethnic whites, and to assess the reasons for this lower perinatal mortality rate.

Methods. Secondary‐analysis based on published data.

Results. This exercise demonstrates that the perinatal mortality rate was lower in ethnic Chinese than in ethnic whites. The birth weight distribution in ethnic Chinese was more favourable with reduced births at two extremes of the distribution, and the exposure to risk factors for perinatal death by their mothers was also lower.

Conclusion: Perinatal mortality rate is lower in ethnic Chinese than in ethnic whites, and the lower perinatal mortality rate in ethnic Chinese is probably caused by their favourable birth weight distribution and lower exposure to risk factors of perinatal death by their mothers.     

Helicobacter pylori-induced diarrhea post-ileogastrostomy

A retrospective study of all ileogastrostomy procedures (n=26) performed in 1993 by one surgeon (IGMC) was carried out to investigate the hypothesis that Helicobacter pylori may be implicated in certain severe cases of postoperation nausea and diarrhea. Ten of 26 persons (38.5%) displayed nausea and notable diarrhea (greater than or equal to ten bowel movements per day), seven of which warranted upper GI investigation. One hundred per cent (seven of seven) of these persons were found to possess H. pylori upon C-14 breath test. In four of six cases eradication therapy (1 g amoxicillin b.i.d./20 mg omeprazole b.i.d. for 2 weeks) corresponded with a resolution of severe nausea and diarrhea (one additional case involved omeprazole use only), suggesting that H. pylori should be considered as a possible cause of these symptoms post-ileogastrostomy. Additionally, in four of seven cases persons were re-tested (C-14 breath analysis) at least 1 month post-therapy and in this group three persons were found to be free of the organism. All three cases of notable diarrhea and nausea resolved with treatment, providing the strongest evidence for a possible association between infection and these symptoms.     

Public involvement in health care priority setting: an economic perspective

Background  Public involvement in health care decision making and priority setting in the UK is being promoted by recent policy initiatives. In 1993, the British Medical Association called for public consultation where rationing of services was to be undertaken. The approach to priority setting advocated by many health economists is the maximization of quality adjusted life years (QALYs). Typically, for a particular health care programme, the QALY calculation takes account of four features: (1) the number of patients receiving the programme, (2) the survival gain, (3) the gain in quality of life and, (4) the probability of treatment success. Only one feature, that relating to quality of life, is based upon public preferences. If the QALY is to be used as a tool for health care resource allocation at a societal level then it should incorporate broader societal preferences.
Methods  This study used an interview-based survey of 91 members of the general public to explore whether the traditional QALY maximization model is a good predictor of public responses to health care priority setting choices.
Results and conclusions  Many respondents did not choose consistently in line with a QALY maximization objective and were most influenced by quality of life concerns. There was little support for health care programmes that provided a prognostic improvement but left patients in relatively poor states of health. The level of respondent engagement in the survey exercise was not sensitive to the provision of supporting clinical information.     

Totally laparoscopic aortobifemoral bypass grafting in an experimental model: Description of technique with initial surgical results

Our aim was to examine the feasibility of a totally laparoscopic insertion of a bifurcated aortofemoral bypass graft in a canine model and to compare the surgical results with those in control animals undergoing standard grafting and laparoscopic-assisted bypass procedures. Using a six-port approach, we exposed and cross clamped the aorta, tunneled a bifurcated Dacron graft, and performed an end-to-end aortic anastomosis while maintaining pneumoperitoneum by means of CO₂. Proximal anastomoses were performed with 4/0 double-ended continuous Prolene sutures and distal anastomoses were performed through standard groin incisions. Total operating and aortic cross-clamp times were measured as was the total blood loss for each procedure. Clinical outcome was also documented. Eight female laboratory-bred hounds underwent successful totally laparoscopic aortobifemoral bypass grafting, eight underwent open grafting, and eight underwent laparoscopic-assisted bypass. Mean operating time was 193 minutes in the animals undergoing totally laparoscopic insertion vs. 156 minutes in the open group and 180 minutes in the laparoscopic-assisted group. Aortic cross-clamping time was also significantly longer at 87 minutes vs. 43 minutes (p < 0.001)=" in=" the=" totally=" laparoscopic=" group,=" but=" blood=" loss=" was=" less.=" all=" eight=" laparotomy=" and=" laparoscopic-assisted=" dogs=" were=" still=" alive=" with=" no=" complications=" at=" 28=" days,=" whereas=" three=" of=" the=" eight=" in=" the=" totally=" laparoscopic=" group=" showed=" evidence=" of=" temporary=" paraplegia.=" this=" experimental=" study=" demonstrates=" that=" a=" totally=" laparoscopic=" approach=" can=" be=" used=" to=" insert=" a=" bifurcated=" aortofemoral=" bypass=" with=" a=" proximal=" end-to-end=" anastomosis=" but=" currently=" does=" not=" save=" time=" and=" may=" increase=" the=" risk=" of=" neurologic=">Presented at the Twentieth Annual Meeting of the Peripheral Vascular Surgery Society, New Orleans, La., June 10, 1995.