Efficacy and tolerability of lower-dose topotecan in recurrent ovarian cancer: a retrospective case review

Topotecan (1.5 mg/m(2)/day for 5 consecutive days of a 21-day cycle) is an established recurrent ovarian cancer treatment, but myelosuppression can be dose limiting. This study evaluates the activity and tolerability of low-dose topotecan in our clinical experience. Case records were reviewed for patients with recurrent ovarian cancer in first through third relapse. Eligible patients had received > or =2 cycles of < or =1.25 mg/m(2) topotecan. Adverse events were evaluated using laboratory and clinical evaluation data. Twenty-seven eligible patients, most with advanced disease, received a total of 209 cycles (median, six cycles). Grade 3 or 4 hematologic toxicities during 184 cycles in 24 assessed patients were neutropenia, leukopenia, thrombocytopenia, and anemia in 35%, 28%, 36%, and 11% of cycles, and 21, 19, 16, and 10 patients, respectively. Only four grade 4 toxicities occurred: anemia (one) and thrombocytopenia (three). Myelosuppression was reversible, noncumulative, and manageable. Moreover, nonhematologic toxicity was generally mild to moderate, and the only two grade 3 events were constipation and deep vein thrombosis. Low-dose topotecan was active in this setting. Lower-dose topotecan is generally well tolerated and active in patients with pretreated ovarian cancer. Prospective clinical trials of low-dose topotecan in recurrent ovarian cancer are warranted.     

A changing paradigm of glioma biology

The past 30 years have witnessed a major paradigm shift in brain tumor research with the development of a wide variety of molecular     

Preoperative embolization of a large vaginal leiomyoma: Report of a case and review of the literature

Leiomyoma of the vagina is a very rare tumour of the lower urogenital tract. These slow‐growing masses may be asymptomatic or present with pain, dyspareunia or urinary symptoms. Rarely, these tumours may present with life‐threatening haemorrhage. These hypervascular tumours are treated by surgical excision. Preoperative embolization therefore may aid in devascularization of these tumours before surgical excision. We present the MRI features of a case of vaginal leiomyoma, which was managed by preoperative embolization and was then excised in toto. To the best of our knowledge, this is the first report where preoperative embolization was performed before excision of a vaginal leiomyoma with minimal peroperative blood loss.     

单核细胞向巨噬细胞分化过程中CD44mRNA表达和黏附功能的变化

目的探讨单核细胞向巨噬细胞分化过程中CD44 mRNA表达和黏附功能的变化。方法应用豆蔻佛波醇乙酯(PMA)诱导单核细胞系U937向巨噬细胞分化;应用RT-PCR分析U937细胞CD44 mRNA表达变化,并以β-actin作为内参进行半定量评价,并对主要条带进行测序;应用荧光染料BCECF/AM作为探针,测定黏附于激活的内皮细胞上的U937细胞数目。结果与对照组比较,PMA诱导的U937细胞CD44 mRNA总体表达显著增加(P=0.01037),异构体/标准CD44比例显著上升(P=0.0005551),测序结果显示PMA刺激后显著增加的是947 bp(V8 V9 V10)和1208 bp(V7 V8 V9 V10)CD44异构体。同时,PMA刺激后U937细胞黏附功能显著增加(P=0.0029)。结论单核细胞向巨噬细胞分化过程中CD44 mRNA,特别是947bp(V8 V9 V10)和1208 bp(V7 V8 V9 V10)CD44异构体的表达显著增加,可能与细胞黏附功能的增强相关。     

Benzo[a]pyrene at an environmentally relevant dose is slowly absorbed by, and extensively metabolized in, tracheal epithelium

While tobacco smoke has been conclusively identified as a lung carcinogen, there is much debate over which smoke constituent(s) are primarily responsible for its carcinogenicity. Previous studies in our laboratory suggested that highly lipophilic carcinogens are slowly absorbed in the thicker epithelium of the conducting airways, potentially allowing for substantial local metabolism. The bioactivation of polycyclic aromatic hydrocarbons in airway epithelium may, hence, be important in tobacco smoke-induced carcinogenesis. In the present study, the hypothesis of slow absorption and substantial local metabolic activation of highly lipophilic carcinogen in airway epithelium was tested in dogs. A single dose of tritiated benzo[a]pyrene (BaP) dissolved in a saline/phospholipid suspension was instilled in the trachea, just anterior to the carina. At intervals of a few minutes up to 30 min over a 3-h period, blood samples were drawn from the azygous vein, which drains the area around the point of instillation, and from the systemic circulation. Tissue samples were taken at the end of the experiment. The concentration of BaP with depth into the tracheal mucosa was determined with autoradiography. BaP was slowly absorbed into the trachea with a half-time of approximately 73 min, which is consistent with diffusion-limited passage through the epithelium and lead to local doses in the tracheal epithelium that were more than a 1000-fold those of other tissues. The long retention of BaP in the epithelium provided the local metabolizing enzymes with high substrate levels over a long period, resulting in extensive metabolism. At 3 h after the exposure, 23% of the BaP-equivalent activity remained in the tracheal mucosa. Of this fraction, 13% was parent compound, 28% was organic extractable, 31% was water-soluble, and 28-7% of the instilled dose was bound to tracheal tissues. These results explain the tendency of highly lipophilic carcinogens, such as BaP, to induce tumors at the site of entry and, furthermore, indicate that the highly lipophilic components of tobacco smoke and polluted air may be the most important contributors to lung tumors of the conducting airways.      

Perinatal stimulation and adaptation of the neonate

The present report describes psychobiological studies of behavior around the time of birth. An adaptive, ecological perspective is presented in which stimulation of the fetus and newborn is purported to instigate adaptive postpartum behavior. Studies describing the perinatal sensory environment are reviewed, with a consideration of emergent sensory function of the fetus. It is asserted that afferent input associated with parturition perturbs the fetus and neonate, producing a general arousal state that facilitates breathing, suckling, and early learning. The view developed herein is that perinatal sensory input induces and canalizes the newborn's behavior, thereby regulating adaptive postpartum function. Deviations in afferent input may alter ontogenetic trajectories and compromise developmental outcome by reducing availability of conditions necessary for adequate postpartum adaptation.     

Cardiac abnormalities in end stage renal failure and anaemia

Thirteen anaemic children on dialysis were assessed to determine the incidence of cardiac changes in end stage renal failure. Nine children had an increased cardiothoracic ratio on radiography. The electrocardiogram was abnormal in every case but no child had left ventricular hypertrophy as assessed by voltage criteria. However, left ventricular hypertrophy, often gross, was found on echocardiography in 12 children and affected the interventricular septum disproportionately. Cardiac index was increased in 10 patients as a result of an increased left ventricular stroke volume rather than heart rate. Left ventricular hypertrophy was significantly greater in those on treatment for hypertension and in those with the highest cardiac index. Abnormal diastolic ventricular function was found in 6/11 children. Children with end stage renal failure have significant cardiac abnormalities that are likely to contribute to the high cardiovascular mortality in this group. Anaemia and hypertension, or its treatment, probably contribute to these changes. Voltage criteria on electrocardiogram are of no value in detecting left ventricular hypertrophy. Echocardiography must be performed, with the results corrected for age and surface area, in order to detect and follow these abnormalities.     

Right heart pressure determination by Doppler in infants with tricuspid regurgitation

Doppler and direct measurements of right ventricle to right atrial pressure drop were made during cardiac catheterisation on 28 occasions in 26 infants with congenital heart disease. Age was 10 days to 12 months (median 4.5 months), and weight was 3.1 to 9.0 kg (median 4.7 kg). We measured peak velocity of tricuspid regurgitation by continuous wave Doppler, and the pressure drop was calculated using the modified Bernoulli equation (delta p = 4v2). There was a high correlation (r = 0.95) between direct and Doppler measurements. Doppler values tended to underestimate the right ventricle to right atrial pressure drop, but this was not of clinical significance (mean 2 mm Hg). The 95% confidence interval for the Doppler velocity was -0.41 to +0.26 m/sec, and was consistent across the range of pressures studied. Variability between observers was tested, by two observers performing sequential paired examinations on 16 newborn babies with tricuspid regurgitation. The coefficient of repeatability was 6.3 mm Hg (95% confidence interval 4.7 to 9.5 mm Hg) or 0.26 m/sec (0.18 to 0.50 m/sec). This method of right ventricular pressure estimation, validated previously only in older children and adults, is a reproducible and accurate technique in infants with tricuspid regurgitation.     

Polypharmacy in a general surgical unit and consequences of drug withdrawal

AIMS: To identify drug usage/withdrawal in surgical patients and the relative risk this imposes on postoperative surgical complications. METHODS: A prospective survey of patients' medicines, oral intake (food/fluids/ medicines) and postoperative complications was carried out in the General Surgical Unit, Dunedin Hospital, Dunedin, New Zealand. RESULTS: One thousand and twenty-five general surgical patients aged >/= 16 years, were entered into the study. Half of the patients were taking medicines unrelated to surgery. On average these patients received 9 different drugs (range 1-47) from a selection of 251, of which 21% were released in the last 10 years. The mean number of these drugs taken increased with age, vascular surgery and other major procedures. The majority of patients (53%) were taking drugs for cardiovascular problems. Only 8% of admissions were on the drugs more traditionally recognized to be of importance to the surgery, i.e. steroids and diabetic therapy. With respect to risk, taking a drug unrelated to surgery was associated with an increased relative risk of a postoperative complication by 2.7 (95% C.I. 1.76-4.04) compared with those who were not taking any drug. Cardiovascular drugs contributed significantly to this risk; when they were excluded from analysis, the risk dropped to 1.8 (95% C.I. 1.14-2.93). Death may be more common in those taking ACE inhibitors. Drug withdrawal and complications were analysed and as the time without medicines increased (range 1-42 days) so did the complication rate (chi2 = 14.7, DF = 2, P = 0.007). Of those patients who were taking a cardiovascular medicine and were without their normal medicines for a period of time postoperatively, 12% suffered a cardiac complication. CONCLUSIONS: Many patients admitted to a general surgical ward, are taking medicines unrelated to surgery. Drug therapy unrelated to surgery is a useful predictor for increased postoperative complications and one for which preventive action can be taken. This study provides evidence that withdrawal of regular medicines may add significant risk to the surgery and further complicate outcome. The longer patients were without their regular medicines the more nonsurgical complications they suffered. Reintroduction of patients' regular medicines early in their postoperative course may decrease morbidity and mortality in-patients.