Combination gemcitabine, platinum, and bevacizumab for the treatment of recurrent ovarian cancer

ObjectiveTo describe the response rate (RR), progression-free survival (PFS), and toxicity profile of combination gemcitabine, platinum, and bevacizumab (GPB) for the treatment of recurrent epithelial ovarian cancer (EOC).MethodsA chart review of all patients with recurrent EOC who were treated with D1, D15 GPB in a 28-day cycle at a single institution was performed. Standard doses were gemcitabine 1000 mg/m², cisplatin 30 mg/m² or carboplatin AUC 3, and bevacizumab 10 mg/kg. All patients were analyzed for toxicity. RR and PFS were assessed in all patients who received at least 2 cycles of GPB.ResultsThirty-five patients were identified, and 33 received at least 2 cycles of GPB. The majority of patients (80%) were platinum sensitive. Patients received a median of 6 cycles of GPB (range 1–24). Sixteen patients (48%) had a complete response (CR), and 10 patients (30%) had a partial response (PR), for a total RR of 78%. An additional 5 patients (15%) had stable disease, and only 2 (6%) patients had progressive disease. The median overall PFS was 12 months (95% CI 7–15), with a median follow-up time of 10 months (2–22). Two patients (6%) had bowel perforations, and both survived. Hematologic toxicities were most common, with 29% and 14% of patients experiencing grade 3 or 4 neutropenia and thrombocytopenia respectively.ConclusionsThe combination of GPB demonstrated excellent efficacy for the treatment of recurrent EOC. However, serious toxicities occurred, and the safety profile of this combination requires further study.     

Liverpool Ultrasound Pictorial Chart: the development of a new method of documenting anal sphincter injury diagnosed by endoanal ultrasound

Objective  To develop and validate a pictorial chart that documents ultrasound examination of the anal sphincter.
Design  A new pictorial chart (Liverpool Ultrasound Pictorial Chart [LUPIC]) depicting the normal anatomy of the anal sphincter was developed.
Methods  To validate LUPIC, two observers documented the findings of 296 endoanal scans. Reliability was assessed between observers using kappa agreement for presence and position of sphincter defects. To validate the use of LUPIC by different observers, a video of ten endoanal ultrasound scans was reviewed by our local expert (gold standard). Seven clinicians underwent test-retest analysis. Kappa agreement was calculated to assess intra-observer and gold standard versus observer agreement for the overall presence of sphincter defects and compared with the gold standard. Complete agreement for the position and level of sphincter defects was assessed for the five abnormal scans.
Main outcome measures  Excellent agreement between the two observers was found for the presence (kappa 0.99), position and level of external anal sphincter defects documented using LUPIC. The intra-observer and gold standard versus observer kappa values of experienced clinicians (A–E) showed good agreement for the overall presence of sphincter defects. Complete agreement for the position and level of sphincter defects was found in 23 of 35 (66%) observations.
Conclusions  LUPIC is designed and validated method of documenting anal sphincter injury diagnosed by endoanal ultrasound. Standardisation of endoanal ultrasound findings by using LUPIC may help correlate the degree of damage with patient symptoms.     

Impact of advanced maternal age on neonatal survival of twin small-for-gestational-age subtypes

AIM: We examined the impact of advanced maternal age (>40 years old) on the survival of twin small-for-gestational-age (SGA) infants, that is, infants who were smaller in size than was expected for the baby's sex, genetic heritage, and gestational age. METHODS: The present study was a retrospective cohort study on twin live births in the USA from 1995 to 1998 inclusive. Two categories of SGA babies were defined: discordant (when only one of a twin pair was SGA) and concordant (when both were SGA). Otherwise, the twin pair was appropriate-for-gestational-age (AGA) concordant. RESULTS: 192,195 twin pairs were analyzed. The incidence of SGA discordance and concordance was 11.8% and 3.9%, respectively. The occurrence of both SGA subtypes tended to decrease with increasing maternal age. The unadjusted risk for neonatal mortality increased when both twins were affected (15.8: 22.8 and 56.6 per 1000 among AGA concordant, SGA discordant and SGA concordant twins; P-value for trend < 0.0001). Using maternal-age-specific AGA babies as reference, the adjusted risk for neonatal mortality climbed progressively with advancing maternal age in a dose-dependent pattern, being lowest among teenagers and highest in mothers aged > or =40 years. CONCLUSIONS: SGA discordance and concordance declined with advancing maternal age. In contrast, neonatal mortality of both SGA subtypes worsened with the increase in maternal age compared with that of the age-specific AGA infants. These findings are potentially useful to care providers in counseling older women, a group that is progressively increasing in size and is most susceptible to twining.     

College students' perceptions of H1N1 flu risk and attitudes toward vaccination

College students are highly susceptible to the H1N1 virus, yet previous studies suggest that college students perceive themselves at low risk for the flu. We surveyed 514 undergraduates to assess their perceptions of H1N1 flu risk and opinions about flu vaccines. A third of respondents stated that they were not at risk of getting the H1N1 flu because they were young. Responses indicated a distrust of the safety and effectiveness of influenza vaccinations; only 15.8% of participants planned on receiving H1N1 vaccination. Top reasons for refusing the H1N1 vaccine included questioning vaccine safety and effectiveness, and concerns about potential serious and/or benign side effects. Top reasons for H1N1 vaccination acceptance included receiving a doctor recommendation for the vaccine, having previously gotten a seasonal vaccine, and being at high-risk for influenza. Our findings suggest that college students are inaccurate in assessing their risk level and are unlikely to seek vaccinations.     

Effects of pimozide on emitted force, duration and rate of operant response maintained at low and high levels of required force

The behavioral effects of pimozide (0.25, 0.5, and 1.0 mg/kg) were assessed in two separate experiments in which session mean peak force, maximum peak force, and response duration served as the dependent variables complementing operant response rate. In the first experiment, two groups of water-deprived rats were trained on a continuous reinforcement (CRF) schedule for reaching out and pressing downward on a force transducer with peak forces of at least 4 g (low-force group) or 40 g (high-force group). In the second experiment a pull-type response topography and fixed ratio 20 were used, and force requirements were 4 g for the low-force group and 100 g for the high-force condition. Under these conditions pimozide decreased response rate and increased response duration irrespective of response topography, required force, or schedule of reinforcement. Neither mean peak force nor maximum peak force were significantly decreased by the drug, and in the low-force CRF condition a small but significant dose-related rise in mean peak force was observed. It was hypothesized that neuroleptics exert their motor-impairing effects primarily in the temporal domain of behavior but do not appreciably affect the force dimension of performance capacity. And these temporal domain effects may be reflected in differences in the kinetic requirements for the overall behavior and not just the response itself. Additionally, the possibility that some of the observed effects could be accounted for by "anhedonia" was addressed.     

Renal toxicity of propyleneimine: assessment by non-invasive techniques in the rat

The nephrotoxicity of three different dose levels of propyleneimine (10, 20 and 30 microliter/kg body wt) administered intraperitoneally to rats was studied and 20 microliters/kg body weight was found to be the most appropriate sublethal dose. Injection of propyleneimine (10 microliters/kg body wt) produced a small rise in N-acetyl-beta-D-glucosaminidase (NAG) activity, minor histological damage but no change in urine volume. Six rats were injected with 20 microliters/kg body weight, and urine was collected over the following 16 days. An immediate increase in urine volume, osmolality together with a concomitant decrease in specific gravity, was accompanied by a small increase in creatinine excretion and a more marked increase in the sodium and potassium content of urine after the administration of the nephrotoxin. NAG activity increased immediately and peaked on day 3, the activity remained elevated until day 12 when it fell to near normal levels. The activity of both beta-D-galactosidase and beta-D-glucosidase increased 9 days after administration of the nephrotoxin. In contrast, no consistent change was found in the excretion of the brush border marker enzymes, leucine aminopeptidase (LAP), alanine aminopeptidase (AAP) or alkaline phosphatase (ALP). Proteinuria increased sharply the day after injection and remained abnormal. Increased urinary albumin excretion and the predominance of low molecular weight proteins was demonstrated by sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis. Evidence is presented that propyleneimine exerts its early toxic effect on the renal papilla.     

Community attitudes toward a proposed nuclear power generating facility as a function of expected outcomes

This study examined the relationship between attitudes toward a proposed nuclear power generating facility and the outcomes expected to accompany it. In a survey of 350 residents of a small rural community, approximately 2/3 expressed favorable attitudes toward the proposed nuclear plant. A principal components factor analysis of the anticipated likelihoods of outcomes of the plant revealed five factors: hazards, economic growth, lower costs, social disruption, and community visibility. Using these factors as predictors, a simple multiple regression equation accounted for 52% of the variation in attitudes toward the plant. The strongest predictor was the perceived likelihood of hazards. These findings are discussed in terms of the relationship between attitudes and expectations, and in relation to decisions regarding public policy.