The specification of fertility planning status.

The principal obstacle to accurate measurement of fertility planning intentions in cross-sectional surveys is the disposition of the respondent to provide the interviewer with a reconstruction of the couple's history which departs more or less from what actually happened...Since married couples in America are now close to effective planning of fertility, the future of reproduction in the United States will depend much more than in the past on reproductive intentions. From this viewpoint, the uncertainty of reproductive intentions as shown here suggests extreme circumspection in using current reproductive orientations for future projections.     

Effect of CO2 on the systemic and coronary circulations and on coronary sinus blood gas tensions.

The responses to hypocapnia and to hypercapnia of both the systemic and the coronary circulations have been studied in the dog during intermittent positive pressure ventilation under halothane anaesthesia. In the absence of significant variations of myocardial contractility, the reduction of cardiac output, because of hypocapnia, was determined by the increase of systemic vascular resistance, while the increase of cardiac output because of hypercapnia was determined by an increase of heart rate without change of stroke volume. The alterations of coronary blood flow (reduction following hypocapnia, augmentation following hypercapnia) were considerably larger than the changes of cardiac output and of myocardial oxygen consumption. Such disparity between oxygen supply and demand, together with the effect of pH and PCO2 on the oxyhaemoglobin dissociation curve led to a marked reduction of coronary sinus PO2 in response to hypocapnia and a marked increase of coronary sinus PO2 in response to hypercapnia. The data suggests that PCO2 (or respiratory alterations of pH) may have a direct effect on the regulation of coronary blood flow. The low coronary sinus PO2 observed at hypocapnia may suggest the risk of myocardial ischaemia.     

Male urethral gonorrhoea -- 5,700 pounds per positive test?

We audited all male urethral gonorrhoea cases from 2003 to determine the additional yield of culture following negative microscopy. Sixty-one episodes were reviewed, of which six were diagnosed by culture alone. In all, 475 cultures were performed to diagnose each case of microscopy-negative infection. As resources in sexual health clinics are limited, it may be appropriate to reconsider our policy of universal male urethral gonococcal culture.     

Heart failure care in a hospital unit: a comparison of standard 3-month and extended 6-month programs

BACKGROUND: We have previously shown that a structured in-hospital and outpatient heart failure (HF) program reduces clinical events over a 3-month period following hospital discharge. AIMS: This prospective randomized controlled study examines the additional benefits of extending the standard 3-month HF program to 6 months on death and readmission over a 2-year follow-up period. METHODS: Of 161 patients admitted with NYHA class IV HF who completed the standard 3-month HF program, 130 consenting patients (mean age 69.9+/-12.2 years, 65% male) were randomized to the extended 6-month HF program (EP; n=62) or standard care (SP; n=68). The primary endpoint was death and/or unplanned rehospitalization for HF at 2 years postrandomization. RESULTS: In the 2-year follow-up period, there were eight people with unplanned hospitalizations for HF and 16 deaths in the EP group (event rate 38.7%) compared to seven people with unplanned HF readmissions and 14 deaths in the SP group (event rate 30.9%, p=0.348 versus EP). Kaplan-Meier survival analysis demonstrated no difference in outcome between standard and extended program (p=0.315). There were no differences between the groups in terms of unscheduled clinic visits or non-HF-related readmissions in the 2-year follow-up period. CONCLUSIONS: There is no measured clinical advantage in terms of death and/or HF readmission in extending a structured hospital-based disease management program for HF beyond 3 months postdischarge. However, it appears that patients continue to need access to the service to help abort clinical deteriorations, and this may have implication for the optimal organisation of such programs.     

Synthesis and structure-activity relationships of novel histamine H1 antagonists: indolylpiperidinyl benzoic acid derivatives

A series of indolylpiperidinyl derivatives were prepared and evaluated for their activity as histamine H(1) antagonists. Structure-activity relationship studies were directed toward improving in vivo activity and pharmacokinetic profile of our first lead (1). Substitution of fluorine in position 6 on the indolyl ring led to higher in vivo activity in the inhibition of histamine-induced cutaneous vascular permeability assay but lower selectivity toward 5HT(2) receptor. Extensive optimization was carried out within this series and a number of histamine H(1) antagonists showing potency and long duration of action in vivo and low brain penetration or cardiotoxic potential were identified. Within this novel series, indolylpiperidines 15, 20, 48,51 and 52 exhibited a long half-life in rat and have been selected for further preclinical evaluation.     

Incidence of cerebral metastases in patients treated with trastuzumab for metastatic breast cancer

Trastuzumab is an effective treatment for patients with metastatic breast cancer (MBC) that overexpresses HER-2. A high incidence of brain metastases (BM) has been noted in patients receiving trastuzumab. A retrospective chart review was conducted of 100 patients commencing trastuzumab for metastatic breast cancer from July 1999 to December 2002, at the Christie Hospital. Seven patients were excluded; five patients developed central nervous system metastases prior to starting trastuzumab, and inadequate data were available for two. Out of the remaining 93 patients, 23 (25%) have developed BM to date. In all, 46 patients have died, and of these 18 (39%) have been diagnosed with BM prior to death. Of the 23 patients developing BM, 18 (78%) were hormone receptor negative and 18 (78%) had visceral disease. Univariate analysis showed a significant association between the development of cerebral disease and both hormone receptor status and the presence of visceral disease. In conclusion, a high proportion of patients with MBC treated with trastuzumab develop symptomatic cerebral metastases. HER-2-positive breast cancer may have a predilection for the brain, or trastuzumab therapy may change the disease pattern by prolonging survival. New strategies to address this problem require investigation in this group of patients.     

Cumulative meta-analysis of systemic antifungal agents for the treatment of onychomycosis

BACKGROUND: Onychomycosis is a common nail disease that is often chronic, difficult to eradicate, and has a tendency to recur. The most common oral therapies for dermatophyte toenail onychomycosis include terbinafine, itraconazole and fluconazole. OBJECTIVES: A cumulative meta-analysis of the randomized controlled trials (RCTs) for antimycotic agents was performed to determine whether the pooled estimate of the cure rates has remained consistent over the years. Furthermore, for each agent we compared the overall meta-analytical average of both mycological and clinical response rates of RCTs vs. open studies. METHODS: We searched MEDLINE (1966 to November 2002) for relevant studies evaluating the efficacy of the oral antifungal agents terbinafine, itraconazole (pulse or continuous), fluconazole and griseofulvin for treating dermatophyte toenail onychomycosis. Studies included in this meta-analysis required a standard accepted dosage regimen, treatment duration and follow-up period. To determine the cumulative meta-analytical average, studies were sequentially pooled by adding one study at a time according to the date of publication (i.e. earliest to the most recent). RESULTS: There were 36 studies included in the analyses. For RCTs the change in efficacy of mycological cure rates from the first trial to the overall cumulative meta-average for each drug comparator is as follows (with 95% confidence interval): terbinafine, 78 +/- 6% (n = 2 studies, 79 patients) to 76 +/- 3% (n = 18 studies, 993 patients) (P = 0.68); itraconazole pulse, 75 +/- 10% (n = 1 study, 20 patients) to 63 +/- 7% (n = 6 studies, 318 patients) (P = 0.25); itraconazole continuous, 63 +/- 5% (n = 1 study, 84 patients) to 59 +/- 5% (n = 7 studies, 1131 patients) (P = 0.47); fluconazole, 53 +/- 6% (n = 1 study, 72 patients) to 48 +/- 5% (n = 3 studies, 131 patients) (P = 0.50); and griseofulvin, 55 +/- 8% (n = 2 studies, 109 patients) to 60 +/- 6% (n = 3 studies, 167 patients) (P = 0.41). The cumulative meta-analytical average of mycological cure rates when comparing RCTs vs. open studies was: terbinafine, 76 +/- 3% (n = 18 studies, 993 patients) vs. 83 +/- 12% (n = 2 studies, 391 patients) (P = 0.0028); itraconazole pulse, 63 +/- 7% (n = 6 studies, 318 patients) vs. 84 +/- 9% (n = 3 studies, 194 patients) (P = 0.0001); and fluconazole, 48 +/- 5% (n = 3 studies, 131 patients) vs. 79 +/- 3% (n = 3 studies, 208 patients) (P = 0.0001). CONCLUSIONS: The cumulative meta-analysis of cure rates for RCTs suggests that over time, as new RCTs have been conducted, the efficacy rates have remained consistent. The efficacy rates of open studies are substantially higher compared with RCTs and may therefore overestimate cure rates.