Effect of genital prolapse on assessment of bladder neck mobility by the Q-tip test

OBJECTIVE: To investigate the effect of vaginal prolapse and bladder fullness on Q-tip test assessment of urethral mobility. METHODS: Twenty-six women with genital prolapse to or beyond the hymen and undergoing urodynamics for urogynecologic dysfunction were assessed by the Q-tip test. Measurements were obtained with the bladder empty, with and without the prolapse reduced by the posterior blade of a Graves speculum. Angles were repeated at bladder capacity. Measured Q-tip angles were compared using the Wilcoxon signed rank test. RESULTS: Q-tip angles were significantly altered by vaginal prolapse and bladder fullness. With an empty bladder, the median Q-tip angle measured with the prolapse reduced was significantly less than that measured without reduction (53 degrees, interquartile range 25-65, versus 68 degrees, interquartile range 45-75; P <.001). With a full bladder, similar but lesser results were obtained (33 degrees, interquartile range 15-55 [reduced] versus 48 degrees, interquartile range 31-60 [unreduced]; P <.001). The median Q-tip angle with an empty bladder was greater than that with a full bladder. With the prolapse reduced, the Q-tip angle was 53 degrees (interquartile range 25-65) with an empty bladder versus 33 degrees (interquartile range 15-55) with a full bladder (P <.001). Without the prolapse reduced, the median Q-tip angle was 68 degrees (interquartile range 45-75) with an empty bladder and 48 degrees (interquartile range 31-60) with a full bladder (P <.001). CONCLUSION? Measurement of urethral mobility by the Q-tip test is significantly affected by genital prolapse. Q-tip angles are less with the reduction of vaginal prolapse and with the bladder full. Standardization of measurement technique is necessary for the development of clinical management recommendations.     

Pharmacokinetics and pharmacodynamics of single-chain recombinant human follicle-stimulating hormone containing the human chorionic gonadotropin carboxyterminal peptide in the rhesus monkey

Objective: To compare the pharmacokinetics of a long-acting FSH analog containing the hCG-β carboxyterminal peptide (recombinant hFSH–CTP) with native recombinant hFSH and describe the pharmacodynamics of recombinant hFSH–CTP after SC injection in female rhesus monkeys.

Design: Rhesus monkey study.

Setting: Academic research environment.

Animal(s): Ten female rhesus monkeys.

Intervention(s): Recombinant hFSH and recombinant hFSH–CTP were administered via a single SC or IV dose to rhesus monkeys, and serial phlebotomy was performed (n = 2 and N = 4 for SC recombinant hFSH and recombinant hFSH–CTP, respectively; for IV dosing, N = 1 in each group). An additional two monkeys were pretreated with SC ganirelix and received SC recombinant hFSH–CTP after confirmation of pituitary suppression.

Main Outcome Measure(s): Plasma disappearance rate of recombinant hFSH and recombinant hFSH–CTP and serum estradiol levels.

Result(s): The elimination half-life of recombinant hFSH–CTP was twofold and fourfold longer than that for recombinant hFSH after SC and IV dosing, respectively. The absorption half-life was approximately threefold longer for recombinant hFSH–CTP than for recombinant hFSH after SC administration. Recombinant hFSH–CTP stimulates estradiol secretion for 5–7 days after an isolated SC dose.

Conclusion(s): Addition of the hCG-β carboxyterminal peptide to hFSH-β results in an FSH analog with longer absorption and elimination half-lives compared with native hormone. This analog is capable of prolonged ovarian stimulation in rhesus monkeys after an isolated SC injection.     

Soy isoflavones in the treatment of prostate cancer

Epidemiological studies suggest an inverse association between soy intake and prostate cancer (Pca) risk. We have previously observed that soy isoflavone genistein induces apoptosis and inhibits growth of both androgen-sensitive and androgen-independent Pca cells in vitro. To determine the clinical effects of soy isoflavones on Pca we conducted a pilot study in patients with Pca who had rising serum prostate-specific antigen (PSA) levels. Patients with Pca were enrolled in the study if they had either newly diagnosed and untreated disease under watchful waiting with rising PSA (group I) or had increasing serum PSA following local therapy (group II) or while receiving hormone therapy (group III). The study intervention consisted of 100 mg of soy isoflavone (Novasoy) taken by mouth twice daily for a minimum of 3 or maximum of 6 mo. Forty-one patients were enrolled (4 in group I, 18 in group II, and 19 in group III) and had a median PSA level of 13.3 ng/ml. Thirty-nine patients could be assessed for response. Soy isoflavone supplementation was given for a median of 5.5 (range 0.8-6) mo per patient. Although there were no sustained decreases in PSA qualifying for a complete or partial response, stabilization of the PSA occurred in 83% of patients in hormone-sensitive (group II) and 35% of hormone-refractory (group III) patients. There was a decrease in the rate of the rise of serum PSA in the whole group (P = 0.01) with rates of rise decreasing from 14 to 6% in group II (P = 0.21) and from 31 to 9% in group III (P = 0.05) following the soy isoflavone intervention. Serum genistein and daidzein levels increased during supplementation from 0.11 to 0.65 microM (P = 0.00002) and from 0.11 to 0.51 microM (P = 0.00001), respectively. No significant changes were observed in serum levels of testosterone, IGF-1, IGFBP-3, or 5-OHmdU. These data suggest that soy isoflavones may benefit some patients with Pca.     

The efficacy and safety of Dermagraft in improving the healing of chronic diabetic foot ulcers: results of a prospective randomized trial

OBJECTIVE: To determine if a human fibroblast-derived dermal substitute could promote the healing of diabetic foot ulcers. RESEARCH DESIGN AND METHODS: A randomized, controlled, multicenter study was undertaken at 35 centers throughout the U.S. and enrolled 314 patients to evaluate complete wound closure by 12 weeks. Patients were randomized to either the Dermagraft treatment group or control (conventional therapy). Except for the application of Dermagraft, treatment of study ulcers was identical for patients in both groups. All patients received pressure-reducing footwear and were allowed to be ambulatory during the study. RESULTS: The results demonstrated that patients with chronic diabetic foot ulcers of >6 weeks duration experienced a significant clinical benefit when treated with Dermagraft versus patients treated with conventional therapy alone. With regard to complete wound closure by week 12, 30.0% (39 of 130) of Dermagraft patients healed compared with 18.3% (21 of 115) of control patients (P = 0.023). The overall incidence of adverse events was similar for both the Dermagraft and control groups, but the Dermagraft group experienced significantly fewer ulcer-related adverse events. CONCLUSIONS: The data from this study show that Dermagraft is a safe and effective treatment for chronic diabetic foot ulcers.     

Efficacy of terbinafine for toenail onychomycosis. A multicenter trial of various treatment durations

The efficacy of terbinafine (250 mg/day) in the treatment of toenail onychomycosis was evaluated in a large open-label, multicenter trial of 12, 18, and 24 weeks of therapy. All 1,534 patients had onychomycosis, confirmed by either positive potassium hydroxide (KOH) wet mount, positive fungal culture, or both, and all received at least 12 weeks of treatment. Treatment was continued for an additional 6 or 12 weeks, depending on the extent of the disease at follow-up. Mycologic cure rates (negative culture plus negative KOH) at week 72 were 72.1% in the 12-week treatment group, 72.5% in the 18-week group, and 77.0% in the 24-week group. In all groups, clinical cure rates were higher at week 72 than at week 48: 49.5% of the 12-week group, 49.2% of the 18-week group, and 44.6% of the 24-week group experienced clinical cure by the end of the study. Both mycologic and clinical recurrence rates were low in all treatment groups at the 72-week assessment. The results of this study confirm the efficacy of terbinafine in the treatment of toenail onychomycosis as demonstrated in previous registration and large-scale clinical trials.     

Intermuscular coherence in Parkinson's disease: relationship to bradykinesia

We hypothesised that bradykinesia may be partly due to the failure of the corticomuscular system to engage in high frequency oscillatory activity in Parkinson's disease (PD). In healthy subjects such oscillations are evident in coherence between active muscles at 15--30 Hz. We therefore investigated the effects of therapeutic stimulation of the basal ganglia on this coherence and related it to changes in bradykinesia in the contralateral arm. Increases in coherence at 15--30 Hz and improvements in bradykinesia upon stimulation were correlated (r = 0.564, p < 0.001). This suggests that the basal ganglia modulate oscillatory activity in the corticomuscular system and that impairment of the motor system's ability to engage in synchronised oscillations at high frequency may contribute to bradykinesia in PD.     

Clotrimazole increases tacrolimus blood levels: a drug interaction in kidney transplant patients

In order to substantiate a previous case report of a drug interaction between tacrolimus and clotrimazole, we randomly assigned tacrolimus-treated renal allograft recipients to therapy with either clotrimazole or nystatin for oral thrush prophylaxis immediately following transplantation. Patients receiving other agents known to interact with cytochrome P450 were excluded from the study. The clotrimazole group consisted of 17 patients and the nystatin group, which served as the control group, consisted of 18 patients. An oral loading dose (approximately 0.3 mg/kg) of tacrolimus was given pre-operatively. Post-transplant, tacrolimus (approximately 0.15 mg/kg) was orally administered twice daily. Clotrimazole therapy consisted of a 10-mg troche administered three times daily. Nystatin therapy consisted of the oral suspension (5 mL) administered as a 'swish and swallow' four times daily. We evaluated tacrolimus trough blood levels and tacrolimus doses on days 1, 3, 5, and 7 following transplantation. On post-transplant day 1, mean tacrolimus trough levels did not differ between clotrimazole- and nystatin-treated patients. Mean tacrolimus blood trough levels were significantly higher in clotrimazole-treated patients on days 3, 5, and 7 post-transplant, 42+/-14, 53+/-7, and 33+/-17 ng/mL, respectively, compared to 15+/-8, 15+/-7, and 14+/-6 ng/mL in nystatin-treated patients (p<0.05). The mean tacrolimus dose was significantly lower in the clotrimazole group by day 7 post-transplant (p<0.05). We conclude that clotrimazole therapy may cause a significant rise in tacrolimus trough blood levels. Recognition of this potential drug interaction is essential to minimize tacrolimus-associated toxicities in the early post-transplant period.     

How do residents prioritize smoking cessation for young "high-risk" women? Factors associated with addressing smoking cessation

BACKGROUND: Sixty-seven percent of physicians report advising their smoking patients to quit. Primary care residents' priorities for preventive health for a young "high-risk" female are unknown. Factors related to residents addressing smoking also need examining. METHODS: One hundred residents completed a survey about preventive health issues for a woman in her 20s "who leads a high-risk lifestyle." Residents indicated which topics they would address, and the likelihood that they would address each of 12 relevant preventive health topics, their outcome expectancies that the patient would follow their advice on each topic, their confidence that they could address the topic, and perceived barriers for addressing the topic. RESULTS: Residents listed STD prevention most frequently. Drug use and smoking cessation were second and third most frequently listed. Residents who believed that the patient would follow their advice were more likely to list smoking cessation than residents who had lower outcome expectancies for that patient. Higher barriers were negatively related to addressing smoking cessation. CONCLUSIONS: When time is not a barrier, residents are likely to address smoking cessation. Teaching residents how to incorporate this subject into their clinical practice is needed. Raising residents' outcome expectancies may increase their likelihood of addressing smoking cessation.