In vitro and in vivo evaluation of seven 50 mg and 100 mg nitrofurantoin tablets

Four 50 mg and three 100 mg marketed nitrofurantoin tablets were studied in 14 healthy male subjects. Urine was collected 1, 2, 3, 4, 6, 8, 12, and 23 h after each dose, and nitrofurantoin was assayed by HPLC. The in vitro dissolution of the tablets was determined using USP Apparatus 1 and 2, with 0.1 N hydrochloric acid and pH 7.2 buffer as the dissolution fluids. One of the 50 mg tablets was more rapidly and completely absorbed than the other six products. The incidence of side-effects for this product was as low or lower than the other products. It was determined that the use of the USP Apparatus 1, at 100 rev min-1, with sampling of the pH 7.2 fluid at 30 min, provided for the best overall relationship between the urinary excretion and in vitro dissolution.     

Outcomes of gynecologic oncology patients undergoing robotic-assisted laparoscopic procedures in a university setting

This study evaluated intraoperative complications and postoperative outcomes of gynecologic oncology patients undergoing robotic-assisted (RA) laparoscopic procedures in a university setting. A retrospective chart review evaluated all gynecologic oncology patients at the University of Alabama at Birmingham who underwent attempted RA procedures between August 2006 and October 2011. Patient demographics, medical/surgical history, intraoperative complications, postoperative outcomes, conversion rates, readmission rates, and length of stay were examined. Total complication rates were assessed over time for each surgeon. 681 patients underwent planned RA procedures by seven gynecologic oncologists. The mean body mass index was 33.5 kg/m² (range 16.6–71.0 kg/m²). 61.4 % were diagnosed with malignancy. The most common procedure was RA hysterectomy with unilateral/bilateral salpingo-oophorectomy (37.2 %). Robotic staging was performed in 291 patients (45.1 %). Mean estimated blood loss was 75 ml (range 5–700 ml). 36 patients (5.3 %) were converted to laparotomy. The most common reason for conversion was adhesions (30.1 %), followed by uterine size (22.2 %). In 107 cases, a surgical modification was required for specimen removal including mini-laparotomy (24), extension of accessory port (36), morcellation (9), and difficult vaginal delivery (38). 3.7 % had intraoperative complications; 6 patients had a cystotomy and 5 had a vascular injury. Postoperatively, 20 patients had a febrile episode, 9 had wound complications, and 3 had a vaginal cuff dehiscence. 27 (4.2 %) patients were readmitted within 30 days. Complication rates and conversion rates were similar per surgeon. Total complication rates for evaluable surgeons were similar between the first 10 cases and subsequent 50 cases. Although patients undergoing RA procedures in a university setting are high risk, the conversion rate to laparotomy is low and intraoperative and postoperative complications are acceptable. Total complication rates for each surgeon were not impacted by the number of cases performed.     

Postmenopausal steroid replacement with micronized dehydroepiandrosterone: preliminary oral bioavailability and dose proportionality studies.

OBJECTIVES: Because dehydroepiandrosterone may protect against neoplasia, osteoporosis, and cardiac disease, we investigated the bioavailability of oral micronized dehydroepiandrosterone, anticipating its adjunctive use in postmenopausal steroid replacement. STUDY DESIGN: Eight postmenopausal women randomly received either a placebo or 150 or 300 mg of oral micronized dehydroepiandrosterone in a lipid matrix. Serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, testosterone, and estradiol were measured periodically over the 12 hours after each dose. All treatments, all doses, and mean serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone were compared with analysis of variance for repeated measures and Newman-Keuls a posteriori test of statistical significance. RESULTS: Mean peak steroid concentrations after 150 mg (300 mg) doses were dehydroepiandrosterone 1617 (2639) ng/dl, 7 (11.5)-fold above placebo; dehydroepiandrosterone S 1185 (1688) micrograms/dl, 14 (20)-fold above placebo; and testosterone 183 (311) ng/dl, 4 (7)-fold above placebo. Estradiol concentrations remained less than 20 pg/ml, but androgen concentrations rose by 1 hour and remained elevated through the twelfth hour. Peak androgen concentrations and areas under the curves exhibited proportionality with both doses. A testosterone radioimmunoassay with celite chromatography revealed a 300% overestimation for testosterone in the direct-assay method used in this study. Thus after appropriate readjustment maximum testosterone concentrations were observed consistently within physiologic premenopausal ranges after the 150 mg dose. CONCLUSIONS: Micronized dehydroepiandrosterone may provide a steroidal postmenopausal replacement that is adjunctive to estrogens and worthy of further investigation.     

Targeting adenovirus to the serotype 3 receptor increases gene transfer efficiency to ovarian cancer cells.

Gene delivery efficiency in clinical cancer gene therapy trials with recombinant adenoviruses (Ads) based on serotype 5 (Ad5) has been limited partly because of variable expression of the primary Ad5 receptor, the coxsackie and adenovirus receptor (CAR), on human primary cancer cells. As a means of circumventing CAR deficiency, Ad vectors have been retargeted by creating chimeric fibers possessing knob domains of alternate Ad serotypes. In this study, we have constructed an Ad5-based vector, Ad5/3luc1, with a chimeric fiber protein featuring a knob domain derived from Ad3. This virus is retargeted to the Ad3 receptor and, therefore, has different tissue tropism. A novel knob binding assay was used to measure expression of CAR and the Ad3 receptor. Further, to evaluate the correlation of receptor expression and infectivity by Ad, a panel of ovarian cancer cell lines and purified primary cancer cells were infected with Ad5luc1 and Ad5/3luc1 at 50, 200, and 1000 viral particles/cell. Our results confirm that Ad5/3luc1 is retargeted to the Ad3 receptor. Furthermore, the Ad3 receptor is present at higher levels than CAR on ovarian adenocarcinoma cells. Also, the amount of binding to primary receptor appears to be the major factor determining the efficiency of transgene expression. The Ad5/3 chimera displays enhanced infectivity for ovarian cancer cell lines and purified primary tumor cells, which could translate into increased efficacy in clinical trials.     

A cost-effectiveness analysis of management strategies for cervical intraepithelial neoplasia grades 2 and 3

OBJECTIVE: This study was performed to compare the cost-effectiveness of strategies for the management of cervical intraepithelial neoplasia, grades 2 and 3 (CIN 2 and CIN 3). STUDY DESIGN: A decision analysis compared six management strategies. The model was applied to hypothetic cohorts of 100,000 patients with CIN 2 and CIN 3. RESULTS: In both analyses, cryotherapy (CRYO) was the least expensive and least effective strategy; total vaginal hysterectomy was the most expensive and most effective strategy. For CIN 2, loop electrosurgical excision procedure (LEEP) was more effective than CRYO but at a cost of $31,437 per additional cure and $1.8 million per additional cancer prevented. For CIN 3, LEEP was more effective than CRYO, but at a cost of $17,592 per additional cure and $1.0 million per additional cancer prevented. CONCLUSION: CRYO is a cost-effective strategy that is appropriate in resource-poor settings. LEEP is also cost-effective, but the improved efficacy compared with CRYO comes at a significant cost. Total vaginal hysterectomy is very effective but is economically unsound because of excessively high costs.     

Predictors of outcome in small cell carcinoma of the cervix--a case series

OBJECTIVE: The objective of this study was to determine whether clinicopathologic findings or the immunohistochemical presence of molecular markers are predictive of clinical outcome in patients with small cell carcinoma of the cervix (SCCC). METHODS: A retrospective review of cases of carcinoma of the cervix was conducted to identify SCCC. From 1978 to 1999, 16 patients were identified at our institution with the diagnosis of SCCC. Microscopic sections of paraffin-embedded tissue specimens were evaluated for confirmation of diagnosis. Specimens were immunohistochemically stained with antibodies to three neuroendocrine markers: neuron-specific enolase, chromagranin (CGR), and synaptophysin. Specimens were also stained for protein expression of p53, erbB2, proliferating cell nuclear antigen, and c-myc. The relationship between molecular markers and clinical outcome was determined. RESULTS: All 16 cases met the histologic criteria for SCCC. Fourteen of 16 tumors (88%) stained positive for neuroendocrine differentiation. Eleven of 16 patients (69%) died from disease with a median survival of 19 months; there were 3 long-term survivors (greater than 5 years). CGR was positive in 8 (50%) specimens and was found to be highly predictive of death (P = 0.001). Complete loss of p53 protein was seen in 8 patients, 7 of whom died with a median survival of 20 months. CONCLUSION: Immunohistochemistry can be helpful in confirming difficult cases of SCCC. Further studies are necessary to define molecular markers that may be predictive of outcome in patients with SCCC.     

Endometrial carcinoma

Opinion statement Endometrial cancer is a common tumor of the female genital tract. The majority of women diagnosed with endometrial cancer present with early-stage disease. Although the optimal treatment for these patients requires hysterectomy, the use of lymphadenectomy is controversial. Growing scientific data support the use of lymphadenectomy in all patients diagnosed with endometrial cancer. When performed by an experienced surgeon, pelvic and para-aortic lymphadenectomy is a safe and potentially therapeutic procedure that provides prognostic information to the patient and physician. This information allows appropriate, cost-effective treatment strategies to be created for all women with endometrial cancer.     

A high-throughput approach towards a novel formulation of fenofibrate in omega-3 oil

A novel lipid formulation containing fenofibrate in omega-3 oil was developed using a novel high-throughput screening platform. The optimized formulation combines the cardiovascular health benefits from omega-3 oil with the potent lipid-regulating effect of fenofibrate. When tested against the current marketed product Tricor^® in healthy human volunteers, the new formulation was shown to be equivalent to Tricor^®.     

Arterial oxygen saturation in sedated patients undergoing gastrointestinal endoscopy and a review of pulse oximetry

The pulse oximeter is a widely used noninvasive monitor which provides a continuous reading of arterial oxygen saturation. We sought to determine if patients with cardiopulmonary disease were at higher risk of oxygen unsaturation than controls during gastrointestinal endoscopy. Patients presenting for upper gastrointestinal endoscopy and/or colonoscopy were placed into one of two groups: A. control population:patients with no history of cardiac and/or pulmonary disease (N = 11); B. test population:patients with a history of cardiac and/or pulmonary disease (N = 39). The procedure was performed by one of 14 equally experienced physicians. The Nellcor N-100 Pulse Oximeter and D-25 finger probe were used to monitor arterial oxygen saturation which was recorded at five minute intervals from commencement of intravenous sedation analgesia to 15 minutes post-procedure. In both groups, the oxygen saturation fell to statistically significant. A: 98.3% to 90.2%; B: 97.7% to 89.5%. However, the amount of unsaturation which occurred in Group B was not statistically different from Group A. Therefore, history of prior cardiac and/or pulmonary disease does not increase the degree of unsaturation from that occurring in patients with no such history. In addition, the effects of age, procedure, duration, I.V. sedation, and individual tolerance on oxygen unsaturation were studied by regression analysis and analysis of variance (ANOVA). Only the upper GI endoscopy patients showed a dependence of oxygen unsaturation upon one of the variables, specifically patient tolerance. It is concluded that patients at risk for hypoxemia during endoscopy or colonoscopy cannot be determined prior to the initiation of the procedure, and it is recommended that all of these patients be given supplemental oxygen as well as monitored with a pulse oximeter.