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Biomedical subjects

D L Warner

Publications and source records attributed to D L Warner.

16 recordsLinked to original sources

The inaccuracy of duplex ultrasonography in predicting patency of transjugular intrahepatic portosystemic shunts.

BACKGROUND & AIMS: A prospective double-blinded study with preset sonographic criteria has not been performed to assess the accuracy of duplex ultrasonography in determining the patency of transjugular intrahepatic portosystemic shunts (TIPS). The purpose of this study was to determine the sensitivity and specificity of duplex ultrasonography in predicting shunt malfunction using accepted preset sonographic criteria. METHODS: Sixty ultrasonographic and venographic follow-up comparisons were made on 38 cirrhotic patients who had undergone TIPS placement for variceal bleeding (n = 28) or intractable ascites (n = 10). Ultrasonographic results were analyzed by one of two board-certified ultrasonographers without knowledge of venographic findings. RESULTS: Of the 31 occluded (n = 8) and stenotic (n = 23) shunts, ultrasonography accurately predicted a shunt malfunction (occlusion or stenosis) in only 11 studies and incorrectly predicted patency in 20. Compared with venography, ultrasonography had a sensitivity of 35% and a specificity of 83% in predicting TIPS stenosis or occlusion. CONCLUSIONS: These results suggest that duplex sonography is not a sensitive test in predicting the presence of a hemodynamically significant stenosis and that shunt status should be assessed by venography and direct portal pressure measurements until a more reliable and proven noninvasive ultrasonographic criterion is devised.

Adult

Facilitating condom use with clients during commercial sex in Nevada's legal brothels.

OBJECTIVES: This study examined condom use in legal Nevada brothels. METHODS: Forty female prostitutes in two brothels were interviewed about client resistance to condoms and techniques for facilitating condom use. RESULTS: Of 3290 clients in the previous month, 2.7% (95% confidence interval [CI] = 2.2%,3.4%) were reluctant to use condoms. Of these individuals, 72% ultimately used condoms, while 12% chose nonpenetrative sex without condoms. The remaining 16% left the brothels without services. Condom use rates were markedly lower with nonpaying sex partners (lowers) than with clients. CONCLUSIONS: Brothel prostitutes may be at greater risk for acquiring HIV and other sexually transmitted diseases from lovers than from clients.

Adult

Phase I and pharmacokinetic study of GI147211, a water-soluble camptothecin analogue, administered for five consecutive days every three weeks.

GI1147211 is a 7-substituted 10,11-ethylenedioxy-20(S)-camptothecin analogue that inhibits the nuclear enzyme topoisomerase I. In this Phase I and pharmacological study, 24 patients with advanced solid malignancies received a total of 72 courses of GI147211 as a 30-min infusion daily for 5 consecutive days, at doses ranging from 0.3 to 1.75 mg/m2/day. Severe neutropenia precluded dose escalation above 1.5 mg/m2/day in minimally pretreated patients, and both severe neutropenia and thrombocytopenia were dose limiting in heavily pretreated patients at doses above 1.0 mg/m2/day. These doses are, therefore, recommended for subsequent Phase II evaluations of GI147211 in patients with comparable prior therapy. Nonhematological toxicities, including nausea, vomiting, fatigue, and anorexia, were mild to moderate. The disposition of GI147211 in blood was described by a linear three-compartment model, with renal elimination accounting for only 11% of drug distribution. No relationship was observed between the pharmacological exposure to GI147211 and effects on neutrophils; however, patients who developed dose-limiting myelosuppression did experience greater exposure to both the lactone and total forms of the drug. The hydrolysis kinetics of GI147211 revealed not only a shift of the drug to the inactive carboxylate form in human serum albumin but also stabilization of the lactone in erythrocytes, perhaps accounting for the observed lactone:total area under the concentration-time curve ratio of 0.27. These results indicate that GI147211 exhibits predictable toxicities and that further studies are warranted to determine the distinct role of this compound among currently available camptothecin analogues.

Adult

Simple and versatile high-performance liquid chromatographic method for the simultaneous quantitation of the lactone and carboxylate forms of camptothecin anticancer drugs.

The well documented hydrolysis of the alpha-hydroxy-delta-lactone ring moiety in camptothecin and related analogues is routinely monitored using high-performance liquid chromatography (HPLC). Previous HPLC separations of the lactone and carboxylate forms of camptothecins have often required mobile phases containing three to four components; ion-pairing reagent to provide adequate retention of the carboxylate form of the drug; buffer to control the ionic strength and pH of the mobile phase; acetonitrile to control the retention of the lactone form and, in some instances, sodium dodecyl sulfate to reduce peak tailing. Because of the complexity of the mobile phases employed, development of these assays can be a laborious process, requiring re-optimization for each new analogue. In this study, we have developed a simple HPLC methodology for the simultaneous separation of the lactone and carboxylate forms of numerous camptothecin analogues. The mobile phase employed includes only triethylamine acetate (TEAA) buffer and acetonitrile. In this application, triethylamine serves multiple roles; as the ion-pairing reagent, as a masking agent for underivatized silanols and as the major buffer component. By altering only the composition of TEAA buffer with respect to acetonitrile, method development becomes a more streamlined and time efficient process. In this publication, we present the simultaneous separation of the lactone and carboxylate forms of camptothecin and four related analogues, namely, topotecan, GI147211, 10-aminocamptothecin and the CPT-11-SN-38 drug-metabolite pair. It is proposed that this new mobile phase, consisting of only triethylamine acetate buffer and acetonitrile, can be used for the analysis of the several camptothecin derivatives presently in clinical trials as well as the numerous other analogues in preclinical development.

Acetonitriles

Histological response to stent graft therapy.

BACKGROUND: The purpose of the present study was to examine the histological consequences of the endoluminal exclusion of blood flow effected with stent graft technology. METHODS AND RESULTS: In 25-kg mongrel dogs, patulous vein patch infrarenal aortoplasty with iliac vein produces a fusiform abdominal aortic dilation (AAD). All aortic tributaries were preserved. Endoluminal exclusion via transfemoral placement of a thin-wall Dacron graft occurred 4 +/- 2 months later (n = 23). Balloon-expandable stents anchored the ends of the graft to the aorta. Hematoxylin and eosin, elastin van Gieson's, and Masson's trichrome staining was performed 6 and 12 months later at death. In control nongrafted AADs, the arterial portion of the AAD was lined by elastin -and collagen-rich intimal hyperplasia, and the venous portion developed medial hyperplasia containing collagen but little elastin. After stent graft placement, the stent struts and the graft were completely incorporated into an elastin-poor, collagen-rich neointima. Fibrosis of the vein patch was observed at 1 year. laminated thrombus did not form in the AAD until immediately after stent graft placement; flow arrest occurred in the space between the graft and the AAD intima despite the patent tributaries. At 6 and 12 months, microscopic recanalization was seen in this thrombus, although macroscopic flow was not discernible by duplex imaging or angiography. No AAD growth was measured. CONCLUSIONS: Aortic dilation was not observed at 1 year after stent graft placement within AADs with patent side branches despite microscopic evidence of thrombus recanalization. A collagen-rich and elastin-poor neointima incorporated the entire stent graft.

Animals

Ketamine plus midazolam, a most effective paediatric oral premedicant.

Healthy children, 1.5 to seven years old, were divided into three groups of 20 each. Group 1 received midazolam 0.5 mg.kg-1, Group 2, ketamine 6 mg.kg-1 and Group 3 a mixture of midazolam 0.4 mg.kg-1 + ketamine 4 mg.kg-1. Each dose was mixed with atropine 0.02 mg.kg-1 plus an equal volume of cherry syrup and was given orally 20 to 30 min prior to surgery. A grade of 1 (asleep, difficult to arouse), 2 (asleep, easily aroused), 3 (awake, calm), 4 (awake, anxious, occasional cry), or 5 (crying, agitated), was assigned at the time of parental separation and again when mask induction was begun. A grade of 1-3 was considered successful. For parental separation, the mixture of ketamine+midazolam was 100% successful, ketamine 90% and midazolam 75%. Successful mask induction for the mixture of ketamine+midazolam was 85%, midazolam 65% and ketamine 42%. This study indicates that a mixture of ketamine+midazolam is the most effective.

Adjuvants, Anesthesia

Condom use among female commercial sex workers in Nevada's legal brothels.

OBJECTIVES: The purpose of this study was to evaluate condom use and the incidence of breakage and slippage during vaginal intercourse among female prostitutes in legal Nevada brothels, where use of condoms is required by law. METHODS: Forty-one licensed prostitutes in three brothels were enrolled in a prospective trial in August 1993. Used condoms were collected to verify reported breaks visually. Retrospective breakage and slippage rates were obtained in a standardized interview. RESULTS: Condoms were used for every act of vaginal intercourse with a brothel client during the study period, as well as in the previous year. In the prospective study phase, condoms were used in 353 acts of vaginal intercourse with clients. No condoms broke, and none fell off the penis during intercourse. Only twice (0.6%) did condoms completely fall off during withdrawal. Twelve times (3.4%) during intercourse and 15 times (4.3%) during withdrawal, condoms slipped down the penis but did not fall off. CONCLUSIONS: These findings, among the lowest breakage and slippage rates published, suggest that regular condom use may lead to condom mastery and the development of techniques to reduce the likelihood of breakage and slippage.

Adult

Condom performance during vaginal intercourse: comparison of Trojan-Enz and Tactylon condoms.

Forty-nine mutually monogamous couples used a total of 478 condoms during vaginal intercourse in a prospective trial whose purpose was to discover whether the performance of a new non-latex hypoallergenic condom was substantially equivalent to that of a leading condom brand already being marketed. Of these 478 condoms, seven (1.46%) either broke or fell off the penis during intercourse. Two (0.42%) of the 471 condoms that did not break or fall off during intercourse fell off the penis when it was being withdrawn from the vagina. Altogether, 469 (98.1%) of the 478 condoms used for intercourse survived intact throughout intercourse and withdrawal. Differences in breakage and slippage rates for the two condom brands were statistically insignificant. The overall 98.1% success rate is much higher than the rate of success found in a previous condom trial with nearly identical research protocol. The reason for the difference is attributed to much more precise questioning of subjects in the current trial.

Adult

New condoms for men and women, diaphragms, cervical caps, and spermicides: overcoming barriers to barriers and spermicides.

Barriers and spermicides are being developed for the prevention of unwanted pregnancy and sexually transmitted infection. The inconvenience of current methods limits their acceptability and leads to higher user failure rates. New methods, such as female condoms, nonlatex male condoms, and new cervical caps are being developed: the Reality (Wisconsin Pharmacal, Jackson, WI) polyurethane vaginal pouch has already received conditional Food and Drug Administration approval for use in the United States. The material used in a Food and Drug Administration-approved nonallergenic glove is being tested for its effectiveness as a condom. In addition, the Fem Cap, a cervical cap that had a life table probability of failure within 1 year of 4.8%, is expected to be available within the next 2 years. It is important for clinicians to be informed of new options becoming available for those patients who may be good candidates for these barrier methods.

Contraceptive Devices

Paediatric anaesthetic management with the aid of a computer.

A computer program has been developed to assist in the preparation of proper drug and anaesthetic doses for children. An individualized reference sheet containing the doses of the more commonly used drugs for the induction and maintenance of anaesthesia, fluid requirements, blood volume information, ventilatory variables, estimated endotracheal tube sizes and emergency drug doses constitutes the output of this program. The importance of such a computer program in improving paediatric anaesthetic management is discussed.

Adolescent

Condom slippage and breakage rates.

A prospective study using two brands of condoms found that of 405 condoms used for intercourse, 7.9% either broke during intercourse or withdrawal or slipped off during intercourse; none of these events were related to condom brand, past condom use or use of additional lubricant. Of the remaining condoms, 7.2% slipped off during withdrawal; slippage was not related to condom brand or past use of condoms, but it was significantly higher when additional lubricant was used.

Adolescent