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Biomedical subjects

Scott Segal

Publications and source records attributed to Scott Segal.

15 recordsLinked to original sources
PubMed2006

Therapeutic potential of the SARMs: revisiting the androgen receptor for drug discovery.

Selective androgen receptor modulators (SARMS) bind to the androgen receptor and demonstrate anabolic activity in a variety of tissues; however, unlike testosterone and other anabolic steroids, these nonsteroidal agents are able to induce bone and muscle growth, as well as shrinking the prostate. The potential of SARMS is to maximise the positive attributes of steroidal androgens as well as minimising negative effects, thus providing therapeutic opportunities in a variety of diseases, including muscle wasting associated with burns, cancer, end-stage renal disease, osteoporosis, frailty and hypogonadism. This review summarises androgen physiology, the current status of the R&D of SARMS and potential therapeutic indications for this emerging class of drugs.

Androgen Antagonists↗
PubMed2005

Efficacy, safety, and treatment satisfaction of tadalafil versus placebo in patients with erectile dysfunction evaluated at tertiary-care academic centers.

OBJECTIVES: To determine the efficacy, safety, and treatment satisfaction of tadalafil 20 mg for erectile dysfunction (ED) in patients evaluated at tertiary-care academic centers. METHODS: In this randomized, double-blind, placebo-controlled trial, patients were randomly allocated to receive fixed-dose tadalafil 20 mg (n = 146) or placebo (n = 49) for 12 weeks. Efficacy was assessed by the International Index of Erectile Function (IIEF), Sexual Encounter Profile (SEP), and Global Assessment Question (GAQ); patient and partner treatment satisfaction by the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) and SEP; and safety by adverse events, laboratory values, and vital signs. RESULTS: Mean baseline IIEF erectile function (EF) domain was 12.98. Fifty-one percent of enrolled patients had severe baseline ED, and 82% had organic ED. Pre-existing, ED-associated comorbid conditions were common. When compared with patients treated with placebo, those receiving tadalafil reported significant improvement from baseline in the IIEF EF domain (P <0.001), successful penetration attempts (SEP question 2; P <0.001), successful intercourse (SEP question 3; P <0.001), and all secondary efficacy outcomes (P <0.001). Patients and their sexual partners were also significantly more satisfied with tadalafil treatment (P <0.001), including overall satisfaction (P <0.001) and length of time the treatment worked (P <0.001). Mild or moderate headache, dyspepsia, and myalgia were the most frequent treatment-emergent adverse events reported. CONCLUSIONS: Tadalafil significantly improved erectile function and patient and partner satisfaction and was well tolerated. These results were observed in a tertiary-care, academic center population with a high incidence of severe, organic ED, and comorbid medical conditions, factors known to compromise erectile function and treatment outcome.

Aged↗
PubMed2005

Ziprasidone in acute bipolar mania: a 21-day randomized, double-blind, placebo-controlled replication trial.

BACKGROUND: In an earlier 21-day, placebo-controlled trial, ziprasidone was efficacious in improving symptoms of mania and was well tolerated. To confirm these results, a similarly designed 21-day trial was conducted. METHODS: Inpatients with bipolar I disorder, manic or mixed, were randomized to ziprasidone (40 to 80 mg BID) or placebo. Efficacy rating scales were derived from the Schedule for Affective Disorders and Schizophrenia-Change Bipolar Scale (SADS-CB). SADS-CB-derived Mania Rating Scale (MRS) total score was the primary efficacy parameter. Secondary SADS-CB-derived efficacy parameters included Manic Syndrome and Behavior and Ideation Subscales, Hamilton Depression Rating Scale (HAM-D), and the Montgomery Asberg Depression Rating Scale (MADRS). The Clinical Global Impression-Severity Scale (CGI-S), the Global Assessment of Functioning (GAF), and the Positive and Negative Syndrome Scale (PANSS) were also assessed. RESULTS: Sixty-five placebo and 137 ziprasidone patients were evaluable for efficacy. Baseline-to-endpoint mean changes in MRS scores were -11.1 for ziprasidone and -5.6 for placebo (all patients, last observation carried forward [LOCF]; P < 0.01). Ziprasidone produced significantly greater improvements in Manic Syndrome (P < or = 0.01) and Behavior and Ideation Subscales (P < or = 0.001), CGI-S score, (P < or = 0.001), PANSS Total (P < or = 0.01) and Positive Subscale (P < or = 0.001) scores, and GAF (P < or = 0.001). With ziprasidone, significant improvements were observed from Day 2 onward for MRS and CGI-S at all time points except Day 4 for MRS. Treatment-related discontinuations due to adverse events were 5.8% for ziprasidone and 1.5% for placebo (P = 0.20). CONCLUSIONS: Ziprasidone was well tolerated, rapidly efficacious, and superior to placebo in improving symptoms and global illness severity in these inpatients with acute bipolar mania, both manic and mixed episodes.

Acute Disease↗
PubMed2005

Single-dose, sustained-release epidural morphine in the management of postoperative pain after elective cesarean delivery: results of a multicenter randomized controlled study.

In this multicenter, randomized, controlled study, we compared the analgesic efficacy and safety profile of a new single-dose extended-release epidural morphine (EREM) formulation (DepoDur) with that of epidural morphine sulfate for the management of postoperative pain for up to 48 h after elective cesarean delivery. ASA physical status I or II parturients (n = 75) were anesthetized with a combined spinal/epidural technique. Parturients received intrathecal bupivacaine 12-15 mg and fentanyl 10 mug for spinal anesthesia and a single epidural injection of either 5 mg of standard (conventional preservative-free) morphine or 5, 10, or 15 mg of extended-release morphine after cord clamping for postoperative pain control. Single-dose EREM 10 and 15 mg groups significantly decreased total supplemental opioid medication use and improved functional ability scores for 48 h after surgery compared with those receiving 5 mg of standard morphine. Visual analog scale pain scores at rest and with activity at 24 to 48 h after dosing were significantly better in the 10- and 15-mg single-dose EREM groups versus the standard morphine group. There were no significant differences between the two 5 mg (single-dose EREM and standard morphine) groups. Single-dose EREM was well tolerated, and most adverse events were mild to moderate in severity. Single-dose EREM is a potentially beneficial epidural analgesic for the management of post-cesarean delivery pain and has particular advantages over standard morphine for the period from 24 to 48 h after surgery.

Adult↗
PubMed2004

A multicenter, randomized, double-blind, crossover study to evaluate patient preference between tadalafil and sildenafil.

PURPOSE: To assess patient preference for erectile dysfunction treatment between either sildenafil or tadalafil, each administered with their respective dosing instructions, and to evaluate preference for either sildenafil or tadalafil dosing instructions during tadalafil therapy. METHODS: We conducted a randomized, double-blind, crossover study consisting of four treatment arms. Because the dosing instructions for sildenafil and tadalafil are different, a unique methodology using sham placebo arms was employed to maintain the blind. To assess drug preference, 219 patients were randomized to either sildenafil 50 mg or tadalafil 20 mg, with dosing instructions reflecting their respective product profiles. To assess dosing instruction preference during tadalafil therapy, 46 patients were randomized to tadalafil 20 mg with either tadalafil or sildenafil dosing instructions. After 12 weeks, patients were crossed-over. After 4 weeks of each treatment, all patients following sildenafil dosing instructions were offered the opportunity for an upward dose titration. In a double-blind fashion, all patients who requested an upward titration received additional capsules. To mimic the pattern of dose usage observed in clinical practice, the number of patients who received additional double-blind active medication was limited to 35% of patients taking sildenafil in each treatment period in each country. Following the crossover treatment period, patients chose their preferred double-blind treatment with dosing instructions to receive in the 12-week extension period. RESULTS: In the drug preference assessment, 132 of 181 (73%) evaluable patients chose to receive tadalafil (p < 0.001) during the extension period. In the dosing instruction preference assessment, 24 of 36 (67%) evaluable patients preferred tadalafil with tadalafil dosing instructions (p = 0.046). Sildenafil and tadalafil were well tolerated. CONCLUSIONS: In the doses utilized in this study, 73% of patients preferred tadalafil with tadalafil dosing instructions for the treatment of their erectile dysfunction over sildenafil with sildenafil dosing instructions. During tadalafil therapy, 67% of patients preferred tadalafil dosing instructions over sildenafil dosing instructions.

Adult↗
PubMed2003

New local anesthetics. Are they worth the cost?

Epidural analgesia that uses dilute concentrations of bupivacaine with fentanyl or sufentanil provides excellent analgesia, good sensory-motor discrimination, and minimal toxicity and is inexpensive. The new local anesthetic agents, ropivacaine and levobupivacaine, offer potential improvements in the risk of toxicity when administered in large doses but probably no important clinical difference when used in dilute concentrations for labor analgesia. After accounting for the potency difference, ropivacaine offers little or no motor-sparing advantage over bupivacaine. Currently, epidural anesthesia with concentrated bupivacaine is rarely used for cesarean section, so there is little indication for the newer anesthetic agents in this setting either. The authors believe that large difference in cost cannot be justified on the basis of currently available data.

Amides↗
PubMed2003

Local anesthetic requirements are greater in dystocia than in normal labor.

BACKGROUND: Dystocia is characterized by abnormal progress of labor and is a common contemporary indication for cesarean delivery in the United States. There has been considerable controversy as to whether epidural analgesia causes dysfunctional labor leading to cesarean delivery for dystocia. The minimum local analgesic concentration (MLAC) is a clinical model used to determine the relative potencies of local anesthetics in the first stage of labor. In this article, the authors report a prospective study determining the MLAC of bupivacaine in early labor of parturients who eventually delivered either vaginally or via cesarean section. METHODS: An up-down sequential allocation technique was used to determine the MLAC of bupivacaine in 57 nulliparous parturients assigned to either vaginal delivery or cesarean section arms. In addition, patients were assigned to groups receiving or not receiving intravenous oxytocin at the time of epidural placement. Only patients who delivered by the assigned delivery mode were included in the MLAC analyses. RESULTS: Parturients who later delivered vaginally had 25% and 31% lower MLAC values (0.078% and 0.085% wt/vol bupivacaine, receiving or not receiving intravenous oxytocin, respectively) than those who later delivered by cesarean section (0.102% and 0.106% wt/vol bupivacaine, receiving or not receiving intravenous oxytocin, respectively). CONCLUSIONS: These data suggest that an increased local anesthetic requirement for epidural labor analgesia is associated with more intense pain related to dystocia. Women in early, clinically normal labor but who later develop dystocia require more local anesthetic and, by inference, are experiencing more severe pain than women who deliver vaginally. This association should be considered when studying the relation between the method of labor analgesia and the course of labor.

Adult↗
PubMed2002

Herbal medicine use in parturients.

UNLABELLED: Alternative medicine use has increased dramatically over the last decade. Recently a 22% incidence of herbal medicine use in presurgical patients was reported. Of concern is the potential for these medications to cause adverse drug-herb interactions or other effects such as bleeding complications. We sought to determine the prevalence and pattern of use of herbal remedies in parturients. A one-page questionnaire examining the use of all prescription and nonprescription medications, including herbal remedies, was sent to parturients expected to deliver within 20 wk who had preregistered with the hospital's admissions office. Sixty-one percent of the parturients responded to the survey, with 7.1% of parturients reporting the use of herbal remedies. Only 14.6% of users considered them to be medications. Parturients in the 41--50 yr age bracket (5.6% of parturients) were the most likely to use herbal remedies (17.1% rate of use in this age group). Many parturients who took herbal remedies (46%) did so on the recommendation of their health care provider. IMPLICATIONS: Herbal medicine use may be less prevalent in the parturient population, however, some health care providers may be promoting their use during pregnancy.

Adult↗
PubMed2002

Pregnancy alters adrenergic mechanisms in uterine arterioles of rats.

UNLABELLED: Pregnancy is associated with altered vascular reactivity. However, the effect of pregnancy on the alpha- and beta-adrenergic responses in the uterine microcirculation remains to be determined. In late-pregnant (Day 20-21, n = 6) and virgin (n = 6) Sprague-Dawley rats, uterine radial arterioles (70-120 microm in internal diameter) were isolated. We studied in vitro arteriolar responses in a pressurized, no-flow state with videomicroscopy. alpha(2)-Adrenergic activation relaxed uterine arterioles; this relaxation was increased with pregnancy and was inhibited after endothelial denudation or inhibition of nitric oxide synthase. Pregnancy significantly increased the contractile response to the alpha(1)-adrenoceptor agonist phenylephrine but decreased the relaxation to the beta-adrenoceptor agonist isoproterenol. The contractile response to the protein kinase C activator phorbol ester and relaxation responses to both the adenylate cyclase activator forskolin and the endothelium-independent cyclic guanosine monophosphate-mediated vaso- dilator nitroprusside were preserved. These results suggest that pregnancy enhances the alpha(2)-adrenoceptor-mediated relaxation of uterine arterioles, probably because of an increase in the release of nitric oxide. The alpha(1)-adrenergic response is upregulated, whereas the beta-adrenergic response is impaired, in the uterine microcirculation of pregnant rats. IMPLICATIONS: Both alpha- and beta-adrenergic responses are important mechanisms for the regulation of uteroplacental perfusion. By use of an in vitromicrovascular technique, we have shown pregnancy-associated alteration in adrenergic responses in the uterine microcirculation of the rat.

Animals↗
PubMed2002

The effect of alterations in a preoperative assessment clinic on reducing the number and improving the yield of cardiology consultations.

UNLABELLED: Although preoperative assessment testing clinics (PATCs) can produce efficiency in the evaluation of surgical candidates, their effect on the use of consultants has not been studied. We hypothesized that changes in PATC procedures, education, and staffing could affect the use and yield of cardiology consultations. All PATC anesthesiologist-requested cardiology consultations for patients undergoing elective noncardiac surgery from 1993 to 1999 were reviewed. This period corresponded to 3 yr before and after a change in the PATC leadership, which resulted in more stringent consultation algorithms, a cardiac assessment and electrocardiogram interpretation educational program, and altered staffing of anesthesiologists and ancillary personnel. A single senior cardiologist completed all consultations. Data including age, sex, reason for consultation, resultant testing, consultant conclusions, cancellations, and surgical procedure and outcomes were collected. In the PRE and POST groups, respectively, 917 and 279 consultations (1.46% versus 0.49% [P = 0.0001] of noncardiovascular surgeries) were ordered despite an increase in the surgical case-mix acuity. In the POST group, significantly fewer consultations were ordered and significantly more required further testing to assess cardiac status. We conclude that changes in PATC consultation algorithms, education, and staffing can significantly decrease the use and yield of preoperative cardiology consultations. IMPLICATIONS: Alterations in preoperative assessment testing clinic consultation algorithms, education, and staffing can significantly reduce the use of preoperative cardiology consultations while improving their overall yield.

Adult↗