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Biomedical subjects

S Auerbach

Publications and source records attributed to S Auerbach.

At least 19 recordsLinked to original sources
PubMed2006

First-dose success with vardenafil in men with erectile dysfunction and associated comorbidities: RELY-I.

First-dose success of phosphodiesterase type 5 (PDE5) inhibitors may be adversely affected in patients with comorbidities. This article reports first-dose success rates for vardenafil 10 mg in men with erectile dysfunction (ED) and associated comorbidities who participated in the challenge phase of the Reliability--Vardenafil for Erectile Dysfunction I study. This study involved an open-label, single-dose, 1-week challenge period where patients who achieved SEP-2 (penetration) success were randomised to vardenafil 10 mg or placebo for 12 weeks in a double-blind manner. The first-dose success rates for SEP-2 and SEP-3 (maintenance of erection to completion of intercourse) were stratified according to comorbidities. Safety was assessed using adverse events (AEs). Of 600 men who received a single 10 mg dose of vardenafil, 32% had hypertension, 16% had diabetes and 19% had dyslipidaemia. Vardenafil demonstrated overall effectiveness, including first-dose SEP-2 and SEP-3 success rates in patients with and without specific comorbidities. Initial overall success rates for SEP-2 and SEP-3 during the challenge phase were 87% and 74% respectively. First-dose SEP-2 and SEP-3 success rates were 84% and 66% in men with hypertension (n = 191); 84% and 72% in men with dyslipidaemia (n = 116); and 75% and 58% in men with diabetes (n = 95). Vardenafil was well tolerated and most AEs, including the most frequently reported flushing (3.5%), were mild to moderate in intensity. Vardenafil 10 mg is generally well tolerated and efficacious, providing first-dose success with a consistently high rate of reliability of penetration and maintenance of erection in men with ED and associated comorbidities.

Adult↗
PubMed2002

Long-term safety and efficacy of oral phentolamine mesylate (Vasomax) in men with mild to moderate erectile dysfunction.

The objectives of this study were to evaluate long-term safety and efficacy of phentolamine mesylate, an orally active, rapid-acting alpha-adrenergic receptor antagonist, for the treatment of men suffering from erectile dysfunction (ED). It was an open-label study involving more than 2000 patients. Men received phentolamine mesylate 40 mg or 80 mg (10 tablets/month) as needed for up to 13 months and self-assessed erectile performance using two validated questionnaires. Treatment with phentolamine mesylate was associated with increases in Erectile Function Domain score of the IIEF, successful vaginal penetrations, and in overall satisfaction. Most adverse events were mild or moderate in severity and consistent with the known pharmacodynamic properties of phentolamine. In conclusion, phentolamine mesylate is safe and effective in the long-term treatment of men with mild to moderate ED.

Administration, Oral↗
PubMed2001

Sildenafil citrate (VIAGRA) improves erectile function in elderly patients with erectile dysfunction: a subgroup analysis.

BACKGROUND: The prevalence of erectile dysfunction (ED) increases with advancing age, with a particularly high prevalence of ED in elderly patients with diabetes. In the United States it is estimated that approximately 45% of men aged 65 to 69 years have moderate or complete ED. The efficacy and safety of oral sildenafil (VIAGRA) for treating ED in elderly men (aged > or = 65 years or older) were assessed. METHODS: We analyzed data obtained from five double-blind, placebo-controlled studies of the efficacy and tolerability of oral sildenafil taken as required (but not more than once daily) over a 12-week to 6-month period. Two subgroups were evaluated: (i) elderly patients with ED of broad-spectrum etiology (n = 411), and (ii) elderly patients with ED and diabetes (n = 71). Efficacy was assessed using a global efficacy question, questions 3 and 4 of the International Index of Erectile Function (IIEF). and the five sexual function domains of the IIEF. RESULTS: All efficacy assessments indicated that sildenafil significantly improved erectile function both in elderly patients with ED of broad-spectrum etiology and in elderly patients with ED and diabetes. The most common adverse events were mild-to-moderate headache, flushing, and dyspepsia. The rates of discontinuation due to adverse events were low and were comparable to the rates with placebo. CONCLUSIONS: Sildenafil is an efficacious and well-tolerated treatment for ED in elderly men.

Aged↗
PubMed2000

Axial penile rigidity as primary efficacy outcome during multi-institutional in-office dose titration clinical trials with alprostadil alfadex in patients with erectile dysfunction. Alprostadil Alfadex Study Group.

The purpose of the study was to utilize axial penile buckling testing as a primary efficacy variable of erection quality during multi-institutional in-office dose titration testing with alprostadil alfadex, prostaglandin E1 (PGE1)-alpha-cyclodextrin, (EDEX /VIRIDAL, Schwarz Pharma) in patients with erectile dysfunction. In 41 study sites, in three different dose titration studies involving 894 patients with impotence >6 months, a buckling test was performed and repeated every 10 min for up to 60 min, within 30 min following alprostadil alfadex administration, or when two consecutive circumference measurements reached maximum values. The buckling device consisted of a standard weight scale attached to a 2 inch diameter plastic cap with a concavity on its ventral surface (H. Eric Richards, Inc., Canton MA). A positive test was associated with absent penile shaft buckling to a downward force of 1.0 kg, slowly applied to the glans in the axis of the erect shaft. A total of 630 (71%) patients experienced at least one positive buckling test. Three consecutive positive buckling tests, implying a functionally rigid erection for at least 20 min, were noted in 521 (58%) patients. There were high correlations between the presence of three consecutive positive buckling tests following alprostadil alfadex injection and the patient's (83% of cases) and the investigator's (88% of cases) evaluation of adequacy of erection for intercourse. Similarly, there were high correlations between the presence of negative buckling tests and the patient's (95% of cases) and the investigator's (96% of cases) evaluation of inadequacy of erection for intercourse. The axial penile buckling test offers a simple, reliable, and inexpensive method to objectively quantify erectile response following in-office dose titration of intracavernosal alprostadil alfadex. The high correlation to subjective patient/investigator assessment adds to the validity of the test.

Adult↗
PubMed1998

5' heterogeneity in epithelial sodium channel alpha-subunit mRNA leads to distinct NH2-terminal variant proteins.

The amiloride-sensitive epithelial sodium channel (ENaC) is composed of three subunits: alpha, beta, and gamma. The human alpha-ENaC subunit is expressed as at least two transcripts (N. Voilley, E. Lingueglia, G. Champigny, M. G. Mattei, R. Waldmann, M. Lazdunski, and P. Barbry. Proc. Natl. Acad. Sci. USA 91: 247-251, 1994). To determine the origin of these transcripts, we characterized the 5' end of the alpha-ENaC gene. Four transcripts that differ at their first exon were identified. Exon 1A splices to exon 2 to form the 5' end of alpha-ENaC1, whereas exon 1B arises separately and continues into exon 2 to form alpha-ENaC2. Other variant mRNAs, alpha-ENaC3 and alpha-ENaC4, are formed by activating 5' splice sites within exon 1B. Although alpha-ENaC3 and -4 did not change the open reading frame for alpha-ENaC, alpha-ENaC2 contains upstream ATGs that add 59 amino acids to the previous (alpha-ENaC1) protein. To address the significance of these isoforms, both proteins were expressed in Xenopus oocytes. The cRNA for each alpha-ENaC transcript when combined with beta- and gamma-ENaC cRNA reconstituted a low-conductance ion channel with amiloride-sensitive currents of similar characteristics. We have thus identified variant alpha-ENaC mRNAs that lead to functional ENaC peptides.

Amino Acid Sequence↗
PubMed1996

The Hytrin Community Assessment Trial study: a one-year study of terazosin versus placebo in the treatment of men with symptomatic benign prostatic hyperplasia. HYCAT Investigator Group.

OBJECTIVES: To determine the clinical effectiveness and safety of alpha(1)-blockade therapy versus placebo in the treatment of men with moderate to severe symptoms of prostatism in a community-based population under usual care conditions. METHODS: The Hytrin Community Assessment Trial is a prospective, placebo-controlled, randomized, double-blinded, 1-year clinical trial, conducted at 15 academic medical centers (regional sites) and 141 private urology practices (satellite sites). A total of 2084 men at least 55 years old with moderate to severe symptoms of benign prostatic hyperplasia (BPH) as determined by an American Urological Association (AUA) Symptom Score (AUA-SS) of 13 or more points and a bother score (AUA-BS) of 8 or more were enrolled. Randomized patients at regional sites were required to have a peak urinary flow rate less that 15 mL/s with voided volume of at least 150 mL. Treatment with terazosin was initiated with 1 mg daily for 3 days, followed by 2 mg daily for 25 days. Thereafter, patients were titrated stepwise to 5 or 10 mg if they failed to achieve a 35% or greater improvement in the AUA-SS. Primary outcome measures were AUA-SS, AUA-BS, BPH Impact Index (BII), disease-specific quality of life (QQL) score, and treatment failure as defined as discontinuation due to persistent or worsening symptoms or need for surgical intervention for BPH. Secondary outcome measures were peak urinary flow rate and postvoid residual urine volume. RESULTS: AUA-SS (0 to 35 point scale) improved from a baseline mean of 20.1 points by 37.8% during terazosin (n=976) and by 18.4% during placebo (n=973) treatment (P<0.001). Similarly, statistically superior improvements were observed in regard to the AUA-BS, BII, and the QQL score in the terazosin-treated patients. Peak urinary flow rate improved from a baseline of 9.6 mL/s (both regional treatment groups) by 2.2 mL/s in the terazosin group (n=137) and by 0.7 mL/s in the placebo group (n=140) (P< or = 0.05). Treatment failure occurred in 11.2% of terazosin- and 25.4% of placebo-treated patients (P<0.001; Kaplan-Meier adjusted withdrawal rates of 365 days). Withdrawal from study drug treatment due to adverse events occurred in 19.7% of terazosin- and 15.2% of placebo-treated patients (P<0.001). CONCLUSIONS: Terazosin given once daily in a dose ranging from 2 to 10 mg in community-based urology practices under conditions simulating usual care is effective in reducing the symptoms, perception of bother, and the impairment of QQL due to urinary symptoms in men with moderate to severe symptoms of prostatism. This effect is superior to placebo and maintained over 12 months of follow-up. Clinical research outcome studies in BPH can be conducted in community-based practices, thus simulating as closely as possible "usual care" conditions.

Adrenergic alpha-Antagonists↗
PubMed1996

Architecture of coatomer: molecular characterization of delta-COP and protein interactions within the complex.

Coatomer is a cytosolic protein complex that forms the coat of COP I-coated transport vesicles. In our attempt to analyze the physical and functional interactions between its seven subunits (coat proteins, [COPs] alpha-zeta), we engaged in a program to clone and characterize the individual coatomer subunits. We have now cloned, sequenced, and overexpressed bovine alpha-COP, the 135-kD subunit of coatomer as well as delta-COP, the 57-kD subunit and have identified a yeast homolog of delta-COP by cDNA sequence comparison and by NH2-terminal peptide sequencing. delta-COP shows homologies to subunits of the clathrin adaptor complexes AP1 and AP2. We show that in Golgi-enriched membrane fractions, the protein is predominantly found in COP I-coated transport vesicles and in the budding regions of the Golgi membranes. A knock-out of the delta-COP gene in yeast is lethal. Immunoprecipitation, as well as analysis exploiting the two-hybrid system in a complete COP screen, showed physical interactions between alpha- and epsilon-COPs and between beta- and delta-COPs. Moreover, the two-hybrid system indicates interactions between gamma- and zeta-COPs as well as between alpha- and beta' COPs. We propose that these interactions reflect in vivo associations of those subunits and thus play a functional role in the assembly of coatomer and/or serve to maintain the molecular architecture of the complex.

Amino Acid Sequence↗
PubMed1995

Mother-child dialogue about emotions and preschoolers' emotional competence.

Conversations about emotions between preschoolers and their mothers constitute an important form of shared meaning. As groundwork for a child's developing theory of mind, such conversations are expected to predict aspects of children's emotional competence. Forty-seven preschoolers and their mothers looked at a picturebook in which characters displayed emotions on almost every page; although the emotions were central to the plot, it was up to each mother and child (dyad) whether to discuss them or not. Conversations were transcribed and coded for frequency and function of emotional language as well as for specific emotions to which both mother and child referred. In general, mothers talked more than their children did about emotions, yet the frequency of emotional utterances that served as simple comments or to guide the other's behavior did not differ for mothers and children. As expected, patterns of emotional language of mothers and children were related to indices of positive social-emotional development.

Child, Preschool↗
PubMed1994

Interrater agreement for diagnosis of Alzheimer's disease: the MIRAGE study.

There are standardized criteria to assist in the diagnosis of Alzheimer's disease (AD), a disorder that lacks unique clinical, morphologic, or biochemical features. Diagnostic reliability of single groups of investigators using these criteria is moderate to substantial. In this study, seven clinicians at separate sites established a criteria-based diagnosis in 42 consecutive memory disorder patients participating in a national genetic epidemiologic study using a quantitative multiaxis AD rating scale (ADRS) that incorporates NINCDS/ADRDA criteria, reliability of information, and comorbidity. Reliability, measured by a generalized kappa statistic for more than two raters, was substantial (0.63 +/- 0.13) when the subjects were grouped as "AD" (probable or possible) versus "not AD," but somewhat lower (0.52 +/- 0.10) when subjects were classified as probable AD, possible AD, or not AD. There was unanimous agreement for two-thirds of the subjects using a dichotomous classification scheme. These findings suggest that the ADRS is a useful diagnostic instrument for multicenter studies.

Alzheimer Disease↗
PubMed1993

Nucleotide sequences of the trpI, trpB, and trpA genes of Pseudomonas syringae: positive control unique to fluorescent pseudomonads.

A 904-bp probe from Pseudomonas aeruginosa was used to identify the trpB, trpA and trpI genes of Pseudomonas syringae. Transcription initiation at the P. syringae trpBA promoter in vitro was activated by the P. aeruginosa TrpI protein in the presence of indoleglycerol phosphate. Thus, trpB and trpA are regulated positively in three species of fluorescent pseudomonads, P. aeruginosa, P. putida, and P. syringae, but in no other eubacteria so far investigated [Crawford, Annu. Rev. Microbiol. 43 (1989) 567-600]. In addition to conservation of protein-coding sequences, there is a high degree of nucleotide sequence identity in the intergenic control region that includes the divergent trpI and trpBA promoters, especially in the binding sites for TrpI protein. Differences in patterns of codon usage distinguish the trpI genes of P. syringae and P. putida from P. aeruginosa trpI and from the trpB and trpA genes of all three species.

Amino Acid Sequence↗
PubMed1993

Membrane topology of the 22 kDa integral peroxisomal membrane protein.

In order to study the membrane topology and the possible function of the rat liver 22 kDa integral peroxisomal membrane protein (PMP 22) at a molecular level, we have cloned PMP 22 from a lambda gt11 expression library and sequenced its cDNA. Hydropathy analysis of the deduced primary structure indicates 4 putative transmembrane segments. The accessibility to exogenous aminopeptidase of PMP 22 in intact peroxisomes suggests that the N-terminus faces the cytosol. A model of the topology of PMP 22 in the peroxisomal membrane is discussed. Homology studies revealed a striking similarity with the Mpv 17 gene product. Lack of this membrane protein causes nephrotic syndrome in mice.

Amino Acid Sequence↗
PubMed1992

Gamma-COP, a coat subunit of non-clathrin-coated vesicles with homology to Sec21p.

Constitutive secretory transport in eukaryotes is likely to be mediated by non-clathrin-coated vesicles, which have been isolated and characterized [(1989) Cell 58, 329-336; (1991) Nature 349, 215-220]. They contain a set of coat proteins (COPs) which are also likely to exist in a preformed cytosolic complex named coatomer [(1991) Nature 349, 248-250]. From peptide sequence and cDNA structure comparisons evidence is presented that one of the subunits of coatomer, gamma-COP, is a true constituent of non-clathrin-coated vesicles, and that gamma-COP is related to sec 21, a secretory mutant of the yeast Saccharomyces cervisiae.

Amino Acid Sequence↗
PubMed1992

A randomized, placebo-controlled multicenter study of the efficacy and safety of terazosin in the treatment of benign prostatic hyperplasia.

The clinical manifestations of benign prostatic hyperplasia (BPH) are related primarily to bladder outlet obstruction resulting from enlargement of the prostate gland. Transurethral prostatectomy is the most common treatment currently offered for BPH in the United States. The primary objective of the present randomized placebo controlled multicenter study was to determine the efficacy and safety of terazosin, a selective long-acting alpha 1-blocker, for the treatment of symptomatic BPH. A total of 285 men with symptomatic BPH was randomly assigned in equal proportions to receive placebo, or 2, 5 or 10 mg. terazosin administered once daily. Of the patients 237 completed the 4-week single-blind placebo lead-in and 12-week double-blind treatment periods. The primary outcome parameters were changes in peak and mean urinary flow rates, and changes in the Boyarsky symptom scores. All terazosin treatment groups exhibited significantly greater decreases in total Boyarsky symptom score than the placebo group. The 10 mg. terazosin group exhibited significantly greater increases in peak and mean urinary flow rates than the placebo group. The improvements in symptom scores and urinary flow rates did not reach a plateau within the dose range evaluated, suggesting that further efficacy may be achieved with doses of terazosin exceeding 10 mg. This study unequivocally demonstrates the safety and efficacy of terazosin for the treatment of BPH. Selective alpha 1-blockade is likely to gain widespread acceptance for the treatment of BPH due to its safety and efficacy.

Adrenergic alpha-Antagonists↗
PubMed1988

Phencyclidine (PCP) injected in the nucleus accumbens increases extracellular dopamine and serotonin as measured by microdialysis.

Phencyclidine (PCP; 20 micrograms in 0.5 microliter) was tested by local brain injection for neurochemical effects in the nucleus accumbens and striatum of rats. Changes in dopamine turnover could not be detected in postmortem tissue assays. In contrast, extracellular levels of dopamine significantly increased as measured by microdialysis in freely moving animals. PCP also increased extracellular levels of serotonin and decreased 3,4-dihydroxyphenylacetic acid (DOPAC), but did not change homovanillic acid (HVA) or 5-hydroxyindoleacetic acid (5HIAA). Microdialysis suggests that PCP acts in some dopamine terminal regions to increase extracellular dopamine and serotonin.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Relationship between lesion extent in 'Wernicke's area' on computed tomographic scan and predicting recovery of comprehension in Wernicke's aphasia.

This study investigated the relationship between severity of auditory comprehension in Wernicke's aphasia and amount of temporal lobe damage within Wernicke's area (posterior two thirds of superior temporal gyrus region) as well as the total temporoparietal lesion size. There was a highly significant correlation between comprehension and the amount of temporal lobe lesion in Wernicke's area. There was no significant correlation between comprehension and the total temporoparietal lesion size. Patients with damage in only half or less than half of Wernicke's area had good comprehension at six months after the onset of stroke. Patients with damage in more than half of Wernicke's area had poor comprehension even one year after the onset of stroke. Additional anterior-inferior temporal lobe lesion extension into the middle temporal gyrus area was associated with particularly poor recovery.

Aged↗
PubMed1987

Denervation of serotonergic fibers in the hippocampus induced a trophic factor which enhances the maturation of transplanted serotonergic neurons but not norepinephrine neurons.

The trophic effects of specific denervation on the growth and survival of fetal serotonergic (5-HT) or norepinephrinergic (NE) neurons grafted into the hippocampus were assessed by means of two transplantation paradigms. In the first, fetal raphe cells (containing 5-HT neurons) were transplanted into the control hippocampus. In the second, the transplantation was performed 2 weeks after the specific removal of 5-HT afferents to the hippocampus with 5,7-dihydroxytryptamine (5,7-DHT). We found that a month after transplantation, the number of 5-HT immunoreactive neurons was not significantly different between the two experimental paradigms. However, transplanted raphe neurons had 400% more 5-HT synaptosomal high-affinity uptake and 380% higher content of 5-HT in the hippocampus with prior 5,7-DHT lesion than in control hippocampus. Furthermore, immunocytochemistry showed that the transplanted 5-HT neurons had denser processes and varicosities in the hippocampus with lesion than in control hippocampus. The somatic area of the neurons with these denser processes and varicosities was 42% larger than that of control group. A greater 5-HT level could be achieved if transplanted neurons in the control hippocampus were treated with the supernatant extracted from the hippocampus with 5,7-DHT lesion. In contrast, the NE level of the implanted fetal locus ceruleus (containing NE neurons) was not significantly higher in the 5-HT denervated hippocampus than in control hippocampus a month after transplantation. These results suggest that 5-HT denervation in the hippocampus induces a trophic substance which promotes the maturation rather than survival of 5-HT neurons but not NE neurons.

5,7-Dihydroxytryptamine↗
PubMed1987

Total phosphate determination in brain tissues: a method for regional determination of total phosphate in rat brain.

A quantitative microassay method is described for brain tissue phosphates. Based on molybdate colorimetric measurements of inorganic phosphate in tissue solutions prepared by acid digestion and high temperature ashing, the method includes the use of calcium to precipitate inorganic phosphate in acid-digested tissues and a correction for contaminants released from porcelain crucibles during the ashing procedure. This method was used to measure the total tissue phosphate concentrations in regional microsamples of rat brain. Averaged values derived from these regional measurements were 100.1 +/- 10.2 mumol/gm wet tissue weight, corresponding closely to whole brain tissue phosphate values reported in the literature. Phosphate concentrations were remarkably uniform in different areas of the cortex and basal ganglia.

Animals↗