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Biomedical subjects

A Melman

Publications and source records attributed to A Melman.

At least 19 recordsLinked to original sources
PubMed2001

Polyethylated aromatic rings: conformation and rotational barriers of 1,2,3,4,5,6,7,8-octaethylanthracene, 1,2,3,4,6,7,8-heptaethylfluorene, and 1,2,3,4,5,6,7,8-octaethylfluorene.

1,2,3,4,5,6,7,8-Octaethylanthracene (5), 1,2,3,4,6,7,8-heptaethylfluorene (7), and 1,2,3,4,5,6,7,8-octaethylfluorene (8) were synthesized by Friedel-Crafts ethylations of 9,10-dihydroanthracene and fluorene. MM3 calculations indicate that the two ethylated six-membered rings of 5 and 7 are conformationally independent. According to the calculations, two low-energy conformers of each compound are possible with the ethyl groups attached to the external aryl rings arranged in an alternated "up-down" orientation. MM3 calculations indicate that in the lowest energy conformation the central fluorene core of 8 adopts a twisted conformation to avoid repulsive steric interactions between the ethyls at the bay region. Two fully alternated up-down conformations are possible for 8, differing in the orientation ("in" or "out") of the ethyls in the bay region. MM3 calculations predict that the lowest energy conformer is the fully alternated "out" form of C(2)() symmetry. The rotational barriers of 5, 7, and 8 are in the 8.7-11.3 kcal mol(-1) range, the largest barrier corresponding to the more crowded octaethylfluorene 8. Anthracene 5 adopts in the crystal a conformation of approximate C(2)(h) symmetry with pairs of peri groups on the same edge of the molecule oriented syn. The conformations adopted in the crystal by 7 and 8 do not correspond to the calculated lowest energy form. In the conformation of 7 in the crystal the ethyl groups on the trisubstituted ring adopt the unusual all syn arrangement. Octaethylfluorene 8 adopts a conformation with a twisted central fluorene core but with a syn arrangement of a pair of vicinal ethyl groups.

Journal Article↗
PubMed2001

Integrative erectile biology. The effects of age and disease on gap junctions and ion channels and their potential value to the treatment of erectile dysfunction.

Initiation, maintenance, and modulation of corporal smooth muscle tone are critically dependent upon agonist-induced changes in intracellular calcium levels and mobilization as well as transmembrane calcium flux. The transient control of myocyte excitability and contractility at the cellular level is inextricably linked to membrane potential, which, in turn, is modulated by potassium ion efflux through one of the four known corporeal smooth muscle potassium ion channels. Corporal tissue responses are subsequently coordinated by means of the movement of intracellular second messenger molecules (i.e., IP3, cAMP, cGMP) and ions (i.e., K+ and Ca2+) among the corporal myocytes by means of intercellular communication through gap junction channels. Knowledge of the critical contribution of these interlinking cellular (nonjunctional ion channels [e.g., maxi-K]) and tissue (gap junction channels [e.g., connexin 43]) systems to the modulation of erectile capacity has provided the scientific rationale for the promulgation of the successful preclinical testing of hSlo ion channel gene therapy for the normalization of erectile status in both aged and diabetic rats.

Aging↗
PubMed2001

Significant physiological roles of ancillary penile nerves on increase in intracavernous pressure in rats: experiments using electrical stimulation of the medial preoptic area.

The objectives of this work were to evaluate the contributions of the ancillary penile nerves to penile erection in male rats in vivo. We investigated the effects of unilateral and bilateral transection of the cavernous nerve (main penile nerve) on the increase in intracavernous pressure (ICP) following electrical stimulation of the medial preoptic area (MPOA) in male rats in vivo. After unilateral or bilateral transection of the cavernous nerve (main penile nerve), the ICP responses showed decreases of 28% and 55%, respectively compared to those ICP responses before transection. In other words, even after bilateral transection of the cavernous nerve, significant increases in the ICP response following central stimulation were observed. In contrast to these findings, the ICP response was completely eliminated following bilateral pelvic nerve transection. These data suggested that the ancillary penile nerves, which originate from the major pelvic ganglia, have a complementary role to the cavernous nerves in the autonomic motor innervation of the penis.

Animals↗
PubMed2000

Priapism of ambiguous classification in a sickle cell patient.

We report a case of recurrent priapism in a sickle cell patient who had undergone physiological transformation from a low-flow state to a mixed high-flow/low-flow picture. An oral alpha-adrenergic agonist/histamine-1 antagonist combination maintained a balance of potency without stutter in the latter state, whereas an oral alpha-adrenergic agonist in the early part of his course did not prevent priapic progression. Concomitant use of a non-steroidal anti-androgenic agent rendered him impotent despite good libido. Other etiologies should be considered in the setting of recurrent priapism and failed standard therapies; duplex ultrasound is useful in order to delineate the hemodynamics. This case supports contentions that priapism is a spectrum phenomenon, and raises questions regarding the mechanism by which alpha-adrenergic agents prevent priapic progression.

Adrenergic alpha-Agonists↗
PubMed2000

Experimental hyperprolactinemia in a rat model: alteration in centrally mediated neuroerectile mechanisms.

INTRODUCTION: The purpose of this study was to induce hyperprolactinemia in adult male rats and determine its effect on the central and peripheral mediated neurogenic as well as myogenic mechanisms of erectile function/dysfunction in a rat model. The use of penile reflexes in awake animals was used to test the effect of both central and peripheral mechanisms. Electrical stimulation of the cavernous nervous was used to test peripheral neural function and intracorporal injection of papaverine was used to test the intactness of the corporal smooth muscles. These mechanisms were further explored by administration of testosterone. METHODS: Eighteen Fisher-344 200-250 g rats aged 10 weeks were used in this study. Group 1 (n = 6) hyperprolactinemia was induced with subcutaneous (SQ) injection of 5 mg rat prolactin (NIDDK-r-PRL-B-7, biopotency 25 IU/mg) in two divided doses daily for 1 week. Testosterone propionate 100 mg/kg dissolved in sesame oil was given intramuscularly on day 1 (weekly dose). Group 2 (n = 6) control animals received SQ injection of vehicle twice daily and sesame oil I/M on day 1. Group 3 (n = 6) received testosterone propionate. Penile reflexes (erections, cups, flips and clusters) were assessed prior to induction (x 3) of and following one-week state of hyperprolactinemia (day 5, 6 and 7). All animals were trained three times before recording the penile reflexes. The penile reflexes being averaged to give a single composite score for each animal. All animals underwent dissections that isolated the cavernosal bodies and cavernosal nerves. Cavernous nerves were activated and intracorporal pressures were recorded at increasing current magnitude (range 0.5-10 mA). Following that corporal smooth muscle reactivity was determined by increasing injection of papaverine (100-3000 microg). Concentration response curves (CRCs) were then generated by plotting percent change (fractional change to make standardized comparison) to increasing neurostimulation or papaverine concentrations at half-log increments. Serum prolactin was determined by rPRL radioimmunoassay Kit-Amersham while serum testosterone was determined Testosterone ELISA Kit-Neogen. RESULTS: Penile reflexes were normal in all groups at the start of experiment but after 1 week of hyperprolactinemia, reflexes were totally abolished in hyperprolactinemia rats (Group 1) and unchanged in Groups 2 and 3. Response to cavernous nerve activation and resulting rise in intracorporal pressure to increasing current (range 0.5-10 mA) were statistically non-significant in any groups. Similarly the intracorporal pressure response to pharmacologic erection induced by papaverine (100-3000 microg) were also non-statistically significant in any groups. Serum prolactin level in all rats receiving prolactin were > 500 ng/ml and the rat group receiving testosterone, serum level were > 20 x higher than the control rat. CONCLUSIONS: This approach allowed more clear separation of central and peripheral mechanism of erection. This study shows a central neurological effect of hyperprolactinemia on erectile function. Hypogonadism does not seem to contribute to the impaired penile reflexes as documented by replacement of testosterone did not recover the centrally mediated penile reflexes. Lowered serum testosterone is secondary phenomenon. These observations may have important implications for the understanding, the mechanism and treatment of men with hyperprolactinemia as well as future research in this field.

Animals↗
PubMed2000

The genetics and immunology of Peyronie's disease.

Peyronie's disease (PD) is a condition characterized by localized and often progressive fibrosis and scarring of the penis. This condition has an unknown etiology although several hypotheses have been proposed. These include traumatic, immunologic and genetic causes. We studied the genetics and immunology of PD using both molecular biologic and molecular genetic techniques. Men (n=283) with PD were identified by retrospective chart review of one physician's office practice. These men were contacted by telephone and asked to submit to an interview and blood test for genetic studies. Simultaneously, tissue and cells collected in the laboratory were examined by Western and Northern blot analysis for examination of protein and RNA for expression of HLA. Of the first 107 men contacted, 24 were available and consented to interview and blood testing. The mean age was 60.3 y with an average duration of PD of 4.9 y. One patient had a family history of PD while no patients had Dupuytren's contracture. Twenty patients were considered to have primary disease while four were secondary. Eleven patients had tissue prepared for Northern blot analysis and nine patients were the subject of Western blot analysis. All tissue, both Peyronie's and control expressed class I MHC while no tissue expressed class II MHC. The expression of mRNA of class I MHC was equal for Peyronie's and control patients while the expression at the protein level was less in the PD patients. We conclude that PD may have multiple etiologic agents. One cannot exclude a class II MHC association but in our population, HLA DQ is not expressed. Class I MHC may be involved as the expression of class I MHC protein is different in Peyronie's patients than in controls. Genetic studies are ongoing. International Journal of Impotence Research (2000) 12, Suppl 4, S127-S132.

Aged↗
PubMed2000

Priapism.

Priapism is a prolonged, painful, penile erection that fails to subside despite orgasm. An erection lasting longer than 4-6 h is considered to be priapic; nevertheless, pain does not usually ensue until 6-8 h have elapsed. Priapism is considered a failure of the detumescence mechanism, which may be due to excess release of contractile neurotransmitters, obstruction of draining venules, malfunction of the intrinsic detumescence mechanism, or prolonged relaxation of intracavernosal smooth muscle. There are essentially two main types of priapism: high flow (non-ischemic) and low flow (ischemic). Low flow priapism is the more common form, and it is associated with a decrease in venous outflow and vascular stasis that, in turn, cause tissue hypoxia and acidosis. This form of priapism is usually quite painful because of tissue ischemia. Penile blood aspirated from cavernous spaces appears dark in color. Immediate treatment is necessary or penile fibrosis will ensue. High flow priapism is usually due to trauma, although, on rare occasions it has been idiopathic or due to sickle cell disease. The hallmark of this type of priapism is an increase in arterial inflow in the setting of normal venous outflow. Aspirated penile blood is noted to be bright red and has a high pO(2). This form of priapism is not usually painful because it is non-ischemic. Treatment is dependent on the wishes of the patient but is not mandatory. International Journal of Impotence Research (2000) 12, Suppl 4, S133-S139.

Humans↗
PubMed1999

Modification of sexual behavior of Long-Evans male rats by drugs acting on the 5-HT1A receptor.

Modulation of the sexual behavior of male rats by the anxiolytic buspirone (S-20499) and its analog gepirone were compared to the effects of 8-OH-DPAT (or DPAT, a selective 5-HT1A reference agonist), and BMY-7378 (a selective 5-HT1A partial agonist). Long-Evans rats were used; modulation of copulatory behavior and alteration of penile reflexes were examined. Modulation of copulatory behavior was assessed by three indices: frequency and length of intromission, and latency of ejaculation. DPAT, at doses of 1-8 mg/kg, reduced these three indices in a time dependent manner such that the effects peaked at 45 min and normalized at 90 min. The dose-effect relationship (assessed 45 min after DPAT injection) is bell-shaped with an ED50 approximately 1 mg/kg on the ascending limb of the curve. The effects of buspirone (2 mg/kg) and gepirone (2 mg/kg) on copulatory behavior were indistinguishable from control. BMY-7378 alone and in combination with these other 5-HT1A agonists reduced copulatory behavior, though not statistically significant. Penile reflexes, including number of erections, cups and flips, were inhibited by these agents: DPAT>buspirone>gepirone (inactive at 2 mg/kg). Furthermore, the latency period to erection was at least doubled by DPAT (2 mg/kg). Buspirone and gepirone, however, reduced the latency period to erection. BMY-7378 inhibited penile reflexes when administered alone and even more in combination with DPAT or buspirone. Two butyrophenone analogs, spiperone (a 5-HT1A and dopamine D2 antagonist) and haloperidol (a D2 antagonist), were also tested for their interaction with DPAT. Both of these drugs (at 0.25 mg/kg, 60 min after administration) reduced all indices of penile reflexes and copulation. Furthermore, in combination with DPAT (2 mg/kg, 45 min), the effects were synergistic such that sexual activity came nearly to a standstill. These opposing effects on putatively brain originated copulatory behavior and spinal mediated penile reflexes indicate that the effects of buspirone and DPAT on sexual behavior in the male rat may be possible at different parts of the central nervous system. If a tentative shared target site by DPAT and buspirone is the 5-HT1A receptor, than the same 5-HT receptor sub-type at different locations (brain, raphe nuclei, spinal cord and autonomic ganglia) may modulate rat sexual behavior in opposing ways.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1999

Pelvic arteriovenous malformation mimicking seminal vesicle cyst.

Congenital pelvic arteriovenous malformations are rare entities, especially in males. Presenting symptoms, if any at all, are commonly a mass, thrill, bruit, or pain. Treatment options include surgical extirpation, embolization, or a combination of both. This case provides support for the last option in a patient presenting with symptoms localized to the seminal vesicles.

Adult↗
PubMed1999

Serum prostate-specific antigen and prostate volume predict long-term changes in symptoms and flow rate: results of a four-year, randomized trial comparing finasteride versus placebo. PLESS Study Group.

OBJECTIVES: To determine whether baseline prostate-specific antigen (PSA), in addition to prostate volume, is associated with long-term changes in symptoms and urinary flow rate. METHODS: Three thousand forty men with benign prostatic hyperplasia enrolled in the PLESS trial were randomly assigned to finasteride 5 mg or placebo for 4 years. Symptoms and flow rate were assessed every 4 months, and data were analyzed by dividing the patients into three groups by baseline PSA tertiles (0 to 1.3, 1.4 to 3.2, and 3.3 ng/mL or greater) and baseline prostate volume tertiles (14 to 41, 42 to 57, and 58 to 1 50 mL). RESULTS: After the initial placebo effect, a slow deterioration in symptoms over time was observed in the placebo-treated men with a baseline PSA 1.4 ng/mL or greater. However, placebo-treated men in the lowest PSA tertile (less than 1.4 ng/mL) had sustained symptomatic improvement that was not seen in placebo-treated men in the higher tertiles (P<0.001). In all finasteride-treated groups, there was initial improvement followed by maintenance or continued symptom improvement over time (approximately 3 to 3.5 points by the end of 4 years). The differences in symptom score improvement between placebo and finasteride were marginal for men with baseline PSA levels less than 1.4 ng/mL (P = 0.128) but were highly significant for men with PSA levels 1.4 ng/mL or greater (P<0.001). Urinary flow rate results were similar to those observed for symptoms. Analysis of symptom and flow rate data by prostate volume tertiles in a 10% subset of men yielded similar results, namely a deterioration of symptoms and flow rate in the two higher tertiles treated with placebo (greater than 41 mL) and a sustained improvement in all three groups of finasteride-treated patients. CONCLUSIONS: Baseline PSA and prostate volume are good predictors of long-term symptomatic and flow rate changes. Baseline PSA levels of 1.4 ng/mL or greater and enlarged prostate glands predict the best long-term response to finasteride compared with placebo.

Enzyme Inhibitors↗
PubMed1999

The reported sex and surgery satisfactions of 28 postoperative male-to-female transsexual patients.

From 1980 to July 1997 sixty-one male-to-female gender transformation surgeries were performed at our university center by one author (A.M.). Data were collected from patients who had surgery up to 1994 (n = 47) to obtain a minimum follow-up of 3 years; 28 patients were contacted. A mail questionnaire was supplemented by personal interviews with 11 patients and telephone interviews with remaining patients to obtain and clarify additional information. Physical and functional results of surgery were judged to be good, with few patients requiring additional corrective surgery. General satisfaction was expressed over the quality of cosmetic (normal appearing genitalia) and functional (ability to perceive orgasm) results. Follow-up showed satisfied who believed they had normal appearing genitalia and the ability to experience orgasm. Most patients were able to return to their jobs and live a more satisfactory social and personal life. One significant outcome was the importance of proper preparation of patients for surgery and especially the need for additional postoperative psychotherapy. None of the patients regretted having had surgery. However, some were, to a degree, disappointed because of difficulties experienced postoperatively in adjusting satisfactorily as women both in their relationships with men and in living their lives generally as women. Findings of this study make a strong case for making a change in the Harry Benjamin Standards of Care to include a period of postoperative psychotherapy.

Adaptation, Psychological↗
PubMed1999

A stretch-sensitive Cl- channel in human corpus cavernosal myocytes.

With the patch clamp method we demonstrate a stretch-sensitive Cl- currents as well as stretch-sensitive Cl- channels in a small group (5%,n 117) of cultured human corpus cavernosal muscle cells. The current and the channel activities had the following characteristics: (1) Their equilibrium potentials changed with extracellular Cl- concentration close to that predicted by Nernst equation provided that the relevant channels had high permeability to Cl- but low permeability to acetate ions; (2) They were blocked by mM concentrations of Zn2+; (3) The i-v relation of single channel current was almost linear for holding potentials varied from -70 to +60 mV; and (4) The channels had unitary conductances of approximately 140-170 pS.

Acetates↗
PubMed1999

The epidemiology and pathophysiology of erectile dysfunction.

PURPOSE: Published studies on the epidemiology of erectile dysfunction and the physiology/ pathophysiology of erectile function are reviewed. MATERIALS AND METHODS: A literature search of more than 400 studies of the epidemiology and pathophysiology of impotence and erectile dysfunction published during the last 3 decades was conducted and the most pertinent articles are discussed. RESULTS: It has been estimated that the prevalence of erectile dysfunction of all degrees is 52% in men 40 to 70 years old, with higher rates in those older than 70 years. Erectile dysfunction has a significant negative impact on quality of life. Risk factors for erectile dysfunction include aging, chronic illnesses, various medications and cigarette smoking. A nitric oxide/cyclic guanosine monophosphate mechanism has an important role in mediating the corporal smooth muscle relaxation necessary for erectile function. Other mechanisms involving neuropeptides, gap junctions and ion channels also may modulate corporal smooth muscle tone. Erectile dysfunction can be due to vasculogenic, neurogenic, hormonal and/or psychogenic factors as well as alterations in the nitric oxide/cyclic guanosine monophosphate pathway or other regulatory mechanisms, resulting in an imbalance in corporal smooth muscle contraction and relaxation. CONCLUSIONS: Erectile dysfunction is a common condition associated with aging, chronic illnesses and various modifiable risk factors. Normal penile erection is a hemodynamic process that is dependent on corporal smooth muscle relaxation mediated by parasympathetic neurotransmission, nitric oxide, and possibly other regulatory factors and electrophysiological events. As more knowledge is gained of the physiology and regulatory factors that mediate normal erectile function, the mechanisms involved in the pathophysiology of erectile dysfunction should be further elucidated.

Erectile Dysfunction↗
PubMed1999

Formation of neoclitoris from glans penis by reduction glansplasty with preservation of neurovascular bundle in male-to-female gender surgery: functional and cosmetic outcome.

PURPOSE: During male-to-female gender reassignment surgery we used an abdominal pedicled inverted penile skin technique to create a vagina and extra folds of skin to create a clitoral hood. Although patients had orgasms with that technique, there was a general request for the placement of a sensate, erectile clitoris. Therefore, in 10 such patients undergoing transsexual surgery a neoclitoris was fashioned from the glans penis. Surgical technique and results are described. MATERIAL AND METHODS: From 1980 to 1995, 57 male-to-female gender surgeries were performed at our university center. In the last 10 such patients undergoing transsexual surgery a neoclitoris was created. Glans volume is reduced to match that of a normal size clitoris and the entire length of the dorsal neurovascular bundle is preserved. The neoclitoris is placed through a buttonhole in the newly constructed introitus. There was minimal bleeding from the bundle intraoperatively. RESULTS: In 8 of 10 patients the neoclitoris remained intact postoperatively with good sensation to touch, vibration and light pressure (sexual sensation). The cosmetic and functional appearance was that of a normal clitoris, and patients were satisfied. In 2 patients the results were not satisfactory because of necrosis of the neoclitoris. CONCLUSIONS: This technique has excellent functional and cosmetic results in the majority of patients. Preservation of the somatic, tactile and vibratory sensation of the neoclitoris is surgically practical, and can afford the patient the possibility of a more functional outcome of gender reassignment surgery.

Adult↗
PubMed1999

Suppression of renal inflammation with vitamins A and E in ascending pyelonephritis in rats.

PURPOSE: We evaluated the effects of vitamin A and E supplementation alone or in combination with non-steroidal anti-inflammatory drugs (NSAIDs) on the development of inflammation in an animal model of ascending pyelonephritis. MATERIALS AND METHODS: Ascending pyelonephritis was induced in adult rats by surgical bladder inoculation with P-pili-forming Escherichia coli. Treatment of pyelonephritic rats was initiated at 72 hours post-infection. Treatment groups included no treatment, or a five day regimen of antibiotic only, antibiotic plus vitamins A and E, or antibiotic, vitamins and either of two NSAIDs. Kidneys were harvested at six weeks post-infection and assessed for histopathologic inflammation. RESULTS: Antibiotic treatment of pyelonephritic rats with vitamins A and E alone or in combination with NSAIDs resulted in significantly less kidney inflammation, as compared with untreated rats or rats treated with antibiotic alone. There was no significant difference in inflammation between animals treated with vitamins alone or vitamins plus NSAIDs. CONCLUSIONS: Antibiotic therapy and diet supplementation with vitamins A and E can significantly reduce the inflammation associated with ascending pyelonephritis, suggesting a potential use in the medical management of reflux nephropathy in children.

Animals↗