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Biomedical subjects

I Goldstein

Publications and source records attributed to I Goldstein.

At least 109 records · Page 6Linked to original sources

Cyclic AMP modulates TGF-beta 1-induced fibrillar collagen synthesis in cultured human corpus cavernosum smooth muscle cells.

INTRODUCTION AND OBJECTIVES: The mechanisms by which PGE1 suppresses transforming growth factor beta 1 (TGF-beta 1) induced fibrillar collagen synthesis in human corpus cavernosum smooth muscle cells (HCC SMC) remain undefined. Since PGE1 induces cyclic AMP (cAMP) synthesis in HCC SMC, the aim of this research is to investigate the role of cAMP in the regulation of connective tissue biosynthesis in human corporal smooth muscle cells in culture. MATERIALS AND METHODS: HCC SMC were incubated for 24 h in media containing [3H] proline with and without TGF-beta 1 in the presence or absence of agents which modulate cAMP or cGMP synthesis, or hydrolysis. Fibrillar collagen synthesis was determined by [3H]-proline incorporation into pepsin-resistant, trichloroacetic acid and precipitable protein. RESULTS: TGF-beta 1-induced collagen synthesis in HCC SMC was inhibited by receptor-mediated (PGE1) and non-receptor-mediated (forskolin) increases in cAMP synthesis, as well as the cell-permeable analog, dibutyryl cAMP. Sodium nitroprusside, a nitric oxide donor, and the cell-permeable analog, dibutyryl cGMP had no effect on TGF-beta 1-induced collagen synthesis. CONCLUSIONS: Cyclic AMP synthesis in HCC SMC inhibits TGF-beta 1-induced collagen synthesis. Agents which increase cAMP through specific G-protein-coupled receptors, direct stimulation of adenylate cyclase, or inhibition of phosphodiesterase activity could have beneficial effects as modulators of corpus cavernosum connective tissue biosynthesis.

Cells, Cultured↗

Preliminary report on the development and characterization of rabbit clitoral smooth muscle cell culture.

PURPOSE: Scientific model systems for physiological evaluation and investigation of pathophysiologies in clitoral function have been limited. The aim was to develop a New Zealand White rabbit clitoral corpus cavernosum smooth muscle cell culture. METHODS: Clitoral corpus cavernosum erectile tissue was harvested and placed in culture. Clitoral smooth muscle cells which migrated out from explants were grown to confluence and subcultured. Characterizations were performed by morphological and biochemical analyses. RESULTS: The cells exhibited typical morphologic characteristics of smooth muscle cells. Indirect immunofluorescence studies confirmed the presence of a-smooth muscle cell actin. Androgen and estrogen receptors were detected by specific antibodies and binding studies. The cells expressed subtypes of TGF-beta receptors. Treatment with 80 pM TGF-beta 1 24 h resulted in induction and/or increased availability of TGF-beta receptors. CONCLUSIONS: An in-vitro cell culture system using rabbit clitoral smooth muscle cells was developed. These smooth muscle cells retain their biochemical and functional integrity. This in-vitro cell culture system may facilitate studies aimed at understanding the molecular basis of female sexual function.

Animals↗

Phentolamine mesylate relaxes penile corpus cavernosum tissue by adrenergic and non-adrenergic mechanisms.

AIM OF THE STUDY: We investigated the biochemical and physiological mechanisms of action of phentolamine mesylate (Vasomax) in regulating erectile tissue smooth muscle contractility in human and rabbit corpus cavernosum. METHODS: The binding activity of phentolamine was investigated in a cell-free system by displacement of specific and selective radiolabelled ligands to alpha 1 and 2 adrenergic receptors. The physiologic activity of phentolamine-mediated relaxation of adrenergic and non-adrenergic pre-contracted erectile tissue strips of human and rabbit corpus cavernosum were studied in organ bath chambers. RESULTS: In corpus cavernosum membranes, phentolamine displaced binding of the selective alpha 1 receptor antagonists [125I]HEAT and [3H]prazosin and the alpha 2 receptor antagonists [3H]rauwolscine and [3H]RX 821002 with relatively high affinity. Phentolamine caused concentration dependent relaxation in erectile tissue strips pre-contracted with adrenergic agonists phenylephrine, norepinephrine, oxymetazoline and UK 14,304, as well as with non-adrenergic contractile agents endothelin and KCl. Biochemical and physiologic studies reveal that the concentration of phentolamine required to displace half maximal binding or to produce half-maximal relaxation was similar to that found in human plasma 30 min after ingestion of 40 mg of Vasomax. Reversible inhibition of nitric oxide synthase by L-nitroarginine or mechanical disruption of endothelium diminished non-adrenergic phentolamine-mediated erectile tissue relaxation. CONCLUSIONS: Phentolamine mesylate induced relaxation of corpus cavernosum erectile tissue by direct antagonism of alpha 1 and 2 adrenergic receptors and by indirect functional antagonism via a non-adrenergic, endothelium-mediated mechanism suggesting nitric oxide synthase activation.

Adrenergic alpha-Agonists↗

Growth of the fetal orbit and lens in normal pregnancies.

OBJECTIVE: To construct nomograms of the size of the fetal orbit and lens during gestation. SUBJECTS: The study group included 349 normal pregnant women at 14-36 weeks' gestation. METHODS: Routine biometric measurements were obtained in all the participants; these included biparietal diameter, head and abdominal circumferences, measurements of the long bones and the diameters of the fetal orbit and lens. The orbital and lens circumference measurements were also related to gestational ages. RESULTS: A linear growth function was observed between gestational age (GA) and orbital diameter (r = 0.94; p < 0.00001; y = -0.66 + 0.5 x GA), orbital circumference (r = 0.94; p < 0.00001; y = -2.1 + 1.5 x GA) and orbital area (r = 0.94; p < 0.00001; y = -98.1 + 8.3 x GA). Significant correlation was also found between femoral length (FL) and orbital diameter (r = 0.95; p < 0.00001; y = 3.3 + 1.9 x FL), orbital circumference (r = 0.95; p < 0.00001; y = 10.3 + 5.9 x FL) and orbital area (r = 0.93; p < 0.00001; y = -28.2 + 32.2 x FL). A linear growth function was observed between orbital circumference and biparietal diameter (r = 0.94; p < 0.00001) and head circumference (r = 0.95; p < 0.00001). A linear growth function was also observed between gestational age and the diameter of the lens (r = 0.89; p < 0.00001; y = 0.88 + 1.4 x GA) the circumference of the lens (r = 0.89; p < 0.00001; y = 2.78 + 0.4 x GA) and the area of the lens (r = 0.89; p < 0.00001; y = -7.95 + 1.0 x GA). The correlation was found between the ratios of the diameters, circumferences and areas of the lens and the orbit. CONCLUSIONS: These results provide normative data of the growth of the fetal orbit and lens and may aid future studies relating to fetal eye anomalies.

Adult↗

A possible mechanism for alteration of human erectile function by digoxin: inhibition of corpus cavernosum sodium/potassium adenosine triphosphatase activity.

PURPOSE: Digoxin use has long been recognized to affect adversely male sexual function but the underlying mechanism is poorly understood. Digoxin is a known inhibitor of sodium/potassium adenosine triphosphatase (sodium pump), a plasma membrane enzyme that has a role in the regulation of smooth muscle tone. We investigated the effects of digoxin on human corpus cavernosum smooth muscle contractility and overall erectile function. MATERIALS AND METHODS: In human corporeal smooth muscle strips the in vitro effects of digoxin were assessed on sodium pump activity as measured by digoxin inhibitable uptake of 86rubidium, basal tone and endothelium dependent, neurogenic and nitric oxide donor induced relaxation. An in vivo prospective double-blind, placebo controlled, crossover, 4-period investigation was performed in 6 healthy male volunteers. The effects of digoxin on serum hormones, erectile function questionnaire, visual sexual stimulation and nocturnal penile tumescence were recorded. RESULTS: In vitro digoxin caused concentration dependent inhibition of 86rubidium uptake (half maximum effect at 0.01 microM.) and contraction of corporeal smooth muscle (half maximum effect at 0.8 microM.). Therapeutic concentrations of digoxin (2 nM.) also inhibited relaxation induced by acetylcholine and electrical field stimulation, which release nitric oxide from corpus cavernosum endothelial cells and nonadrenergic noncholinergic nerves, respectively. In vivo digoxin diminished penile rigidity during visual sexual stimulation and nocturnal penile tumescence testing compared to placebo without influencing libido or serum testosterone, estrogen or luteinizing hormone levels. CONCLUSIONS: Digoxin associated alteration of human erectile function may be explained, in part, by inhibition of corporeal smooth muscle sodium pump activity, which promotes contraction and impedes nitric oxide induced relaxation. Such findings suggest therapeutic use of digoxin for treatment of recurrent priapism states.

Adenosine Triphosphate↗

Mechanisms of ischemia-induced cavernosal smooth muscle relaxation impairment in a rabbit model of vasculogenic erectile dysfunction.

PURPOSE: To determine the effects of hypercholesterolemia and atherosclerosis-induced chronic cavernosal arterial insufficiency on cavernosal smooth muscle tone, nitric oxide synthase (NOS) activity and cavernosal tissue synthesis of constrictor eicosanoids. To study whether inhibition of the cyclooxygenase pathway by indomethacin and tissue treatment with nitric oxide (NO) precursor L-arginine improve hypercholesterolemia and ischemia-induced impaired endothelium-dependent and neurogenic relaxation of cavernosal tissue. MATERIALS AND METHODS: New Zealand White rabbits were divided into control (n = 10, fed a regular diet), hypercholesterolemia (Hch, n = 13, fed a diet containing 0.5% cholesterol) and chronic cavernosal ischemia (CCI, n = 14) groups. The CCI group underwent balloon deendothelialization of iliac arteries and received a diet containing 0.5% cholesterol. After 16 weeks, we examined the effects of Hch and balloon de-endothelialization induced arterial occlusive disease on iliac arterial blood flow, reactivity of cavernosal tissue, cavernosal NOS activity and cavernosal tissue synthesis of constrictor eicosanoids. RESULTS: Histology revealed significant atherosclerotic arterial occlusive disease in the CCI group. Iliac artery blood flow in the CCI group was significantly reduced compared with the control and Hch groups. In the Hch and CCI groups, endothelium-dependent relaxation of cavernosal tissue to acetylcholine was significantly reduced compared with the control group. Electrical field stimulation-induced neurogenic relaxation and cavernosal NOS activity were significantly reduced in the CCI group but not in the Hch group. The basal release of cavernosal constrictor eicosanoids, prostaglandin F2alpha (PGF2alpha) and thromboxane A2 (TXA2) was significantly increased in the CCI group. Indomethacin increased endothelium-dependent relaxation in all groups and neurogenic relaxation in the CCI group, but failed to normalize the differences in relaxation between treated and control groups. In the presence of indomethacin, L-arginine improved endothelium-dependent relaxation of cavernosal tissue in the Hch group but did not normalize endothelium-dependent or neurogenic relaxations in the CCI group. Relaxation to NO donor sodium nitroprusside and papaverine was similar in cavernosal tissue from all groups. CONCLUSIONS: Impairment of endothelium-dependent relaxation by Hch occurs secondary to disruption of the NO formation in cavernosal endothelium. Improvement of endothelium-dependent relaxation by L-arginine may suggest lack of availability of L-arginine in cavernosal tissue from the Hch animals. Impairment of endothelium-dependent and neurogenic relaxation by CCI occurs secondary to disruption of the NO formation due to an alteration in the expression or activity of NOS and increased output of constrictor eicosanoids in cavernosal tissue. These studies show that Hch and atherosclerosis-induced chronic cavernosal arterial insufficiency, beyond decreasing cavernosal perfusion pressure, also adversely affect smooth muscle relaxation mechanisms in cavernosal tissue.

Animals↗

Sexual dysfunction associated with the management of prostate cancer.

Improvements in the management of prostate cancer have increased the need to consider patients' quality of life, in particular in relation to sexual function. The causes of sexual dysfunction are varied and derive from both the condition and its management. Health professionals must choose their treatment strategies with great care. Patient expectations must be understood, and patients should be offered counselling, as an understanding of what can reasonably be expected contributes to patients' perception of their quality of life. There are few studies on sexual dysfunction in patients with prostate cancer. A first step would be to develop reliable questionnaires for the assessment of the problem. This article describes and discusses the findings of one such recently developed questionnaire. When baseline measures of sexual function have been established and the extent of sexual dysfunction in patients with prostate cancer is reliably quantified, large multicentre trials can be performed to evaluate the impact of different therapies on sexual function and quality of life. Sexual dysfunction is an area which will be of increasing importance to urologists who manage prostate cancer and one that should not be underestimated.

Aged↗

Axial penile rigidity: determinants and relation to hemodynamic parameters.

Erectile dysfunction may be defined in terms of axial penile rigidity, the physical property that enables the erection to be utilized as a penetration tool during sexual activity. Erectile dysfunction occurs when inadequate axial penile rigidity results in buckling of the penile column when subjected to axial compressive loading situations during vaginal intromission. New multi-disciplinary engineering studies of penile hemodynamic and structural dynamic relationships are reviewed concerning the determinants of axial penile rigidity. Axial penile rigidity develops as a continuum during the increases in intracavernosal pressure and volume changes from the flaccid state and is influenced by intracavernosal pressure, penile tissue mechanical properties and penile geometry. Two penile tissue mechanical properties are especially relevant; cavernosal maximum volume at relatively low intracavernosal pressure, and tunical distensibility, the relative volume of the fully erect to completely flaccid pendulous penis. Two penile geometric properties are critical; the penile aspect ratio, defined as the diameter to length ratio of the pendulous penis, and the magnitude of the flaccid penile diameter. Clinically measured values of axial buckling forces in patients undergoing dynamic pharmacocavernosometry strongly correlated to theoretic-based analytic derived magnitudes of axial penile rigidity based on these above pressure, tissue and geometric determinants. Since axial penile rigidity is not exclusively dependent upon intracavernosal pressure, patients with normal erectile hemodynamics may be erroneously labelled as having psychogenic dysfunction where their true pathophysiology may be related to abnormal penile tissue properties and/or penile geometric factors. Similarly, some patients may claim sufficient rigidity for penetration, but have abnormal hemodynamic erectile function studies. They may have uniquely advantageous tissue mechanical and/or geometric properties. More research is needed concerning axial penile rigidity, a most influential factor determining functional erectile quality, erectile potency and successful coitus.

Hemodynamics↗

Vasculogenic female sexual dysfunction: vaginal engorgement and clitoral erectile insufficiency syndromes.

The first phase of the female sexual response, associated with neurotransmitter-mediated vascular smooth muscle relaxation, results in increased vaginal lubrication, wall engorgement and luminal diameter as well as increased clitoral length and diameter. Specific physiologic impairments of vasculogenic female sexual dysfunction include vaginal engorgement and clitoral erectile insufficiency syndromes. These syndromes exist when during sexual stimulation abnormal arterial circulation into the vagina or clitoris, usually from atherosclerotic vascular disease, interferes with normal vascular physiologic processes. Clinical symptoms may include delayed vaginal engorgement, diminished vaginal lubrication, pain or discomfort with intercourse, diminished vaginal sensation, diminished vaginal orgasm, diminished clitoral sensation or diminished clitoral orgasm. An animal model of this syndrome, with significant physiologic responses between the control and the atherosclerotic pelvic nerve stimulated hemodynamic responses, is discussed. Non-atherosclerotic, traumatic vascular disease of the ilio-hypogastric-pudendal arterial bed from pelvic fractures or blunt perineal trauma may also result in diminished vaginal/clitoral arterial blood flow following sexual stimulation. Diagnostic studies assessing the hemodynamic integrity of the ilio-hypogastric-pudendal arterial bed to the vagina and clitoris and new oral/topical pharmacologic strategies for enhancing vaginal/clitoral blood flow in patients with vasculogenic female sexual dysfunction are discussed. There is a growing body of evidence that women with sexual dysfunction will commonly have physiologic abnormalities, such as vasculogenic female sexual dysfunction, contributing to their overall sexual health problems.

Animals↗

The influence of prenatal ultrasound on the prevalence of congenital anomalies at birth.

The objectives of the study were (1) to assess whether prenatal ultrasound examinations affected the prevalence of congenital anomalies at birth and the incidence of terminations of pregnancy for fetal anomalies and (2) to examine the detection rate of the main fetal anomalies. We studied all births and stillbirths with congenital defects, and all terminations of pregnancy for fetal anomalies in the Rambam Medical Center during a 5-year period (1989-1993) and correlated them to ultrasound findings. There were 23439 births during the study period. The incidence of newborns with anomalies decreased from 1.95 to 1.34 per cent (P < 0.01). The incidence of termination of pregnancy because of fetal anomalies increased from 0.35 to 0.83 per cent (P < 0.003) and the detection rate of malformations increased from 53.94 to 79.60 per cent (P < 0.001). It is concluded that terminations of pregnancy after ultrasound detection of fetal anomalies had an impact on the prevalence of anomalies in newborns. There was also continuing significant improvement in the detection rate of ultrasound examinations.

Abortion, Therapeutic↗

Intracavernosal forskolin: role in management of vasculogenic impotence resistant to standard 3-agent pharmacotherapy.

PURPOSE: We investigated forskolin, a direct adenylate cyclase activator, as an intracavernosal vasoactive agent in management of vasculogenic impotence. MATERIALS AND METHODS: Concentration responses for forskolin and prostaglandin E1 induced relaxation of phenylephrine precontracted strips of human corpus cavernosum smooth muscle were constructed in vitro. Cyclic adenosine monophosphate (cAMP) synthesis was determined with papaverine, phentolamine, prostaglandin E1 and forskolin in human corpus cavernosum smooth muscle cell cultures. Dose-dependent hemodynamic responses to intracavernosal forskolin (5 to 20 micrograms) were evaluated in a New Zealand White rabbit model. Safety and efficacy outcome data were obtained in vasculogenically impotent patients who signed informed consent and met strict inclusion and exclusion criteria that included having had standard self-injection therapies fail. RESULTS: In vitro forskolin and prostaglandin E1 alone caused concentration dependent relaxation with an EC50 of approximately 200 nm. and 16 nm., respectively. When the 2 agents were combined, the concentration response curve for relaxation shifted to the left. cAMP production was highest in cells treated with prostaglandin E1 and forskolin and was unaffected by papaverine or phentolamine. In 3 animals, equilibrium intracavernosal pressure and duration of erection had a dose dependent increase. Clinical investigation in 31 patients showed no adverse events with a mean of 14 +/- 4, range 11 to 18 months of followup. Overall 61% reported improvement in rigidity and/or erection duration using intracavernosal forskolin (98 micrograms./ml.), papaverine (29 mg./ml.), phentolamine (0.98 mg./ml.) and prostaglandin E1 (9.8 micrograms./ml.). CONCLUSIONS: Forskolin is a United States Food and Drug Administration nonapproved vasoactive agent that acts in synergism with prostaglandin E1 to induce smooth muscle relaxation. In combination with other vasoactive agents, forskolin has demonstrated preliminary safety and efficacy in patients with vasculogenic impotence resistant to standard 3-agent pharmacotherapy.

Alprostadil↗

Fetal transcerebellar diameter in Down syndrome.

OBJECTIVE: To determine whether cerebellar hypoplasia in Down syndrome is established and clinically recognizable in the second trimester of pregnancy and to evaluate the screening utility of transverse cerebellar diameter measurements for Down syndrome fetuses. METHODS: Ultrasonographic biometry data obtained before genetic amniocenteses on 42 fetuses with Down syndrome and 1161 karyotypically normal fetuses were analyzed. Mean transverse cerebellar diameters stratified by gestational age were compared. A regression equation relating transverse cerebellar diameters to gestational age was calculated for 387 normal fetuses and applied to the remaining normal (n = 774) and all Down syndrome fetuses. Ratios of observed to expected cerebellar diameters were calculated. Sensitivity, specificity, and positive predictive values were calculated for various cutoff points and Down syndrome prevalences. RESULTS: Cerebellar diameters in Down syndrome fetuses were smaller than in normal controls at all gestational ages (P < .005) by an average of 0.67-0.87 mm. A ratio of 0.92 for observed/expected cerebellar diameters yielded a sensitivity of 21%, specificity of 95%, and positive predictive values of 1.66% and 0.56% in populations with a risk for Down syndrome of one in 250 and one in 750, respectively. CONCLUSIONS: Cerebellar hypoplasia is developmentally established and sonographically recognizable in second-trimester Down syndrome fetuses. However, cerebellar size differences between normal and Down syndrome fetuses are too small to be clinically useful.

Anthropometry↗

Vasculogenic female sexual dysfunction: the hemodynamic basis for vaginal engorgement insufficiency and clitoral erectile insufficiency.

OBJECTIVE: Organic female sexual dysfunction may be related in part to vasculogenic impairment of the hypogastric-vaginal/clitoral arterial bed. The aim was to develop an animal model of vaginal engorgement insufficiency and clitoral erectile insufficiency. METHODS: Pelvic nerve stimulated vaginal engorgement and clitoral erection were achieved in control (normal diet, n = 8) and atherosclerotic (balloon injury of aorto-iliac arteries and 0.5% cholesterol diet, n = 7) New Zealand White female rabbits. After 16 weeks, novel hemodynamic variables including vaginal wall and clitoral blood flow, vaginal wall and clitoral intracavernosal pressure, vaginal length, vaginal luminal pressure, blood levels of cholesterol and triglycerides, aorto-iliac angiography and vaginal wall and clitoral erectile tissue histology were recorded in the two groups. RESULTS: Concerning pelvic nerve stimulated vaginal hemodynamic changes, there was significantly less increase in blood flow (ml/min/100 gm tissue), wall pressure (mmHg) and length changes (mm) in atherosclerotic (9.3 +/- 3.7, 4.8 +/- 3.8, 67.3 +/- 8.3) compared to control (13.9 +/- 4.5, 5.5 +/- 2.6, 74.1 +/- 10.0) animals respectively. Histologic examination of clitoral erectile tissue demonstrated cavernosal artery atherosclerotic changes and diffuse vaginal and clitoral fibrosis. Aorto-iliac angiography in atherosclerotic animals revealed diffuse moderate to severe atherosclerotic occlusion. CONCLUSIONS: Vaginal engorgement and clitoral erection depend on increased blood inflow. Atherosclerosis is associated with vaginal engorgement insufficiency and clitoral erectile insufficiency.

Adrenergic alpha-Antagonists↗

Growth of the fetal nose width and nostril distance in normal pregnancies.

The study was planned to obtain the dimensions of the fetal nose width and nostril distance during normal pregnancy as a basis for further studies and for identification of deviations in growth. The study group included 302 healthy pregnant women at 14-40 weeks' gestation. Routine biometric measurements were obtained from all the participants, including biparietal diameter, head and abdominal circumferences, measurements of the long bones and dimensions of the fetal nose width and nostril distance. The nose width and nostril distance were also calculated for each gestational age. A linear growth relationship was observed between nose width and gestational age (r = 0.88; p < 0.0001; y = 0.27 + 0.57 x gestational age), biparietal diameter (r = 0.92; p < 0.0001; y = 0.41 + 0.23 x biparietal diameter), head circumference (r = 0.91; p < 0.00001; y = 0.85 + 0.63 x head circumference), femoral length (r = 0.91; p < 0.0001; y = 3.18 + 0.26 x femoral length) and humeral length (r = 0.73; p < 0.0001; y = 1.94 + 0.11 humeral length). A linear growth function was also observed between nostril distance and gestational age (r = 0.54; p < 0.00001; y = 2.77 + 0.15 x gestational age), biparietal diameter (r = 0.71; p < 0.00001; y = 1.83 + 0.08 x biparietal diameter), head circumference (r = 0.70; p < 0.00001; y = 1.99 + 0.2 x head circumference), femoral length (r = 0.75; p < 0.00001; y = 2.49 + 0.09 x femoral length) and humeral length (r = 0.91; p < 0.00001; y = 1.89 + 0.32 x humeral length). A linear growth relationship was found between nose width and nostril distance (r = 0.71; p < 0.00001; y = 1.81 + 0.31 x nose width). These results provide normative data of the fetal nose width and nostril distance in various dimensions and across gestational age. In addition, the data offer the potential for prenatal diagnosis of nose and nostril abnormalities.

Female↗

Early prenatal diagnosis of hydrocephalus.

The aim of the present study was to assess the accuracy of various measurements of the lateral ventricles (LVs) for the early prenatal diagnosis of evolving congenital hydrocephalus. A prospective study was conducted among 61 normal pregnancies, and 20 pregnancies complicated by neural axis malformations, between 19 and 24 weeks' gestation. The following ultrasound measurements were obtained: atrial width (AW); atrial-width/cerebro-atrial distance (CAD); left ventricular width/hemispheric distance, and cerebro-frontal horn/hemispheric width (HW) distance. Atrial width or AW/CAD had the highest diagnostic accuracy of 97.1% between 19-21 weeks; and 100% between 22-24 weeks. The other two parameters had improved accuracy as gestational age increased. However, between 19-21 weeks the other parameters were below 90% in their diagnostic accuracy. These data demonstrate that the simple measurement of the AW, used either singly or as a ratio with the CAD is effective for the early prenatal diagnosis of evolving hydrocephalus.

Agenesis of Corpus Callosum↗

Drugs for the treatment of impotence.

Penile erection is a complex neurovascular event that represents a balance between corporal smooth muscle relaxation and contraction. This balance is determined by the interaction between proerectile and antierectile neurotransmitters. It is believed that nitric oxide is the primary erectogenic neurotransmitter and that noradrenaline (norepinephrine) is the primary erectolytic neurotransmitter. There are a number of pharmacological approaches to the management of erectile dysfunction and manipulation of the neurotransmitter systems. These involve direct delivery of drugs into the erectile chambers (intracavernosal injection therapy), administration of medications into the urethra (transurethral delivery), application of medications to the skin (transdermal delivery) and it is hoped that oral agents will be available in the very near future. This article reviews the world literature on the medications that have been investigated to date and their delivery routes.

Adenylyl Cyclase Inhibitors↗