Biomedical subjects

A Apostolidis

Publications and source records attributed to A Apostolidis.

11 recordsLinked to original sources

PubMed2005

Decreased sensory receptors P2X3 and TRPV1 in suburothelial nerve fibers following intradetrusor injections of botulinum toxin for human detrusor overactivity.

PURPOSE: Botulinum neurotoxin type A (BoNT/A) is effective in the treatment of intractable detrusor overactivity (DO). In addition to its known inhibitory effect on presynaptic release of acetylcholine by motor terminals, there is increasing evidence that BoNT/A may affect sensory fibers. We investigated a possible effect of BoNT/A on human bladder afferent mechanisms by studying the sensory receptors P2X3 and TRPV1 in biopsies from patients with neurogenic or idiopathic DO. MATERIALS AND METHODS: A total of 38 patients (22 with neurogenic DO, 16 with idiopathic DO) with intractable DO were treated with intradetrusor BoNT/A, and bladder biopsies were taken at 4 and 16 weeks. Urodynamics and voiding diary were also recorded. Specimens were studied immunohistochemically for P2X3, TRPV1 and the pan-neuronal marker PGP9.5, in comparison with controls. RESULTS: P2X3-immunoreactive and TRPV1-immunoreactive (-IR) fibers were decreased at 4 weeks after BoNT/A, and more significantly at 16 weeks (paired t test p=0.0004 and p=0.0008, respectively), when significant improvements were observed in clinical and urodynamic parameters. P2X3-IR fiber decrease was significantly correlated with reduction of urgency episodes at 4 and 16 weeks (p=0.0013 at 4 weeks and p=0.02 at 16 weeks), but not maximum cystometric capacity or detrusor pressures. TRPV1-IR fiber decrease showed a similar trend. PGP9.5-IR suburothelial fibers remained unchanged after treatment at both followups (p=0.85 and p=0.21 at 4 and 16 weeks, respectively). Urothelial cell P2X3-IR and TRPV1-IR also appeared unchanged. CONCLUSIONS: Decreased levels of sensory receptors P2X3 and/or TRPV1 may contribute to the clinical effect of BoNT/A in detrusor overactivity.

Adult↗

PubMed2004

Fetal tachycardia: is digitalis still the first-line therapy?

Medical treatment of fetal tachycardias has substantially improved neonatal outcome over the past years. Digitalis has been often used as first-line therapy in these cases, and more recently the use of several newer agents have been reported. We present four cases of fetal tachycardia with a favorable neonatal outcome after successful treatment with digitalis. Rapid transplacental digitalization appears to be an effective and reliable treatment option for fetal tachycardia, particularly in non-hydropic fetuses. In hydropic fetuses, however, digitalis alone appears to be less effective and administration of a second drug is usually needed.

Adult↗

PubMed2003

Normal hemodynamic parameters do not always predict the presence of a rigid erection: a quantitative assessment of functional erectile impairment.

The purpose was to assess objectively and quantitatively the hemodynamic status and the degree of functional erectile impairment in a group of impotent patients. A clinical study was designed, incorporating pharmacocavernosometry (to evaluate arterial and veno-occlusive function) with axial buckling forces and penile geometry measurements in a group of impotent patients. The pressure gradient between the intracavernosal pressure associated with the presence of penile axial rigidity and the equilibrium intracavernosal pressure was calculated (axial rigidity gradient, ARG); such methodology allowed a quantitative characterization of functional impairment, as ARG expresses the intracavernosal pressure increase necessary to achieve axial rigidity and therefore potency. Penile geometry characteristics were also expressed by calculating the penile aspect ratio (diameter/length, D/L). In 83 consecutive patients tested (mean age 42.89+/-9.96), rigidity occurred at intracavernosal pressures between 50 and 100 mm Hg. A conversely proportional relation was noticed between penile aspect ratio values and the intracavernosal pressure associated with rigidity values, clearly demonstrating the important functional role of penile geometry. ARG demonstrated a wide range of values (3-69 mm Hg), reflective of the severity of the erectile dysfunction on each patient. Half (50.6%) of the patients had ARG values < or =20 mm Hg, indicative of minimal and minimal-to-moderate erectile impairment, while 20.48% had ARG between 21-30 and 28.92% >30 mm Hg, indicative of moderate and severe erectile dysfunction (ED) respectively. In all, 6% of the study group, all of them with primary ED, ARG <20 mm Hg had normal hemodynamics, but low penile aspect ratio values indicating that penile geometry may be the cause of insufficient rigidity. Hemodynamic integrity is the most critical, but not the only determinant of penile rigidity, as erectile impairment may be noticed in patients with normal arterial inflow and corporal veno-occlusive function. In such cases, unfavorable penile geometry should be considered as the possible etiological factor of impotence.

Adult↗

PubMed2003

Protective role of the glans penis during coitus.

To examine the hypothesis that the glans penis acts protectively, absorbing forces, during coitus. Five potent patients (mean age 46.8+/-9.7 y), who had indication for surgical excision of the glans for penile carcinoma were included in the present study. Intraoperatively, intracavernosal pressure (ICP) was adjusted by saline infusion and maintained by a pressure feedback infusion pump to a pressure value of 70 mmHg. Using a dynamometer, an external compressive force of 0.5 kg was applied at the glans penis and the changes in ICP were monitored. Measurements were repeated after surgical excision of the glans. Significant ICP changes were noticed in all patients after excision of the glans. Mean preoperative ICP was 161+/-11.5 mmHg, while after glansectomy it reached 206.6+/-13 mmHg. DeltaICP was 45.8+/-10.57 mmHg. Two of the patients' partners reported pain during intercourse postoperatively, possibly due to the impact of the force applied by the rigid corpora cavernosa on the anterior vaginal wall without any absorption by the glans. The glans penis restricts the increase in ICP during sexual intercourse, playing a protective role for both the corpora cavernosa and the female genitalia.

Adult↗

PubMed2001

Glansectomy: an alternative surgical treatment for Buschke-Löwenstein tumors of the penis.

OBJECTIVES: To present the surgical excision of the glans penis (glansectomy) as an alternative surgical treatment to penectomy. Buschke-Löwenstein tumors of the penis include the entities described in published reports as verrucous carcinoma and giant condyloma acuminatum of the penis. Both types are well-differentiated tumors, typically confined to the glans penis, with distinctly rare metastatic activity. METHODS: The study included 7 patients, 40 to 63 years of age, with exophytic, papillary lesions involving the glans penis. Biopsy led to the diagnosis of verrucous carcinoma in 4 patients and giant condyloma acuminatum in 3 patients. All patients reported normal erectile function. Because of the low malignant potential of the tumor and its confinement to the glans penis, a simple glansectomy was performed in all patients to preserve the maximal penile length and functional integrity of the corpora cavernosa. RESULTS: The postoperative course was uncomplicated. With 18 to 65 months of follow-up, all patients were disease free. One patient required more aggressive treatment because of local recurrence of the tumor. All patients returned to normal sexual activity 1 month postoperatively. The only change during sexual activity, noted by two of the patients' partners, was vaginal pain, possibly due to the absence of the glans. CONCLUSIONS: Glansectomy may be considered the treatment of choice in patients with Buschke-Löwenstein tumors of the penis, with more radical techniques reserved for second-line treatment.

Adult↗

PubMed2001

Effects of oral phentolamine, taken before sleep, on nocturnal erectile activity: a double-blind, placebo-controlled, crossover study.

The objective of this study was to determine the effects of oral phentolamine, administered before sleep, on nocturnal penile erectile activity of men with mild to moderate erectile dysfunction (ED). We studied five patients with mild to moderate ED (mean age 34.8 +/- 8.13 and mean duration of ED 31.8 +/- 23.5 months), in a double-blind, placebo-controlled, crossover study. All patients received oral phentolamine (Vasomax) at a dose of 40 mg and placebo for three consecutive nights respectively and were submitted to nocturnal penile tumescence and rigidity monitoring (NPTR) with the Rigiscan device. NPTR parameters of the two 3-night recordings were evaluated and compared. Administration of oral phentolamine before sleep was associated with a statistically significant increase in the number of erectile events with rigidity > or = 60% lasting > or = 10 min (P = 0.02), as well as the rigidity activity units (RAU) value per hour sleep, both at the base (P = 0.023) and the tip of the penis (P = 0.019). The number of events as measured by Rigiscan software (20% change in circumference), as well as tumescence activity units (TAU)/h values did not show any statistical difference. No adverse effects were recorded. It is concluded that oral phentolamine administered before sleep enhanced NPTR parameters associated with the quality of the erectile events. Such results provide a pathway for the development of a prevention strategy for ED. Future studies will elucidate whether vasoactive agents taken on a regular basis before sleep, can prevent ED in men at risk, protecting also minimally and moderately impotent patients to become moderately and severely impotent respectively.

Administration, Oral↗

PubMed2001

Mitochondrial DNA sequence variation in Greeks.

Mitochondrial DNA (mtDNA) control region sequences were determined in 54 unrelated Greeks, coming from different regions in Greece, for both segments HVR-I and HVR-II. Fifty-two different mtDNA haplotypes were revealed, one of which was shared by three individuals. A very low heterogeneity was found among Greek regions. No one cluster of lineages was specific to individuals coming from a certain region. The average pairwise difference distribution showed a value of 7.599. The data were compared with that for other European or neighbor populations (British, French, Germans, Tuscans, Bulgarians, and Turks). The genetic trees that were constructed revealed homogeneity between Europeans. Median networks revealed that most of the Greek mtDNA haplotypes are clustered to the five known haplogroups and that a number of haplotypes are shared among Greeks and other European and Near Eastern populations.

Base Sequence↗

PubMed2000

Sildenafil versus intracavernous injection therapy: efficacy and preference in patients on intracavernous injection for more than 1 year.

PURPOSE: To our knowledge comparative data on the effectiveness of and patient preference for intracavernous injection therapy and sildenafil are still not available. We evaluated the efficacy of sildenafil as well as patient preference in a group of impotent men on intracavernous injection for more than a year. MATERIALS AND METHODS: Patients on intracavernous injection therapy for more than a year without neurological disease and/or a contraindication to sildenafil treatment were recruited for study. In phase 1 we determined the efficacy of 50 and 100 mg. sildenafil citrate at home. In phase 2 responders to sildenafil were asked to use the preferred dose orally for a month and choose intracavernous injection or sildenafil. In phase 3 patients were asked to continue either treatment for 3 more months. Patient preferences were reported at the end of phases 2 and 3. RESULTS: Of the 180 men recruited 155 with a mean age of 56.4 +/- 12.6 years on intracavernous injection for a mean of 26 +/- 9 months accepted and were included in our series. Overall 116 men (74.8%) responded to sildenafil during study phase 1. After 1 month of treatment 71 responders (61.2%) preferred to continue with the oral drug, 31 (26.7%) returned to intracavernous injection and 14 (12.1%) used each drug alternately. Three months later 74 of the 116 responders (63.8%) preferred oral treatment and 38 (32.8%) chose intracavernous injection, while 4 (3. 4%) continued to use each treatment alternately. CONCLUSIONS: Sildenafil is highly effective in intracavernous injection responders, although a certain group prefer to continue intracavernous injection. While sildenafil should be considered first line treatment, men with erectile dysfunction should be aware of all treatment options available because nonresponders to sildenafil may respond to intracavernous injection.

Adult↗

PubMed1999

Hemodynamic characterization of a functional erection. Arterial and corporeal veno-occlusive function in patients with a positive intracavernosal injection test.

OBJECTIVES: To characterize hemodynamically a functional/rigid erection and study the hypothesis that a positive intracavernosal injection test indicates normal arterial and corporeal veno-occlusive function. METHODS: 33 patients (mean age 39.5 +/- 9 years), who developed rigid erection during pharmacocavernosometry, included in the present study. The presence of axial rigidity was determined at steady state equilibrium intracavernosal pressure, by absence of buckling to axial force of 1 kg, applied to the erect penis and sustained for >/=15 min. Arterial and veno-occlusive hemodynamic parameters were analyzed. RESULTS: Flow-to-maintain at intracavernosal pressure 150 mm Hg and mean pressure decay values ranged between 0.5-13 ml/min and 5-85 mm Hg, respectively. Flow-to-maintain values >5 ml/min were noticed in 8 patients (24. 24%), while pressure decay values >45 mm Hg in 13 patients (39.39%). Pharmacocavernosography revealed moderate opacification of venous structures in 7 cases (21.21%). Abnormal systemic-cavernosal systolic arterial pressure gradients in both cavernosal arteries were noticed in 9 patients (27.27%). All patients with flow-to-maintain values >5 ml/min had normal arterial function. CONCLUSIONS: A functional/rigid erectile response may coexist with arterial insufficiency or corporeal veno-occlusive dysfunction. Presence of normal or borderline arterial inflow may compensate minimal or moderate veno-occlusive dysfunction, resulting in a functional - but not normal - erection. Such information is critical when the intracavernosal injection test is used for diagnostic purposes.

Adult↗

PubMed1997

Divergence in the G-protein-coupled receptor mitogenic signalling pathway at the level of Raf kinase.

While activation of tyrosine kinase growth factor receptors is accompanied by hyperphosphorylation of Raf-1, stimulation of receptors coupled to G-proteins has in some cases been shown to result in activation of a non-Raf MEKK rather than of Raf itself. Our finding (Weiss, R. H., and Nuccitelli, R. (1992) J. Biol. Chem. 267, 5608-5613) that the thrombin receptor requires tyrosine phosphorylation for its mitogenic effect in vascular smooth muscle cells led us to search for the molecules which are being tyrosine phosphorylated by this receptor. To determine whether mitogenic signalling of G-protein-coupled growth factor receptors results in tyrosine phosphorylation of Raf, we examined activation of Raf by two such receptors. Both thrombin and angiotensin II are mitogenic in NIH3T3 cells, but only thrombin causes hyperphosphorylation of Raf-1. Activation of Raf by thrombin is associated with phosphorylation of Raf-1 on tyrosine residues, whereas activation of Raf by angiotensin II does not involve significant tyrosine phosphorylation. However, Shc is tyrosine phosphorylated by both thrombin and angiotensin II. Thus, there exists a divergence in the mitogenic signalling pathways of the G-protein-coupled receptors relative to the Raf signalling cascade. While both thrombin and angiotensin II phosphorylate Shc and activate Raf catalytic activity, only thrombin phosphorylated Raf-1 on tyrosine. This signalling through disparate Raf-coupled pathways suggests one means by which the G-protein-coupled receptors may confer specificity in their signalling properties.

3T3 Cells↗

PubMed1995

Dissociation of phosphatidylinositol-3 kinase activity and mitogenic inhibition in vascular smooth muscle cells.

Phosphatidylinositol-3 kinase becomes activated upon association with stimulated tyrosine kinase coupled receptors, but it is also catalytically active in platelets incubated with the G-protein coupled growth factor receptor agonist, thrombin. Furthermore, phorbol esters have been shown to be growth inhibitory when added to vascular smooth muscle cells simultaneously with thrombin. In order to clarify the role of phosphatidylinositol-3 (PI-3) kinase in thrombin-induced mitogenesis, we asked whether PI-3 kinase activity is decreased in parallel to mitogenesis in cells stimulated with phorbol-12-myristate-13-acetate (PMA) and thrombin. Although PMA inhibits thrombin-stimulated growth by 92% when the two compounds are added simultaneously, the level of PI-3 kinase activity under similar conditions is not decreased. This phenomenon is independent of protein kinase C, since there is no difference in PI-3 kinase activity when similar experiments are performed after protein kinase C is down-regulated by 24 h pre-incubation with PMA. We conclude that either (i) PI-3 kinase is not required for the mitogenic signalling of thrombin, or (ii) PMA is acting downstream of PI-3 kinase in thrombin's signalling pathway.

Animals↗