Guidelines on erectile dysfunction

The introduction of new oral therapies has completely changed the diagnostic and therapeutic approach to erectile dysfunction. A panel of experts in this field have developed guidelines for clinical evaluation and treatment based on the review of available scientific information.     

Sensitivity of HaCat keratinocytes to diabetogenic toxins

Metabolic, genetic and environmental factors very likely play an important role in the development of skin lesions in diabetes mellitus. While these lesions are involved in secondary diabetes complications, various diabetogenic genotoxic agents may induce direct skin damage. In the present study we examined the potential of known diabetogenic agents (streptozotocin (STZ) and alloxan (AL)), with different mechanisms of action, for induction of direct injury in an immortal human keratinocyte HaCat cell line. In contrast to STZ, which induces alkylation of DNA, a genotoxic effect of AL is achieved through reactive oxygen species. We found that HaCat cells are highly sensitive to STZ, but not to AL. At a concentration of 10mM STZ, cell viability decreased to 32 +/-13% of control (P<0.05), as compared to 82 +/-14% with 10mM of AL. Cells treated with 10 and 20mM STZ showed a significant increase in apoptosis (3.9- and 6.7-fold), but not in necrosis, compared to naive cells (P<0.05). In contrast to STZ, no increase in apoptotic and necrotic cell death was observed after AL treatment. Pretreatment with non-metabolizable 3-O-methyl glucose (3-OMG), which can blockade glucose transporter, or with poly(ADP-ribose) polymerase inhibitors (nicotinamide or 3-aminobenzamide), did not protect keratinocytes from STZ injury. Our results show that STZ, but not AL, is highly toxic to the HaCat cell line. Unlike insulin-producing cells, STZ-induced injury of immortal human keratinocyte HaCat cells is independent of the glucose transporters as well as of the activation of poly(ADP-ribose) polymerase.     

Retinal voltage-dependent anion channel: characterization and cellular localization

PURPOSE: To characterize and localize retinal voltage-dependent anion channel (VDAC) and to understand its possible contribution to mitochondrial function and dysfunction. METHODS: VDAC was characterized by a method involving purification from isolated mitochondria and reconstitution into a planar lipid bilayer (PLB). The permeability transition pore (PTP) was monitored by Ca(2+) accumulation in isolated mitochondria and swelling of mitochondria. Localization was studied by immunocytochemistry and in situ hybridization. RESULTS: Retinal VDACs exhibited the electrophysiological fingerprint of the VDAC superfamily. It had a maximal chord conductance of 3.7 +/- 0.1 nanosiemens (nS) in 1 M NaCl, and a voltage-dependent conductance that was highest at transmembrane potential close to zero. It was modulated by glutamate, which decreased the channel's open probability, and by La(3+) and ruthenium amine binuclear complex (Ru360), which closed the channel. Energized and freshly prepared retinal mitochondria accumulated Ca(2+) that is inhibited by La(3+) ruthenium red and Ru360. Subsequent to Ca(2+) accumulation, mitochondria released the accumulated Ca(2+), probably through activation of the PTP. Ru360 inhibited Ca(2+) release and mitochondrial swelling. VDAC was present in mitochondria of all retinal cell types: photoreceptor, bipolar, horizontal, amacrine, and ganglion cells. Most cells primarily expressed VDAC-1, but they also expressed VDAC-2 and -3. CONCLUSIONS: These results suggest that VDAC is involved in PTP activity and/or regulation and thus is an important player in retinal degeneration associated with PTP-mediated mitochondrial dysfunction.     

The feasibility of early administration of combination chemotherapy following cytoreductive surgery and second-look operation in patients with stage III ovarian carcinoma: a pilot study

The purpose of this study is to evaluate the feasibility of early use of modified PAC-1 chemotherapy following debulking surgery and its efficacy by assessing disease status during a second-look operation. Twenty-six consecutive previously untreated patients with stage III ovarian carcinoma were evaluated in a prospective study over the 5-year period March 1981 to August 1986. Initial exploratory laparotomy was performed for staging and maximum cytoreduction. Within 24 hr postoperative modified PAC-1 (M-PAC-1) combination chemotherapy was administered and then repeated every 4 weeks for 11 months which was then followed by second-look operation. Patients were analyzed according to the following pretreatment characteristics: age, FIGO stage, histologic tumor type, extent of initial surgery, size of residual tumor, and findings during second-look. Nineteen patients were evaluable. No evidence of either microscopic or macroscopic disease was noted in 15 patients (79%), whereas the remaining 4 (21%) exhibited persistent disease. Of the remaining 7 patients not undergoing SLO, 4 completed 12 courses of chemotherapy but did not undergo surgery for medical reason (n = 2) or patient refusal (n = 2). Two more patients refused chemotherapy after 9 courses and the seventh patient expired with persistent disease after 8 courses. The early use of combination chemotherapy was well tolerated. Neurological, hematological, and renal toxicity was never severe enough to cause discontinuation of therapy.     

Efficacy of melatonin as protectant against oxidative stress and structural changes in liver tissue in pinealectomized rats

Previous observations demonstrated that physiological levels of melatonin, the pineal secretory product, are important in protecting against oxidative stress-induced tissue damage. We investigated the effects of pinealectomy and administration of exogenous melatonin on liver tissue in rats. Pinealectomized (Px) and sham-operated (non-Px) rats were used. We evaluated structural changes, reduced glutathione (GSH) levels and malondialdehyde (MDA) levels. Rats were divided into three groups (10 rats in each group): control (non-Px), Px+vehicle and Px+melatonin (4 mg/kg given daily intraperitoneally for 10 days). Liver GSH levels were significantly lower in Px rats than in the control group. Melatonin administration significantly increased GSH levels (p < 0.05). Px caused a significant increase in MDA levels as compared with the control group and melatonin administration to Px rats significantly reduced MDA levels in the liver (p < 0.05). Sinusoidal dilatation to a varying degree developed in all Px rats. Severity of mononuclear cell infiltration and sinusoidal congestion were lower in Px+melatonin group than in the Px group. These findings suggest that a significant increase in oxidative and structural changes occur in rat livers after pinealectomy, which can be diminished by melatonin treatment.     

Functional activity of insulinoma cells (INS-1E) and pancreatic islets cultured in agarose cryogel sponges

Here, we describe the preparation, structure, and properties of cryogel sponges, which represent a new type of macroporous biomaterial for tissue engineering. Cryogels were produced through freeze-thawing techniques, either from agarose alone or from agarose with grafted gelatin. The aim of this study was to evaluate agarose cryogel sponges as scaffolds for culturing both isolated pancreatic islets and insulinoma cells (INS-1E). In order to evaluate the effect of cell entrapment in artificial scaffolds, cell function reflected by insulin secretion and content was studied in cells cultivated for a 2-week period either in culture plastic plates or in cryogel sponge disks. Our results show that tumor-derived INS-1E cells grown either on plastic or on cryogels do not differ in their proliferation, morphology, insulin release, and intracellular insulin content. However, isolated pancreatic islets cultivated on cryogels sponge show 15-fold higher basal insulin secretion at 3.0 mM glucose than islets cultivated on plastic plates and fail to respond to stimulation with 16.7 mM glucose. In addition, these islets have about 2-fold lower insulin content compared to those grown in plastic plates. It is possible that the cell dysfunction noted in these in vitro experiments is due to the effect of the limited oxygen supply to the islets cultivated in cryogel sponge. Further in vivo studies are needed to clarify the nature of such an observation since according to previous reports, agarose and gelatin induce new vessel formation supporting enhanced oxygen supply.     

Normative values for female genital sensation

Objectives. Neurologic disorders might be responsible for many cases of female sexual dysfunction. Yet, they are currently undiagnosed because of the lack of measurement tools to assess genital neural function. Therefore, our objective is to provide norms for sensory thresholds in the vagina and clitoris, for a wide range of patient ages.Methods. Vaginal and clitoral warm, cold, and vibratory sensory thresholds were measured in 89 healthy paid volunteers by the method of limits. Normograms were derived from this group of healthy volunteers. An additional 61 patients were also tested, for a total of 150 individuals. Sixty-two individuals (42 healthy volunteers and 20 patients) from the total group were tested twice to provide test-to-test repeatability data across the range of clinical (normal and abnormal) responses.Results. Normograms are presented, providing age-corrected upper and lower normal values, expressed as 95% confidence limits for warm, cold, and vibratory thresholds. Intertest repeatability is also reported.Conclusions. Thermal and vibratory thresholds of both the vaginal and clitoral region are clinically feasible, valid, and repeatable. These can be applied as a valuable diagnostic tool to assess neural dysfunction through sensory assessment of the female genitalia.     

Adapting prognostic respiratory variables of ARDS in children to small-scale community needs

PURPOSE: The clinical literature on the incidence and subsequent mortality of adult respiratory distress syndrome (ARDS) has come primarily from the experiences of large tertiary referral centers, particularly in Western Europe and North America. Consequently, very little has been published on the incidence, management, and outcome of ARDS in smaller community-based intensive care units. We aimed to delineate early clinical respiratory predictors of death in children with ARDS on the modest scale of a community hospital. MATERIALS AND METHODS: A retrospective chart review of children with ARDS needing conventional mechanical ventilation admitted to our pediatric intensive care unit from 1984 to 1997. The diagnosis of ARDS was based on acute onset of diffuse, bilateral pulmonary infiltrates of noncardiac origin and severe hypoxemia defined by partial pressure of oxygen <200 mm Hg during positive end-expiratory pressure (PEEP) of 6 cm H2O or greater for a minimum of 24 hours. Demographic, clinical, and physiological data including PaO2/ FIO2, A-aDo2, and ventilation index were retrieved. RESULTS: Fifty-six children with ARDS aged 8 +/- 5.5 years (range, 50 days to 21 years) were identified. The mortality rate was 50%. Early predictors of death included the peak inspiratory pressure (PIP), ventilation index, and PEEP on the third day after diagnosis: Nonsurvivors had significantly higher PIP (35.3 +/- 10.5 cm H2O vs 44.4 +/- 10.7 cm H2O, P < .001), PEEP (8 +/- 2.8 cm H2O vs 10.7.0 +/- 3.5 cm H2O, P < .01), and ventilation index (49.14 +/- 20.4 mm Hg x cm H2O/minute vs 61.6 +/- 51.1 mm Hg cm H2O/minute) than survivors. In contrast, PAO2/FIO2 and A-a DO2 were capable of predicting outcome by day 5 and thereafter. CONCLUSIONS: A small-scale mortality outcome for ARDS is comparable to large tertiary referral institutions. The PIP, PEEP, and ventilation index are valuable for predicting outcome in ARDS by the third day of conventional therapy. The development of a local risk profile may assist in decision-making of early application of supportive therapies in this population.     

Physiological changes in female genital sensation during sexual stimulation

IntroductionA normal sexual response in the female depends on the integrity of afferent sensory input from the genital region. So far genital sensation has been investigated only during a non-excitatory state, and the sensory physiological changes, which occur during the sexual cycle in this region, are still obscured.AimTo investigate the sensory status of the female genital region during sexual arousal and orgasm.Main Outcome MeasuresGenital sensory thresholds measured by Quantitative Sensory Testing (vibratory and thermal) were compared in a non-excitatory vs. excitatory state in normal sexually functioning females.MethodsEleven healthy female volunteers were recruited and attended three separate visits. During each session only one anatomical site, either clitoris or vagina was tested for either vibratory or thermal stimuli. A psychophysical method of limits was employed for threshold determination of warm or vibratory stimuli. In each session, all women were tested at baseline, immediately after arousal, after orgasm and three more measurements – 5, 10, and 20 minutes during the recovery state.ResultsA significant decrease in clitoral vibratory sensation threshold was observed between the baseline and the arousal phases (P = 0.003). Comparison of vibratory sensation between baseline and following orgasm at the clitoral and vaginal region showed a significant difference (P < 0.001) for both regions. These changes were not significant for thermal threshold sensation at the clitoral region (P = 0.6).ConclusionsThis is the first time that genital sensation has been measured during the excitatory phase of the female sexual cycle. This normative data may serve as a baseline for further investigations of the sensory input of the genital organs during intercourse in pathological states. Gruenwald I, Lowenstein L, Gartman I, and Vardi Y. Physiological changes in female genital sensation during sexual stimulation.     

Suspected macrosomia? Better not tell

OBJECTIVE: To evaluate the management policy of delivery in a suspected macrosomic fetus and to describe the outcome of this policy. STUDY DESIGN: For this prospective observational study we followed the management by reviewing the medical records of 145 women and their infants. The study population included women at term admitted to the obstetrics department with suspected macrosomic infants, as was diagnosed by an obstetrician and/or by fetal sonographic weight estimation of >/=4,000 g. The comparison group (n = 5,943) consisted of all women who gave birth during the data collection period. RESULTS: Induction of labor and cesarean delivery rates in the macrosomic pregnancies (actual birth weight >4,000 g) of the study group were significantly higher when compared with the macrosomic pregnancies of the comparison group. When comparing the non-macrosomic to the macrosomic pregnancies (actual birth weight 4,000 g) of the study group no significant difference was demonstrated regarding maternal or infant complications. The sensitivity, specificity and positive predictive value of the methods used for detecting macrosomia were 21.6, 98.6 and 43.5%, respectively. CONCLUSION: Our ability to predict macrosomia is poor. Our management policy of suspected macrosomic pregnancies raises induction of labor and cesarean delivery rates without improving maternal or fetal outcome.