Long-term reendothelialization of excimer laser-assisted nonocclusive anastomoses compared with conventionally sutured anastomoses in pigs

OBJECT: In contrast to conventional anastomosis methods, the excimer laser-assisted nonocclusive anastomosis (ELANA) technique involves a platinum ring and intima-adventitia apposition with a rim of medial and adventitial layers exposed to the bloodstream. The authors assessed the reendothelialization of porcine carotid arteries through ELANA compared with conventional anastomosis by using scanning electron microscopy. METHODS: In 28 pigs a bypass with one ELANA and one conventional anastomosis was made on the left common carotid artery. All patent anastomoses were evaluated intraoperatively with the aid of an ultrasonographic flowmeter and postoperatively by using scanning electron microscopy at 2 weeks, 2 months, 3 months, and 6 months thereafter. Twenty-four of 28 bypasses (48 of 56 end-to-side anastomoses) were fully patent at the time of evaluation. On scanning electron microscopic evaluation of the bypasses, all 48 patent anastomoses showed complete reendothelialization, including all 24 ELANAs in which the endothelium covered the rim and the laser-ablated edge completely. No endothelial difference was observed between conventional anastomoses and ELANAs, aside from the obvious anatomical differences like the platinum ring, which had been completely covered with endothelium. At 6 months postsurgery, remodeling of the ELANA was observed, leaving the ring covered with a layer of endothelium as the most narrow part of the anastomosis. CONCLUSIONS: In long-term experiments, ELANA allows reendothelialization comparable to that achieved with conventional anastomosis. Considering its nonocclusive and high-flow characteristics, the ELANA technique is preferable in cerebral revascularization procedures.     

Gabapentin in the treatment of uremic itch: an index case and a pilot evaluation

BACKGROUND: The prevalence of renal itch in patients on dialysis is approximately 30%, but its treatment is often ineffective. We describe an index case of a hemodialysis (HD) patient suffering from painful diabetic neuropathy (PDN) treated with gabapentin; the first administration of the drug led to the complete remission of the concomitant uremic pruritus. Subsequently, we report the results of a pilot evaluation aimed at testing the effectiveness and safety of low gabapentin doses in HD patients with uremic pruritus. METHODS: Five consecutive HD patients unresponsive to antihistamines received 4-week gabapentin treatment at a starting dose of 100 mg after every thrice-weekly HD, which was subsequently adjusted based on clinical response. Puritus severity was evaluated by means of a visual analogue scale (VAS) before each HD session on days 0, 2, 4, 7, 14, 21, 28 and 35. Safety was assessed using adverse event data. RESULTS: All patients experienced a rapid subjective improvement in pruritus, with the mean VAS score decreasing from 8.4-1.6 after the first drug administration. Three patients required a dose increase to 100 mg four times a week to obtain better itch control. Two patients experienced complete itch remission. CONCLUSION: Although a double-blind placebo-controlled clinical trial should be conducted to better elucidate the efficacy and toxicity of gabapentin in patients with uremic itch, our data suggest that gabapentin could be considered an effective and safe alternative treatment for uremic pruritus.     

Nonmedical costs associated with rotavirus disease requiring hospitalization

BACKGROUND: As the most common cause of severe diarrhea among children, rotavirus has a significant economic impact. Previous studies focused on the direct medical costs of rotavirus infections; however, nonmedical costs account for the majority of the financial burden from this disease. Herein, we report the results from the largest prospective study in the United States determining the nonmedical costs of severe rotavirus infections. METHODS: Prospective, active, gastroenteritis case surveillance was conducted between November 1997 and December 1999 at 3 pediatric medical centers. Rotavirus infection was identified for 548 children admitted between 2 weeks and 5 years of age. Detailed information about nonmedical costs during the prehospitalization, hospitalization and posthospitalization periods was obtained through interviews. RESULTS: The average nonmedical cost per case of rotavirus disease was USD $448.77, including $359.04 for missed work, $56.66 for transportation, $11.90 for oral rehydration solutions, $9.59 for diapers, $6.83 for child care changes, $3.82 for special foods and $0.93 for formula changes. More than one-half of these expenses (53%) occurred outside the hospitalization period, and 80% of the cost was attributable to missed work. CONCLUSIONS: With an estimated 50,000 hospitalizations attributable to rotavirus each year in the United States, the nonmedical costs of severe rotavirus infections may exceed USD $22 million annually. Previous cost effectiveness analyses of rotavirus vaccines substantially underestimated this burden, suggesting that the nonmedical costs associated with mild to moderate rotavirus disease have been similarly underestimated. These findings are needed to assess accurately the cost effectiveness of future rotavirus immunization strategies.     

Inhibition and superactivation of the calcium-stimulated isoforms of adenylyl cyclase

It was shown previously that chronic exposure to opiate agonists increases adenylyl cyclase (AC) activity, a phenomenon termed AC superactivation (or supersensitization). More recently, we showed that acute Gi/o- coupled receptor activation inhibits the activity of several AC isozymes, including Ca2+/calmodulin-stimulated AC-I and -VIII, whereas chronic receptor activation induces their superactivation. Here, we report that both acute Mu-opioid receptor-induced inhibition and chronic induced superactivation of AC-I and -VIII are pertussis toxin sensitive. In addition, we show that proteins that interfere with the activity of Gbetagamma subunits (Gbetagamma scavengers) strongly attenuate the acute inhibition of AC-I and -VIII and the superactivation of AC-I, and abolish the superactivation of AC-VIII. Based on these results, we suggest that Gbetagamma is involved in the acute inhibition and chronic agonist-induced superactivation of AC types I and VIII.     

Preferential alternate segregation in the common t(11;22)(q23;q11) reciprocal translocation: sperm FISH analysis in two brothers

Segregation behaviour studies in t(11;22) carriers have reported controversial results. Whereas some authors have detected a preponderance of 3:1 products, no evidence of such prevalence was found by others. This study reports a fluorescence in-situ hybridization (FISH) segregation analysis on decondensed spermatozoa in two brothers, carriers of the same t(11;22)(q23;q11) rearrangement. Data revealed a similar meiotic segregation pattern in both carriers, 2:2 Alternate segregation being the most frequent (42.94 and 45%), while 3:1 genotypes were the least frequent in both patients, with percentages around 10%. The production of three chiasmata, based on the presence of G-light bands along the translocated segments and the presence of recombination sites at 11q and 22q distal regions, are proposed as the cause of a preponderance of the Alternate segregation. Interchromosomal effects involving chromosomes 13, 18, 21, X and Y were also evaluated. An increased frequency of sex chromosome disomies was detected in one patient. Reviewing the literature, a relationship between this phenomenon and the involvement of acrocentric chromosomes in the reorganization is suggested. FISH segregation and interchromosomal effects studies in spermatozoa are encouraged to gather information to establish the best approach for preimplantational genetic diagnosis in reorganization carriers.     

Healthy girl born after cryopreservation of gametes and ICSI in a patient with seminoma

This study reports birth in a case of intracytoplasmic sperm injection with cryopreserved oocytes and spermatozoa banked after radiotherapy and prior to chemotherapy due the occurrence of two non-synchronous seminomas. A 30-year-old male with a diagnosis of seminoma cryopreserved six vials of spermatozoa. After oncological treatment was completed, his partner, a 24-year-old woman, underwent ovarian stimulation. Seventeen oocytes were retrieved; one was at the germinal vesicle stage and two were injected, resulting in two embryos. Fourteen metaphase II oocytes were frozen. The woman presented moderated ovarian hyperstimulation syndrome, and embryo cryopreservation was indicated. After endometrial preparation, two embryos were transferred and a pregnancy was achieved. The woman suffered eclampsia during week 28 of gestation. Caesarean section was performed and a preterm girl weighing 1000 g was born, but died 2 weeks after delivery. A year later, a second procedure was begun. Frozen oocytes and one vial of semen were thawed. Eight of the 14 oocytes survived and were microinjected; two became fertilized and one good quality cleaved embryo was transferred. Pregnancy was achieved and a healthy girl was born with a birth weight of 2800 g. Oocyte cryopreservation associated with sperm banking in cancer patients is a useful tool for couples seeking deferred parenthood.     

Misoprostol outpatient cervical ripening without subsequent induction of labor: a randomized trial

OBJECTIVE: To estimate the effect of outpatient administration of a single dose of vaginal misoprostol at term on the interval to delivery in women with unfavorable cervices. METHODS: Randomized, double blind, placebo-controlled trial comparing a single 25-microg outpatient intravaginal dose of misoprostol to placebo in pregnant women with Bishop scores less than 9 at 40 weeks or greater. After placement of the study medication, subjects were permitted to go into spontaneous labor unless an indication for induction developed. Analysis was by intent to treat. The interval to delivery, defined as the time from medication placement to delivery, was compared by Student t test and by survival analysis with the log-rank test. RESULTS: Thirty-three women were randomly assigned to receive misoprostol, and 35 were assigned to receive placebo. The mean interval to delivery was significantly less in the misoprostol group, 4.2 +/- 4.1 compared with 6.1 +/- 3.6 days, P =.04. The interval to delivery for only the nulliparous patients was significantly less in the misoprostol group, 4.2 +/- 4.0 compared with 7.2 +/- 3.7 days, P =.02. The survival curves for the interval to delivery were significantly different (P =.04 by log-rank test) with 4.1 days median interval to delivery for misoprostol compared with 9.2 days for placebo. There were no adverse outcomes in either group. CONCLUSION: A single 25-microg outpatient intravaginal dose of misoprostol is effective in decreasing the interval to delivery in women with unfavorable cervices at term.     

Abnormal uterine bleeding: medical treatment with vaginal danazol and five-year follow-up

STUDY OBJECTIVE: To evaluate the clinical efficacy and patient satisfaction of long-term danazol delivered vaginally as treatment for heavy menstrual bleeding. DESIGN: Prospective study (Canadian Task Force classification II-3). SETTING: University hospital. PATIENTS: Twenty premenopausal women with endometrial hyperplasia or endometrial polyps. INTERVENTION: After curettage or hysteroscopic-directed biopsies, women used one 200-mg tablet of danazol vaginally every day, continuing the therapy as long as they were totally satisfied with it. MEASUREMENTS AND MAIN RESULTS: Women were instructed to keep a diary of menstrual bleeding and to rate blood loss on a visual analog scale from zero (no blood loss) to 10 (gushing-type bleeding). They were seen every month for 3 months, then every 3 months for 9 months, and then every 6 months for 4 years for Papanicolau smear, pelvic examination, and transvaginal ultrasonography. They were asked to bring their diary of menstrual bleeding. They were asked about side effects and their satisfaction with the therapy. Peripheral blood was drawn for blood count and serum chemistries. Hysteroscopic-directed biopsies were repeated after 3 months of therapy in women with endometrial hyperplasia. The severity of blood loss was significantly reduced in all women after 3 months of treatment. All women with endometrial hyperplasia had regression of hyperplastic endometrium. None of the women with endometrial polyps had sonographic signs of recurrence during therapy. Only 10 women (50%) completed 1-year follow-up, and only 5 women (25%) completed 5-year follow-up. CONCLUSION: These results suggest that long-term administration of vaginal danazol after curettage or hysteroscopic-directed biopsy is both efficacious and safe in women with heavy menstrual bleeding, but the rate of discontinuance is high.     

Neurotoxicity of amphetamine derivatives is mediated by caspase pathway activation in rat cerebellar granule cells

The neurotoxic action of the abuse drugs methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA) on cerebellar granule neurones (CGNs) culture was examined. Treatment for 48 h with METH or MDMA (1-5 mM) induced a higher decrease in viability than 24 h treatment. z.VAD.fmk (100 microM) but not MK-801 nor NBQX recovered control viability values. In both cases, cell death was characterised as apoptotic rather than necrotic by morphology cell observation. Apoptosis measured by flow cytometry indicated an increase in the hypodiploid population after 48 h treatment with METH and MDMA. Apoptosis was reverted by the presence of z.VAD.fmk (100 microM) but not by 10 microM MK-801 or NBQX. Similar results were obtained by analysing nuclear chromatine condensation. These results ruled out excitotoxic participation in amphetamine derivative-induced neurotoxicity in CGNs. Participation of radical oxygen species (ROS) was evaluated using alpha-tocopherol (1-15 microM) and cytometric studies. The co-treatment with 4 mM METH or MDMA for 48 h partially reverted neurotoxic action and apoptotic features, indicating ROS implication in CGNs death by amphetamine derivatives. Alteration of mitochondrial function induced cytochrome C (Cyt C) release after 48-h treatment with METH and MDMA (4 mM). There was also indication of caspase-3-like activation, measured by immunoanalysis and biochemically. Finally, neurodegenerative action caused by amphetamine derivatives may be prevented by using caspase inhibitors.