The mitochondrial K(ATP) channel opener BMS-191095 reduces neuronal damage after transient focal cerebral ischemia in rats.

Activation of mitochondrial ATP-sensitive potassium (mitoK(ATP)) channels protects the brain against ischemic or chemical challenge. Unfortunately, the prototype mitoK(ATP) channel opener, diazoxide, has mitoK(ATP) channel-independent actions. We examined the effects of BMS-191095, a novel selective mitoK(ATP) channel opener, on transient ischemia induced by middle cerebral artery occlusion (MCAO) in rats. Male Wister rats were subjected to 90 mins of MCAO. BMS-191095 (25 microg; estimated brain concentration of 40 micromol/L) or vehicle was infused intraventricularly before the onset of ischemia. In addition, the effects of BMS-191095 on plasma and mitochondrial membrane potentials and reactive oxygen species (ROS) production in cultured neurons were examined. Finally, we determined the effects of BMS-191095 on cerebral blood flow (CBF) and potassium currents in cerebrovascular myocytes. Treatment with BMS-191095 24 h before the onset of ischemia reduced total infarct volume by 32% and cortical infarct volume by 38%. However, BMS-191095 administered 30 or 60 mins before MCAO had no effect. The protective effects of BMS-191095 were prevented by co-treatment with 5-hydroxydecanoate (5-HD), a mitoK(ATP) channel antagonist. In cultured neurons, BMS-191095 (40 micromol/L) depolarized the mitochondria without affecting ROS levels, and this effect was inhibited by 5-HD. BMS-191095, similar to the vehicle, caused an unexplained but modest reduction in the CBF. Importantly, BMS-191095 did not affect either the potassium currents in cerebrovascular myocytes or the plasma membrane potential of neurons. Thus, BMS-191095 afforded protection against cerebral ischemia by delayed preconditioning via selective opening of mitoK(ATP) channels and without ROS generation.     

Voice prosthesis insertion after endoscopic balloon-catheter dilatation in case of a stenotic hypopharyngo-oesophageal junction

Stenosis of the hypopharyngo-oesophageal junction can be a rare complication of laryngectomy and/or partial pharyngectomy and makes the insertion of voice prosthesis extremely difficult. This study describes the authors’ experiences gained by endoscopic balloon-catheter dilatation of hypopharyngo-oesophageal stenoses prior to implantation of voice prostheses in four cases. In two patients a single balloon-catheter dilatation resulted in wide enough pharyngo-oesophageal lumen on the long run. The average prosthesis wearing-times were 6.8 months in case 1 and 4.6 months in case 2, corresponding to the published literature data. In case 3, repeated dilatation of the pharyngo-oesophageal transition had proved to be unsuccessful despite taking every effort with the endoscopic balloon-catheter method. Having excised the stenotic segment, reconstruction with pectoralis major myocutaneous flap (PMMF) was indicated. Eighteen months later, a repeated restenosis was observed and a free jejunal flap needed to be performed as a final solution. In case 4, the insertion was carried out into a previously dilated jejunal free flap, which became gradually ischemic and stenotic since the major head-and neck procedure was carried out that resulted in prosthesis rejection after just 1 week. The authors emphasize that correct indication of pedicled and free flaps in head and neck reconstruction is a prerequisite from the aspect of prevention of pharyngo-oesophageal strictures. Endoscopic balloon-catheter dilatation is a safe and established method for dilatating hypopharyngo-oesophageal stenoses of different origin. The procedure provides maximum patient benefit with minimal trauma and morbidity; moreover, facilitates insertion of voice prostheses. However, a single balloon-catheter dilatation cannot always result in wide enough oesophageal lumen on the long run (case 3). Insertion of a voice prosthesis into a previously dilated ischemic jejunal segment is challenging and avoidable due to risks of complications.     

Surgical wound infection by Aspergillus fumigatus in liver transplant recipients.

Cutaneous aspergillosis is generally associated with immunosuppression, burns, and major trauma. Most cases are acquired by direct inoculation, although cutaneous involvement does occasionally occur with disseminated disease. Surgical wound infections caused by Aspergillus species are very unusual and to our knowledge have not been described in the setting of organ transplantation. We describe two liver transplant recipients who developed wound aspergillosis during a nosocomial outbreak of Aspergillus infection. Infection developed in the second and fourth postoperative week respectively, and in both cases wound appearance mimicked necrotizing fasciitis. Both patients died despite local debridement and antifungal therapy with amphotericin B. Aspergillus must be added to the list of potential pathogens of surgical wounds, especially in the setting of organ transplantation.     

Treatment of severe acute lung allograft rejection with OKT3 and temporary extracorporeal membrane oxygenation bridging.

OBJECTIVES: The use of OKT3 for treatment of advanced high-grade acute rejection episodes eventually can result in cytokine release and consecutive pulmonary edema. Temporary extracorporeal membrane oxygenation (ECMO) bridging can be used to overcome this crucial period before the beneficial effects of OKT3 can be observed. METHODS: We summarize our experience with three patients, who underwent lung transplantation and presented with severe acute rejection episodes. OKT3 had to be initiated due to insufficient response to standard rejection therapy with corticosteroids. Upon initiation of OKT3 treatment, a massive life-threatening deterioration of lung function in spite of heavily invasive respirator treatment was seen and temporary ECMO support was imperative to support graft function. Results of this treatment were retrospectively reviewed. RESULTS: In all cases femoro-femoral veno-arterial ECMO was used for support of the impaired graft and after a period of 4-5 days led to a massive improvement of graft function. In the further course two patients could be discharged from hospital and are still alive 30 and 36 months, respectively, after the described incident. One patient died 4 months later due to liver failure. CONCLUSIONS: We conclude that the use of ECMO support in patients experiencing significant side effects from OKT3 therapy is a useful and effective therapeutic tool to overcome the initial critical period until the lung has sufficiently recovered.     

Magnesium-orotate supplementation for idiopathic infertile male patients: a randomized, placebo-controlled clinical pilot study.

A randomized, placebo-controlled clinical pilot study was performed in order to examine the effect of magnesium-orotate in male idiopathic infertility. Ten males were treated daily for 90 consecutive days with 3000 mg magnesium-orotate (Magnerot) tablets (Group M). As a control, ten other males were treated in the same way with placebo (Group P). Conventional microscopic sperm characteristics (sperm concentration, motility ratio, total number of motile sperm cells, normal morphology ratio), plus total and ionized magnesium levels in seminal plasma and blood serum were evaluated both prior to treatment and on day 90, at the conclusion of the study. No significant changes in sperm characteristics, blood ionized or total Mg, or ejaculate total Mg levels were detected. However, ejaculate ionized Mg levels increased in Group M from 0.18 +/- 0.05 to 0.30 +/- 0.05 (mmol/l; mean +/- SD, p < 0.05). Within the observation period of 3 months, one pregnancy occurred in the partner of a male from Group M. In conclusion, magnesium-orotate treatment at a dose of 3000 mg/day leads neither to a significant improvement of sperm variables nor does it increase the pregnancy rates of female partners of treated males as compared to those of controls. Thus, magnesium-orotate treatment was not shown to be effective therapy for idiopathic male infertility.     

Characteristics of pollinosis caused by Betula in patients from Ourense (Galicia, Spain).

A retrospective study was performed to describe the features of the pollinosis caused by Betula in the area of Ourense, Spain. The pollen count was carried out with a Lanzoni volumetric Hirts spore trap (1993-2000). The Betula pollen represented 5% over the annual total (annual mean quantity: 965 grains). It was present in the air from March to mid-May. The highest peaks took place in April (maximum values mean: 131 grains/m3). The medical records of 222 patients (mean age 25.66 years) diagnosed with pollinosis (1998-2000), who lived at less than 30 km. from the spore trap, were reviewed. In all of them, the skin-prick test (SPT) was carried out with pollen allergens. The percentages of positive SPT were: Lolium perenne, 91.89% (16.6% monosensitized); Plantago lanceolata, 71.17% (1.26% monosensitized); Betula alba, 41.89% (10.75% monosensitized); Platanus hybrida, 34.95%; Olea europea, 10.36%; and Parietaria judaica, 6.3%. The mean age of Betula monosensitized patients was 44.7 years. The majority of them had symptoms in March-April, 40% had asthma symptoms, 80% had lived in Central Europe, and 30% of them presented an oral allergy syndrome to fruits. There were 41.93% of the patients with positive SPT to Betula pollen who had asthma symptoms, in comparison with 23.25% of the patients with negative SPT to Betula (p = 0.0034). There were 20.28% of the patients with positive SPT to Betula pollen, who had lived in Central Europe, in comparison with 4.27% of the patients with negative SPT to Betula, p: 0.00049. The relative risk of sensitization was 2.05. CONCLUSIONS: Betula pollen was the second cause of clinical pollinosis in our patients, after grass, being responsible of the symptoms in the early spring, in a small number of the patients in their forties. The presence of asthma was higher in Betula sensitized patients, and the residence in Central Europe was a sensitization risk factor.