Neurological complications of balloon angioplasty in children

Summary We report on the occurrence of cerebrovascular accidents as a possible complication of balloon angioplasty in children. The first patient underwent balloon angioplasty for aortic stenosis and subsequently developed a right temporoparietal infarct in the vascular territory of the right middle cerebral artery. The second patient developed a right temporoparietal infarct also in the vascular territory of the right middle cerebral artery following balloon angioplasty of native coarctation of the aorta. This experience suggests that, in addition to the previously reported complications of balloon angioplasty, the occurrence of a potential cerebrovascular accident must be considered in the risk-benefit analysis of this procedure.     

Identification of the monomeric G-protein, Rhes, as an efaroxan-regulated protein in the pancreatic beta-cell

Efaroxan induces membrane depolarization by interaction with the pore forming subunit of the ATP-sensitive potassium channel, Kir6.2. However, this effect is not responsible for its full secretory activity. In this study we have used an anti-idiotypic approach to generate antibodies that recognize additional proteins that may be regulated by efaroxan in pancreatic beta-cells. Using these antisera in an expression cloning strategy we have identified a monomeric GTP-binding protein, Rhes, as a potential target for regulation by imidazoline ligands. Rhes is shown to be expressed in beta-cells and its expression is regulated by efaroxan under conditions when a structurally related molecule, KU14R, is ineffective. The results reveal that beta-cells express Rhes and suggest that changes in the expression of this molecule may regulate the sensitivity of beta-cells to imidazoline secretagogues.     

Long-term results of TPMT activity monitoring in azathioprine-treated renal allograft recipients

Thiopurine methyltransferase (TPMT) is implicated in the metabolism of azathioprine. The consequences of differential TPMT activity induction by azathioprine on the long-term results after renal transplantation were investigated. The erythrocyte TPMT activity in 82 patients on days 0, 7, and 30 was prospectively evaluated. Because various patterns of TPMT activity variation were noted, the population was subsequently divided between inductors (n = 47) and noninductors (n = 35). Data regarding patient and graft survival and acute rejection episodes were collected. Renal allograft assessment was performed at 3 mo and 2 yr to evaluate the renal function and the histologic lesions on routine biopsies. Data regarding azathioprine-related toxicity also were collected. In a subgroup of patients (n = 19), azathioprine blood levels were determined at day 7 and day 30. The graft survival censoring death was statistically improved in TPMT inductor patients when compared with non-TPMT inductors (P < 0.05). Among TPMT inductors, an acute rejection episode was observed in 34% of the patients versus 69% among non-TPMT inductors (P = 0.002). At 3 mo, serum creatinine was significantly lower among TPMT inductors when compared with non-TPMT inductors (123.1 +/- 7.6 and 161.4 +/- 13.9 micromol/L, respectively; P = 0.01). On routine allograft biopsies at 2 yr (n = 61), grade 2 or 3 chronic lesions were present in 19% versus 25%, respectively (P = NS). At days 7 and 30, the azathioprine blood levels were higher among patients who experienced acute rejection (P < 0.02). TPMT activity induction was observed in 57% of renal transplant recipients who received azathioprine. This induction was associated with better graft outcome. The appropriate conversion from azathioprine, which is a pro-drug, into 6-mercaptopurine could explain both better graft outcome and TPMT induction. Assessing the ability of azathioprine metabolism at an individualized level before transplantation may allow a more accurate choice among the different immunosuppressive treatments.     

Laser oximetry: A novel noninvasive method to determine changes in penile hemodynamics in an anesthetized rabbit model

This study was designed to determine the utility and validity of laser oximetry in measuring changes in penile hemodynamics. Anesthetized male New Zealand White Rabbits were divided into 2 groups, and penile hemodynamics were assessed by either laser oximetry (oxyhemoglobin, deoxyhemoglobin concentration, and oxygen saturation) or intracavernosal pressure (ICP) monitoring during penile erection induced by pelvic nerve stimulation (PNS) or intracavernosal administration of phentolamine, nitroprusside, papaverine, or sildenafil. PNS caused significant frequency-dependent increases in penile ICP. PNS also caused significant increases in penile tissue oxyhemoglobin concentrations and tissue oxygen saturation in a frequency-dependent manner. The changes in oxyhemoglobin concentrations and oxygen saturation correlated with frequency-dependent increases in ICP. Intracavernosal vasoactive drug administration produced significant increases in ICP, tissue oxyhemoglobin concentration, oxygen saturation, and duration of response as a function of increasing drug concentration. Laser oximetry permits reproducible and valid assessment of changes in penile hemodynamics comparable to conventional ICP measurements. Thus, we consider laser oximetry a reliable technique in evaluating penile hemodynamics. Its sensitivity in detecting small changes in oxyhemoglobin concentration and its noninvasive nature make it advantageous over invasive methods such as ICP monitoring and laser Doppler flowmetry.     

Circulating leptin levels and weight loss in Alzheimer's disease patients

Weight loss is common in Alzheimer's disease (AD) and is predictive of mortality. Leptin, an adipocyte-derived peptide hormone is implicated in the regulation of satiety and energy expenditure. It acts on the hypothalamus to suppress appetite and increase energy expenditure. We undertook this study to determine if inappropriately elevated leptin levels play a role in AD-associated weight loss. Serum leptin levels of 8 patients in each of the following groups were determined: (1) AD, body mass index (BMI) >25; (2) AD, BMI <20; (3) non-Alzheimer's (vascular) dementia (VaD), BMI >25, and (4) VaD, BMI <20. Mean serum leptin levels were significantly lower in below-appropriate-weight patients (both AD and VaD) than in appropriate-weight controls. Below-appropriate-weight AD patients had a significantly lower mean serum leptin concentration than appropriate-weight VaD controls. Weight loss is a feature of AD. Inappropriately elevated leptin levels do not appear to be implicated. Indeed, we have shown that the afferent limb of the leptin feedback loop is intact in below-appropriate-weight AD patients and suggest hypothalamic dysfunction may underlie this feature.     

Biologic alternatives to stents and grafts

The quest for biologic alternatives to stents and arterial grafts is a source of intense research at the basic and preclinical level. Several new devices and conduits currently under investigation may extend the uses of both stents and grafts beyond their current revascularization role into newer applications in the fields of regional pharmacology and gene therapy. This exciting prospect, although still unrealized, has general medical implications beyond cardiovascular disease. Development of such synergies between device, grafts, pharmacologic, molecular, and tissue engineering research is essential if the burgeoning data on new therapeutic genes is to be harnessed for clinical benefit.     

A Canadian model for developing mental health services in rural communities through linkages with urban centers

The development of mental health care services in rural areas has been a constant challenge in most countries of significant geographical size. By use of a case study from Canada, the development of a relationship between rural and urban mental health services was described. Issues including referral patterns, service accessibility, professional recruitment and the development of service in rural regions were studied. It is advanced that mental health administrators, policy-makers, clinical service coordinators and educators will find that this approach to the development of mental health services in rural areas has some utility in Canada and in other countries.