Complications after Single versus Dual Chamber Pacemaker Implantation

To compare the complication rate in patients having a dual chamber versus a single chamber pacing system, 337 consecutive procedures performed during a 3-year period were analyzed prospectively. Two hundred fifty-eight patients (77%) received a VVI pacemaker and 75 (23%) a DDD unit. Thirteen VVI (5%) and 4 DDD (5.3%) needed reintervention. Lead displacement with reoperation was required for three ventricular leads (1%) and one atrial lead (1.3%). Infection occurred in two VVI units (0.77%) and one DDD (1.33%) unit. Muscular stimulation was noticed among three DDD (4%) and nine VVI systems (3.5%). Urgent reprogramming was needed for 23 VVI (9%) and six DDD units (8%). There was no increase in complications with dual chamber pacing compared to single chamber systems.     

CYP1B1 mutation profile of Iranian primary congenital glaucoma patients and associated haplotypes

The mutation spectrum of CYP1B1 among 104 primary congenital glaucoma patients of the genetically heterogeneous Iranian population was investigated by sequencing. We also determined intragenic single nucleotide polymorphism (SNP) haplotypes associated with the mutations and compared these with haplotypes of other populations. Finally, the frequency distribution of the haplotypes was compared among primary congenital glaucoma patients with and without CYP1B1 mutations and normal controls. Genotype classification of six high-frequency SNPs was performed using the PHASE 2.0 software. CYP1B1 mutations in the Iranian patients were very heterogeneous. Nineteen nonconservative mutations associated with disease, and 10 variations not associated with disease were identified. Ten mutations and three variations not associated with disease were novel. The 13 novel variations make a notable contribution to the approximately 70 known variations in the gene. CYP1B1 mutations were identified in 70% of the patients. The four most common mutations were G61E, R368H, R390H, and R469W, which together constituted 76.2% of the CYP1B1 mutated alleles found. Six unique core SNP haplotypes were identified, four of which were common to the patients with and without CYP1B1 mutations and controls studied. Three SNP blocks determined the haplotypes. Comparison of haplotypes with those of other populations suggests a common origin for many of the mutations.     

Chronic epinephrine treatment fails to alter prejunctional adrenoceptor modulation of sympathetic neurotransmission in the rat mesentery.

Rats were treated chronically with epinephrine (EPI-T; 100 micrograms/kg/hr, s.c.) for 6 days. On day 6 of treatment, the rats were anesthetized and the mesenteric vascular bed was isolated and perfused with Krebs' bicarbonate buffer containing cocaine (10 microM) and corticosterone (40 microM). Stimulus-induced (2 Hz, 120 pulses) overflow of neurotransmitter and its modulation by prejunctional adrenoceptors was studied. After chronic exposure to EPI, 50% of the mesenteric catecholamine stores consisted of EPI with no increase in total catecholamine content as compared to the control group (C). Absolute and fractional overflows of catecholamines upon periarterial nerve stimulation (2 Hz, 1 min) were not significantly different in the two groups. Beta adrenoceptor blockade by propranolol (10(-10) to 10(-6) M) did not alter the overflow of catecholamines. Alpha adrenoceptor blockade by phentolamine (10(-5) M) increased neurotransmitter overflow in both EPI-T and C groups. However, there was no significant difference in total catecholamine overflows between the two groups. Moreover, in the presence of phentolamine, propranolol (10(-6) M) remained without effect on overflow in both groups. These data suggest that EPI-T did not significantly increase the stimulus-induced overflow of catecholamines in the rat mesentery, nor did EPI-T result in prejunctional beta adrenoceptor modulation of neurotransmitter release in the mesenteric vascular bed.     

Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 (PPARgamma-2) gene is associated with greater insulin sensitivity and decreased risk of type 2 diabetes in an Iranian population.

BACKGROUND: The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 (PPARgamma-2) gene has been variably associated with insulin resistance, obesity and type 2 diabetes in several populations. However, this association has not been studied in Iranian subjects and we hypothesized that this variation might be associated with insulin resistance, type 2 diabetes and related metabolic traits in this population. METHODS: The Pro12Ala genotypes were determined by PCR-restriction fragment length polymorphism in 696 unrelated subjects including 412 non-diabetic controls and 284 type 2 diabetic patients. RESULTS: The frequency of the Ala allele was 9.4% and 5.9% in controls and type 2 diabetic subjects, respectively [adjusted odds ratio (OR) 0.457, p=0.005]. The Ala allele did not show a significant effect on anthropometric and biochemical parameters in the type 2 diabetic group, whereas in non-diabetic subjects, carriers of the Ala allele had significantly lower fasting insulin (p=0.007) and homeostasis model assessment of insulin resistance (HOMA-IR) (p=0.009) levels compared to Pro/Pro subjects. Multivariate logistic regression analysis showed that Pro12Ala polymorphism was an independent determinant of type 2 diabetes in this population. CONCLUSIONS: Our results for a sample of Iranian type 2 diabetes cases and controls provide evidence that the Pro/Ala genotype of the PPARgamma-2 gene is associated with insulin sensitivity and may also have protective role against type 2 diabetes.     

Decreasing plasma soluble IL‐1 receptor antagonist and increasing monocyte activation early post‐transplant may be involved in pathogenesis of delayed graft function in renal transplant recipients

Sadeghi M, Daniel V, Naujokat C, Schmidt J, Mehrabi A, Zeier M, Opelz G. Decreasing plasma soluble IL‐1 receptor antagonist and increasing monocyte activation early post‐transplant may be involved in pathogenesis of delayed graft function in renal transplant recipients
Clin Transplant 2010: 24: 415–423. © 2009 John Wiley & Sons A/S. Abstract: Delayed graft function (DGF) increases the risk of acute allograft rejection and may affect long‐term graft survival. We compared pre‐transplant, early post‐transplant, and late post‐transplant serum creatinine (Cr) and plasma levels of neopterin, cytokines, and cytokine receptors/antagonists in patients with DGF (n = 39), slow graft function (SGF) (n = 43), or immediate graft function (IGF) (n = 30). Three and eight days post‐transplant, plasma neopterin (p < 0.001; p < 0.001), Soluble Interleukin‐6 (IL‐6) receptor (R) (p = 0.002; p = 0.001), and IL‐10 (p = 0.003; p = 0.001) were higher in DGF than IGF patients. One month post‐transplant, plasma neopterin (p < 0.001) and IL‐10 (p < 0.001) were higher in DGF than IGF patients. Three days post‐transplant, the results indicated reduced sIL‐1 receptor antognist (RA) production in DGF patients (p = 0.001). Simultaneously, plasma sIL‐6R and IL‐10 increased in DGF (p < 0.001; p = 0.003) and SGF (p = 0.007; p = 0.030) patients, indicating increased production of sIL‐6R and IL‐10. Lower sIL‐1 production in DGF than IGF patients early post‐transplant might promote the increased production of monocyte‐derived neopterin, sIL‐6R, and IL‐10. This monocyte/macrophage activation might induce inflammation in the graft and subsequently cause an impairment of graft function. Blocking of monocyte activity after renal transplantation may be considered a potential approach for improving graft outcome.     

Neue Entwicklungen der endovenösen Lasertherapie

Endovenous laser therapy (ELT) has been applied in clinical practice as a therapy for truncal vein insufficiency for about 10 years now. One characteristic of ELT is the broad spectrum of different treatment protocols using a variety of laser systems and forms of endovenous application. Despite good clinical results with effective and relatively pain-free occlusion of insufficient truncal veins, undesired side effects such as ecchymoses, phlebitis, and recanalization have been observed. These can be traced mainly to thermal lesions in the vein wall and are focused in spots with perforations and transmural ablations of the tissue. In recent years, systematic experimental investigations and the analysis of clinical results have increased understanding of the connection between endovenous laser application and clinical results. This has led to continuous development and optimization of ELT. In particular, the use of longer wavelengths, radially irradiating fiber optic cables, and endovenous laser irradiation with continuous pull-back of the optical fiber seem to have a positive influence on occlusion rate and side effects. As a result, ELT treatment is coming closer to the goal of a standardized effective method for treating varicose veins. Further controlled studies are required to compare optimized ELT with other endovenous modes of treatment and open surgery.     

Multimodal integration after unilateral labyrinthine lesion: single vestibular nuclei neuron responses and implications for postural compensation

Plasticity in neuronal responses is necessary for compensation following brain lesions and adaptation to new conditions and motor learning. In a previous study, we showed that compensatory changes in the vestibuloocular reflex (VOR) following unilateral vestibular loss were characterized by dynamic reweighting of inputs from vestibular and extravestibular modalities at the level of single neurons that constitute the first central stage of VOR signal processing. Here, we studied another class of neurons, i.e., the vestibular-only neurons, in the vestibular nuclei that mediate vestibulospinal reflexes and provide information for higher brain areas. We investigated changes in the relative contribution of vestibular, neck proprioceptive, and efference copy signals in the response of these neurons during compensation after contralateral vestibular loss in Macaca mulata monkeys. We show that the time course of recovery of vestibular sensitivity of neurons corresponds with that of lower extremity muscle and tendon reflexes reported in previous studies. More important, we found that information from neck proprioceptors, which did not influence neuronal responses before the lesion, were unmasked after lesion. Such inputs influenced the early stages of the compensation process evidenced by faster and more substantial recovery of the resting discharge in proprioceptive-sensitive neurons. Interestingly, unlike our previous study of VOR interneurons, the improvement in the sensitivity of the two groups of neurons did not show any difference in the early or late stages after lesion. Finally, neuronal responses during active head movements were not different before and after lesion and were attenuated relative to passive movements over the course of recovery, similar to that observed in control conditions. Comparison of compensatory changes observed in the vestibuloocular and vestibulospinal pathways provides evidence for similarities and differences between the two classes of neurons that mediate these pathways at the functional and cellular levels.     

Activated alphavbeta3 integrin targeting in injury-induced vascular remodeling

There is currently no imaging modality to track the remodeling process, a common feature of a broad spectrum of vasculopathies, in vivo. alphavbeta3 Integrin is up-regulated in proliferating vascular cells. RP748, a novel peptidomimetic tracer, binds specifically to the activated alphavbeta3 conformer and exhibits favorable binding characteristics for in vivo imaging. In a model of injury-induced vascular remodeling in apoE null mice, RP748 localization to the injured carotid arteries parallels vascular cell proliferation, providing an opportunity to image the remodeling process in vivo.     

Topiramate add-on treatment in schizophrenia: a randomised, double-blind, placebo-controlled clinical trial

Glutamate antagonists such as topiramate have been proposed based on the glutamate hypothesis of schizophrenia because its properties encourage its exploration and possible development as a medication for the treatment of schizophrenia. A randomised, double-blind, placebo-controlled clinical trial was performed on 18- to 45-year-old patients with schizophrenia. Baseline information including vital signs, height, weight, smoking status, demographic characteristics, (past) psychiatric history, medication history and medication-related adverse effects were collected. Patients were randomly assigned to a topiramate or placebo group. Efficacy of medication was measured by administering Positive and Negative Syndrome Scale (PANSS), and tolerability of treatment was recorded on day 0 (baseline), day 28 and day 56. PANSS values (95% confidence interval) at baseline, day 28 and day 56 in the topiramate group were 96.87 (85.37-108.37), 85.68 (74.67-96.70) and 76.87 (66.06-87.69), respectively; compared with 101.87 (90.37-113.37), 100.31 (89.29-111.32) and 100.56 (89.74-111.37) in the placebo group. General linear model for repeated measures analysis showed that topiramate has lowered PANSS values significantly compared with the placebo group. Similar significant decline patterns were found in all three subscales (negative, positive and psychopathology sign). Clinical response (more than 20% reduction in PANSS) was significantly higher in topiramate-treated subjects than controls (50% vs 12.5%). Topiramate can be an effective medication in controlling schizophrenic symptoms, considering its effect on negative symptoms and controlling antipsychotic-associated weight gain.