Partial angiotensin-converting enzyme inhibition during acute orthostatic stress in persons with tetraplegia

INTRODUCTION: Individuals with tetraplegia rely on the renin-angiotensin system for orthostatic blood pressure control. OBJECTIVES: To determine the effect of partial angiotensin-converting enzyme (ACE) inhibition on heart rate (HR), active plasma renin (PR), and mean arterial blood pressure (MAP) during acute orthostasis in subjects with tetraplegia (n = 7) and nondisabled persons (n = 8). METHODS: Subjects were instructed to avoid caffeine and alcohol for 24 hours before testing and to report to the laboratory between 10 AM and 1 PM. Progressive head-up tilt (15 degrees, 25 degrees, 35 degrees, and 45 degrees) was performed on 2 separate days; Day 1: without ACE inhibition; Day 2: after intravenous (IV) infusion of enalaprilat (0.625 mg). RESULTS: HR was reduced during orthostasis in the tetraplegia compared with the nondisabled group (P < 0.0001), and was unaffected by ACE inhibition in either group. PR was not increased with orthostasis in either group, but was increased after ACE inhibition in both groups (P < 0.001). MAP was not affected by orthostasis in either group, but was reduced with ACE inhibition in both groups (P < 0.01). In the tetraplegia group, MAP was initially reduced after ACE inhibition, but was maintained thereafter with increasing angles of tilt, and no subject complained of symptomatic orthostatic hypotension. CONCLUSION: Subjects with tetraplegia were tolerant of an acute bout of orthostatic stress after partial ACE inhibition. This may have clinical relevance because of the increased prevalence of type 2 diabetes mellitus in this population and the use of ACE inhibitors for the treatment of progressive renal and cardiovascular disease.     

Long-term outcome of patients with antineutrophil cytoplasmic autoantibody-associated vasculitis with renal involvement

BACKGROUND: Despite treatment, renal involvement in antineutrophil cytoplasmic autoantibody (ANCA)-positive vasculitis is still associated with significant long-term mortality and remains an important cause of end-stage renal failure. METHODS: We retrospectively analyzed a series of 61 consecutive patients with newly diagnosed ANCA-associated renal vasculitis (54.1% Wegener's granulomatosis, 23% renal-limited vasculitis, 16.4% microscopic polyangiitis, 4.9% Churg-Strauss syndrome) diagnosed between 1986 and 1997. RESULTS: The median creatinine level at diagnosis was 221.5 (63-762) micromol/l, i.e. 2.5 (0.7-8.6) mg/dl, 32.8% were dialysis-dependent. All patients were treated with cyclophosphamide. Remission was achieved in 87% of patients. Relapses occurred in 44.7%. The median renal disease-free interval was 62.5 (0-138) months. The estimated patient survival at 5 and 10 years was 78.3 and 62.2%, respectively. Mortality was associated with age (p = 0.04 when age limit 50 years) and advanced renal failure (p = 0.038 when compared dialysis-dependent and independent patients). Estimated renal survival time at 5 and 10 years was 69.2 and 55.8%, respectively. At the end of follow-up, 50.8% of patients were in complete remission, 31% had died. The median serum creatinine level was 137.5 (77-469) micromol/l, i.e. 1.56 (0.87-5.3) mg/dl, 24.6% of patients were on regular dialysis treatment. CONCLUSION: Patient survival, relapse rate and mortality were comparable to similar reports. In view of the severity of the renal disease and the length of follow-up, renal survival was very good. Despite effective treatment, the long-term outcome of patients with ANCA-associated renal vasculitis remains unsatisfactory.     

Surgical treatment of the knee osteoarthritis

Surgical treatment of initial osteoarthritis consists of palliative arthroscopic operation, joint toilet, arthroscopic lavage, chondrectomy, meniscectomy, sinovyectomy, meniscus toilet, abrasion arthroplasty, microfracture, mosaicplasty, transplantation of autologic chondrocytes. To cure deviation of axis it is proposed corrective osteotomy in pre-osteoarthritis phase. Partial or total arthroplasty is recommended in treatment of advanced knee degenerative process.     

Cervids as Babesiae hosts, Slovenia

We describe cervids as potential reservoir hosts of Babesia EU1 and B. divergens. Both babesial parasites were found in roe deer. Sequence analysis of 18S rRNA showed 99.7% identity of roe deer Babesia EU1 with the human EU1 strain. B. divergens detected in cervids was 99.6% identical to bovine B. divergens.     

The impact of sleep deprivation on product quality and procedure effectiveness in a laparoscopic physical simulator: a randomized controlled trial

BACKGROUND: To compare the impact of sleep deprivation after 24-hour duty (post-call) with that of 8-hour work (post-work) on product quality (PQ) and procedure effectiveness (PE) in a laparoscopic physical simulator. METHODS: Voluntary surgeons and nurses were pretested with the Epworth Sleepiness Scale (ESS) and Minimally Invasive Surgical Trainer-Virtual Reality (MIST-VR). Surgical task was suturing perforated ulcer on a foam stomach in a physical simulator. PQ and PE were measured by accuracy error (AE), tissue damage (TD) leak rate (LR), goal- (GDA) non-goal-directed actions (NGDA), and operating time (OT), respectively. Construct validity was assessed comparing measures when surgeons and nurses performed the surgical task. Inter-rater reliability (IRR) was assessed by Kendall's tau b coefficient. An 80% power parallel block randomization design at alpha = .05 required 60 subjects. RESULTS: Thirty-two post-call surgeons and 32 post-work surgeons were well matched for age, gender, practice duration, and ESS and MIST-VR scores. The amount of time slept in the previous 24 hours was 1.5 versus 6.5 hours (P < .05). AE (1.0 mm vs. .5 mm), TD (2.18 mm vs. 2.18 mm), LR (56.2% vs. 65.6%), GDA (33.5 vs. 32.5), NGDA (.56 vs. .31), and OT (381.0 seconds vs. 364.5 seconds) were not significantly different when 32 surgeons in the post-call arm were compared with their 32 counterparts in the post-work arm, respectively. Construct validity was shown by significant improvement in 4 outcome measures (AE 1.0 mm vs. 2.0 mm, P = .00001; GDA 32.5 vs. 39.0, P = .07, NGDA .43 vs. .96, P = .045; and OT 377.5 vs. 557.0, P = .0005) when 64 surgeons performed the task as compared to 64 nurses. Tau b for IRR was 1.0 (P < .0001) for AE, TD, LR, and OT, .75 (P = .325) for GDA, and .77 (P = .305) for NGDA. CONCLUSIONS: Sleep deprivation had no impact on the studied outcome measures of a surgical task performed in a laparoscopic simulator.     

Chronobiological aspects of adult-onset Crohn disease

PURPOSE: To study the time course of Crohn disease and its signs. To compare the results with the world literature and draw conclusions for practice. BASIC PROCEDURES: Fifty-six patients were studied retrospectively: 31 males aged 19-48 years with disease duration 1-8 years, and 25 females aged 21-65 with disease duration 1-13 years. The disease was active (Crohn disease activity index > 150) in 25 patients and inactive in 31. Plasma levels of interleukin-6 (normal upper value 8 pg/ml) were investigated with radioimmunoassay. Bone mineral density was measured as the T-score (normal range between -1 and 0 standard deviations) in the forearm using dual-energy X-ray absorptiometry. The seasonality of births of the patients in relation to the total Slovak population and seasonality of severity of three important disease signs were examined with Halberg cosinor regression. The dependence of the signs on age and duration of disease was evaluated using quadratic regression. Results are presented as 95% confidence intervals (for means) and 95% tolerance intervals (for individuals). The level of statistical significance was set at alpha = 0.05. MAIN FINDINGS: Significant seasonality in births was found: decreased frequency in May-June and increased frequency in September-January. Significant spring elevation of interleukin-6 levels, accompanied by significant spring rise of the disease activity index and by decrease of bone density, is described. Among patients with active disease, interleukin-6 levels significantly increased up to the age of 41 years, whereas linear increase of disease activity during aging was on the borderline level of significance in the same subgroup. No significant age trend was encountered in T-score for either subgroup. The same was true for interleukin-6 and disease activity versus duration. Significant decrease in T-score paralleled disease duration up to seven years in the subgroup with active disease. PRINCIPAL CONCLUSIONS: The course of Crohn disease is influenced by time, including the seasons of the year. However, this does not find full agreement in the world literature, probably because of geographic, socioeconomic and epidemiologic differences, as well as varying approaches in method. In practice, regular monitoring of the time course is necessary in provision of appropriately timed treatment.     

Fast, long-range, reversible conformational fluctuations in nucleosomes revealed by single-pair fluorescence resonance energy transfer

The nucleosome core particle, the basic repeated structure in chromatin fibers, consists of an octamer of eight core histone molecules, organized as dimers (H2A/H2B) and tetramers [(H3/H4)2] around which DNA wraps tightly in almost two left-handed turns. The nucleosome has to undergo certain conformational changes to allow processes that need access to the DNA template to occur. By single-pair fluorescence resonance energy transfer, we demonstrate fast, long-range, reversible conformational fluctuations in nucleosomes between two states: fully folded (closed), with the DNA wrapped around the histone core, or open, with the DNA significantly unraveled from the histone octamer. The brief excursions into an extended open state may create windows of opportunity for protein factors involved in DNA transactions to bind to or translocate along the DNA.     

Bidirectional effects of benzodiazepine binding site ligands in the passive avoidance task: differential antagonism by flumazenil and beta-CCt

Recent research on genetically modified mice has attributed the amnesic effect of benzodiazepines mainly to the alpha1-containing GABA(A) receptor subtypes. The pharmacological approach, using subtype selective ligands, is needed to complement genetic studies. We tested the effects of the non-selective antagonist flumazenil (0-20.0 mg/kg), the preferential alpha1-subunit selective antagonist beta-carboline-3-carboxylate-t-butyl ester (beta-CCt) (0-30.0 mg/kg), the non-selective agonist midazolam (0-2.0 mg/kg), the preferential alpha1-subunit selective agonist zolpidem (0-3.0 mg/kg), and the non-selective inverse agonist methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) (0-2.0 mg/kg) in the one-trial step-through passive avoidance task in rats. The compounds were administered intraperitoneally, before the acquisition test. Flumazenil and beta-CCt did not affect retention performance. Midazolam and zolpidem induced amnesia in a dose-dependent manner. The complete reversal of amnesia was unattainable. The effects of zolpidem were significantly attenuated by the both, flumazenil (10.0 mg/kg) and beta-CCt (30.0 mg/kg); by contrast, only flumazenil was considerably effective when combined with midazolam. DMCM exerted promnesic effects at 0.2mg/kg, in an inverted U-shape manner. Both antagonists tended to abolish this action. The results indicate that some other alpha-subunit(s), in addition to the alpha1-subunit, contribute to the amnesic actions of non-selective benzodiazepine site agonists in the passive avoidance task. On the other hand, a significant part of the DMCM-induced promnesic effect could involve the alpha1-subunit and/or other putative beta-CCt-sensitive binding site(s).     

Immunization with the glutamate receptor-derived peptide GluR3B induces neuronal death and reactive gliosis, but confers partial protection from pentylenetetrazole-induced seizures

Do autoantibodies (Ab's) against glutamate/AMPA receptor subtype 3 affect the severity of seizures? Rats immunized with the GluR3B-peptide (amino acids (aa) 372-395) or with the control GluR3A-peptide (aa 245-274) produced the respective anti-GluR3B and anti-GluR3A Ab's (both types of Ab's found in some epilepsy patients). The GluR3B-immunized rats exhibited neuronal death and reactive gliosis in the brain, but not overt spontaneous seizures. Surprisingly, in response to the chemoconvulsant pentylenetetrazole, the GluR3B-immunized rats displayed fewer jerks, a lower percentage of generalized seizures, and a lower overall seizure-severity score than GluR3A-immunized, scrambled GluR3B-immunized or non-immunized control rats. These findings, combined with the previously demonstrated ability of anti-GluR3B Ab's to bind, activate, and kill neurons and glia, suggest that if these Ab's are present in the brain they may cause neuronal death, which by itself may be pro-epileptic, but they may also decrease the excitability of seizure-related neural circuits, thereby conferring partial protection from seizures induced by other exogenously applied epileptogenic stimuli. The present results could have clinical implications for epilepsy.