Temporary leukocyte depletion reduces ventricular dysfunction during prolonged postischemic reperfusion

Leukocyte depletion improves early postischemic ventricular performance in neonatal models of global myocardial ischemia. However, the rate of leukocyte reaccumulation after cardiopulmonary bypass and its subsequent impact on myocardial function is not known. This laboratory study examined the effect of leukocyte depletion on myocardial performance during the initial 6-hour period after bypass in an in situ, in vivo porcine model of neonatal cardiac surgery. Fifteen 3- to 5-day-old piglets (eight control and seven leukocyte depleted animals) were instrumented by placement of left ventricular short-axis sonomicrometry crystals and an intraventricular micromanometer catheter. Mechanical leukocyte depletion was achieved with Pall RC100 filters (Pall Biomedical, Inc., Fajardo, Puerto Rico) in the cardiopulmonary bypass circuit. Neonatal hearts were subjected to 90 minutes of hypothermic ischemia after a single dose of cold crystalloid cardioplegia. Two control animals died after the operation and were excluded from data analysis. Leukocyte filtration reduced the granulocyte count during initial myocardial reperfusion to 0.8% of control values. However, circulating granulocyte counts increased in leukocyte depleted animals throughout the postoperative period, reaching 68% of control values by 6 hours. Despite this rapid return of circulating granulocytes, animals subjected to leukocyte depletion had significantly better preservation of left ventricular performance (measured by preload recruitable stroke work, p < or = 0.02), left ventricular systolic function (measured by end-systolic pressure-volume relationship, p < or = 0.05), and ventricular compliance (p < or = 0.04) during the experiment. These changes in ventricular function were associated with a significant increase in left ventricular water content (p < or = 0.02) and tissue myeloperoxidase activity (p < or = 0.005) in control animals compared with leukocyte depleted animals. This study demonstrates that leukocyte depletion during initial reperfusion results in sustained improvement in postischemic left ventricular function despite the rapid return of granulocytes to the circulation.     

Immunohistochemical localization of p21(WAF1/CIP1) in normal, hyperplastic, and neoplastic uterine tissues

Assuming that the chemical reactions used to synthesize a combinatorial library member are successful, then knowledge of the specific reaction sequence is equivalent to knowing the member's chemical identity. Because the determination of chemical identity is typically not automatable and requires a substantial amount of material, schemes that encode a member's reaction history onto the reaction platform are of value. The primary benefits of encoding are relational nomenclature (all methods) and automated handling (some methods). Encoding methods evaluated to date are spatial, graphical, chemical, spectrometric, electronic, and physical.     

Neuropsychological functioning of girls with attention-deficit/hyperactivity disorder followed prospectively into adolescence: Evidence for continuing deficits?

The current study prospectively followed girls with attention-deficit/hyperactivity disorder (ADHD), along with a matched comparison sample, 5 years after childhood neuropsychological assessments. Follow-up neuropsychological measures emphasized attentional skills, executive functions, and language abilities. Paralleling childhood findings, the childhood-diagnosed ADHD group displayed moderate to large deficits in executive/attentional performance as well as in rapid naming relative to the comparison group at follow up (Mage 14.2 years). ADHD-inattentive versus ADHD-combined contrasts were nonsignificant and of negligible effect size, even when a refined, sluggish cognitive tempo subgroup of the inattentive type was examined. Although ADHD versus comparison group differences largely withstood statistical control of baseline demographics and comorbidities, control of childhood IQ reduced executive function differences to nonsignificance. Yet when the subset of girls meeting diagnostic criteria for ADHD in adolescence was compared with the remainder of the participants, neuropsychological deficits emerged even with full statistical control. Overall, childhood ADHD in girls portends neuropsychological and executive deficits that persist for at least 5 years. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Current issues in nerve repair

Although accepted surgical techniques for peripheral nerve repair remain largely unchanged over the past three decades, much progress has been made toward understanding the mechanisms involved in nerve regeneration, and consequently toward providing adjunctive measures to enhance this regenerative process. We present a comprehensive review of the significant advances made in several aspects of nerve repair over the past decade, and particularly the past few years, and provide a few examples of facial nerve repair using the standard neurorrhaphy techniques recommended today. Several conclusions were drawn after thorough review of the literature. Early repair of injured nerves is preferred, and there appears to be no benefit to waiting for 3 weeks. Severed nerves should be repaired with monofilament 9-0 nylon suture placed in epineurial fashion. Fibrin glue confers no benefit in reattaching injured nerves. Likewise, theoretical advantages of laser neurorrhaphy have not resulted in improved nerve regeneration. Finally, trophic factors, such as apolipoproteins and nerve growth factor, and tubulization both appear to offer promise for future experimental and clinical progress in nerve repair. However, further work must be done to prove their efficacy.     

Supramedullary modulation of sympathetic vasomotor function

1. Supramedullary structures including the ventral medial prefrontal cortex (MPFC) and the midbrain cuneiform nucleus (CnF) project directly and indirectly to premotor sympatho-excitatory neurons of the rostral ventrolateral medulla (RVLM) that are critically involved in the generation of sympathetic vasomotor tone. 2. Electrophysiological studies have demonstrated that activation of depressor sites within the MPFC is associated with splanchnic sympathetic vasomotor inhibition and inhibition of the activity of RVLM sympathoexcitatory neurons. 3. Antidromic mapping and anatomical studies support the notion that a relay in the nucleus tractus solitarius is involved in the cardiovascular response to MPFC stimulation. 4. The midbrain CnF, which lies adjacent to the midbrain periaqueductal grey, is a sympathoexcitatory region of the midbrain reticular formation. Sympathoexcitatory responses evoked from the CnF are associated with short-latency excitation of RVLM neurons. 5. Cuneiform nucleus stimulation induces the expression of mRNA for the immediate early genes c-fos and NGFI-A in mid-brain, pontine and hypothalamic structures. 6. The MPFC and CnF are supramedullary structures with opposing modulatory influences on sympathetic vasomotor drive, whose roles in cardiovascular control mechanisms warrant further investigation.     

Transrectal electrostimulation therapy for neuropathic bowel dysfunction in children with myelomeningocele

PURPOSE: We attempted to evaluate the efficacy of transrectal bowel stimulation for neurogenic bowel dysfunction in children with myelodysplasia. MATERIALS AND METHODS: Daily sessions of transrectal electrostimulation were performed on an outpatient basis for 2 to 3 weeks on children with myelodysplasia and stool incontinence. If benefits were noted, 5 to 10 additional daily sessions were performed. Complete success was defined as improvement in all parameters of interest, including decrease in the frequency of daily bowel movements, increased sensation, increased ability to hold stool and a significant subjective change in bowel habits. Moderate success implied improvement in 1 to 3 parameters and treatment failure was defined as lack of improvement in any parameter. RESULTS: A total of 55 children 2 to 14 years old (mean age 6.7) completed a mean of 18 daily sessions per patient of bowel electrostimulation. Followup ranged from 1 to 6 years. Diapers are no longer required due to defecation problems in 14 children older than 3 years. Complete success was achieved in 20 cases (36.3%) and moderate success in an additional 30 (54.5%, overall success rate 90.8%). Specifically, 89% of the patients reported elimination of stooling accidents, 82% reported increased sensation and 71% were able to hold the bowel movement. Overall 68% of the patients noticed significantly improved bowel function. Complete/moderate success of transrectal electro-stimulation was statistically significant for all 4 parameters (p < 0.05), and complete success was significant for increased sensation, ability to hold and episodes of accidents. Therapy failed in 5 children (9%). There were no untoward effects. CONCLUSIONS: Transrectal electrostimulation is a well tolerated and minimally invasive modality that provides sustainable improvement in stool continence in children with myelomeningocele and neuropathic bowel dysfunction.     

Evidence for disturbed S-adenosylmethionine : S-adenosylhomocysteine ratio in patients with end-stage renal failure: a cause for disturbed methylation reactions?

BACKGROUND: Elevated homocysteine concentrations have been associated with premature arteriosclerosis and with impairment of key methylation reactions through accumulation of the homocysteine metabolite S-adenosylhomocysteine. In end-stage renal failure high homocysteine concentrations are commonly found but thus far the concentrations of related adenosylated metabolites in plasma have not been assessed. METHODS: In this prospective study we determined plasma homocysteine and related metabolites in 25 patients on regular haemodialysis, and in 40 healthy volunteers. Blood samples from patients were drawn immediately before and in 10 patients additionally after the dialysis session. RESULTS: Folic acid and vitamin B12 in plasma were similar in patients (mean +/- SEM 25+/-2 nmol/l and 400+/-41 pmol/l respectively) and controls (24+/-3 and 324+/-23 respectively). In patients plasma homocysteine, S-adenosylmethionine and S-adenosylhomocysteine were markedly elevated (36.6+/-3.6 micromol/l, 381+/-32nmol/l and 1074+/-55 nmol/l respectively) compared to the control values (6.8+/-0.4 micromol/l, 60+/-3 nmol/l and 24.4+/-1.1 nmol/l respectively) whereas the molar ratio of plasma S-adenosylmethionine and S-adenosylhomocysteine was significantly decreased (0.36+/-0.02 and 2.7+/-0.2 in patients and controls respectively). Haemodialysis failed to normalize the abnormal levels of these metabolites. CONCLUSION: Since the ratio of S-adenosylmethionine : S-adenosylhomocysteine is closely linked to the activity of numerous enzymatic methylation reactions, these results suggest that methylation may be impaired in these patients.