Pulmonary function, body composition, and protein catabolism in adults with cystic fibrosis

Increased survival in cystic fibrosis (CF) is associated with bone thinning and fat-free mass (FFM) loss. We hypothesized that the severity of lung disease would be associated with increased protein catabolism and systemic inflammatory status in clinically stable patients. Forty adults with CF and 22 age-matched healthy subjects were studied. Body composition was determined by dual-energy X-ray absorptiometry. Urinary pseudouridine (PSU), a marker of protein breakdown, and cross-linked N-telopeptides of type I collagen (NTx), a marker of bone connective tissue breakdown, serum tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and their soluble receptors were measured. A 3-d food intake diary revealed 21 patients had a low energy intake. Excretion of PSU (p = 0.019) and NTx (p < 0.01) was increased in patients and was inversely related to FEV(1); PSU (r = - 0.53, p = 0.001) and NTx (r = - 0.43, p < 0.01). Increased excretion of PSU and NTx (p < 0.05 for both) was also related to a low FFM. All inflammatory mediators were greater in patients and were related to PSU and NTx. Clinically stable adults were catabolic with both cellular and connective tissue protein breakdown, which was related to lung disease severity, systemic inflammation, and body composition.     

Sleepiness in children and adolescents: clinical implications

Over the past decade, excessive sleepiness among children and adolescents has been identified as a major societal concern. Professionals working with pediatric groups must increasingly factor sleepiness into assessments of waking function. We define and discuss excessive sleepiness in children and adolescents and review available evidence regarding effects on behavior, mood, and performance. Findings for daytime sleepiness and subsequent impairment in these domains are classified as robust to unknown. Empirical evidence clearly indicates that children and adolescents experience significant daytime sleepiness as a result of inadequate or disturbed sleep. The specific effect of sleepiness on functional domains in pediatric groups are less well-studied, but existing data suggests that children are likely to experience impairment in behavioral, mood, and performance domains. However, such variables as developmental differences in the type and degree of impairment, the degree of sleep disturbance required to produce impairments, and potential risk and protective factors for the effects of sleepiness in children have yet to be described. Further research is clearly warranted, and we discuss important questions and methodological concerns to encourage inquiry in both clinical and experimental settings. Advice is offered with regard to screening for sleep problems and associated sleepiness with children and adolescents.     

Seasonality of symptom onset in first-episode schizophrenia

BACKGROUND: There have been numerous reports of seasonal trends in psychotic illnesses. In schizophrenia, seasonal trends in incidence have been shown to be especially apparent in first-episode cases. Most previous research has used date of admission as a proxy for date of incidence of disorder; we present results of an investigation into seasonal trends in dates of onset of symptoms in a group of 295 first-episode cases of schizophrenia and schizophreniform disorder. METHOD: Data were analysed using statistical methods appropriate for detecting seasonal trends in pooled data over 6 years. RESULTS: Only male cases of schizophrenia and schizophreniform disorder showed a significant seasonal distribution to dates of onset of symptoms, with a peak in August (winter). CONCLUSION: True seasonal patterns are present in schizophrenia incidence, but their consistency with other published studies and wider significance, is difficult to ascertain because of different methods used in dating incidence of disorder.     

Isolation and genotypic comparison of oral streptococci from experimental bitemarks

The feasibility of recovering and genotypically comparing oral bacteria from bitemarks for forensic purposes was assessed experimentally. Volunteers firmly bit their own upper arms and bitemarks were sampled at intervals to recover viable Streptococcus isolates. The recoverability of bacteria decreased over time but an average of more than one thousand viable organisms was recovered 24 hrs after biting, provided the site remained relatively undisturbed. Physical exertion, manual rubbing and application of moisturizing lotion all decreased bacterial recoverability compared to controls. Streptococci could also be recovered from bites inflicted on various fabrics. Genomic profiles (DNA "fingerprints") of bacteria recovered from bitemarks could be identified exclusively with those from the teeth of the individual responsible. These findings suggest that a bacterial genotyping approach to bitemark analysis could have forensic application in situations where the perpetrator's DNA cannot be recovered from an oral contact site.     

Cost-Effectiveness of the Implantable Cardioverter Defibrillator

Many clinicians and policymakers are concerned whether use of the implantable defibrillator (ICD) is justified in view of its high cost. Three randomized trials of the ICD have reported economic outcomes. Each trial found a large difference in cost between patients assigned to an ICD versus patients assigned to conventional therapy that persisted over three to six years of follow-up. Each trial also found better survival among ICD patients, and calculated ICD cost-effectiveness (CE) ratios between 27,000 dollars per life year added and 139,000 dollars per life year added. The variability in the cost-effectiveness ratios among trials is mainly due to variability in the years of life added by the ICD among the trials and, by extension, among patient subgroups. A rough rule of thumb is that the ICD will be economically attractive when it prolongs mean survival by six months or more, which is attainable in higher risk patient subgroups.     

New horizons for OR nurses--lessons learned from the World Trade Center attack

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THE TERRORIST ATTACKS of Sept 11, 2001, were a horrifying wake-up call for the United States and the rest of the world.

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THE ATTACKS led to the deployment of the disaster medical assistance team (DMAT) from Massachusetts General Hospital in Boston.

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IN THIS ARTICLE, members of the team outline what they did during the days after Sept 11 and the lessons they brought back to better prepare their DMAT for the next disaster. AORN J 78 (August 2003) 240-245.

     

Neuropharmacology of paroxetine

Paroxetine is a potent and selective serotonin reuptake inhibitor (SSRI) with some neuropharmacologic properties unique among this class of compounds. The findings of early in vitro studies demonstrated the potency of paroxetine at inhibiting 5-HT uptake in rat synaptosomes. Paroxetine also has been shown to be a potent and selective inhibitor of the human serotonin transporter (SERT) and has recently been demonstrated to have moderate affinity for the norepinephrine transporter (NET). Because of the affinity and in vitro selectivity of this SSRI, tritiated paroxetine is now widely used as a marker for SERT in laboratory settings, and its use has advanced our understanding of neurotransmitter function in the brain and periphery. The in vivo pharmacologic properties of paroxetine are well characterized, especially following acute administration. However, the pharmacologic effects of chronically administered paroxetine remain an active area of study. Paroxetine administration in laboratory animals has been shown to be associated with decreased SERT density and function, maintenance of normal firing rates and release of 5-HT, and increased activation of postsynaptic 5-HT receptors. Using a novel ex vivo assay, we have demonstrated that paroxetine exhibits dose-related inhibition of the NET in patients treated for depression. At usual clinical doses (ie, 20 mg/d), paroxetine is a potent and selective inhibitor of the SERT; however, at higher doses (ie, 40 mg/d), paroxetine can exhibit marked NET inhibition. The application of these findings of in vivo NET inhibition by paroxetine in the treatment of mood and anxiety disorders will be informed by further clinical studies.     

Contribution of stem cells and differentiated cells to epidermal tumours

The outer covering of the skin--the epidermis--is subject to sustained environmental assaults. As a result, many cells acquire potentially oncogenic mutations. Most cells are lost through differentiation, and only long-term epidermal residents, such as stem cells, accumulate the number of genetic hits that are necessary for tumour development. So, what genetic and environmental factors determine whether a mutant stem cell forms a tumour and what type of tumour will develop?     

Dihydropyrimidine dehydrogenase (DPD) rapidly regenerates after inactivation by eniluracil (GW776C85) in primary and metastatic colorectal cancer

Purpose Catabolism of 5-fluorouracil (5-FU) is primarily regulated by DPD. Inactivation of DPD using eniluracil is advantageous in that it renders 5-FU orally bioavailable with more predictable pharmacokinetics and blocks one of the major potential mechanisms of 5-FU chemoresistance. The purpose of this study was to initially document inactivation of DPD by eniluracil in primary and metastatic colorectal cancer (CRC) and then to assess the time-course of the regeneration of DPD activity in peripheral blood (and where possible, additional tissues).Methods Of 28 patients entered, 23 were randomized to preoperative oral eniluracil (20 mg orally twice daily) or placebo prior to definitive resection of primary or metastatic CRC. Three patients were replaced, two because they had no residual tumor on pathologic evaluation and one for not taking the study drug. Patients received eniluracil 48, 36, 24 and approximately 12 h prior to surgical resection. In a second part of the study to document tissue regeneration of DPD, the additional five patients received eniluracil 144, 132, 120 and 108 h prior to surgical resection. DPD activity was measured in normal tissues, tumors and peripheral blood mononuclear cells (PBMC). Serum eniluracil and plasma uracil concentrations were determined before and through 28 days after eniluracil dosing. Data are presented as means±SEM, and significance defined as P<0.05.Results Eniluracil inactivated DPD below the level of detection in primary and metastatic CRC as well as in normal tissues (0.0 pmol/min per mg protein) compared to primary tumor, metastatic tumor, PBMC, normal mucosa, and normal liver of patients receiving placebo (57±12, 119±19, 157±22, 77±12, 243±24 pmol/min/mg protein, respectively; P<0.05). At the time of surgery, serum eniluracil and uracil concentrations were 207±36 ng/ml and 2700±170 ng/ml in drug-treated patients. Within 6 days following treatment with eniluracil, serum eniluracil and uracil concentrations were undetectable, while DPD activity in PBMC had returned to baseline. The second group of patients (n=5) were given eniluracil 8 and 7 days prior to surgery to evaluate DPD regeneration in normal tissues and primary CRC tissue. In samples of these tissues, collected 6 days after the last eniluracil dose, DPD activity approached baseline in normal mucosa, normal liver and primary tumor (28±12, 94±23 and 20±8 pmol/min per mg protein, respectively).Conclusions These results demonstrate that oral administration of eniluracil inactivated DPD below the level of detection in normal tissues as well as in primary and metastatic CRC. After discontinuation of eniluracil, DPD rapidly returned toward baseline within 6 days in PBMC, normal intestinal mucosa and normal liver.This work was funded by an investigator initiated research grant through GlaxoSmithKline, Research Triangle Park, NC.The work was presented at the ASCO National Meeting, 21–23 May 2000, New Orleans, LA.     

Relations of adiposity and effects of training on the left ventricle in obese youths

PURPOSE: 1) To determine the relations of left ventricular (LV) structure and function to total body composition, visceral adipose tissue (VAT), and hemodynamics in obese children; 2) to determine the effects of 4-month of physical training (PT) on LV structure and function and hemodynamics; and 3) to explore determinants of individual variability in response to PT. METHODS: Measurements included LV structure/function with echocardiography, total body composition with dual-energy x-ray absorptiometry, VAT with magnetic resonance imaging (MRI), and resting and exercising hemodynamics with a Dinamap monitor and Doppler-echocardiography. Youths were randomly assigned to engage in PT for the first or second 4-month periods of the 8-month intervention period. RESULTS: Correlation and regression at baseline showed that elevated LV mass was associated with excess general and visceral adiposity, and elevated cardiac output. Although the PT had favorable effects on percent body fat and VAT, no significant changes were found in LV or hemodynamic variables. Over the 4-month period of the PT intervention, those who increased the most in VAT tended to increase the most in LV mass. CONCLUSION: General and visceral adiposity were associated with elevated LV mass. However, no evidence was provided that 4 months of PT had a significant effect on LV or hemodynamic variables.