In the shadow of the dam - Hydrology of the Little Conemaugh river and its South Fork, with insights about past and future flooding.

The Little Conemaugh River watershed and its South Fork sub-basin figure prominently in historical flooding of Johnstown, Pennsylvania and nearby communities with catastrophic flooding in 1889, 1936, and 1977 (reviewed herein). Historical stream gage data and data from a new gage on the South Fork (established via a novel, portable cableway system) are used with Nexrad rainfall data to assess watershed response and provide novel analysis of flood hydrology in the Little Conemaugh basin and the sub-basin. Using unit hydrograph estimates for longer duration storms (>8 h) and different baseflow conditions, we probe possible effects of several design storms, including those stemming from a hurricane remnant scenario (Agnes in 1972) and 50-, 100-, and 500-year 12-hour precipitation depths. The unit hydrographs provided peak discharge (Qpeak) estimates for 1977 (the only flood event with available hourly rainfall data) that are in good agreement with empirical peak discharges. Significant channel improvements completed in 1943 were designed to carry the largest known natural flow on record at that time (1936 Qpeak). Preliminary results from design storm scenarios indicate the need for a careful evaluation of extreme discharges and their return periods (including snowmelt-related contributions), as future flood levels in Johnstown may occur more frequently than originally thought. The 1977 flood, which triggered 7 dam failures and eclipsed 1936 Qpeak, resulted from less than 40% the estimated probable maximum precipitation (PMP) for a 12-hour storm. Peak discharges of similar magnitude would have ensued in 1972 had remnants of Hurricane Agnes tracked slightly westward. Flooding and infrastructure problems could be compounded for storms of 24-hour or longer durations, similar to record flooding seen in central Pennsylvania and New York in 1972. Flood recurrence, emergency procedures, and dam safety (particularly, spillway capacity in the Little Conemaugh basin and surrounding region) should likely be reassessed and protective early-warning measures (ineffective in 1977) implemented for the people of Johnstown.

The role of the humoral immune response to Clostridium difficile toxins A and B in susceptibility to C. difficile infection: a case-control study.

Antibody levels to Clostridium difficile toxin A (TcdA), but not toxin B (TcdB), have been found to determine risk of C. difficile infection (CDI). Historically, TcdA was thought to be the key virulence factor; however the importance of TcdB in disease is now established. We re-evaluated the role of antibodies to TcdA and TcdB in determining patient susceptibility to CDI in two separate patient cohorts. In contrast to earlier studies, we find that CDI patients have lower pre-existing IgA titres to TcdB, but not TcdA, when compared to control patients. Our findings suggest that mucosal immunity to TcdB may be important in the early stages of infection and identifies a possible target for preventing CDI progression.

Leveraging non-binding instruments for global health governance: reflections from the Global AIDS Reporting Mechanism for WHO reform.

As countries contend with an increasingly complex global environment with direct implications for population health, the international community is seeking novel mechanisms to incentivize coordinated national and international action towards shared health goals. Binding legal instruments have garnered increasing attention since the World Health Organization adopted its first convention in 2003. This paper seeks to expand the discourse on future global health lawmaking by exploring the potential value of non-binding instruments in global health governance, drawing on the case of the 2001 United Nations General Assembly Special Session Declaration of Commitment on HIV/AIDS. In other realms of international concern ranging from the environment to human rights to arms control, non-binding instruments are increasingly used as effective instruments of international cooperation. The experience of the Global AIDS Reporting Mechanism, established pursuant to the Declaration, evidences that, at times, non-binding legal instruments can offer benefits over slower, more rigid binding legal approaches to governance. The global AIDS response has demonstrated that the use of a non-binding instrument can be remarkably effective in galvanizing increasingly deep commitments, action, reporting compliance and ultimately accountability for results. Based on this case, the authors argued that non-binding instruments deserve serious consideration by the international community for the future of global health governance, including in the context of WHO reform.

High yield expression of biologically active recombinant full length human tuftelin protein in baculovirus-infected insect cells.

Tuftelin is an acidic protein expressed at very early stages of mouse odontogenesis. It was suggested to play a role during epithelial-mesenchymal interactions, and later, when enamel formation commences, to be involved in enamel mineralization. Tuftelin was also detected in several normal soft tissues of different origins and some of their corresponding cancerous tissues. Tuftelin is expressed in low quantities, and undergoes degradation in the enamel extracellular matrix. To investigate the structure and function of tuftelin, the full length recombinant human tuftelin protein was produced. The full length human tuftelin cDNA was cloned using Gateway recombination into the Bac-to-Bac system compatible transfer vector pDest10. This vector adds a hexahistidine tag to the N-terminus of the expressed protein, enabling one-step affinity purification on nickel column. The recombinant human tuftelin protein was transposed into the bacmid and expressed in Spodoptera frugiperda (Sf9) insect cells. The yield of the purified, his-tagged recombinant full length human Tuftelin (rHTuft+) was 5-8 mg/L culture. rHTuft+ was characterized by SDS-PAGE, Western blot, ESI-TOF spectrometry, restriction mapping and MS/MS sequencing. The availability of the purified, full length recombinant human tuftelin protein opened up the possibility to investigate novel functions of tuftelin. Application of rHTuft+ agarose beads onto embryonic mouse mandibular explants caused changes in the surrounding epithelial cells, including morphology, orientation and spatial organization. Further studies using DiI labeling, revealed that rHTuft+, placed on the tooth germ region, brought about recruitment of adjacent embryonic mesenchymal cells. These findings support the hypothesis that tuftelin plays an important role during embryogenesis.

Tumour necrosis factor inhibitors in ankylosing spondylitis.

Ankylosing spondylitis (AS) is the most common form of spondyloarthropathy. Non-steroidal anti-inflammatory medications and exercise are used to manage the chronic inflammatory spinal pain and stiffness. Up to 20% of patients have a peripheral inflammatory arthritis, which is treated with standard disease-modifying anti-rheumatic drugs especially sulfasalazine and methotrexate. Patients may also have extra-articular manifestations, such as anterior uveitis, psoriasiform skin lesions and inflammatory bowel disease. Anti-tumour necrosis (TNF) therapy has been used with great success in rheumatoid arthritis. There are now good data of the efficacy of anti-TNF therapies in the short and medium terms in AS. Etanercept, infliximab and adalimumab have been shown in randomized placebo-controlled trials of short duration to significantly reduce disease activity, including pain and stiffness as well as improving function, spinal movement and quality of life. It is hoped that long-term therapy will prevent radiologic progression and ankylosis and studies of long-term efficacy are awaited. Anti-TNF therapies are generally well tolerated in AS. It is important to screen for latent tuberculosis before the commencement of anti-TNF therapy. The side-effect profile of anti-TNF therapies in AS does not appear different from that in rheumatoid arthritis. Currently, treatment with anti-TNF therapy in AS is indicated in established disease with radiographic damage. There is evidence that response to therapy is greater in patients with earlier disease and less damage. Future developments may see this therapy extended to patients with pre-radiographic AS.

Effects of probiotic supplementation for the first 6 months of life on allergen- and vaccine-specific immune responses.

BACKGROUND: A reduction in microbial burden during infancy when allergen-specific memory is evolving has become a prominent explanation for the allergy epidemic. OBJECTIVE: We sought to determine whether probiotic dietary supplementation in the first 6 months of life could modify allergen- and vaccine-specific immune responses. METHODS: Two hundred and thirty-one pregnant women with a history of allergic disease and positive allergen skin prick test (SPT) were recruited into a randomized-controlled trial. The infants received either a probiotic (3 x 10(9)Lactobacillus acidophilus LAVRI-A1; Probiomics) or placebo (maltodextrin alone) daily for the first 6 months of life, given independent of feeding methods. One hundred and seventy-eight children completed the study; blood samples were available from 60 children in the placebo group and 58 children in the probiotic group. Infant cytokine (IL-5, IL-6, IL-10, IL-13, TNF-alpha or TGF-beta) responses to tetanus toxoid (TT), house dust mite (HDM), ovalbumin (OVA), beta-lactoglobulin (BLG), Staphylococcus enterotoxin B (SEB) and phytohaemaglutinin (PHA) were measured at 6 months of age. RESULTS: Children who received the probiotics showed reduced production of IL-5 and TGF-beta in response to polyclonal (SEB) stimulation (P=0.044 and 0.015, respectively). They also demonstrated significantly lower IL-10 responses to TT vaccine antigen compared with the placebo group (P=0.03), and this was not due to any differences in vaccination. However, there were no significant effects of probiotics on either Type 1 (Th1) or Type 2 (Th2) T helper cell responses to allergens or other stimuli. The only other effects observed were for reduced TNF-alpha and IL-10 responsiveness to HDM allergens in children receiving probiotics (P=0.046 and 0.014, respectively). CONCLUSIONS: In summary, although we did not see any consistent effects on allergen-specific responses, our study suggests that probiotics may have immunomodulatory effects on vaccine responses. The significance and clinical relevance of this need to be determined in further studies.

Predicting response to recombinant factor VIIa in non-haemophiliac patients with severe haemorrhage.

BACKGROUND: Despite increasing use of recombinant factor VIIa (rFVIIa) in non-haemophiliac patients, it is unclear when rFVIIa might be effective. METHODS: A single centre review of consecutive non-haemophiliac patients receiving rFVIIa for the management of severe haemorrhage. Treatments with rFVIIa were at a dose of 90 mug kg(-1) repeated at three hourly intervals at the clinicians' discretion. RESULTS: Eighteen patients received rFVIIa. Six patients survived to discharge and 12 patients died in hospital. The median (range) Sequential Organ Failure Assessment (SOFA) score at the time of administration of rFVIIa for the group that survived was 8.0 (5-12) compared with the group that died 12.0 (7.0-14.0) (P=0.03). One of the patients who survived (17%) had organ failure at the time of rFVIIa administration compared with 11 of those who died (92%) (P=0.004). Fifteen patients survived long enough to consider a second dose of rFVIIa, one patient who survived to discharge needed more than one dose (1/6, 17%), compared with seven of those who later died in hospital (7/9, 78%) (P=0.04). The survivors had a significant reduction in blood product requirements after rFVIIa, while patients who died did not. Neither the prothrombin time nor the activated partial thromboplastin time before or after rFVIIa predicted survival. CONCLUSIONS: High SOFA score and failure to respond to one adequate dose of rFVIIa appear to identify patients with poor prognosis. These observations may help in determining when rFVIIa treatment is likely to be futile.

Left ventricular diastolic dysfunction in children and young adults with Marfan syndrome.

Adults with Marfan syndrome (MFS) demonstrate abnormal aortic elastic properties manifest by decreased aortic distensibility and increased aortic stiffness. Left ventricular (LV) diastolic dysfunction has been reported in adults with MFS. The objective of this study was to assess the frequency of LV diastolic dysfunction in a group of children and young adults with MFS and to determine whether diastolic dysfunction is associated with hemodynamic alterations of the aorta. Review of echocardiographic findings in 40 patients with MFS was performed to assess LV size, systolic function, isovolumic relaxation time (IVRT), mitral inflow velocities, deceleration time (DT) of mitral E wave, and aortic root dimension. No patient had significant valvar disease or was on any cardiac medication at the time of study. A group of 40 age and sex-matched healthy subjects undergoing echocardiography served as controls. Significant differences in LV diastolic function were found between MFS patients and controls. MFS patients had prolonged DT and IVRT and decreased mitral E/A ratio, suggesting impaired LV relaxation. No relationship between aortic root dimension and diastolic performance was identified. Left ventricular diastolic dysfunction may be an early marker of myocardial involvement in young MFS patients occurring independently of aortic root dilatation.

Exercise capacity in pediatric heart transplant candidates: is there any role for the 14 ml/kg/min guideline?

A peak oxygen consumption (VO2) of < 14 ml/kg/min has been identified as a predictor of l-year mortality in adults with congestive heart failure (CHF) and is used as a criterion for listing for cardiac transplantation (OHT). The role of VO2 measurement in children awaiting OHT has not been thoroughly evaluated. We sought to assess the degree of exercise impairment and the clinical applicability of the 14 ml/kg/min rule in children awaiting OHT. Cardiopulmonary exercise test (CPT) and cardiac catheterization data in all patients listed for OHT during the period of 1995-2003 were reviewed. Fourteen patients with a mean age of 15.5 +/- 2.9 years underwent CPT with no serious adverse events at an interval of 6.6 +/- 5.1 months prior to OHT. The etiology of CHF was multifactorial. Patients had impaired aerobic capacity with a mean peak VO2 of 20.4 +/- 6.8 ml/kg/min. Eleven of 14 patients (79%) had a peak VO2 higher than the adult cutoff value of 14 ml/kg/min. Pediatric ambulatory patients with CHF can safely undergo CPT. Because of age-related differences in oxygen consumption and varied etiologies of CHF a peak VO2 of < 14 ml/kg/min is not a useful criterion for listing for OHT in this population.

Single-dose metronidazole vs 5-day multi-drug antibiotic regimen in excision of pilonidal sinuses with primary closure: a prospective, randomized, double-blinded pilot study.

AIM: To compare infection-related wound complications following excision of pilonidal sinuses with primary closure using either single-dose intravenous (i.v.) administration of metronidazole preoperatively or a broad-spectrum multi-drug regimen. PATIENTS AND METHODS: This is a double-blinded study wherein 50 patients were randomized into receiving either single-drug (metronidazole 500 mg i.v.) prophylaxis preoperatively or multi-drug cover (cefuroxime 1.5 g i.v. and metronidazole 0.5 g i.v. preoperatively, and co-amoxiclav 375 mg orally 8-hourly postoperatively for 5 days). They were reviewed at 1, 2 and 4 weeks postoperatively. Wounds were graded as follows: I, healthy; II, redness and swelling of edges; III, abscess in relation to a suture; IV, spreading wound infection; and V, wound breakdown. Other factors considered were the distance from the lowest wound margin to the anal verge and previous local surgery. RESULTS: Fifty patients (38 men and 12 women, mean age 27 years) underwent pilonidal sinus surgery. At week 1, there was no difference in wound infection rates (p=0.9). However, there were significantly more wound infections in the single-drug group at week 2 (p<0.0001) and week 4 (p=0.03). Seventy-two per cent of all patients had complete wound healing at week 4. Distance from the anal verge and previous surgery did not affect wound infection rates (p> or =0.2). Treating such complications costs 73,219.20 dollars per 100 patients. CONCLUSION: A broad-spectrum 5-day regimen is superior to 'single-shot' antibiotic prophylaxis in preventing infection-related wound complications. However, this study needs to be conducted in a larger number of patients to have statistical power.

Effects of n-3 polyunsaturated fatty acid supplementation in pregnancy on maternal and fetal erythrocyte fatty acid composition.

OBJECTIVE: The aim of this study was to assess the effects of fish oil supplementation in pregnancy on maternal erythrocyte fatty acid composition at different stages of pregnancy and in the post-partum period, and on neonatal erythrocyte fatty acid composition. DESIGN: A double-blind, randomised, placebo-controlled study. SETTING: : Subiaco, Western Australia. SUBJECTS: In all, 98 women booked for delivery at St John of God Hospital, Subiaco, were recruited from private rooms of obstetricians. In total, 83 women and their healthy full-term babies completed the study. INTERVENTION: Women received either 4 g of fish oil (n=52) (56% docosahexaenoic acid (DHA) and 28% eicosapentaenoic acid (EPA) or placebo (olive oil) (n=46) per day from 20 weeks gestation until delivery. MAIN OUTCOME MEASURES: Erythrocyte phospholipid fatty acids were measured in maternal peripheral blood at 20, 30 and 37 weeks of pregnancy and at 6 weeks post partum, and from cord blood collected at birth. RESULTS: Compared to the control group, maternal EPA and DHA were significantly higher in the fish oil group at 30 and 37 weeks gestation, and remained elevated at 6 weeks post partum (P<0.001). The proportions of n-6 polyunsaturated (arachidonic acid, 22:3n-6 and 22:4n-6) were significantly lower in the fish oil supplemented group at the same time periods (P<0.001). Similarly, the proportions of EPA and DHA were significantly higher (P<0.001), and those of n-6 polyunsaturated fatty acids arachidonic acid, 20:3n-6, 22:3n-6 and 22:4n-6 were significantly lower (P<0.001), in erythrocytes from neonates in the fish oil group, compared to those in the control group. CONCLUSION: Fish oil supplementation from 20 weeks of pregnancy until birth is an effective means of enhancing n-3 fatty acid status of both mothers and neonates. Furthermore, the changes in maternal erythrocyte fatty acid composition are retained until at least 6 weeks post partum. It is essential to assess the effects of concomitant decreases in arachidonic acid status before any dietary recommendations can be made. SPONSORSHIP: The study was supported by grants from the NH & MRC and Raine Medical Research Foundation, Australia.

Training on a visual task improves the outcome of optic nerve regeneration.

Optic nerve regeneration in a lizard, Ctenophorus ornatus, is dysfunctional despite survival of most retinal ganglion cells and axon regeneration to the optic tectum. The regenerated retino-tectal projection at 6 months has crude topography but by 1 year is disordered; visually-elicited behavior is absent via the experimental eye. Here, we assess the influence of training on the outcome of optic nerve regeneration. Lizards were trained to catch prey presented within the monocular field of either eye. One optic nerve was then severed and visual stimulation resumed throughout regeneration. In the trained group, presentation was restricted to the eye undergoing optic nerve regeneration; for the untrained group, the unoperated eye was stimulated. Pupil responses returned in trained but not in untrained animals. At 1 year, trained animals oriented to and captured prey; untrained animals demonstrated minimal orienting and failed to capture prey. Regenerated retino-tectal projections were topographic in the trained but not in the untrained group as assessed by in vitro electrophysiological recording and by carbocyanine dye tracing. In vitro electrophysiological recording during application of neurotransmitter antagonists to the tectum revealed that the level of GABAergic inhibition was modest in trained animals but elevated in the untrained group; responses were mainly AMPA-mediated in both groups. We conclude that training improves the behavioral outcome of regeneration, presumably by stabilizing and refining the transient retino-tectal map and preventing a build-up of tectal inhibition. The results suggest that for successful central nerve regeneration to occur in mammals, it may be necessary to introduce training to complement procedures stimulating axon regeneration.

Maternal fish oil supplementation in pregnancy reduces interleukin-13 levels in cord blood of infants at high risk of atopy.

BACKGROUND AND OBJECTIVES: The epidemiological association between higher dietary n-3 polyunsaturated fatty acids (PUFA) and lower prevalence of asthma, has led to interest in the role of early dietary modification in allergic disease prevention. In this study we examined the effects of maternal n-3 (PUFA)-rich fish oil supplementation on cord blood (CB) IgE and cytokine levels in neonates at risk of developing allergic disease. METHODS: In a randomized double-blind, placebo-controlled trial, 83 atopic pregnant women received either fish oil capsules (n = 40) containing 3.7 g n-3 PUFA/day or placebo capsules (n = 43) from 20 weeks gestation until delivery. CB cytokine levels (IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, TNF-alpha and IFN-gamma) and total IgE levels were measured and compared between the two groups. Fatty acid composition of red cell membranes was analysed by gas chromatography and the relationships among PUFA, cytokine and IgE levels were examined. RESULTS: Maternal fish oil supplementation resulted in a significant increase in n-3 PUFA levels (P < 0.001) in neonatal erythrocyte membranes. Neonates whose mothers had fish oil supplementation had significantly lower plasma IL-13 (P < 0.05) compared to the control group. There was also a significant inverse relationship between levels of n-3 PUFA in neonatal cell membranes and plasma IL-13. There was no difference in levels of IgE and the other cytokines measured. CONCLUSIONS: This study provides preliminary evidence that increasing neonatal n-3 PUFA levels with maternal dietary supplementation can achieve subtle modification of neonatal cytokine levels. Further assessment of immune function and clinical follow-up of these infants will help determine if there are any significant effects on postnatal immune development and expression of allergic disease.

Day-case ureteroscopy: an observational study.

OBJECTIVE: To evaluate the outcome after day-case ureteroscopy (used in diagnosing and managing ureteric disease, primarily urolithiasis), as awareness of reduced resources has resulted in increasing pressure to undertake procedures in a day-surgery setting. PATIENTS AND METHODS: All patients presenting to the unit and requiring ureteroscopy between May 1995 and May 2000 were considered for a day-surgery procedure. The assessment of suitability comprised anaesthetic and social factors; no urological criteria precluded a day-surgery procedure. Outcomes after day-case ureteroscopy, including immediate or delayed admissions and subsequent inpatient management, were reviewed retrospectively. RESULTS: Sixty-three day-case ureteroscopies were performed on 56 patients (mean age 47 years, range 19-78); eight procedures were diagnostic. Therapeutic ureteroscopies included one balloon dilatation of a ureteric stricture and 54 procedures for urolithiasis, with 98% stone clearance. Most patients were discharged with a JJ stent in situ. Of nine patients requiring immediate admission, seven were for pain control; eight were discharged on the following day. Seven patients required delayed admission 1-13 days after the procedure, three for stent-related symptoms and three for infection. No significant predictors of immediate or delayed admission were identified, although antibiotic prophylaxis was associated with a reduced admission rate. CONCLUSION: Ureteroscopy can be used successfully as a planned day-case procedure in a dedicated day-surgery unit, with few patients requiring hospitalization. Implementation of analgesia protocols and routine antibiotic prophylaxis may reduce admission after day-case ureteroscopy.

Race and the decision to refer for coronary revascularization: the effect of physician awareness of patient ethnicity.

OBJECTIVES: We sought to assess whether there were differences, relative to racial ethnicity, in coronary revascularization recommendations made by a panel that had no knowledge of the patients' ethnicity. BACKGROUND: Coronary revascularization is employed less frequently in African American than in white patients. It is unclear whether this utilization pattern is driven by clinical differences between the two populations or by nonclinical factors. METHODS: Data were reviewed from 938 (26.5% African American, 73.5% white) consecutive cardiac catheterizations done between 1993 and 1995. Revascularization recommendations were made by cardiologists and cardiothoracic surgeons provided with the patients' clinical and angiographic data, but without knowledge of their ethnicity. Revascularization recommendations were compared between African American and white patients and correlated with clinical characteristics. RESULTS: No difference was noted in the percentage of African American and white patients recommended for revascularization, without reference to whether the recommendation was for percutaneous transluminal coronary angioplasty (PTCA) or for coronary artery bypass graft surgery (CABG) 40 vs. 46%, p = NS). African Americans were recommended more frequently for PTCA (22 vs. 18%, p = NS), whereas CABG was recommended for more white patients (28 vs. 18%, p = 0.002). Significantly fewer African Americans had disease in the left main or left anterior descending coronary artery or in multiple arteries. After adjusting for age, co-morbidity, left ventricular dysfunction and the extent of coronary disease, African Americans were more likely to have a recommendation for PTCA (odds ratio [OR] 1.42, 95% confidence interval [CI] 0.96 to 2.11, p = 0.08) and less likely to have a recommendation for CABG (OR 0.59, 95% CI 0.37 to 0.94, p = 0.02). CONCLUSIONS: This study suggests that when only clinical factors are considered, the rates of recommendations for revascularization will be similar for white and African American patients; but the type of revascularization procedure may differ by ethnicity and may depend, in part, on clinical factors.

Relationship between 24-H blood pressure and sleep disordered breathing in a normotensive community sample.

Sleep disordered breathing (SDB) and hypertension are commonly associated. In this study, we assessed how longitudinal measures of SDB predict a 24-h ambulatory blood pressure monitoring (ABPM) profile. Participants (n = 82) were recruited from a community-based urban (26% African American) sample and included family members of patients with laboratory diagnosed SDB (cases) and family members of neighborhood control subjects evaluated at baseline and at 5 years. Nearly all participants were normotensive and were not receiving therapy for SDB. During both examinations, the respiratory distress index (RDI) was assessed with overnight in-home polysomnography. Seated blood pressure (BP) was assessed at a baseline examination (t,) and after a 5-year follow-up period (t5), when 24-h ABPM also was performed. The change in RDI (t5-t1) over 5 years was significantly associated with 24-h mean systolic blood pressure (SBP) (P = .04), 24-h maximum diastolic blood pressure (DBP) (P = .03), sleep mean SBP (P = .05), sleep mean DBP (P < .05), and sleep maximum SBP (P = .02). Regression analysis revealed that average 24-h mean arterial pressure (MAP) and mean 24-h DBP were each best predicted by change in RDI, explaining 5% of the variance in these 24-h BP readings, and by current smoking status. After accounting for these variables, BP was not predicted by any of the other potential confounders (all P > .10). Mean RDI (averaged between t5 and t1) was associated with mean MAP, mean SBP, and maximal SBP measured during sleep. This study documents for the first time the association between changes in sleep apnea activity and BP and in a community-based normotensive sample. Further long-term evaluation of the effects of these findings and the long-term consequences of hypertension are needed.

Percutaneous endoscopic gastrostomy in patients with ventriculoperitoneal shunts.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) may be required in neurosurgical patients with a persistently depressed neurological status or severe lower cranial nerve palsies. Such patients may have a coexisting hydrocephalus requiring cerebrospinal fluid (CSF) diversion. Despite the risk of infection resulting from exposure to oropharyngeal flora by the pull-through PEG technique and the secondary pneumoperitoneum seen in one-third of patients, simultaneous peritoneal placement of CSF shunt catheters with PEG is the current practice. The aim of the study was to determine the frequency of CSF diversionary procedures in neurosurgical patients undergoing PEG insertion and the occurrence of infective complications in patients with simultaneous placement of a PEG and a ventriculoperitoneal (VP) shunt. METHODS: This was a retrospective review of all neurosurgical patients undergoing PEG. The presence of hydrocephalus, mode of CSF diversion and the development of subsequent infection in those having coexistent distal peritoneal catheter placement and PEG were determined. RESULTS: PEGs were placed in 42 neurosurgical patients (9.3 per cent of all PEGs inserted), of whom 21 had a coexisting hydrocephalus. Eight of 16 shunts with distal catheter placement in the peritoneal cavity developed infection requiring revision. Infections occurred with greater frequency in patients with a tracheostomy. There were no shunt infections requiring revision in a second group of 21 patients who had a coexisting shunt and tracheostomy without PEG. CONCLUSION: Simultaneous placement of a PEG and a VP shunt should be avoided in the acute phase of a patient's hospital admission.

Effect of gender on fast-track recovery after coronary artery bypass graft surgery.

OBJECTIVE: To examine the effects of gender on time to extubation after coronary artery bypass graft (CABG) surgery and intensive care unit and hospital length of stay. DESIGN: Retrospective study comparing outcomes as related to gender. SETTING: Tertiary care university teaching hospital. PARTICIPANTS: Consecutive patients (n = 561; 376 men, 185 women) undergoing CABG surgery between January 1995 and December 1997. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Early extubation was possible in 74% of men versus 64% of women (p = 0.03); length of stay was < or =5 days in 60% of men versus 48% of women (p = 0.008); overall postoperative length of stay was 5.7 days for men versus 6.5 days for women (p = 0.003); morbidity and mortality were not significantly different between groups. CONCLUSION: Women undergoing CABG surgery with a standardized fast-track protocol have longer intubation times, intensive care unit length of stay, and hospital length of stay than their male counterparts.

A role for syndecan-1 in coupling fascin spike formation by thrombospondin-1.

An important role of cell matrix adhesion receptors is to mediate transmembrane coupling between extracellular matrix attachment, actin reorganization, and cell spreading. Thrombospondin (TSP)-1 is a modulatory component of matrix expressed during development, immune response, or wound repair. Cell adhesion to TSP-1 involves formation of biochemically distinct matrix contacts based on stable fascin spikes. The cell surface adhesion receptors required have not been identified. We report here that antibody clustering of syndecan-1 proteoglycan specifically transduces organization of cortical actin and fascin bundles in several cell types. Transfection of COS-7 cells with syndecan-1 is sufficient to stimulate cell spreading, fascin spike assembly, and extensive protrusive lateral ruffling on TSP-1 or on syndecan-1 antibody. The underlying molecular mechanism depends on glycosaminoglycan (GAG) modification of the syndecan-1 core protein at residues S45 or S47 for cell membrane spreading and on the VC2 region of the cytoplasmic domain for spreading and fascin spike formation. Expression of the VC2 deletion mutant or GAG-negative syndecan-1 showed that syndecan-1 is necessary in spreading and fascin spike formation by C2C12 cells on TSP-1. These results establish a novel role for syndecan-1 protein in coupling a physiological matrix ligand to formation of a specific matrix contact structure.

SERMs, ethnicity, and clinical trials: opportunities and challenges.

Selective estrogen receptor modulators (SERMs) are an exciting new class of pharmacotherapeutics that may have application in a wide variety of disease states. The science, both basic and clinical, that would guide the usage of these agents is in some respects at a relatively early developmental stage. Thus, the research community has an opportunity, before their use becomes widespread, to structure clinical trials such that the most complete profiles of benefits and risks are described. Tamoxifen is the SERM that has been most extensively studied and for which there are indications for both treatment and prevention of breast cancer based on trials involving more than 50,000 women. Despite this seemingly adequate sample size, an extremely important question remains unanswered--namely, whether there are ethnic differences in benefit and adverse effects of SERMs. It has generally been the case that new pharmacologic agents are tested in relatively small numbers of subjects, often only male, in North America and western Europe. While the populations are multi-ethnic, clinical trial subjects are most often not representative of the ethnic variability of these areas. Guidelines for usage of new drugs based on data from small, ethnically limited population groups are then generalized to other population groups, without consideration that differences in drug metabolism and/or responsiveness might exist.