Fifteen years' experience with an antirefluxing biliary drainage valve

PURPOSE: The aim of this study was to examine the efficacy of the antirefluxing, mucosal-flap valve (AMFV) for biliary drainage relative to technical feasibility, surgical complications, and incidence of ascending cholangitis (AC). METHODS: Twenty-seven infants requiring biliary tract reconstruction underwent valve construction. Twenty biliary atresia (BA) patients received the Kasai procedure, and 7 choledochal cyst (CC) infants had cystectomy and hepatoenterostomy. A retrospective review of all patients was performed including radiographic evaluation of the current valve function in 10 patients. RESULTS: Construction was successful in all cases, and no morbidity was incurred by incorporation of the valve. Of 7 CC patients, there have been no known episodes of AC with mean follow-up of 4.4+/-4.2 years. Of 20 BA patients, there have been 5 deaths (25%), 7 liver transplants (35%), 2 (10%) lost to follow-up, and 6 (30%) survivors. Nine BA patients (45%) have had AC, with patients in all 4 outcome categories represented. Ten patients (5 CC and 5 BA) have been evaluated with barium small bowel radiographs, with no reflux to the liver hilum in all cases. CONCLUSIONS: The AMFV has caused no morbidity and continues to prevent reflux to the liver hilum. Despite functioning as designed, it does not appear to influence the occurrence of AC. Because CC patients had no AC, we feel that infection is related to the underlying atresia rather than to reflux.     

Exposure of Adult Mice to Environmental Tobacco Smoke Fails to Enhance the Immune Response to Inhaled Antigen

Epidemiologic evidence supports a role for environmental tobacco smoke (ETS) in the occurrence and severity of allergies/asthma. However, neither the precise combination of ETS and allergen exposure nor the mechanism (or mechanisms) by which these factors interact and contribute to asthma induction is known. Animal model studies have failed to establish a convincing relationship between ETS exposure and asthma induction, perhaps because of methodological inadequacies. Here, we tested the hypothesis that ETS inhalation would provoke an asthmatic response by overcoming normal airway tolerance to inhaled antigens. Our protocol combined daily ETS exposure with nose-only sensitization to ovalbumin. Three strains of mice were tested, each with a different level of susceptibility to airway hypersensitivity. Immunological responses were assessed by immunoglobulin production. Airway inflammation was assessed by bronchoalveolar lavage differentials and lung histopathology. Airway hyperresponsiveness was determined by methacholine challenge. The mice produced ovalbumin-specific antibodies following ovalbumin exposure in a strain-dependent manner. Only the A/J mice produced detectable levels of ovalbumin-specific immunoglobulin (Ig) E. Both A/J and BALB/c mice produced ovalbumin-specific IgG1 antibodies. The C57Bl/6 mice did not produce detectable levels of antibodies. The A/J mice also exhibited airway inflammation following ovalbumin exposure. Neither the C57Bl/6 nor the BALB/c mice exhibited signs of airway inflammation. Exposure to ETS failed to enhance ovalbumin-specific antibody production, airway inflammation, or hyperresponsiveness. Together these results indicate that ETS exposure accompanied by nose-only allergen sensitization fails to overcome aerosol tolerance in adult mice.     

Using a Decision Support Algorithm for Referrals to Post-Acute Care

Objectives

Although hospital clinicians strive to effectively refer patients who require post-acute care (PAC), their discharge planning processes often vary greatly, and typically are not evidence-based.

Viral causes of cardiac inflammation

Over the past year there have been few significant breakthroughs in the understanding of the etiologies of viral myocarditis or dilated cardiomyopathy (DCM). One interesting trend has been the increasing number of reports of myocarditis associated with parvovirus B19 infection. Whether this is simply a result of improved diagnostics, or reflects an underlying change in the etiology is unclear. However, studies of the underlying mechanisms of these disorders have resulted in several reports linking the acquired and viral forms. Over the past few years the cytoarchitecture has been a focus of study for familial DCM. During the last year, one key molecule, dystrophin, has been shown to be disrupted in patients with end-stage cardiomyopathy, irrespective or etiology, mutated in patients with sporadic forms of disease and identified as a potential susceptibility gene for viral infection of the myocardium. The shared cellular receptor, the Coxsackievirus B-Adenovirus receptor (CAR), for the two most common viral agents associated with acquired myocarditis and DCM, was shown to be up-regulated in patients with DCM, potentially making the expression of this protein a marker of susceptibility to virus infection. However, a study of the CAR gene in patients with DCM or myocarditis did not identify any genetic mutations in these patients. Finally a receptor for viral double stranded RNA (TLR-3) was identified. The role of this receptor in the innate immune response against cardiotropic viruses has yet to be elucidated.     

Calcium channel blockade as primary therapy for stable angina pectoris. A double-blind placebo-controlled comparison of verapamil and propranolol

The effectiveness and safety of the beta-adrenergic blocking agent propranolol and the calcium channel antagonist verapamil were compared in 22 patients with chronic stable angina pectoris using a double-blind randomized placebo-controlled crossover protocol. The double-blind phase was preceded by a 2 week single-blind placebo period, followed by randomization to either 4 weeks' therapy with verapamil, 360 mg/day, or propranolol, 240 mg/day, followed by crossover to the other drug. Both verapamil and propranolol increased exercise tolerance (5.5 +/- 0.4 minutes with placebo, 7.8 +/- 0.5 minutes with propranolol [p less than 0.001], and 9.1 +/- 0.5 minutes with verapamil [p less than 0.001]), but the increase with verapamil was significantly greater (p less than 0.01). Both drugs prolonged the exercise duration to 1 mm S-T depression (3.3 +/- 0.4 minutes with placebo, 5.7 +/- 0.5 minutes with propranolol [p less than 0.001] and 5.5 +/- 0.6 minutes with verapamil [p less than 0.001]); the degree of improvement was similar with both active drugs. Both drugs decreased the resting heart rate (76 +/- 3 beats/min with placebo, 56 +/- 2 beats/min with propranolol [p less than 0.001], and 71 +/- 3 beats/min with verapamil [p less than 0.01]), but the heart rate decreased more with propranolol than with verapamil (p less than 0.001). Neither drug produced significant adverse reactions. This study, along with 8 similar double-blind placebo-controlled randomized investigations which have compared verapamil with propranolol, indicate that verapamil is as effective and safe as propranolol in relieving symptoms and improving exercise tolerance in patients with chronic stable angina pectoris and may be considered a first-line therapeutic agent in patients with ischemic heart disease.     

The effect of hyperoxia on migration of alveolar macrophages in vitro.

There is in vitro evidence to support the notion that directed migration (chemotaxis) is involved in the recruitment of alveolar macrophages in vivo. Because O2 is widely used in the treatment of pulmonary diseases, we examined the effect of hyperoxia on migration of guinea pig alveolar macrophages in vitro. Migration was measured in blind-well chambers incubated in either room air or hyperoxia. N-formyl-methionyl-phenylalanine was used to stimulate random migration and to produce directed migration. Migration was quantified by counting the number of mononuclear cells per oil immersion field that had migrated completely through a polycarbonate filter with 5-micrometer pores. The average PO2 in the cell suspensions incubated in room air was 100 mm Hg. In the hyperoxic environments, the average PO2 at 1 h was 260 mm Hg, whereas at 2 and 3 h, it was 410 and 425 mm Hg, respectively. In 6 separate experiments, there was no significant difference between the mean response to N-formyl-methionyl phenylalanine in hyperoxia and in room air after 1 h of incubation. After 2 and 3h of incubation, however, the response in hyperoxia was significantly (P less than 0.002) lower than that in room air. The decreased response in hyperoxia did not appear to result from loss of viability of responding cells, diminished adherence of cells to the filters, loss of activity of N-formyl-methionyl phenylalanine exposed to high PO2, or failure of the cells to exhibit directed migration. Instead, it appeared that hyperoxia decreased the response of alveolar macrophages primarily by impairing random migration.     

Prostacyclin analogs stimulate receptor-mediated cAMP synthesis and ATP release from rabbit and human erythrocytes

Objectives: The purpose of this study was to establish that the prostacyclin (PGI₂) receptor (IP receptor) is present on rabbit and human erythrocytes and that its activation stimulates cyclic adenosine monophosphate (cAMP) synthesis and adenosine triphosphate (ATP) release. Methods: The effect of incubation of erythrocytes with the active PGI₂ analogs, iloprost or UT‐15C, on cAMP levels and ATP release was determined in the absence and presence of the IP receptor antagonist, CAY10441. Western analysis was used to determine the presence of the IP receptor on isolated membranes. To establish that effects of PGI₂ analogs were not due to prostaglandin E₂(PGE₂) receptor activation, the effect of PGE₂ on cAMP levels and ATP release was determined. Results: Rabbit and human erythrocytes possess IP receptors. Iloprost and UT‐15C stimulated increases in cAMP and ATP release that were prevented by the IP receptor antagonist, CAY10441. PGE₂ did not stimulate cAMP accumulation or ATP release and did not inhibit iloprost‐induced increases in cAMP. Conclusions: This study establishes that the IP receptor is present on rabbit and human erythrocytes and that its activation results in increases in cAMP and ATP release. These results suggest a novel mechanism by which PGI₂ and its active analogs, when administered pharmacologically, could produce vasodilation.     

A UK Single Centre Retrospective Analysis of the Relationship between Haemodynamic Changes and Outcome in Patients Undergoing Prolonged Left Ventricular Assist Device Support

Purpose: Despite their efficacy, LVADs remain associated with serious complications. The relationship between haemodynamic changes during support and outcome remains inadequately characterised. This association was investigated in LVAD recipients undergoing prolonged support.Methods: Forty patients receiving LVAD therapy for >2 years were reviewed retrospectively (mean support duration was 38.62 ± 15.28). Pre- and on-LVAD haemodynamic data were assessed in three groups: (1) those receiving ongoing support (n = 24); (2) those who underwent cardiac transplantation (n = 4); (3) those who died during support (n = 12).Results: For group 1 and 2, LVAD support achieved a decrease in mean PAP, mean PCWP, TPG, and PVR and an increase in thermodilution blood flow (TBF) with significance at ≤5% level. For group 3, there were non-significant changes in TPG and PVR at the 5% level but for mean PAP, mean PCWP, and TBF the changes were similar to Groups 1 and 2 with significance at ≤5% level. Aggregated data from all three groups showed a 58% increase in TBF on LVAD support.Conclusion: Highly significant and favourable haemodynamic changes were found. However, group 3 did not undergo decrease in TPG and PVR possibly because of suboptimal LVAD flow, right heart dysfunction and unavoidable prolongation of support.