Does limited placement of bioresorbable membrane of modified sodium hyaluronate and carboxymethylcellulose (Seprafilm®) have possible short-term beneficial impact?

PURPOSE: The aim of the study was to assess the impact of sodium hyaluronate and carboxymethylcellulose membrane (Seprafilm®) on postoperative intestinal obstruction as judged by the rates of bowel obstruction and laparotomy for bowel obstruction. A secondary aim was to assess early postoperative morbidity. METHODS: All patients who had Seprafilm® placed during colorectal surgery between June 1993 and October 1998 were included in the study group and compared with a matched group of patients without Seprafilm®. All patients were assessed for intestinal obstruction and complications by telephone interview and chart review. Statistical tests for independence were used where appropriate; alpha was 0.05 for all tests, and the two groups were tested for case matching. Fisher's exact test was used to compare gender distribution, nature of diagnosis (inflammatoryvs. noninflammatory), and urgency of surgery (electivevs. emergency). The age distribution, number of prior abdominal surgeries, and operative time were compared by Student'st-test. Approximation of Katz test was used for independent proportions to compare the two groups for early postoperative morbidity and overall incidence of intestinal obstruction and surgical enterolysis. The incidence of intestinal obstruction between the two groups was also compared with Kaplan-Meier product limit method and log-rank test. RESULTS: Two hundred fifty-nine patients in whom Seprafilm® was placed were compared with a well-matched control cohort of 179 patients. The two groups did not differ in gender or age. One-half of each group had inflammatory conditions, and approximately 90 percent of each group underwent elective operations. The operative times were similar. Both groups had a similar number of abdominal operations before inclusion (mean = 1.2, both groups). Early morbidity rates were 17.8 percent for the Seprafilm® group and 15.6 percent for the controls, with mortality rates of 0.8 percent and 0.0 percent, respectively. There were 12 intestinal obstructions in 12 patients in the Seprafilm® group and 12 intestinal obstructions in 11 patients in the control group at a follow-up period of 65 months in the Seprafilm® group and 81 months in the control group. Eight of the 12 intestinal obstructions in the Seprafilm® group resolved with conservative management while only 5 of 12 in the control group responded without surgery. Thus the enterolysis rate was 1.5 percent in the Seprafilm® group and 3.9 percent in the control group, demonstrating a trend in favor of Seprafilm®. There were no statistically significant differences in the incidence of either overall or abdominopelvic septic complications between the Seprafilm® (3.4 percent) and control (1.1 percent) groups. CONCLUSION: During short-term follow-up in this nonprospective, nonrandomized study, limited placement of Seprafilm® did not significantly reduce the need for surgical enterolysis for intestinal obstruction or significantly adversely affect the morbidity rate. However, a long-term, prospective, randomized trial is underway to elucidate these issues.Supported by an educational grant from Genzyme Surgical Products, Inc.Presented at the Association of Coloproctology of Great Britain and Ireland, Southport, UK, July 10 to 12, 1999.     

Tau hyperphosphorylation affects Smad 2/3 translocation

Transforming growth factors β (TGFβ) regulate multiple biological activities. TGFβ activation of the Smad pathway results in activation of genes encoding extracellular matrix molecules, proteases, protease activators and protease inhibitors. In Alzheimer's disease (AD), TGFβ protein and mRNA levels are raised, which would be expected to be neuroprotective. However, recent observations suggest that TGFβ-Smad signalling is disrupted by the hyperphosphorylation of tau, the primary component of neurofibrillary tangles: phosphorylated Smad2/3 (pSmad 2/3) co-localises with phosphorylated tau in the neuronal cytoplasm and levels are reduced in the nucleus. We have investigated whether in vitro induction of tau hyperphosphorylation influences pSmad 2/3 localisation in rat primary cortical cells. Treatment with okadaic acid, a protein phosphatase 1 and 2A inhibitor caused hyperphosphorylation of tau at epitopes hyperphosphorylated in AD and disrupted pSmad 2/3 translocation into the nucleus. The disruptive effect of tau phosphorylation on pSmad 2/3 translocation was confirmed by treatment of primary cortical cells with synthetic oligomeric Aβ_1-42, a more physiologically relevant model of AD. Our findings suggest that despite the increased level of TGFβ in AD, the TGFβ-Smad signalling pathway is impeded within neurones due to sequestration of pSmad 2/3 by hyperphosphorylated tau. This may compromise neuroprotective actions of TGFβ and contribute to neurodegeneration in AD.     

MMP-2, -3 and -9 levels and activity are not related to Abeta load in the frontal cortex in Alzheimer's disease

Matrix metalloproteinases (MMPs) -2, -3 and -9 are up-regulated in several cell types on exposure to amyloid β peptide (Aβ) and have Aβ-degrading activity in vitro . The aims of this study were to determine (i) the distribution of MMP-2, -3 and -9 in the cerebral cortex in Alzheimer's disease (AD) and control brains; (ii) whether the levels and activity of these proteases are increased in AD; and (iii) whether their activity is related to Aβ load. In addition, we examined whether promoter polymorphisms in the MMP-3 and -9 genes are associated with AD in the study cohort. Paraffin sections of frontal lobe from AD and control cases were immunostained for MMP-2, -3 and -9 and tissue homogenates used for MMP activity assays. DNA from these cases was genotyped for the MMP-3 5A/6A (-1171) and MMP-9 C-1562T promoter polymorphisms. Immunohistochemistry revealed MMP-3 in plaques and both MMP-3 and -9 around scattered neurones. The levels and activity of all three MMPs were similar in AD and control brains and bore no relationship to Aβ load. Analysis of MMP-3 -1171 5A/6A allele frequencies showed that the 6A allele (with reduced promoter activity) was associated with AD; the MMP-9 C-1562T polymorphism was not. The levels and activities of MMP-2, -3 and -9 are not increased in the frontal cortex in AD and are not related to Aβ load. Our findings suggest that altered expression of these proteases does not make a significant contribution to the accumulation of Aβ in AD.     

Metastable Equilibrium Solubility Behavior of Carbonated Apatite in the Presence of Solution Strontium

The purpose of this study was to use the concept of metastable equilibrium solubility (MES) to describe the anomalous solubility behavior of carbonated apatite (CAP) in the presence of solution strontium. A CAP sample (4.8 wt% CO₃, synthesized at 70°C) was prepared by precipitation. Baseline MES distributions were determined in a series of 0.1 M acetate buffers containing only calcium and phosphate (no strontium) over a broad range of solution conditions. In order to assess the influence of strontium, MES profiles were then determined in a similar fashion with 20, 30, 40, 50, 60, 70, and 80% of the solution calcium being replaced on an equal molar basis by solution strontium. From the compositions of the equilibrating buffer solutions, ion activity products (IAPs) of the form Ca_10-nSr_n(PO₄)₆(OH)₂ (n = 0–10) were calculated in an attempt to determine the correct function governing the dissolution of the CAP preparation. The results demonstrate the following important findings: (a) at high solution strontium/calcium ratios (i.e., when 60% or more of the solution calcium was replaced by strontium), the MES profiles in all the experiments were found to be essentially superimposable when the solution IAPs were calculated using the stoichiometry of Ca₆Sr₄(PO₄)₆(OH)₂, and (b), at low solution strontium/calcium ratios (i.e., when 40% or less of the solution calcium was replaced by strontium), the stoichiometry yielding MES data superpositioning was found to be that of hydroxyapatite. When other stoichiometries were assumed, good superpositioning of the data was not possible.     

Variability in serotonin and enterochromaffin cells in patients with colonic inertia and idiopathic diarrhoea as compared to normal controls

Aim To evaluate differences in distribution, density and staining intensity of enterochromaffin cells (EC) and serotonin cells (SC) in the colonic mucosa of patients with colonic inertia (CI), idiopathic diarrhoea (ID) and a control group. Methods Three groups were studied: 19 patients' colons after subtotal colectomy for CI, and 17 patients' biopsies for diarrhoea (>3 bowel movements/day) with histological findings of normal mucosa (excluding microscopic, eosinophillic and collagenous colitis). The third group included 15 patients who underwent colonoscopy and biopsy for indications other than constipation, inflammatory bowel disease, diarrhoea or neoplasm (control group). Specimen blocks were obtained in each case from the right and left colon. Immunohistochemical staining for EC and SC were done on 4 µm sections from Hollandes fixed, paraffin embedded tissues with primary rabbit antibody against chromagranin A or serotonin, and biotynylated secondary antibody and enzyme labelled streptavidin. Results The number of EC in the mucosa of the left colon in patients with CI (16.8 ± 10.2) and ID (19.9 ± 9.7) were significantly higher than they were on the right side (CI: 9.4 ± 6.0, ID: 12.1 ± 5.3). However, there were no significant differences between the left and right sides in the control group (L: 10.3 ± 5.3; R: 13.4 ± 7.6). Although the quantity of EC in the left colon in both patients with CI (P < 0.05) and ID (P < 0.01) were significantly higher than in the controls, there was no significant difference between CI and ID. In both the right and left colon, the percentage of EC with low positive density was significantly higher (P < 0.01) while those cells with moderate or low staining intensity were significantly lower in patients with CI than in either patients with ID or control group. In patients with CI, the quantity of SC in the mucosa of the left colon (12.1 ± 6.4) was higher than in the right (CI: 7.9 ± 3.6; control 4.6 ± 3.3; ID 4.6 ± 2.9) (P = 0.0057). In contrast there was no significant difference in SC in either the ID or control groups. The quantity of SC in both sides of the colon was significantly higher both in patients with CI as compared to the control group (P < 0.01) and patients with CI vs. patients with ID (L = P < 0.01; R = P < 0.05). There was a significantly positive correlation between the numbers of EC and SC in patients with CI (L: r = 0.5425, P < 0.05; R: r = 0.745, P < 0.01). Conclusion In patients with CI, EC increases possibly due to an increase in SC. Conversely, in patients with ID, the EC increase results from peptides other than SC. Our results suggest that different aetiological factors contribute to ID and CI.     

Can central neuropeptides be implicated in carotid sinus reflex hypersensitivity?

Carotid sinus reflex hypersensitivity involves profound and intermittent changes in heart rate and blood pressure associated with symptoms of dizziness and syncope. This involves a reflex arc in which the main defect is believed to lie within the central nervous system. The discovery of classical and peptidergic neurotransmitters within the same neurone, and the presence of these peptides within the central nervous system raises the possibility that carotid sinus reflex hypersensitivity may be related to an abnormality of peptide distribution or function.     

Antigen dependent adjuvant activity of a polydispersed beta-(1,4)-linked acetylated mannan (acemannan).

The adjuvant properties of a polydispersed beta-(1,4)-linked acetylated mannan, acemannan (ACE-M), were evaluated. Day-old broiler chicks were randomly selected and allocated to four flocks (Vac 1-4). The Vac 1 flock was sham vaccinated with saline. The Vac 2 flock was vaccinated with an oil-based vaccine (Breedervac III; Newcastle disease virus (NDV), infectious bursal disease virus (IBDV) and infectious bronchitis virus). The Vac 3 flock was vaccinated with a vaccine-ACE-M mixture, and the Vac 4 flock was vaccinated with vaccine and ACE-M at separate anatomical sites. ELISA titres to NDV and IBDV were determined. The immune response to NDV at 21 days postvaccination (PV) was significantly enhanced (P less than or equal to 0.05) by the addition of ACE-M to the vaccine, compared with vaccination without ACE-M. Subsequently, the vaccine-ACE-M mixture appeared to suppress the immune response to NDV. However, at day 35 PV, 95% of the Vac 3 chicks compared with 90% of the Vac 2 and 89% of the Vac 4 chicks exhibited protective titres. The response to IBDV differed from that to NDV. At day 21 PV the immune response to IBDV was essentially the same for all flocks that received vaccine, i.e. addition of ACE-M to the vaccine did not significantly enhance the immune response; however, it did significantly (P less than or equal to 0.05) sustain the immune response at days 28 and 35. In addition to the observed effect on titres to NDV and IBDV, ACE-M also had an effect on flock immunity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Developing High-specificity Anti-hypertensive Alerts by Therapeutic State Analysis of Electronic Prescribing Records

Objective

This paper presents a model for analysis of chronic disease prescribing action over time in terms of transitions in status of therapy as indicated in electronic prescribing records. The quality of alerts derived from these therapeutic state transitions is assessed in the context of antihypertensive prescribing.

Design

A set of alert criteria is developed based on analysis of state-transition in past antihypertensive prescribing of a rural Australian General Practice. Thirty active patients coded as hypertensive with alerts on six months of previously un-reviewed prescribing, and 30 hypertensive patients without alerts, are randomly sampled and independently reviewed by the practice’s two main general practice physicians (GPs), each GP reviewing 20 alert and 20 non-alert cases (providing 10 alert and 10 non-alert cases for agreement assessment).

Measurements

GPs provide blind assessment of quality of hypertension management and retrospective assessment of alert relevance.

Results

Alerts were found on 66 of 611 cases with coded hypertension with 37 alerts on the 30 sampled alert cases. GPs assessed alerting sensitivity as 74% (CI 52% - 89%) and specificity as 61% (CI 45% - 74%) for the sample, which is estimated as 26% sensitivity and 93% specificity for the antihypertensive population. Agreement between the GPs on assessment of alert relevance was fair (kappa = 0.37).

Conclusions

Data-driven development of alerts from electronic prescribing records using analysis of therapeutic state transition shows promise for derivation of high-specificity alerts to improve the quality of chronic disease management activities.