‘Understanding Disability’: Evaluating a contact-based approach to enhancing attitudes and disability literacy of medical students

Background

Health disparities and disparities in the provision of healthcare to people with disabilities remains a topic of concern. Research demonstrates that attitudes of healthcare providers contribute to this disparity. The approach to disability education and training in medical school warrants evaluation.

Cytogenetic and histologic correlations in malignant lymphoma

Although a number of studies have indicated correlations between histologic subtypes of tumors and certain nonrandom chromosome changes, cytogenetic studies of lymphoma are in an early stage compared to those of leukemia. No comprehensive analysis of available data has so far been attempted in the literature either. Here we present an analysis of chromosome changes and their correlation with subtypes of lymphoma studied by conventional histology and cell surface markers, as observed in two sets of data: a group of 65 karyotypically abnormal tumors sequentially ascertained and studied by us during the period January 1, 1984 to April 30, 1985, and a larger data set derived by combining our data with those from two published series from the University of Minnesota that are comparable to our data. These combined data, which comprise the largest data set on the cytogenetics of lymphomas assembled so far, enabled a comprehensive analysis of correlation between chromosome change and tumor histology and the patterns of chromosome instability in these tumors. We found several significant associations, some previously described and others now recognized, between nonrandom chromosome gains, breaks, translocations, and deletions and histologic subtypes of tumors that characterize lymphomas. The data indicate that finding of chromosome breaks at certain sites (eg, 8q24, 14q32, 18q21) is of diagnostic value in dealing with cases of unusual lymphoma. Furthermore, nonrandom chromosome breakage exhibited three distinct patterns that reflected three levels of etiologically relevant genetic change.     

Hemorrhagic tumor necrosis during a pilot trial of tumor necrosis factor-alpha and anti-GD3 ganglioside monoclonal antibody in patients with metastatic melanoma

Hemorrhagic tumor necrosis is an inflammatory event that leads to selective destruction of malignant tissues, with both potentially toxic and beneficial consequences. A pilot clinical trial was undertaken combining tumor necrosis factor-alpha (TNF-alpha) with the monoclonal antibody R24 (MoAb R24) against GD3 ganglioside in patients with metastatic melanoma. Patients received MoAb R24 to recruit leukocytes to the tumor followed by low doses of recombinant TNF-alpha to activate leukocytes. Eight patients were treated and seven patients had mild toxicity. One patient with extensive metastatic melanoma developed tumor lysis syndrome within hours after treatment with almost complete necrosis of bulky tumors in multiple visceral sites. To our knowledge, this is the first documented case of hemorrhagic tumor necrosis in a patient with metastatic cancer in multiple visceral sites.     

Detection of placental growth hormone variant and chorionic somatomammotropin-L RNA expression in normal and diabetic pregnancy by reverse transcriptase-polymerase chain reaction

Diabetes is a common complication encountered during pregnancy. Earlier studies indicated that diabetic placentas bear morphological alterations consistent with modified placental differentiation, including alterations in the villous cellular content, structure, and total surface. Limited data associating the diabetic status with the expression of terminal placental differentiation markers are available. The human growth hormone/chorionic somatomammotropin (hGH/CS) family consists of five genes, one of which (GH-N) is expressed efficiently in pituitary while the other four (CS-A, B, L, and hGH-V) are expressed in placenta and represent ultimate placental differentiation markers. We developed and applied a sensitive RT-PCR method coupled with diagnostic restriction digestion to determine the relative levels of the hGH/CS family in normal pregnancies and examine whether their mRNA expression pattern is altered in pregnancies complicated by diabetes. We show that relative hCS-L content changes during placental development. Specifically, normal term placentas express higher relative levels of hCS-L, lower relative hGH-V levels and a 70-fold lower hGH-V/CS-L mRNA ratio compared to early placentas. Also, many term placentas from diabetic pregnancies express lower relative levels of hCS-L mRNA and a much higher hGH-V/CS-L mRNA ratio compared to normal term placenta, resembling more an early placenta pattern of expression. Thus, our study suggests that the expression of terminal placental differentiation markers, such as the hGH/CS genes, is altered in term placentas from these diabetics reflecting either impaired placental differentiation or post-differentiation impairment of normal placental function.     

Construction and characterization of a single-chain catalytic antibody.

The antigen-binding (Fab) fragment of the catalytic monoclonal antibody NPN43C9 has recently been cloned by using bacteriophage lambda. By inserting the variable regions of this Fab coding sequence into a (NH2)-VL-linker-VH-(COOH) construct (where VL and VH represent the heavy and light chain variable regions), we have assembled a recombinant gene encoding a catalytic single-chain antigen-binding protein. This protein has been expressed in Escherichia coli and exhibits the same catalytic parameters as the parent monoclonal antibody NPN43C9. Single-chain forms of catalytic antibodies may prove valuable for structural and site-directed mutagenesis studies as well as for large-scale applications of catalytic antibodies.     

Platelets modulate the proteolysis of factor VIII:C protein by plasmin

Factor VIII coagulant protein (VIII:C) functions as a critical cofactor with factor IXa, calcium ions, and phospholipid during the activation of factor X. In the course of this reaction, the activity of VIII:C is first increased and then is destroyed by one or more serine proteases that are part of the coagulation sequence. In this study, we have investigated the influence of platelets on the inactivation of VIII:C by plasmin. Platelets were separated from plasma proteins in the presence of granule release inhibitors and were incubated with plasmin and isolated VIII:C or the complex of purified VIII:C/von Willebrand factor (vWF); VIII:C activity and antigen levels were assessed over time. In the presence of platelets, the isolated VIII:C showed an initial increase in VIII:C activity that was not present when platelets were absent, and the VIII:C/vWF showed an increase in VIII:C activity over that seen when platelets were absent. In addition, platelets stabilized VIII:C activity over a one-hour time course when compared with buffer. The VIII:C antigen did not increase and decreased slowly whether platelets were present or absent. Preincubating the platelets with ristocetin, collagen, or plasmin did not alter the results, and experiments using platelets from a patient with severe von Willebrand's disease also showed a pattern similar to that seen with normal platelets. Experiments using fixed platelets or phospholipid vesicles showed that they did not support the activation reaction or delay the inactivation reaction. These studies demonstrate that platelets modulate the activation and inactivation of VIII:C by plasmin, apparently by a mechanism that is independent of the platelet release reaction.     

Cost of illness of inflammatory bowel disease in the UK: a single centre retrospective study

BACKGROUND AND AIMS: The potentially high costs of care associated with inflammatory bowel disease (IBD) are recognised but we have little knowledge of the scale, profile, or determinants of these costs in the UK. This study aimed to describe costs of illness for a group of IBD patients and determine factors associated with increased healthcare costs. SETTING: A university hospital serving a target population of approximately 330 000. PATIENTS AND METHODS: A six month cohort of IBD patients receiving any form of secondary care was identified, comprising 307 cases of ulcerative (or indeterminate) colitis and 172 cases of Crohn's disease. Demographic and clinical data were abstracted from clinical records and individual resource use was itemised for all attributable costs (including extraintestinal manifestations). Item costs were derived from national and local sources. Cost data were expressed as mean six month costs per patient (with 95% confidence interval (CI)) obtained using non-parametric bootstrapping. Determinants of cost were analysed using generalised linear regression modelling. A postal survey of patients was undertaken to examine indirect costs, out of pocket expenses, and primary care visits. RESULTS: Inpatient services (medical and/or surgical) were required by 67 patients (14%) but accounted for 49% of total secondary care costs. Drug costs accounted for less than a quarter of total costs. Individual patient costs ranged from 73 to 33,254 UK pounds per six months. Mean (95% CI) six month costs per patient were 1256 UK pounds ( 988 pounds, 1721 pounds) for colitis and 1652 UK pounds (1221 pounds, 2239 pounds) for Crohn's disease. Hospitalisation, disease severity grade, and disease extent correlated positively with cost of illness but costs were independent of age or sex. Compared with quiescent cases of IBD, disease relapse was associated with a 2-3-fold increase in costs for non-hospitalised cases and a 20-fold increase in costs for hospitalised cases. Survey data suggested average six month costs were < 30 UK pounds per patient for primary care visits (both diseases) and median loss of earnings were 239 UK pounds for colitis and 299 UK pounds for Crohn's disease. CONCLUSIONS: This study represents the first detailed characterisation of the scale and determinants of costs of illness for IBD in a British hospital. Hospitalisation affected a minority of sufferers but accounted for half of the total direct costs falling on the healthcare system.     

Evaluation of delivery of enhanced diabetes care to patients of South Asian ethnicity: the United Kingdom Asian Diabetes Study (UKADS).

AIMS: We tested the hypothesis that enhanced care for diabetes, tailored to the needs of the South Asian community with Type 2 diabetes, would improve risk factors for diabetic vascular complications and ultimately reduce morbidity and mortality. PATIENTS AND METHODS: The study was a cluster randomized controlled trial (RCT) with general practice the unit of randomization. Six West Midlands general practices with a high proportion of South Asian patients were randomized to 'enhanced care' using Asian link workers and extra community diabetes specialist nurse sessions (intervention) or continued standard practice care (control). RESULTS: Of 401 patients recruited to the study, 361 (90%), comprising 178 from Coventry and 183 from Birmingham were eligible and included in the analyses. The mean age at baseline (standard deviation, SD) was 58.9 (11.7 years) with median (interquartile range; IQR) duration of diabetes 6.5 (3-11) years. At one year follow-up there was a significant difference in reduction of systolic (4.6 mmHg, P = 0.035) and diastolic blood pressure (3.4 mmHg, P = 0.003) and total cholesterol (0.4 mmol/l, P = 0.005), comparing the intervention and control groups. After adjusting for baseline measurement and age, only differential reduction in diastolic blood pressure remained significant. There was no significant change in HbA(1c) and no difference between the groups. CONCLUSIONS: Using link workers and extra community diabetes specialist nurse input together with treatment protocols in primary care might prove a useful strategy in working towards NSF targets for diabetes management. In this study, small reductions in blood pressure and cholesterol were achieved. Improvement in glycaemic control may require longer and possibly different strategies. Further research is required to evaluate fully the effectiveness, including the costs and longer term sustainability of culturally sensitive initiatives.     

Effect of Asthma Call-back Survey methodology changes on work-related asthma estimates, 19 states, 2007–2012

Objective: Asthma Call-back Survey methodology has been changed recently, as a new sampling design, weights calculation (2011–2012), and revised work-related asthma (WRA) section (2012) were implemented. To assess the effect of these changes on the WRA and possible WRA estimates among ever-employed adults with current asthma, we analyzed 2007–2012 data for 37?505 ever-employed adults (≥18 years) collected from 19 US states (representing an estimated 10 million adults each year). Methods: Using data from landline telephone (LLP) households, we calculated estimates applying poststratification weights (2007–2010) and “raking” weights (2011–2012). Also, using data from LLP/cellular telephone (CP) households combined, we calculated estimates applying “raking” weights (2012). Results: Based on LLP household data, the WRA estimates ranged from 7.8% to 9.7% during 2007–2010, was 9.1% in 2011 and 15.4% in 2012. Possible WRA estimates ranged from 35.1% to 38.1% during 2007–2010, was 38.1% in 2011 and 39.8% in 2012. Using the 2012 LLP/CP household data, the WRA and possible WRA estimates were 15.4% and 38.9%, respectively. Conclusions: Implementation of “raking” weights did not substantially change the WRA or possible WRA estimates among ever-employed adults with current asthma. The WRA and possible WRA estimates based on LLP and LLP/CP samples in 2012 were comparable, as CP users are younger and less likely to have WRA. The substantial upward shift in the 2012 WRA estimates likely was associated with the revision to the WRA section.