Characterization of murine monoclonal anti-endothelial cell antibodies (AECA) produced by idiotypic manipulation with human AECA

The IgG fraction of human anti-endothelial cell antibodies (AECA) obtained from a patient with Wegener's granulomatosis was used as immunogen to raise AECA mAb in mice selected among those which developed vasculitis-like lesions after immunization. Three mAb (BGM, 3C8 and 7G2), selected by cyto-ELISA and flow cytometry analyses, featured a specific reactivity with human umbilical vein endothelial cells (HUVEC) and the mouse endothelial cell line H5V; on the contrary, HEp2 cells, the murine melanoma B16 cell line, the extracellular matrix as well as several other antigens tested were not recognized. BGM mAb, an IgG3 precipitating a 70 kDa structure from HUVEC, was able to induce endothelial cells to secrete amounts of IL-6 significantly higher than irrelevant controls or mAb binding different endothelial antigens (i.e. CD31, CD29, ICAM-1 and HLA class I). BGM mAb induced significant levels of antibody-dependent cell cytotoxicity (13 +/- 2.5 versus 0.6 +/- 0.03%). To the best of our knowledge, BGM is the first murine mAb specific for human endothelial cells generated by idiotypic manipulation; secondly, its biological properties further support the notion of a pathogenic role for AECA in autoimmune-mediated diseases.     

Ruptured abdominal aortic aneurysms: factors affecting the early postoperative outcome

Long-term experience with 63 polyurethane, pail handle, coiled tip peritoneal dialysis catheters surgically implanted in 57 consecutive patients with renal failure is presented. One hundred percent follow-up of the study group represented 1,248 patient-months of observation. Cumulative catheter survival rates were 80.8% at 12 months, 62.3% at 24 months, and 48.1% through 51 months. Catheter half-life was 32.6 months. Infection was the most frequent catheter related complication. Incidence rate of peritonitis was 0.73, and exit site/tunnel infection was 0.42 episodes per patient-year. Median time to first episode was 11.7 months for peritonitis, and 26.3 months for exit site/tunnel infection. Infection led to removal of 28.6% of implanted devices, mechanical blockage resulted in 6.4% loss, and pericatheter leak and tubing break each accounted for 1.6% of catheter removals. The polyurethane, pail handle, coiled tip peritoneal catheter was found to be a reliable long-term access device compared with reported performances of other catheter types. An adverse outcome was identified in the current clinical series with a model design using a permanently attached catheter adapter that caused large exit site wounds that were predisposed to infection and catheter loss.     

Coughing and wheezing children: improvement after parents stop smoking]

Three children, boys aged 6, 4 and 4 years presented with recurrent cough and (or) wheeze. Exposure to tobacco smoke at home was considered an aggravating factor. Symptoms in all three cases improved considerably or resolved completely when the patients' (grand)parent(s) stopped smoking. There is little literature on the beneficial effect of parents' giving up smoking on symptoms of childhood asthma. These cases, however, illustrate that advising parents of children with recurrent respiratory symptoms to give up smoking can be a rewarding and successful form of therapy.     

Effects of flutamide on pituitary and adrenal responsiveness to corticotrophin releasing factor (CRF)

Although most studies have indicated that Ber-EP4 immunostaining can assist in differentiating epithelial pleural mesotheliomas from adenocarcinomas that metastasize to the pleura, the percentage of positive cases has varied greatly among different studies. Authors of a recent publication concluded that Ber-EP4 has no diagnostic utility in separating these conditions. To determine whether Ber-EP4 has any value in distinguishing mesothelioma from adenocarcinoma, 70 formalin-fixed epithelial pleural mesotheliomas, 20 pulmonary adenocarcinomas, 59 nonpulmonary adenocarcinomas, 4 squamous cell carcinomas of the lung, 6 transitional cell carcinomas, and 31 adenocarcinomas of unknown origin that metastasized to the pleura were stained with this antibody. Reactivity was observed in 18 (26%) of 70 mesotheliomas and in all 20 (100%) of the pulmonary adenocarcinomas, in 55 (93%) of the 59 nonpulmonary adenocarcinomas, in 4 (100%) of 4 squamous cell carcinomas of the lung, in 4 (67%) of 6 transitional cell carcinomas, and in 26 (84%) of 31 adenocarcinomas of unknown origin that metastasized to the pleura. The staining in the mesotheliomas was focal and restricted to a limited number of cells, in contrast with staining in the pulmonary adenocarcinomas in which it was invariably diffuse. The extent of the staining in the nonpulmonary adenocarcinomas and the metastatic adenocarcinomas of unknown origin was less consistent--negative or focal in some cases and diffuse in others. Therefore, while Ber-EP4 seems to be helpful in separating epithelial pleural mesotheliomas from lung adenocarcinomas, its value in distinguishing mesotheliomas from other tumors metastatic to the pleura is more limited and depends largely on the site of origin of the metastatic tumor.     

Price elasticities of demand for curative health care with control for sample selectivity on endogenous illness: an analysis for Sri Lanka

Estimation of demand for health care with samples of only the ill may bias estimates. Additionally, the lack of exogenous information, especially distance, about the alternative care providers causes omitted variable problems. This paper alleviates both problems through geographic mapping of facility information to individuals, combined with joint estimation of illness (health production) and health care demand. The joint estimation full sample demand results are compared to those from one equation estimation for only the ill sample. The results indicate that the selectivity problem is significant, but that for this sample the magnitude of the bias on the price coefficient is small.     

Treatment of subglottic laryngitis (pseudocroup): steroids instead of steam]

Traditionally, steaming with warm moist air was recommended for the treatment of subglottic laryngitis (pseudocroup). However, no favourable effect has ever been demonstrated. Consequently, steaming is no longer to be advised. Systemic corticosteroids, already of proven effectiveness in severe croup, were shown to be also effective when administered in a single oral dose in moderately severe disease. Besides, in various studies, nebulisation of budesonide (2000 micrograms) with a jet nebuliser had a good effect on the clinical course of croup. However, dose-effect studies are still lacking. A single dose of corticosteroids, either systemic or inhaled via a jet nebuliser, should be the first line therapy in moderate and severe croup syndrome. In milder cases no specific treatment is needed as the disease is self-limiting.     

Modification of natural immunity in mice by imipenem/cilastatin

SETTING: A tuberculosis programme in hill and mountain districts of Nepal supported by an international non-governmental organisation (NGO). OBJECTIVE: To evaluate under programme conditions the effectiveness of unsupervised monthly-monitored treatment using an oral short-course regimen. DESIGN: In this prospective cohort study, outcomes for new cases of smear-positive tuberculosis starting treatment over a two-year period in four districts in which a 6-month rifampicin-containing regimen was introduced as first-line treatment (subjects) were compared to outcomes for similarly defined cases in four districts where a 12-month regimen with daily streptomycin injections in the intensive phase continued to be used (controls). RESULTS: Of 359 subjects started on the 6-month regimen, 85.2% completed an initial course of treatment compared to 62.8% of 304 controls started on the 12-month regimen (P < 0.001); 78.8% of subjects and 51.0% of controls were confirmed smear-negative at the end of treatment (P < 0.001). The case-fatality rate during treatment was 5.0% among subjects and 11.2% among controls (P = 0.003). Among those whose status was known at two years, 76.9% of subjects were smear-negative without retreatment, compared to 60.9% of controls (P < 0.001). CONCLUSION: In an NGO-supported tuberculosis control programme in remote districts of Nepal, patient-responsible short-course therapy supported by rapid tracing of defaulters achieved acceptable outcomes. Where access and health care infrastructure are poor, district-level tuberculosis teams responsible for treatment planning, drug delivery and programme monitoring can be an appropriate service model.     

Economic implications of hepatic arterial infusion chemotherapy in treatment of nonresectable colorectal liver metastases. Meta-Analysis Group in Cancer

BACKGROUND: Approximately 20% of patients with colorectal cancer die of metastases confined to the liver. A meta-analysis recently performed by our group confirmed that in these patients hepatic arterial infusion of 5-fluoro-2'-deoxyuridine, compared with intravenous chemotherapy with fluoropyrimidines or supportive care (including symptom palliation when necessary), improved tumor response. PURPOSE: Because of the high cost of hepatic arterial infusion, we undertook a cost-effectiveness analysis that related the cost of such therapy to its medical efficacy. METHODS: The patient population was drawn from the seven randomized clinical trials included in the meta-analysis and included individual data on 654 patients. Of these seven trials, five compared hepatic arterial infusion and intravenous chemotherapy and two compared hepatic arterial infusion and a control group in which some patients could be left untreated. Patients assigned to receive hepatic arterial infusion made up the hepatic arterial infusion group; the other patients constituted the control group. The measures of efficacy were survival and tumor response. Health-care costs (in 1995 U.S. dollars) were computed over the duration of patient follow-up and were derived from actual costs in two centers, one at Henri Mondor Hospital (Paris, France) and the other at Stanford University Medical Center (Palo Alto, CA). The total cost of treatment included the initial procedure, chemotherapy cycles, and main complications. RESULTS: The mean gain in life expectancy in the hepatic arterial infusion group compared with the control group was 3.2 months (standard error = 1.0 month). For patients treated by hepatic arterial infusion in Paris, the hepatic arterial infusion pump, initial hospitalization, and the entire process (including follow-up and complications) cost, on average, $8400, $15172, and $29562, respectively; in Palo Alto, these costs were $4700, $13784, and $25 208, respectively. For patients in the control groups in Paris and Palo Alto, the total treatment costs were, on average, $9926 and $5928. The additional costs of hepatic arterial infusion over control treatment were $19636 in Paris and $19280 in Palo Alto. The cost-effectiveness (i.e., the additional cost divided by the additional benefit) with respect to survival of the patients in the hepatic arterial infusion group compared with the patients in the control group was $73635 per life-year in Paris and $72300 per life-year in Palo Alto. CONCLUSIONS AND IMPLICATIONS: The cost-effectiveness of localized chemotherapy for colorectal liver metastases is within the range of accepted treatments for serious medical conditions, although it might be considered borderline by policy-makers in some countries. Prospective clinical trials should be conducted to more definitively answer this question.     

Leiomyosarcoma of the maxillary sinus: CT and MRI findings

This report describes the CT and MRI appearances of a leiomyosarcoma of the maxillary sinus. CT showed frank bony destruction, no calcification and a low attenuation area within the mass. MRI showed intermediate intensity on T1 weighted images, intermediate to slightly high signal intensity on T2 weighted images and moderate inhomogeneous enhancement. Precise identification of the extent of the tumour, especially of orbital invasion, is of utmost importance because local recurrence is common after the resection of leiomyosarcomas.