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Biomedical subjects

F Scott

Publications and source records attributed to F Scott.

At least 37 records · Page 2Linked to original sources

Distal gangrene in a polycythemic recipient fetus in twin-twin transfusion.

BACKGROUND: Gangrene of an extremity in a twin pregnancy has been attributed to the release of thromboplastin from a dead fetus or to a combination of polycythemia and anomalous vasculature. It has not been described in a situation where both twins survived. CASE: In a pregnancy complicated by twin-twin transfusion syndrome and managed with repeated amniocenteses, both twins survived. The recipient twin had necrosis of the left lower leg, which had appeared in the antenatal period and was associated with polycythemia, but not anomalous vasculature. CONCLUSION: Antenatally, polycythemia alone may cause necrosis of an extremity. Necrosis could be detected with ultrasound examination and may be an additional argument for laser photocoagulation of the chorioangiopagus.

Adult

Maternal serum screening and routine 18-week ultrasound in the detection of all chromosomal abnormalities.

Over a 15-month period, maternal serum screening (alpha fetoprotein, oestriol, chorionic gonadotrophin) and ultrasound were evaluated in the detection of all chromosomal abnormalities. Of the 981 screened, there were 8 chromosomally abnormal pregnancies. Six of these were considered to be at increased risk on serum screening, all of which were detected. Of the remaining 2, one was detected by ultrasound and the other resulted in a liveborn baby with trisomy 21. The positive and negative predictive values for serum screening for all chromosomal abnormalities was 7.8% and 99.9% respectively. The sensitivity and specificity was 87.5% and 91.5% respectively. Serum screening is useful in the detection of many chromosomal abnormalities, not just Down syndrome. The combination of maternal serum screening and ultrasound has a high negative predictive value and is valuable in providing reassurance of no underlying chromosomal abnormality. With a positive predictive value of 7.8% a chromosomal abnormality will be found once in every 13 amniocenteses performed.

Adult

Molecular markers in early cancer detection. New screening tools.

Better early detection strategies for lung cancer are clearly needed. About 20 years ago, cytomorphologic criteria were developed for use in staging bronchial epithelium carcinoma. Yet, when sputum cytology was added to chest radiograph in the largest early-screening-of-lung-cancer study carried out to date, the three-arm trial sponsored by the National Cancer Institute, no major outcome benefit was shown. Sputum samples of participants in one of these trials, the Johns Hopkins Lung Project, have been archived. Currently, sputum immunostaining using two monoclonal antibodies directed at a difucosylated Lewis X epitope and a 31-kilodalton protein show correlation between positive staining of these samples and eventual development of lung cancer in the sampled population. Strategies to neutralize the stimulation of growth factors like gastrin-releasing peptide, which are seen in small-cell disease, are also being explored. Development of an epithelial-directed diagnostic test is the most important goal in obtaining early detection tools for lung cancer. Several new tests await prospective trials to evaluate their utility. In developing an early detection test for lung cancer, due to the chronic nature of the risk and the vast at-risk population, cost and patient compliance are two major concerns.

Antibodies, Monoclonal

Chronic hepatitis C virus infection in haemophilic patients: clinical significance of viral genotype.

We have undertaken a comprehensive study of hepatitis C virus (HCV) genotype and its clinical significance in haemophilic patients. 189 HCV RNA positive were typed, using the Simmonds classification scheme, by restriction fragment length polymorphism (RFLP) in an amplified segment of the 5' non-coding region of the HCV genome. Type 1 was found in 121 (64.0%), type 2 in 23 (12.2%), type 3 in 36 (19.0%), type 4 in 3 (1.6%), type 5 in 2 (1.1%) and mixed infection in 3 (1.6%). There were no type 6 infections and one patient (0.5%) could not be typed. Genotype was not associated with diagnosis, age, or with HIV infection. Type 1 was associated with higher serum HCV RNA levels, and with a poor response to interferon. Progression to hepatic decompensation has been seen less frequently in those with type 3 compared to type 1 infection (p = 0.07). Three out of eleven patients studied over a longer time course showed a change in genotype, the remainder were persistently infected with HCV type 1. In conclusion, HCV genotype has clinical relevance in the management of haemophilic patients. Those with type 1 are probably more likely to develop serious liver disease and since they respond poorly to interferon-alpha, should be considered for new treatment strategies aimed at sustained clearance of HCV RNA.

Chronic Disease

Thalidomide as therapy for primary biliary cirrhosis: a double-blind placebo controlled pilot study.

Thalidomide has been reported to be effective in treating graft-versus-host disease, a condition with many clinical and pathological similarities to primary biliary cirrhosis. We performed a double-blind, placebo-controlled pilot study to assess the efficacy of thalidomide in 18 patients with biopsy-proven primary biliary cirrhosis (10 thalidomide, 8 placebo). Each patient was treated for 6 months and had a liver biopsy before and after treatment. Side effects, particularly sedation and fatigue, were more common on thalidomide and two patients were withdrawn from this group. There were no improvements in liver function tests or in liver histology, assessed morphometrically. A number of patients treated with thalidomide reported an improvement in pruritus. This study suggests that thalidomide is unlikely to be effective in altering the natural history of primary biliary cirrhosis.

Biopsy

The progression of HCV-associated liver disease in a cohort of haemophilic patients.

We have studied morbidity and mortality related to hepatitis C virus infection in haemophilic patients treated at our centre. 11/255 HCV seropositive patients have developed hepatic decompensation. 20 years after first exposure to lyophilized clotting factor concentrate the risk of hepatic decompensation is estimated to be 10.8% (95% CI 3.8-17.8%). There is a significantly increased risk associated with HIV infection, and also with increased age. For HIV seropositive patients the rates of decline in CD4 lymphocyte count and the development of p24 antigenaemia are significant risk factors for hepatic decompensation. Cirrhosis was seen in 9/19 HIV seropositive patients at post mortem. There was an association of cirrhosis with increased age but not with CD4 count, p24 antigenaemia, or AIDS. In conclusion, HCV infection is associated with serious liver disease in haemophilic patients, but so far this has been restricted to a minority of those at risk. HIV co-infection accelerates progression to hepatic decompensation, and we speculate that this is probably due to enhanced HCV replication in the presence of immune deficiency.

Adolescent

Scientific basis for cancer prevention. Intermediate cancer markers.

Promising cancer clinical trials results involving the disruption of early stages of cancer with intervention agents such as tamoxifen or retinoids have led to significant new research interest in developing preventative strategy for the control of epithelial cancers. Key to the efficient progress in this field is a clear understanding of the complex biology of the early stages of cancerization that proceed on the epithelial surface. Systematic analysis of the biology of strategic targets such as growth factors is one approach to this problem. Gastrin-releasing peptide is an autocrine growth factor for certain types of lung cancer cells. Mechanisms involved in the production and activation of this peptide are discussed as an example of how rational approaches to neutralization of cancer promotion biology can be achieved. The tools to monitor the success of this type of intervention also emerge from the understanding of the biology of growth factors, and intermediate end point markers that determine the presence or effects of a growth factor are attractive candidates for evaluation. Additional biologic tools reflecting the early stages of the cancer process need to be validated for use in serially evaluating the status of the relevant epithelium so that the ongoing success of a cancer intervention procedure can be established. Through this type of translational research, important applications of molecular biology may greatly improve the success of preventative strategies for cancer control.

Anticarcinogenic Agents

Prospective trial evaluating immunocytochemical-based sputum techniques for early lung cancer detection: assays for promotion factors in the bronchial lavage.

To confirm the results of a previous report on the use of monoclonal antibodies in immunocytochemical assays of sputums for the early detection of lung cancer, we designed a new prospective trial in an independent clinical trial population. Since well-characterized Stage I resected non-small cell lung cancer patients have a low rate of tumor relapse and a high (1-3%/year) chance of developing a second primary lung cancer, they comprise a very favorable group for conducting an early lung cancer detection trial. The rate of new lung cancer is about 10-fold in excess of a standard "high" risk population of smokers. To optimize the chance for a favorable outcome, all of the technical components for the trial have been systematically evaluated to ensure that optimal procedures are employed. For example, automated immunostaining of the sputum specimens will be performed. Bronchial lavages will be analyzed in a subset of the trial participants to define additional targets for early lung cancer detection. Two markers will be quantitated, including gastrin releasing peptide and peptidyl glycine alpha-amidating monooxygenase activity. These two markers assess the epithelium's capacity to produce growth factors which may be central to the biology of tumor promotion. Since these assays have not been performed in this context before, we attempted to optimize the specimen handling to permit the receipt of the material from a range of collaborating clinical sites in a condition that permits accurate quantitation of these two biomarkers. Efforts to standardize the assay endpoint stimulated the development of computer-assisted methods of immunocytochemical analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Anthracycline-induced tension in permeabilized cardiac fibers: evidence for the activation of the calcium release channel of sarcoplasmic reticulum.

Anthracyclines, such as doxorubicin (DOX), are important cancer chemotherapeutic agents that are cardiotoxic. The mechanism for the cardiotoxicity is not well-defined. Recent studies have concluded that anthracyclines release calcium (Ca2+) from membrane fractions containing sarcoplasmic reticulum (SR). To determine whether anthracyclines release Ca2+ in situ from cardiac SR, the effects of DOX on Ca(2+)-activated contractions were analyzed in membrane-permeabilized and membrane-intact fibers from rabbit heart. DOX (10-120 microM) induced tension development in calcium-preloaded permeabilized fibers. DOX-induced tension required submicromolar Ca2+, and was blocked by ruthenium red (20 microM) and Triton X-100 treatment, characteristics shared by caffeine-induced tension referable to SR Ca(2+)-release. DOX (50 microM) did not alter the maximum Ca(2+)-activated tension or shift the Ca2+ concentration-tension relationship of permeabilized fibers, indicating no effect of DOX on the myofilaments. DOX (44-350 microM) depressed post-rest isometric contractility of membrane-intact fibers but did not inhibit steady-state contractility (at 1 Hz; 2.5 Mm Ca2+), similar to effects of caffeine and submicromolar ryanodine. The specific effects of DOX on post-rest contractility of membrane-intact fibers are consistent with DOX-induced Ca2+ release from the SR of membrane-permeabilized fibers. Thus, DOX alters SR Ca2+ release in situ which may contribute to the inotropic and lusitropic dysfunction observed with anthracyclines.

Animals

Evaluation of antibody-dependent enhancement of feline infectious peritonitis virus infectivity using in situ hybridization.

Infection of primary macrophages in vitro by feline infectious peritonitis virus (FIPV) was used as a model system to study the kinetics of Fc receptor-mediated antibody-dependent enhancement (FcR-ADE) of virus infectivity at the single cell level. Cells were examined for evidence of viral RNA synthesis at various times points after infection, using 35S-labeled riboprobes and in situ hybridization. At each time point, infection of macrophages with FIPV in the presence of enhancing antiserum was compared to infection with FIPV alone. Both positive- and negative-sense FIPV RNA synthesis began at the same time point after infection in each case. In addition, the level of enhancement was the same from the earliest time of detectable RNA synthesis onward. Therefore, the degree of enhancement appears to be determined at an early point in the infection cycle. These results indicate that Fc-ADE does not induce more rapid viral RNA synthesis compared to infection with FIPV alone. Our results are compared to those of recent work concerning ADE of human immunodeficiency virus (HIV) in the presence of complement.

Animals

The environmental connection.

Both the World Health Organization and the Canadian Health for All concept recognize that healthy environments are fundamental to human health. Usually, the responsibility for environmental protection is assigned to public health inspectors. But there is more to a healthy environment than protection. Creating a healthy environment means "altering or adapting our social, economic and physical surroundings in ways that not only preserve but also enhance our health." Clearly, health promotion is an integral part of the concept. As experts in community health promotion, public health nurses (PHNs) could--and should--complement the work of health inspectors.

Canada

Maternal chest radiography as supporting evidence for the diagnosis of tuberculosis in childhood.

Routine chest radiography of the mothers of 163 children investigated for possible tuberculosis accompanied by sputum culture from those mothers with suspicious chest radiographs identified active pulmonary tuberculosis in 12 (10 per cent) of the mothers of the 117 children with probable (49 cases) and confirmed (68 cases) tuberculosis. All but one of the cases of active maternal tuberculosis were identified in the mothers of children less than 1 1/2 years of age. Chest radiography of the mothers of children less than 1 1/2 years of age will aid the diagnosis of tuberculosis in the child and expedite the reduction of the infectious pool of active pulmonary tuberculosis cases in adults in the community.

Adult

The operative repair of displaced patellar fractures.

Open reduction and internal fixation was used to treat 17 patients with displaced patellar fractures. The fractures were classified as transverse in five patients, transverse with comminuted distal pole in nine, and comminuted in three. The type of the fracture sustained was consistent with the mechanism of injury (eg, a fall, dashboard injury, motorcycle or pedestrian accident). Follow-up averaged 4 years (minimum, 1 year) including clinical and roentgenographic evaluation. Results in 11 patients were categorized as excellent, four as good, and two as unsatisfactory. The primary fixation method was modified tension band, which worked well in transverse fractures and in patients with minimal comminution. When the patella was comminuted, partial excision of the small fragments and internal fixation provided better results than fixation of all the fragments. The roentgenographic analysis did not always correlate with the clinical result. Two patients sustained a medial femoral condylar injury with their patellar fracture and had complicated treatment courses. These concurrent injuries may be predictive of a poor result.

Adult

Genital tuberculosis associated with female infertility in the western Cape.

Infertility is a common presenting symptom in women with genital tuberculosis. A study was undertaken to determine the prevalence and characteristics of this disease among the infertile patients (A and B income group) attending the Reproductive Biology Unit at Tygerberg Hospital. Between June 1986 and December 1987, the menstrual fluid from 451 infertile women was cultured for Mycobacterium tuberculosis using Löwenstein-Jensen medium. A prevalence of 7.98% (36/451) was found. Laparoscopic examination of the pelvis revealed bilateral tubal occlusion in 3 patients (8.3%); peritubular adhesions were present in 17 patients (47.2%). In the remaining 16 patients (44.5%), the pelvis was considered normal. No culture-positive patient gave a history of previous infection or contact with tuberculosis. Radiography of the chest and histological examination of the endometrium showed no evidence of infection. Of the 34 patients treated, 13 (38.2%) became pregnant after antituberculosis treatment was completed. If tuberculosis occurs in a population, menstrual fluid of infertile women should be cultured routinely for M. tuberculosis, especially if there is evidence of tubal damage.

Adolescent