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Biomedical subjects

C Lewis

Publications and source records attributed to C Lewis.

At least 37 records · Page 2Linked to original sources
PubMed1994

A review of the use of chemoprotectants in cancer chemotherapy.

Dose-limiting toxicity secondary to antineoplastic chemotherapy is principally due to the inability of the drugs to differentiate between normal and malignant cells. This results in normal tissue damage, as well as the desired antitumour effect. Toxicity may be acute, as in cisplatin-induced nephrotoxicity or alkylating agent myelotoxicity and haemorrhagic cystitis, or cumulative, as in anthracycline-related cardiac toxicity or cisplatin neurotoxicity. The consequences of this often include serious adverse effects and the inability to deliver adequate dose-intensive therapy against the cancer. Chemoprotective agents have been developed to provide site-specific protection against normal tissue toxicity, without compromising antitumour activity. Several chemoprotective compounds have recently been developed, including dexrazoxane (ICRF-187), amifostine (ethiofos: WR-2721), mesna and ORG-2766. Initial results confirm their promise as selective protective agents, although further randomised trials are required to identify their optimal role when used alone or in combination with other toxicity modifiers, including haematopoietic growth factors, with the ultimate aim being adequate dose escalation of chemotherapy to overcome tumour resistance.

Adrenocorticotropic Hormone↗
PubMed1994

Skewed T-cell receptor usage and junctional heterogeneity among isletitis alpha beta and gamma delta T-cells in human IDDM [corrected].

Because of anatomical limitations, molecular characterization of islet-inflammatory T-cells in human insulin-dependent diabetes mellitus (IDDM) has remained elusive. We have isolated isletitis T-cells from pancreas graft biopsies of two patients (syngeneic and allogeneic, respectively) shortly after onset of recurrent IDDM and have characterized their repertoire by sequencing T-cell receptor (TcR)-specific cDNAs. Histopathological analysis of the grafts revealed selective beta-cell loss and isletitis characteristic of recurrent disease with no evidence of chronic inflammation or rejection. Most of the in vivo-activated isletitis T-cells were CD8+TcR alpha beta+ and CD4-CD8-TcR gamma delta+ in both patients. Comparison of the different TcR alpha,beta,gamma, and delta sequences revealed V(D)J junctional heterogeneity but skewed TcR usage within patients. Eighth of 13 different isletitis TcR beta sequences (19 of 26 cDNAs) from the syngeneic graft of patient 1 were V beta 3+, as opposed to only 1 of 31 peripheral TcR beta sequences (1 of 31 cDNAs) (61.5 vs. 3.2%, P < 0.0001). Of the 19 different isletitis TcR alpha clonotypes of this patient (24 of 42 cDNAs), 5 were V alpha 14+. The isletitis TcR beta clonotypes of the human leukocyte antigen-identical allogeneic graft of patient 2 showed selective J beta, but not V beta, gene usage. Two of three predominant isletitis clonotypes of patient 2 were V alpha 22+ (19 of 28 cDNAs) and the other (5 of 28 cDNAs) was also V alpha 14+.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Assessment of general practitioners' management of hyperlipidaemia. A study using personal visits and a scenario-based questionnaire.

In summary our study has looked at the current management practices of hyperlipidaemia by general practitioners in an innovative way. Our results suggest that most GPs are managing this condition appropriately. Where their management differs from current guidelines is mainly in introducing medication early. We obtained significantly lower participation rates in the metropolitan as compared with the regional and rural areas, but we found no significant differences in the overall assessment of appropriate management between the different geographical regions of Victoria.

Data Collection↗
PubMed1994

Evaluation of two AIDS education programs for impoverished Latina women.

This paper evaluates and contrasts the effectiveness of two culturally sensitive AIDS education programs developed by the UCLA AIDS Nursing Network and delivered to 213 impoverished Latina homeless or drug-addicted women in Los Angeles. The Comprehensive Health Seeking and Coping Paradigm guided the program, which was implemented by specially trained Latina nurses and outreach workers. A quasi-experimental design was employed where women were randomized by site into Specialized (N = 82) and Traditional (N = 131) programs. Repeated measures ANOVAS and log-linear models were used to evaluate improvement over a two-week period for women in both groups and to identify interactions with program type. Two-week posttest analyses were also conducted to assess program effectiveness, controlling for baseline values of the measure in question, nonequivalency between groups at baseline, and selected demographic characteristics, including acculturation. Results indicated that women in both AIDS education programs improved significantly in cognitive, behavioral, and psychologic outcomes.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Molecular heterogeneity of a Graves' thyroid-infiltrating T cell population rich in CD8+ and gamma delta+ T cells.

We report here on the isolation and repertoire characterization of a Graves' thyroid T cell population which, unlike most Graves' thyroid T cell isolates reported before, was rich in CD4-CD8- T cells (16%, all TcR gamma delta+) and CD8+ T cells (75%) [TcR alpha beta+ (59%) and TcR gamma delta+ (16%)]. Only 7% of the isolated T cells were CD4+. By contrast, < 2% of peripheral blood mononuclear cells from the same patient were gamma delta+ and < 14% were CD8+. Sequence analysis of 18 TcR delta cDNAs prepared from these cells indicated the presence of at least 17 different gamma delta+ T cell clonotypes with molecularly heterogeneous antigen-binding site sequences. As opposed to most peripheral blood gamma delta+ T cells (express V delta 2 TcRs), 13 of the 17 different TcR delta clonotypes used a V delta 1 gene, although PCR amplification of TcR gamma- and TcR delta-specific cDNAs with V delta- and V gamma-gene family-specific oligonucleotides confirmed usage of all 4 V gamma and all 6 V delta families. Sequence analysis of 21 TcR alpha cDNAs from a TcR alpha-specific cDNA library indicated the presence of at least 12 different clonotypes, using 8 different V alpha gene families and heterogeneous antigen-binding site sequences. These results are in contrast with the selective V alpha gene usage reported for other intrathyroidal T cell subpopulations in autoimmune thyroid disease.

Adolescent↗
PubMed1993

The role of helplessness in the response to disease modifying drugs in rheumatoid arthritis.

Fifty patients with rheumatoid arthritis participated in an assessment of their helplessness before and after a 3-month disease modifying drug trial. A multidimensional approach measuring helplessness was used, assessing cognitive, affective, and behavioral components. Both before and after the drug trial, helplessness indices accounted for a highly significant amount of variation in self-reported pain and functional disability. Moreover, Time 1 helplessness predicted greater flare activity after the drug trial. Helplessness indices, however, did not correlate with joint examination measures within time periods, nor did they predict change in these measures over the drug trial. The importance of the role of helplessness in subjective and objective measures of clinical status in persons undergoing drug therapy is discussed.

Adult↗
PubMed1992

Comparison of recombinant tissue factor pathway inhibitors expressed in human SK hepatoma, mouse C127, baby hamster kidney, and Chinese hamster ovary cells.

Recombinant tissue factor pathway inhibitor (rTFPI) has been expressed in four mammalian expression systems using human SK hepatoma, mouse C127, baby hamster kidney (BHK), and Chinese hamster ovary (CHO) cells as hosts. On sodium dodecyl sulfate polyacrylamide gel electrophoresis, the immunoaffinity purified rTFPIs all show broad bands and the mean molecular weight of SK hepatoma and C127 rTFPIs (M(r) approximately 38,000) appear larger than those of BHK and CHO rTFPIs (M(r) approximately 35,000). All these proteins inhibit factor Xa and appear to bind factor Xa with 1:1 stoichiometry. The ability of these proteins to inhibit tissue factor-induced coagulation in plasma was examined using a prothrombin time assay. The relative activities of SK rTFPI:C127 rTFPI:BHK rTFPI:CHO rTFPI were found to be 28:15:2.1:1. By Western blot using specific antisera against the amino- and carboxy-termini of TFPI as probes, it is found that all the immunoaffinity purified rTFPIs possess approximately equal amounts of the amino terminus, but the C127 and BHK rTFPIs are deficient in carboxy terminus and the CHO rTFPI is essentially devoid of this region of the protein. Mono S chromatography allowed separation of the full-length and the truncated molecules with high and low anticoagulant activities, respectively. The above results suggest that proteolysis of the carboxy terminus of TFPI occurs to different extent when TFPI is expressed in different cells and that the carboxy terminal region of the TFPI molecule is important for the inhibition of tissue factor-induced coagulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Self-administered patient questionnaire for assessing knowledge about joint arthroplasty prior to surgery.

This article assesses the discriminant validity of a questionnaire designed to test patients' knowledge about total joint arthroplasty prior to preoperative educational intervention. The method employed was to compare responses on the test by surgeons, health care workers, and patients and to evaluate whether the test could discriminate among groups. A total of 148 patients, 59 health care workers and 28 orthopedic surgeons completed the questionnaire. The results show that patients are knowledgeable about the benefits of surgery, but are in need of information about surgical risks and complications. The test was able to discriminate between surgeons and the other two groups, but there were few differences between health care workers and patients. Item analysis also demonstrates that the test is reliable. Although the test exhibits acceptable psychometric properties, a major problem in using this test in evaluating educational interventions is the relatively high average score and the potential ceiling effect that prevents measurement of further gains in knowledge. More work is needed on expanding the test to include more items where knowledge of total joint arthroplasty is limited.

Discriminant Analysis↗
PubMed1992

Sources of genotoxicity and cancer risk in ambient air.

Products of incomplete combustion are identified as a major source of carcinogenic risk in urban areas, especially those from small non-industrial sources. The major ubiquitous emission sources outdoors in populated areas are residential home heating and motor vehicles. Indoors the major combustion source is environmental tobacco smoke. Polycyclic organic matter adsorbed onto the particles emitted from incomplete combustion are estimated to make the largest contribution to human genotoxic and cancer risk. Mutagenic emission factors combined with dispersion modelling indicated that automobiles and heating sources were major sources of mutagens. Ambient air studies to apportion the sources of mutagens in non-industrial areas confirmed this prediction. To apportion and estimate the cancer risk of ambient organic matter from particles in vivo animal tumour data, receptor modelling and human exposure data were combined. Tumourigenicity studies of the source apportioned ambient organic matter provided the relative tumour potencies of two ambient samples of different source composition. The human cancer unit risks were developed based on the comparative potency method using tumour data from these ambient samples. Residential wood combustion accounted for 75% of the exposure to particle associated organics, but only 20% of the estimated cancer risk. The remaining 80% of the risk appears to be associated with the mobile source component and atmospheric transformation products from these source emissions.

Air Pollutants↗
PubMed1992

Behavioral consequences of illness: childhood asthma as a model.

Several areas of research on childhood asthma are discussed within a transactional model of asthma. The model emphasizes the multidirectional influences that affect the severity of asthma and associated behavioral disability. The initial focus is on how the clinical presentation and morbidity of asthma are affected both by somatic predisposition and by interactions with multiple internal and external elements. Specific elements include emotional factors, neuroimmunology, temperament, and medication side effects. Second, the impact of asthma on the child, his or her family, and segments of the community are described, as are consequences of the disorder on quality of life. Third, there is a synopsis of preventative interventions for reducing the medical and behavioral impact of childhood asthma. The motif is that the interaction of medical and behavioral procedures can improve the management of asthma while consequences of the disorder are mollified. Finally, as examples of a transactional model of asthma, self-management programs for teaching children to become partners with their physicians in establishing and maintaining control over the disorder are described. A representative of self-management--the ACT (Asthma Care Training) program--is described, along with the impact such programs have on children, their families, and institutions. The conclusion emphasizes that asthma is a complicated and unpredictable disorder that puzzles physicians, behavioral scientists, and patients. Although new treatments may be over the horizon, controlling childhood asthma and its consequences currently rests on the cooperation and increased interaction of medical and behavioral scientists.

Asthma↗
PubMed1992

Malignant melanoma in inflammatory bowel disease.

Malignant melanoma occurred in 11 patients with inflammatory bowel disease (IBD). Six cases occurred in patients with ileocolitis, two in regional enteritis, one in granulomatous colitis, and two in patients with ulcerative colitis. The mean age at development of IBD was 24 yr, and at development of melanoma was 40 yr: the mean duration from onset of IBD to development of melanoma was thus 16 yr. All patients for whom complete information was available, except two, had received steroids and azulfidine for approximately a decade, as well as blood transfusions, usually multiple, and on repeated occasions. Six of the 11 patients had undergone one to seven prior operations (mean 3.5). All patients had wide radical excision of the melanoma, with or without concomitant or subsequent nodal dissection. Two patients (ages 25 and 36 yr) died rapidly from widely disseminated malignant melanoma. These cases may be coincidental, or else there may be an association between IBD and melanoma, related to immunosuppression either from the disease itself, from the medical and surgical therapy, and/or from x-ray exposure.

Adolescent↗
PubMed1991

Medium effects in antibody-catalyzed reactions.

Catalytic antibody technology has been used to explore the contribution of medium effects to the overall rate of an enzyme-catalyzed reaction. An antibody generated against a derivative of 2-acetamido-1,5-napthalenedisulfonate efficiently catalyzes the decarboxylation of 5-nitro-3-carboxybenzisoxazole. This unimolecular reaction is not susceptible to general acid-base catalysis but is highly sensitive to microenvironment; thus, it provides a simple chemical model for biologically important decarboxylations. The 10(4)-fold rate acceleration observed for the antibody reflects the kinetic advantage of the low-dielectric environment of the binding pocket acting to destabilize the substrate by desolvation and to stabilize the charge-delocalized transition state through dispersion interactions. These results are pertinent to an understanding of solvent effects in enzymic reactions in general and suggest approaches for developing antibody catalysts for numerous other reactions that involve large changes in charge distribution as the reaction coordinate is traversed.

Anilino Naphthalenesulfonates↗
PubMed1991

Factors underlying illusory self-assessment of driving skill in males and females.

While it is known that drivers as a group rate their skills as better than the average, the mechanism underlying this illusion is unclear. It is possible, for example, that it is due either to a "positive-self" or "negative-other" bias. A test of these alternative hypotheses revealed that judgments are consistent with a "positive-self" bias. An attempt was made to determine whether the illusion was present in all areas of driving skill or whether there were specific components where the illusion was absent. For men, the bias was present in all the driving components examined. For women, there were several areas where they rated themselves less positively than the men, and four areas where they showed no evidence of any bias. When the effects of driving experience were statistically controlled for, however, these sex differences were found to be substantially reduced.

Adolescent↗
PubMed1991

Advances in drug delivery and targeting.

This review covers a variety of techniques aimed at improving the specificity of delivery of both biologic and cytotoxic agents to tumor tissue while sparing normal tissue. The major areas reported on include further attempts to increase the ability of monoclonal antibodies, both conjugated and unconjugated, to target tumor tissue. It also examines the early clinical trials of liposomes as carriers of both biologics and cytotoxics and the potential problems of this modality. A number of studies in the area of regional drug delivery, including intraperitoneal, intravesical, intra-arterial, and intratumor, highlight the many clinical problems still to be resolved. Improved targeting of antitumor agents to sites of malignant disease appears likely over the next decade judging by the recent developments we review. Although much clinical and laboratory research will be required to achieve this goal, the likely directions appear to be established.

Antibodies, Monoclonal↗
PubMed1991

Quantifying serum antibody class and subclass responses by enzyme immunoassay in humidifier-related disease.

Antibody activity in the major classes and IgG subclasses against antigens in factory humidifier water was quantified by enzyme immunoassay (EIA) in 88 subjects who were exposed at work to the output from these contaminated humidifiers. Those with work-related symptoms had significantly higher mean titres than those who were symptom free, although values overlapped. The individuals with the highest IgG antibody titres also had the highest titres of IgM and IgA antibody, and these parameters did not discriminate between those with and without symptoms any better than the IgG titre. This was also true for the IgG subclasses where activity was predominantly measured in IgG1. Quantifying the IgG antibody allowed us to demonstrate a significant correlation with years of work exposure (P less than 0.001). There was no significant association between antibody and cigarette smoking, as assessed by smoking history and confirmed objectively by serum cotinine levels. There was a significant correlation with total IgG level (P less than 0.001) suggesting that a non-specific immune enhancement may accompany the specific response. The antibody titres were followed up to 3 years after modification of the humidification systems, and during this time symptoms resolved and the antibody levels progressively fell to undetectable levels. The EIA was adapted to measure antigen at nanogram levels thus providing a rapid test for screening of humidifer water as well as a technique that may help identify the nature of the antigens involved.

Air Conditioning↗
PubMed1991

Mobile versus fixed site lithotripsy.

The efficacy of a mobile Dornier HM4 lithotriptor, was compared with that of a fixed site Siemens Lithostar. A total of 115 calculi in 98 patients were treated, 55 on the mobile Dornier and 60 on the Lithostar. The groups were similar except for stone size, the mean of the Lithostar group being 11 mm compared with 7.7 mm in the Dornier group. Fragmentation rates were not significantly different, 88% and 75% on the mobile and fixed site machines, respectively and, at 3 months follow-up 66% and 46% were stone free or with fragments of less than 2 mm. There were no serious complications, and the incidence of mild complications was similar in the two groups. We conclude that the mobile Dornier HM4 is an effective lithotriptor and can offer several advantages over fixed site machines.

Female↗