Implementing the patient's charter in outpatient services.
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Biomedical subjects
Publications and source records attributed to C Collins.
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The development and testing of a multidimensional instrument to assess the reactions of family members caring for elderly persons with physical impairments, Alzheimer's disease, and cancer is reported. Forty items were administered to a sample of 377 caregivers of persons with physical impairments and Alzheimer's disease. Five dimensions of caregivers' reactions were identified through exploratory factor analysis. Using confirmatory factor analysis on an independent sample (N = 377), these dimensions were tested for factorial invariance across spouse and nonspouse caregivers and between caregivers of persons with cancer and those caring for persons with Alzheimer's disease. The subscales also had a high level of factorial invariance across a three-wave panel study (N = 185). The subscales appeared consistent with first order tests of construct validity.
In this study, the hypothesis that DNA ploidy and the presence of HPV 16 and HPV 18 DNA affects survival of patients with squamous cell carcinoma of the cervix was tested. Archival paraffin blocks from biopsy and surgical specimens were obtained from 127 women diagnosed in 1977-1984. Determination of DNA ploidy was by flow cytometry and HPV 16 and HPV 18 DNA status by polymerase chain reaction with subsequent dot-blot hybridization. For each patient, age, stage, treatment modality, and 5-year survival were correlated with ploidy and HPV status. HPV 16 DNA was present in 53% of the tumors. HPV 18 was not detected in this population. HPV 16 DNA was found twice as often in Stages IB and IIA than in advanced-stage disease (III and IV). These advanced-stage tumors were more commonly aneuploid. Neither HPV status nor DNA ploidy were predictive of survival for any stage of disease or therapeutic modality.
We have identified and sequenced cDNA clones that encode for the human beta-subunit of rod cGMP phosphodiesterase (PDEB). A single 2565-bp open reading frame that codes for an 854-amino-acid protein was identified. The human beta-subunit protein is 90% identical to the bovine beta-subunit and 91% identical to the mouse protein. Northern blot analysis indicates that the gene is expressed as an abundant 3.5-kb transcript in retina and as a rare 2.9-kb transcript in brain. The isolation of cDNAs from human brain cDNA libraries confirms the brain as a site of expression for this gene. The molecular defect underlying retinal degeneration in the rd mouse has been found to be a nonsense mutation in the beta-subunit of the mouse cGMP PDE, resulting in a truncated protein (Pittler et al., 1991b, Proc. Natl. Acad. Sci. USA. 88: 8322-8326). The molecular cloning of the cDNA encoding for the PDEB represents the first step in establishing whether this gene plays a causative role in any one of the several human hereditary retinopathies or, based on its localization to chromosome 4p 16.3, in the pathogenesis of Huntington disease.
To identify expressed sequences within candidate regions for the Huntington's disease (HD) gene in 4p16.3, we isolated the gene encoding the beta subunit of the human cGMP phosphodiesterase (PDEB). We formally assessed this as a candidate gene for HD based on it's expression in brain, the demonstration of linkage disequilibrium between intragenic DNA markers and HD, and the demonstration that mice with a mutation in this gene have a reduction of neurons in particular brain regions. We investigated all 22 exons of PDEB and 5'-flanking region for point mutations in 16 HD patients of different ethnic origins using single strand conformational polymorphism analysis. The underlying DNA changes found initially exclusively in HD patients were excluded as the cause for HD.
No detectable rearrangements involving chromosome 4p16.3 have been observed in patients with Huntington's disease (HD). New mutations for HD could involve structural alterations which might aid the localization of the defective gene. We have reinvestigated a well documented sporadic case of HD. DNA haplotyping with markers between D4S10 and the telomeric locus D4S141 reveals a recombination event in one chromosome of the sporadic HD patient. The site of recombination maps within a 50 kilobase (kb) region, about 700 kb from the 4p telomere. Based on the extremely low HD mutation rate and significantly decreased recombination in the distal region of 4p, we hypothesize a direct link between the site of the recombination and HD in this patient.
The authors sampled more than 600 University of Arizona students to determine how student attitudes, beliefs, and practices should be considered by healthcare personnel in planning campus health education programs. The survey found that students worried more about diet, exercise, and weight than they did about more serious health problems and that, although generally positive and optimistic, the students frequently felt anxious and overwhelmed. Two thirds of the students were sexually active, 74% of those who were active used various contraceptive methods. More than three quarters of those surveyed indicated they currently drank alcoholic beverages; one quarter of the drinkers said they frequently downed three or more drinks on one occasion, and 44% of the drinkers reported driving while under the influence of alcohol.
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A firmly adherent mass of slime plus organisms (biofilm) accumulates on the sides of culture tubes when some strains of coagulase-negative staphylococci are grown in a chemically-defined medium containing [14C]glucose. This mass was washed (to remove labelled medium) and then counted after adding scintillation fluid. Organisms from the liquid culture were also washed and counted to check that [14C]glucose had been utilised to label the bacteria. Nine strains were examined in this way, and the results were compared with those obtained with four older techniques for recognising slime production or adherent bacteria. The new method is quick, and has advantages of reproducibility and good discrimination between strains; there was a 15-fold difference in counts in the biofilm between slime-producing and non-producing strains respectively. With the new radiolabel assay, the effects of several antibacterial compounds on the build-up of the biofilm were investigated with four slime-producing strains. Tunicamycin, chloramphenicol and 5-fluorouracil, at levels below their minimum growth-inhibitory concentrations, each greatly diminished biofilm formation; several other drugs had less effect.
Management of breast cancer during pregnancy is complicated by the high risks of abortion and foetal malformation from the use of radiotherapy and chemotherapy. A case of breast cancer during pregnancy, treated with radiotherapy, and the estimated foetal dose is reported.
PURPOSE: Two consecutive protocols of continuous intravenous (CIV) infusion interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells were carried out in patients with metastatic renal cell carcinoma (RCC) to determine the response rate and toxicity. PATIENTS AND METHODS: In both protocols, patients received induction IL-2 at 6 x 10(6) U/m2/d on days 1 to 5, and underwent leukapheresis on days 7 to 9 at the peak of rebound lymphocytosis. LAK cells were generated by a 5-day incubation with IL-2 at 1,000 U/mL, and were infused on days 12 to 14. For the first 20 patients (protocol A), maintenance IL-2 was administered at 6 x 10(6) U/m2/d on days 12 to 16. On the assumption that less IL-2 might be required to maintain rather than to induce LAK activity, and that a longer duration of maintenance IL-2 might enhance LAK survival and function in vivo, the protocol for the subsequent 22 patients (protocol B) was altered so that the maintenance phase consisted of a lower dose of IL-2 (2 x 10(6) U/m2/d) administered for a longer period of time (days 10 to 20). RESULTS: In protocol A, there were two complete responses (CRs) and three partial responses (PRs), for a total response rate of 25%. One PR was surgically converted into a CR. The durations of the CRs are 36+, 18+, and 18+ months. Hypotension and capillary leak were most severe during maintenance, which limited the median duration of maintenance IL-2 to 4 days. In protocol B, no patient experienced severe hypotension, and the median duration of maintenance IL-2 was 9 days. Two patients exhibited a CR and seven a PR, for a total response rate of 41%. Two PRs were surgically converted to CRs. The durations of CR are 14+, 9+, 6+, and 5+ months. In both protocols, the CIV induction regimen resulted in marked rebound lymphocytosis (mean, 11,097/microL) and LAK-cell yield (mean, 18.1 x 10(10)). The cumulative response rate was 14 of 42 patients, or 33% (95% confidence interval, 19% to 47%). CONCLUSION: These results demonstrate that both protocols of CIV IL-2 plus LAK cells have substantial antitumor activity, and that a longer maintenance phase of IL-2 at a lower dose is associated with significantly less toxicity without a loss of therapeutic efficacy.
The production of particulate wear debris is a recognised complication of joint arthroplasty, but interest has concentrated on local tissue reactions and a possible association with implant loosening. The fate of wear products in the body remains unknown, although some of the metals used in the construction of orthopaedic implants are known to have toxic and oncogenic properties. We report histological and electron-microscopic evidence from two cases which shows that metallic debris can be identified in the lymphoreticular tissues of the body distant from the hip some years after joint replacement. The increase in the use of total arthroplasty in younger patients, the development of new alloys and the use of porous coatings must raise concern for the long-term effects of the accumulation of wear debris in the body.
Myosin participates in a varying repertoire of cellular functions ranging from cytokinesis, receptor capping and secretion to sarcomere contraction. In vertebrates this functional complexity is achieved through the regulated expression of gene families encoding isoproteins for each of the myosin subunits. We report here the identification and characterization of a gene (MYL5) that encodes a novel regulatory myosin light chain isoprotein and maps 700 kb from the human chromosome 4p telomere. Identical cDNAs have been isolated from human adult retina and fetal muscle cDNA libraries. A full length 519 bp open reading frame was identified in the cDNA sequence encoding a predicted protein of 173 residues. Sequence analysis of a 5.6 kb genomic region that encodes these cDNAs revealed the presence of 7 exons which span 4 kb. Expression of this gene has been detected in human adult retina, cerebellum, basal ganglia and fetal skeletal muscle. Whereas Northern analysis fails to detect transcription of this gene in human adult skeletal muscle it reveals an abundant transcript in monkey skeletal muscle. Phylogenetic comparison of the predicted proteins primary structure to those of related myosin light chains from Drosophila, rat and human reveal evolutionarily conserved structural motifs important for both calcium binding and phosphorylation.
The defect causing Huntington disease (HD) has been mapped to 4p16.3, distal to the DNA marker D4S10. Subsequently, additional polymorphic markers closer to the HD gene have been isolated, which has led to the establishment of predictive testing programs for individuals at risk for HD. Approximately 17% of persons presenting to the Canadian collaborative study for predictive testing for HD have not received any modification of risk, in part because of limited informativeness of currently available DNA markers. Therefore, more highly polymorphic DNA markers are needed, which will further increase the accuracy and availability of predictive testing, specifically for families with complex or incomplete pedigree structures. In addition, new markers are urgently needed in order to refine the breakpoints in the few known recombinant HD chromosomes, which could allow a more accurate localization of the HD gene within 4p16.3 and, therefore, accelerate the cloning of the disease gene. In this study we present the identification and characterization of nine new polymorphic DNA markers, including three markers which detect highly informative multiallelic VNTR-like polymorphisms with PIC values of up to .84. These markers have been isolated from a cloned region of DNA which has been previously mapped approximately 1,000 kb from the 4p telomere.
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As part of the search for the Huntington disease (HD) gene we have cloned and sequenced 34 kb of genomic DNA containing the full-length gene for the beta-subunit of the human cGMP phosphodiesterase (beta-cGMP PDE). This gene is localized to 4p16.3 about 700 kb proximal to the 4p telomere and represents the most telomeric gene characterized on 4p to date. We show that this gene is comprised of 22 exons spanning approximately 43 kb of genomic DNA. We also provide 400 bp immediately 5' to the putative initiator methionine and 700 bp of 3' flanking sequences. Northern blot analysis of several human tissues revealed a highly abundant 3.5 kb transcript and a minor signal of 4.5 kb in retinal tissue. Alignment of the deduced amino acid sequence to the previously identified beta-subunits of the cGMP PDEs of mouse and cow demonstrates highly significant similarities and, therefore, confirms the identity of the cloned gene. A defect in the beta-subunit of the cGMP PDE gene has been shown recently to be the cause for the retinal degeneration in the rd mouse. The cloning of the human homolog and the knowledge of its genomic organization with exon/intron boundaries will allow rapid assessment of the role of this gene in the causation of human retinopathies.
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Two women with Stage II breast carcinoma treated with lumpectomy followed by breast irradiation and adjuvant chemotherapy developed Pneumocystis carinii pneumonia while receiving cytotoxic chemotherapy. Neither woman had evidence of immunosuppression before therapy. They both had profound lymphopenia, reversed CD4/CD8 ratios, and normal peripheral blood total leukocyte counts at the time of their infections. Both women were seronegative for human immunodeficiency virus type 1 and had no risk factors for such an infection. The patients' CD4 lymphocyte counts increased after chemotherapy for breast carcinoma was discontinued. Thus, it appears that the therapy they received may have caused severe T-lymphocyte mediated immunosuppression.