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Biomedical subjects

R J Shaw

Publications and source records attributed to R J Shaw.

At least 109 records · Page 6Linked to original sources
PubMed1994

Epidemiology of an outbreak of drug-resistant tuberculosis in the U.K. using restriction fragment length polymorphism.

1. Drug-resistant tuberculosis is a growing health care problem. When a series of cases occur, it is essential to know if patients with multidrug-resistant disease represent one or a number of separate outbreaks. 2. The epidemiology of an outbreak of isoniazid- and streptomycin-resistant tuberculosis in Blackburn was studied by restriction fragment length polymorphism using a probe for the IS6110 DNA sequence. 3. Mycobacterium tuberculosis from four cases of isoniazid- and streptomycin-resistant disease had an identical restriction fragment length polymorphism pattern. This pattern was not shared by drug-sensitive isolates of M. tuberculosis obtained from Blackburn (n = 8) or London (n = 13) or a M. tuberculosis isolate from a fifth Blackburn case which was resistant to isoniazid alone. 4. This methodology confirmed that all four cases of isoniazid- and streptomycin-resistant disease were part of a single epidemiologically related outbreak of drug-resistant disease. This study demonstrates how the epidemiology of an outbreak of multidrug-resistant tuberculosis in the U.K. can be confirmed by restriction fragment length polymorphism.

Adolescent↗
PubMed1994

Type 1 procollagen as a marker of severity of scarring after sternotomy: effects of topical corticosteroids.

AIMS: To determine whether the abundance of newly formed collagen in healing surgical wounds correlated with scar severity, and whether topical application of steroid cream reduced new collagen formation in patients who have undergone median sternotomy. METHODS: Thirty three patients six weeks after sternotomy, and 12 controls were studied. Scars were photographed, and biopsy specimens from scars at sites treated or untreated with topical corticosteroids (clobetasol proprionate 0.5%) were examined using immunohistochemical staining for type 1 procollagen (PCP 1) and transforming growth factor beta (TGF-beta), and in situ hybridisation for type 1 procollagen messenger RNA (mRNA). RESULTS: The degree of hypertrophy of the scar and the abundance of PCP 1 immunostaining were ranked independently, blind, and a correlation between these two variables was observed (r = 0.604, p < 0.001). The PCP 1 immunostaining was accompanied by a great abundance of PCP 1 mRNA and only a slight increase in TGF-beta immunostaining, when compared with normal skin or mature scars. Following the application of topical corticosteroids, for either 48 hours or twice daily for seven days, there was no reduction in PCP 1 immunostaining nor the abundance of PCP 1 mRNA. CONCLUSIONS: These data suggest that the extent of new collagen formation as assessed by PCP 1 immunohistochemistry may be a useful marker of the exuberance of the scarring process following sternotomy, and that topical corticosteroids are ineffective in reducing this component of the fibrotic response.

Base Sequence↗
PubMed1994

Evidence for a Th1-like bronchoalveolar T-cell subset and predominance of interferon-gamma gene activation in pulmonary tuberculosis.

Mycobacterium-specific human helper T-cell clones produce a Th1 pattern of cytokines in vitro: interferon-gamma (IFN-gamma) and interleukin-2 (IL-2), but little or no IL-4 or IL-5. To test the hypothesis that a similar Th1-like pattern of cytokine gene expression occurs in vivo in pulmonary tuberculosis we used in situ hybridization to detect cytokine mRNA expression by bronchoalveolar lavage cells from nine patients with microbiologically confirmed tuberculosis and nine control subjects. Because IFN-gamma may also originate from alveolar macrophages, simultaneous immunocytochemistry and in situ hybridization was applied to determine whether cytokine mRNA was localized to bronchoalveolar macrophages in addition to T-lymphocytes. When samples from patients with tuberculosis and control subjects were compared, there was a significant increase in numbers of IFN-gamma mRNA-positive BAL cells per 1,000 among patients with tuberculosis (p < 0.01). Differences between the two groups in the proportions of cells expressing IL-2, IL-4, or IL-5 mRNA were not significant. Expression of IFN-gamma mRNA by macrophages was detected (median, 14.3% of IFN-gamma mRNA-positive BAL cells). However, the majority of IFN-gamma mRNA expressing BAL cells were T-lymphocytes (median, 80.7%). Activation of Th1-like bronchoalveolar T-lymphocytes, together with production of IFN-gamma by alveolar macrophages, may contribute to the local cellular immune response in pulmonary tuberculosis.

Adolescent↗
PubMed1994

Platelet-derived growth factor-beta mRNA in human alveolar macrophages in vivo in asthma.

Collagen deposition and myofibroblast proliferation beneath the epithelial basement membrane in patients with asthma is now increasingly recognized, although the molecular pathogenesis remains obscure. We have evaluated messenger ribonucleic acid (mRNA) expression of the profibrotic cytokine, platelet-derived growth factor-beta (PDGF-beta), in alveolar macrophages obtained following fibreoptic bronchoscopy and bronchoalveolar lavage in patients with asthma. Three subject groups were studied: 1) asthmatics using regular inhaled glucocorticoid medication (ASTST, n = 9), 2) asthmatics using intermittent inhaled beta 2-agonist therapy only (ASTBR, n = 10); 3) nonasthmatic control volunteers (n = 10). Alveolar macrophage mRNA was extracted and PDGF-beta mRNA quantified by reverse-transcriptase polymerase chain reaction (PCR) (RT-PCR) and expressed as the ratio to that of a control gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH). There were no significant differences in PDGF-beta mRNA expression between the groups, or between all asthmatic (n = 19) and control subjects. Furthermore, there was no correlation between alveolar macrophage PDGF-beta mRNA expression and airway spirometry, or duration of glucocorticoid usage or dose. Thus, in contrast to other fibrotic lung diseases, we found little evidence of enhanced expression of PDGF-beta mRNA in alveolar macrophages in clinically stable bronchial asthma.

Adult↗
PubMed1994

A survey of symptoms in hospice patients in Singapore.

A descriptive study was done on patients referred to a hospice home care service in Singapore. The demographic profile, type of disease, presenting symptoms and performance status were noted. Particular attention was paid to the incidence of pain and types of analgesics used. The patients referred were representative of the population at large, as was their incidence of cancer. Eastern Cooperative Oncology Group (ECOG) performance status was poor (ECOG 3 or 4) in 93 (93%) of the patients referred, indicative of the lateness of referral in many cases. The number of symptoms per patient averaged 5.8, and pattern of symptoms were similar to those of comparable groups of patients in other parts of the world. Pain was present in 82 (82%) patients and controlled only in 22 (22%) of these at presentation. Strong opioids had been prescribed for 51 (51%) patients. In these, oral morphine mixture was incorrectly prescribed in 17 (47%) out of 36 cases. Education in palliative care is needed so that patients are referred to palliative care services appropriately. Though there is some indication of improvement, medical education in pain management continues to be necessary, particularly in the correct prescription of morphine.

Adolescent↗
PubMed1994

Evolution of a hospice home care service in Singapore.

The hospice movement in Singapore was started in 1985 when St Joseph's Home opened its doors to terminally ill patients by setting aside 16 beds for hospice care. A newspaper article about this work brought together a group of volunteers who started a hospice home care service under the auspices of the Singapore Cancer Society in 1987. This service was originally entirely staffed by volunteers until a charitable foundation made possible the employment of a nurse coordinator in 1988. Nearly two years later, in December 1989, the Hospice Care Association, a new charitable organization specifically devoted to the promotion and provision of hospice care, was formed. With charitable funding from the community, the new organization built on the experience of the volunteer-run hospice home care service and developed it into one in which professionals provide most of the care, supported by volunteers. Full-time staff were responsible for the day-to-day running of the service, providing for reliability and setting and maintaining of standards, while the role of volunteers changed to that of supporting, supplementing and enhancing the quality of the care given to patients. This paper chronicles the evolution of this service and describes its present functioning.

Health Personnel↗
PubMed1993

Pharmacological modulation of c-fos mRNA expression in the HL60 and U937 cell lines.

A variety of drugs known to act via increasing intracellular cAMP are used in the treatment of asthma. In this study we asked whether anti-asthma drugs are capable of altering gene activation. We determined whether phosphodiesterase inhibitors, either alone or in combination with adrenoceptor agonists, were able to alter the abundance of mRNA of the cAMP responsive gene c-fos in the cell-lines HL60 and U937. Incubation of cells with phosphodiesterase inhibitors aminophylline, theophylline or pentoxyphylline all resulted in an increase in c-fos mRNA. Further upregulation of c-fos mRNA abundance was observed when the cells were stimulated with the combination of aminophylline and adrenoceptor agonists with beta 2-agonist activity. These increases in c-fos mRNA were accompanied by increases in intracellular concentration of cAMP. These data suggest that in these in vitro models, combinations of beta 2-adrenoceptor agonists and phosphodiesterase inhibitors can increase intracellular cAMP and affect gene activation.

Adrenergic beta-Agonists↗
PubMed1993

Up-regulation of alveolar macrophage platelet-derived growth factor-B (PDGF-B) mRNA by interferon-gamma from Mycobacterium tuberculosis antigen (PPD)-stimulated lymphocytes.

Macrophage production of PDGF-B is believed to be important in the pathogenesis of diseases where chronic lung inflammation develops into fibrosis. Since tuberculosis is characterized by chronic inflammation and tissue fibrosis, we asked if lymphokines from lymphocytes stimulated by the Mycobacterium tuberculosis antigen PPD, contained factors capable of increasing human alveolar macrophage PDGF-B mRNA. Supernatants from both phytohaemagglutinin (PHA)- and purified protein derivative (PPD)-stimulated lymphocytes, when added to macrophages, induced an increase in the mRNA of PDGF-B, but not transforming growth factor-beta (TGF-beta). When lymphocytes from contacts of patients with tuberculosis, patients with tuberculosis, and normal subjects were compared following PPD stimulation, the lymphocytes from the contacts had the greatest proliferation response, the greatest production of interferon-gamma (IFN-gamma), and their lymphokines induced the greatest increase in PDGF-B mRNA in macrophages. Recombinant human IFN-gamma reproduced this ability of lymphokines to increase macrophage PDGF-B mRNA. Finally, the increase in macrophage PDGF-B mRNA following incubation with supernatants from PPD-stimulated lymphocytes was shown to be due to IFN-gamma, when the increase in macrophage PDGF-B mRNA was prevented by addition of anti-human IFN-gamma antibody to the lymphocyte supernatant. This study indicated that antigen-stimulated lymphocytes released IFN-gamma, which in turn resulted in an increase in PDGF-B mRNA in alveolar macrophages. Such a mechanism provides a link between the DTH response and the first stages of a fibrotic reaction, and may offer an explanation for the progression of chronic inflammation to fibrosis, as occurs in the lungs of patients with untreated pulmonary tuberculosis.

Base Sequence↗
PubMed1993

Serial pulmonary function tests in the diagnosis of P. carinii pneumonia.

The predictive value of serial versus isolated measurements of transfer factor for carbon monoxide (TLCO) in the diagnosis of pneumocystis carinii pneumonia (PCP) in a cohort of 474 HIV-1 seropositive patients, with all stages of HIV disease, was evaluated. Two groups of patients were studied, one group with serial lung function measurements (Group 1) and another with only a single set of measurements (Group 2). During the study period 118 patients performing serial tests developed a respiratory illness of which 58 were performing monthly and 60 three monthly measurements of lung function (Group 1). In 36 patients from Group 1, where PCP was diagnosed, monthly lung function tests showed a decrease in TLCO from 68% (+/- 3.2) (SEM), (8 weeks prior to illness), to 44% (+/- 2.5) predicted normal at presentation, whereas in 22 patients who did not have PCP, TLCO fell from 71% (+/- 4.5) to 57% (+/- 3.1). TLCO was thus reduced to lower values in these with PCP than in those without PCP (p < 0.05). A fall of TLCO of 5% from initial values when used as predictive for presence of PCP had a sensitivity of 75% and a specificty of 28% (positive predictive value 56%; negative predictive value 48%). TLCO was < 70% predicted in 72/78 patients with PCP who performed only single lung function tests (Group 2), which gave a sensitivity of 92% and a specificity of 71% as a diagnostic test for PCP when compared with the cohort as a whole. The positive predictive value was 34%, negative predictive value was 98%.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1992

Effect of environmental support on implicit and explicit memory in younger and older adults.

The study addressed 2 major issues: whether there are age differences on an implicit word-stem-completion task and whether age differences on both implicit and explicit memory would decrease with increased environmental support. A total of 287 Ss were presented with words in an incidental learning task with structural or semantic processing. Following 2 filler tasks, Ss received an implicit or an explicit word-stem-completion task. The number of letters in the stem varied from 2 to 4. Results yielded an Age x Memory Task dissociation such that there were large age differences on the explicit task and no age difference on the implicit task, regardless of whether Ss aware of the memory test were included or excluded. There was no evidence that environmental support improved older adults' performance more than that of younger adults on either memory task.

Adolescent↗
PubMed1992

Comparison of polymerase chain reaction amplification of two mycobacterial DNA sequences, IS6110 and the 65kDa antigen gene, in the diagnosis of tuberculosis.

BACKGROUND: Knowledge of the sequences of mycobacterial genes and the availability of DNA amplification techniques have raised the possibility that identification of mycobacterial DNA may offer a rapid and specific diagnostic test for tuberculosis. The correlation between the presence of Mycobacterium tuberculosis DNA and clinical tuberculosis, however, is not known. This study compared the results of polymerase chain reaction amplification of two M tuberculosis DNA sequences, IS6110 and the gene encoding the 65kDa heat shock protein (65kDa Ag), from sputum, bronchoscopy washings, and bronchoalveolar lavage fluid and related these findings to the presence of active and past tuberculosis. METHODS: Highly specific primers were used for amplification of IS6110 and 65kDa Ag DNA. Analysis was performed on one or more samples from 87 patients. RESULTS: IS6110 DNA was identified in samples from all six patients with active tuberculosis, from 15 to 18 patients with past tuberculosis, from five of nine contacts of patients with tuberculosis, and from nine of 54 patients with lung disease unrelated to tuberculosis. The 65kDa Ag DNA was identified in samples from all patients with active and past tuberculosis, from contacts of patients with tuberculosis, and from 14 of 42 patients with non-tuberculous lung diseases. CONCLUSION: These data suggest that the presence of IS6110 DNA correlates more closely with a tuberculosis related diagnosis than that of 65kDa Ag DNA and that both DNAs are found in most subjects with past tuberculosis or contacts of patients with tuberculosis. This may limit the clinical usefulness of these tests.

Base Sequence↗
PubMed1992

Pulmonary function in human immunodeficiency virus infection. A prospective 18-month study of serial lung function in 474 patients.

To investigate the development of a reduced DLCO in patients with HIV-related disease, we studied 474 HIV-seropositive patients and performed serial lung function measurements over 18 months. The mean values of DLCO at presentation were lower in patients with more advanced HIV disease compared with asymptomatic HIV-seropositive patients (DLCO 88% of predicted). When compared with the DLCO in asymptomatic HIV-seropositive patients, the DLCO had reduced values in patients with persistent generalized lymphadenopathy (PGL) (82% of predicted, p less than 0.05), acquired deficiency syndrome-related complex (ARC) (73% predicted, p less than 0.001), nonpulmonary Kaposi's sarcoma (KS) (72% of predicted, p less than 0.001), nonpulmonary complications of AIDS excluding KS (73% of predicted, p less than 0.001), pulmonary KS (63% of predicted, p less than 0.001), pulmonary mycobacterial infection (68% of predicted, p less than 0.05), pyogenic infection (70%, p less than 0.05), acute Pneumocystis carinii pneumonia (PCP; 49%, p less than 0.001), and following recovery from PCP (71%, p less than 0.001). Serial lung function measurements over 18 months revealed no change in DLCO within any patient group, and in particular there was no tendency for a gradual decline. Clinical deterioration due to the development of PCP was associated with a reduction in DLCO. Conversely, in patients recovering from PCP, there was a partial improvement in DLCO over 3 months. Zidovudine (AZT) use did not affect DLCO within any diagnostic group or the recovery in DLCO following PCP. However, cigarette smoking was associated with further reductions in DLCO in all patient groups and with an impaired recovery of DLCO following acute PCP.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Complex↗
PubMed1992

Dexamethasone-induced increase in platelet-derived growth factor (B) mRNA in human alveolar macrophages and myelomonocytic HL60 macrophage-like cells.

Platelet-derived growth factor (B) (PDGF(B)) from alveolar macrophages is thought to play a central role in orchestrating the fibrotic response. Because corticosteroids are widely used in the treatment of patients with lung fibrosis, we asked whether corticosteroids modulated PDGF(B) gene activation in macrophages. PDGF(B) mRNA in alveolar macrophages obtained from smokers was increased after culture in the presence of dexamethasone (P less than 0.05), interferon-gamma (IFN-gamma) (P less than 0.05), or both in combination (P less than 0.05). Dexamethasone did not alter the abundance of mRNA encoding transforming growth factor-beta (TGF-beta), but did decrease the mRNA of early growth response gene 2 (EGR2). These initial experiments required large numbers of cells and thus were performed on macrophages from smokers. The results were reproduced when PDGF(B) mRNA abundance in macrophages from healthy nonsmoking volunteers was measured by the reverse-transcriptase polymerase chain reaction (RT-PCR). There was an increase in PDGF(B) mRNA in macrophages from nonsmokers after stimulation with dexamethasone alone (P less than 0.05) or in combination with IFN-gamma (P less than 0.05). To provide adequate cell numbers for kinetic and dose-response studies, the in vitro model of phorbol ester (TPA)-induced differentiation of HL60 cells to macrophage-like cells was used. In these cells, dexamethasone caused a 20-fold increase in the abundance of PDGF(B) mRNA, which was concentration and time dependent but not associated with changes in TGF-beta or EGR2 mRNA. This study suggests that in addition to their anti-inflammatory effects, corticosteroids may also increase the abundance of PDGF(B) mRNA.

Adult↗
PubMed1992

Coping effectiveness in nursing home residents. The role of control.

The purpose of this study was to investigate the role of perceived control in the selection and effectiveness of coping strategies used by nursing home residents. A path analysis of a model of coping effectiveness was conducted using a cluster sample of 100 nursing home residents. Respondents were assisted in completing the Importance, Locus, and Range of Activities Checklist, the Jalowiec Coping Scale, two self-anchoring ladders measuring coping effectiveness, and an item measuring perceived health. Mental status was measured with the Pfeiffer Short Portable Mental Status Questionnaire. Results demonstrated that mental status and functional ability were positively related to perceived control (p < .01). Perceived health and the use of secondary control (e.g., prayer, getting help from family, and depending on others) were the only two variables positively influencing coping effectiveness (p < .01 and p < .05, respectively). Longitudinal studies are recommended to investigate these relationships as they evolve.

Activities of Daily Living↗