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Biomedical subjects

R Chapman

Publications and source records attributed to R Chapman.

At least 55 records · Page 3Linked to original sources
PubMed1999

Asbestos exposure and mesothelioma in South Africa.

OBJECTIVES: To describe the exposure experiences of South African mesothelioma cases, with emphasis on the contribution made to the caseload by different fibre types, the proportion of subjects with no recall of asbestos exposure and only environmental contact, and the importance of putative causes other than asbestos. DESIGN: A multi-centred case-control study. SUBJECTS AND SETTING: 123 patients with mesothelioma interviewed by trained interviewers in study centres established in Johannesburg, Kimberley, Pretoria, Bloemfontein, Cape Town and Port Elizabeth. RESULTS: A convincing history of asbestos exposure was obtained in the overwhelming majority of cases (only 5 cases had unlikely asbestos exposure). Twenty-three subjects had worked on Cape crocidolite mines, 3 at Penge (an amosite mine), 3 on mines producing amosite and Transvaal crocidolite and 1 on a Transvaal crocidolite mine. Exclusively environmental exposure accounted for at least 18% of cases; 91% of these cases (20/22 subjects) had had contact with Cape crocidolite. There was a relative paucity of cases linked to amosite and no convincing chrysotile case. Non-asbestos causes occur rarely, if at all, in South Africa. CONCLUSION: The preponderance of crocidolite cases, followed by amosite and then chrysotile cases, is consistent with the view that there is a fibre gradient of mesotheliomagenic potential for South African asbestos (crocidolite > amosite > chrysotile).

Asbestos, Amosite↗
PubMed1998

New therapeutic technique for treatment of uterine leiomyomas using laser-induced interstitial thermotherapy (LITT) by a minimally invasive method.

BACKGROUND AND OBJECTIVE: This study was undertaken to see if uterine leiomyomas would respond to LITT, as had certain other tumours, and leave behind a uterus capable of child bearing. STUDY DESIGN/MATERIALS AND METHODS: Preliminary research to determine laser power and energy requirements to coagulate leiomyomas was carried out on such tumours at the time of myomectomy or hysterectomy. The information gleaned permitted subsequent volunteer patients to be treated by a minimally invasive route. LITT was employed to treat 300 patients, 293 of them with the KTP/YAG laser with a bare fibre laparoscopically or through the hysteroscope. The remaining seven were treated with the Diode laser, five of them being treated percutaneously with fibre splitter and four fibres. RESULTS: Symptomatic patients (300) with 950 myomas between them were treated. Follow-up has been between 6 months and 6 years. No significant complications occurred, and the procedure(s) were successful in 294 patients. CONCLUSIONS: It is the treatment of choice for those leiomyomas that are difficult to remove because of their size or position. Fertility is enhanced, oestrogen receptors and epidermal growth factor are destroyed, and healing occurs without scarring.

Adult↗
PubMed1998

The unfolded protein response: an intracellular signalling pathway with many surprising features.

The unfolded protein response (UPR) is an intracellular signalling pathway--originating in the endoplasmic reticulum (ER) and leading to the cell nucleus--that controls transcription of genes encoding ER-resident proteins. Recent developments in this field show that this pathway utilizes unique regulatory mechanisms, including translational attenuation and a regulated mRNA splicing step catalysed by a bifunctional transmembrane kinase/endoribonuclease and tRNA ligase. This review describes the characterization of the UPR signalling pathway, focusing on the novel regulatory mechanisms that it has revealed.

Endoplasmic Reticulum↗
PubMed1998

Fatal CMV pneumonia associated with steroid therapy after autologous transplantation in patients previously treated with fludarabine.

Fludarabine has been associated with an increased risk of opportunistic infections, possibly related to the induction of profound CD4+ lymphopenia. We observed two cases of cytomegalovirus pneumonia (CMV-IP) in a total of nine patients over a 5-year period who had previously received fludarabine and who proceeded to autografting. Both patients also received steroids post-transplant. CMV-IP was observed in one of 104 other autograft recipients over this time who had not received prior fludarabine. This observation suggests that the combination of fludarabine pre-transplant and steroids post-transplant may increase the risk of invasive CMV disease in autograft recipients.

Adult↗
PubMed1998

Intracellular signaling from the endoplasmic reticulum to the nucleus.

Cells respond to an accumulation of unfolded proteins in the endoplasmic reticulum (ER) by increasing transcription of genes encoding ER resident proteins. The information is transmitted from the ER lumen to the nucleus by an intracellular signaling pathway called the unfolded protein response (UPR). Recent work has shown that this signaling pathway utilizes several novel mechanisms, including translational attenuation and a regulated mRNA splicing step. In this review we aim to integrate these recent advances with current knowledge about maintenance of ER composition and abundance.

Animals↗
PubMed1998

Hospital management decision support: a balanced scorecard approach.

Hospital management teams receive voluminous data from a wide variety of sources, but are unable to distill the essential data they require to make good decisions. We have used a methodology, which helps teams define and use important management data coupled with an information system that makes this data accessible. Results of our evaluation indicate that the process of developing a Balanced Scorecard indicator system helps management teams to define meaningful strategic objectives and measurable performance indicators. The framework combined with the information acts as an integrating force, providing a shared understanding of the unit's goals. We conclude that a customized decision support system, which integrates multiple measures in a balanced Scorecard framework, is a powerful tool for enabling complex decision making by a management team.

Cardiovascular Diseases↗
PubMed1997

Cloning of two candidate tumor suppressor genes within a 10 kb region on chromosome 13q14, frequently deleted in chronic lymphocytic leukemia.

Previous studies have indicated the presence of a putative tumor suppressor gene on chromosome 13q14, commonly deleted in patients with B-cell chronic lymphocytic leukemia (B-CLL). We have previously defined a minimally deleted region of 130 kb centromeric to the marker D13S272, and constructed a PAC and cosmid contig encompassing this area. In the present study we have made a detailed restriction and transcriptional map of the region of interest. Using these tools we have screened a panel of 206 primary CLL clones and three cell lines. In five CLL cases we found limited deletions defining the region of interest to an area of no more than 10 kb. Two adjacent genes, termed Leu1 and Leu2 (leukemia-associated gene 1 and 2), were mapped to the minimally deleted region, with several patients showing deletion borders within these genes. The Leu1 and Leu2 genes show little homology to previously published genes at the nucleotide and expected translated amino acid sequence level. Mutational analysis of the Leu1 and 2 genes in 170 CLL samples revealed no small intragenic mutations or point mutations. However, in all cases of 13q14 loss examined, the first exon of both genes, which are only 300 bp apart, were deleted. We conclude that the Leu1 and Leu2 genes are strong candidates as tumor suppressor gene(s) involved in B-CLL leukemogenesis.

Amino Acid Sequence↗
PubMed1997

Telomere length in myelodysplastic syndromes.

We have studied telomere length in the bone marrow cells or the granulocyte and lymphocyte cell fractions of 54 patients with myelodysplastic syndromes (MDS) by Southern blot hybridization using the (TTAGGG)4 probe. The average telomere length expressed as the peak telomere repeat array (TRA) in the peripheral blood, or bone marrow samples obtained from a group of 21 healthy age-matched controls (26-89 years old, mean age 55), ranged between 7.5 and 9.5 kb (mean peak TRA 8.6 kb). Twenty-four patients with refractory anemia (RA) were studied; 10/24 (42%) had telomere reduction (<7.5 kb) relative to age-matched controls and the mean peak TRA was 7.5 kb (range 4.0-9.0 kb). Eleven patients with RA with excess blasts (RAEB) were studied; 5/11 (45%) had reduced telomeres relative to age-matched controls and the mean peak TRA was 7.1 kb (range 5.0-9.0 kb). Eighteen patients with MDS in transformation to AML, comprising 15 with RAEB in transformation (RAEBt) and 3 with CMML in transformation (CMMLt), were also studied. Thirteen of eighteen patients (72%) had telomere reduction relative to age-matched controls and the mean peak TRA was 6.1 kb (range 3.5-9.0 kb). Thirty-six patients included in the study had either a normal karyotype or a simple karyotype (1 karyotypic change) and 20/36 (55%) of these had telomere reduction and the mean peak TRA was 7.1 kb (range 4.3-9.0 kb); 8 patients had a complex karyotype (3 or more karyotypic changes) and 5/8 (62%) of these had telomere reduction and the mean peak TRA was 6.1 kb (range 3.5-9.0 kb). We conclude, firstly that there is heterogeneity of telomere length in MDS and that this is observed throughout the spectrum of FAB-subtypes. Secondly, these data show that a marked reduction in telomere length in MDS if often associated with leukemic transformation and with the presence of complex karyotypic abnormalities.

Adult↗
PubMed1997

Atypical lymphocyte morphology: an adverse prognostic factor for disease progression in stage A CLL independent of trisomy 12.

We studied 270 patients with Binet stage A chronic lymphocytic leukaemia looking for adverse prognostic factors. In a multivariate analysis the following features were found to be risk factors for disease progression: atypical lymphocyte morphology (defined as either > 10% prolymphocytes or > 15% lymphocytes with cleaved nuclei or lymphoplasmacytoid cells); more than two karyotypic abnormalities; lymphocyte count > 30 x 10(9)/l; lymphocyte doubling time < 1 year; enlargement of one or more lymph node groups. In a univariate analysis the presence of trisomy 12 also correlated with progressive disease, but this was largely a consequence of the association between trisomy 12 and atypical lymphocyte morphology. Atypical lymphocyte morphology is an important prognostic factor in stage A CLL, and one which incurs no additional investigational cost.

Adult↗
PubMed1997

A comparison of ICAGD (immediate complete anterior guidance development) to mock ICAGD for symptom reductions in chronic myofascial pain dysfunction patients.

The purpose of this study is to assess what impact shortening disclusion time to less than .5 seconds during right and left mandibular excursions has on myofascial pain(s) symptoms present in a dental student population. Twenty-five dental students, who exhibited symptomatology consistent with myofascial pains patient, were divided into a treatment, control, and an untreated group. They participated in an occlusal adjustment study which measured changes in disclusion time, as well as, myofascial pains muscular symptom remissions resultant from treatment. The treated group of ten subjects received ICAGD occlusal adjustments to shorten their disclusion time to less than .5 seconds per mandibular excursion. The goal of this therapy was to totally disclude the posterior teeth in a measurable time frame of .5 seconds or less. The control group of eight subjects received mock ICAGD with tooth polishing. The goal of this therapy was to simulate ICAGD adjustments for possible placebo effect on symptom remissions. The untreated group had their disclusion times measured but received no treatment to adjust, or to simulate adjustment to their occlusion. The goal of analyzing an untreated group was to attempt to show that mock treatment (performed on the control subjects), or no treatment (performed on the untreated subjects), resulted in no measurable change in the disclusion time in either of these two subject groups. Each subject was recalled for disclusion time measurement four to five times in a one-year period of observation, at which time, they were required to report their myofascial pains symptom status by answering an ordinal scale questionnaire. The results suggest that shortening disclusion time to less than .5 seconds per mandibular excursion can induce remissions of many muscular myofascial pains symptoms. Additionally, mock ICAGD occlusal adjustments did not appear to be a factor in the control subjects treatment response, as this group showed no statistically significant symptom remissions.

Adult↗
PubMed1997

Detection of antineutrophil cytoplasmic antibodies in primary sclerosing cholangitis: a comparison of the alkaline phosphatase and immunofluorescent techniques.

BACKGROUND: The reported prevalence of antineutrophil cytoplasmic antibodies (ANCA) in primary sclerosing cholangitis (PSC) varies considerably (26-85%). Part of this may reflect methodological differences but part may reflect the differences in the patient groups analysed. To resolve this issue we compared the sensitivity and specificity of the immunoalkaline phosphatase (IALP) and immunofluorescence (IF) techniques in four different populations. METHOD: Sera from four centres were tested blind on alcohol-fixed neutrophils using both techniques. PATIENTS: USA: 14 PSC, 14 primary biliary cirrhosis (PBC); Sweden: 32 PSC, 3 autoimmune hepatitis (AIH), 14 PBC, 11 chronic liver disease; Norway: 32 PSC, 14 AIH, 13 PBC, 1 hepatitis C. Italy: 8 PSC, 14 PBC, 8 viral hepatitis. Thirty-six normal healthy volunteers from Oxford, together with positive and negative controls, were also tested. RESULTS: The healthy controls were all ANCA negative. The diagnostic sensitivity and specificity, respectively, of ANCA for PSC using the IALP technique for the different test sera were: USA 71% and 93%, Sweden 66% and 96%, Norway 69% and 46%, Italy 50% and 95%. The diagnostic sensitivity and specificity, respectively, of the IF technique on the same sera were: USA 50% and 86%, Sweden 56% and 86%, Norway 47% and 61%, Italy 50% and 91%. Overall, combining all four groups, detection of ANCA using the IALP technique gave a diagnostic sensitivity of 66% with a specificity of 74% for PSC. In contrast, the IF technique gave an overall diagnostic of only 51% (P = 0.044, compared with IALP) with a specificity of 73%. Although overall the IALP technique was more sensitive than IF, the differences in sensitivity and specificity between the two techniques did not reach statistical significance for any individual group. Furthermore, the small differences in sensitivity between the four groups using either technique were not significant. However, the IALP technique had greater specificity in the US, Swedish and Italian groups compared with the Norwegian group (P < 0.05) whereas no statistically significant differences in specificity were noted between the groups using the IF technique. CONCLUSION: This study shows that the IALP method of ANCA detection is at least as sensitive as IF for the serological diagnosis of PSC. Indeed, combining data from all four centres, the IALP technique was significantly more sensitive than IF. We therefore recommend the use of the IALP technique, which is also easier to interpret and does not require the use of a specialist fluorescent microscope. The lack of a wide variation in sensitivity between IALP and IF for any individual patient group reported in this study suggests that the previously reported regional differences in ANCA prevalence in PSC of between 26% and 85% may be patient, related, rather than due to ethnic or methodological differences in ANCA detection, perhaps reflecting possible disease heterogeneity within PSC, or case selection bias. Further studies are needed to investigate this intriguing possibility. Such differences, if confirmed, will need to be taken into account when assessing the use of ANCA as a serological marker of PSC.

Adult↗