Worcester Development Project and Powick Hospital.
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Biomedical subjects
Publications and source records attributed to P Hall.
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The Stockholm-Gotland Cancer Register was used to study the risk of developing second primary malignancies (SPM) in women diagnosed with cancer of the uterine cervix, uterine corpus and ovaries during the period 1958-1992. Among 5,325 patients with uterine cervix cancer, 619 developed SPM. Standardized incidence ratio (SIR) was 1.29 (95% confidence interval (CI) 1.19-1.39). Significantly increased risks were observed for cancer of the colon, rectum, lung, vulva, kidney and bladder. A total of 4,815 women with uterine corpus cancer were followed and 660 SPM were found. The overall SIR was 1.21 (95% CI 1.12-1.30) with significantly increased risk for cancer of the colon, ovary, vulva and bladder. The incidence of leukemia was also significantly elevated (SIR = 3.03; 95% CI 1.70-5.00). Among 5,060 patients with ovarian cancer, 379 SPM were found (SIR 1.49; 95% CI 1.34-1.64). Increased risks of cancer of the colon, rectum, breast, uterine corpus, bladder and leukemia were observed. All three primary sites showed elevated risks of cancer of the colon and bladder. For patients with a primary cancer of the corpus and ovary an elevated risk of leukemia was also noted. The conclusion from these findings is that SPM to some extent can be explained by previously known factors, i.e. treatment and common risk factors. However, further studies concerning the role of common etiology, for instance hereditary and hormonal factors, are needed to increase the knowledge on the etiology of second primary malignancies.
Intracoronary stents can be implanted with a low incidence of stent thrombosis (< 1%) when the stent procedure is guided by intravascular ultrasound. The long-term clinical and angiographic effects, however, have not been reported. This study assesses the 6 month clinical and angiographic results of a consecutive series of patients with intravascular ultrasound guided Palmaz-Schatz stent deployment that were not treated with subsequent anticoagulation after a successful stent implantation procedure. From March, 1993 to April 1994, 411 patients underwent Palmaz-Schatz stent implantation. There were 26 patients that had uncomplicated Palmaz-Schatz stent implantation that were treated with a standard anticoagulation regimen that are not evaluated in this study. Thus, this study includes an assessment of 385 patients that had either a successful intravascular ultrasound guided stent implantation procedure and did not receive post procedure anticoagulation or had a procedural complication. Procedural success was achieved in 369 patients (96%). Clinical success (procedure success without early post procedure event) was achieved in 363 patients (94%). There were 2 acute stent thrombosis events (0.5%) and 1 subacute stent thrombosis (0.3%) in the group of 369 patients with 454 lesions treated without anticoagulation. At 6 month clinical follow-up the incidence of myocardial infarction was 4.9% and the rate of coronary bypass surgery was 6.2%. There was a 2.1% incidence of death. Emergency intervention (emergency angioplasty or bailout stent implantation was necessary in 3 patients (0.8%). The total incidence of repeat percutaneous intervention was 11.4%. By 6 months clinical follow-up, major events had occurred in 19.2% of patients. The angiographic lesion restenosis rate, according to 50% diameter stenosis criteria, was 19%. The incidence of restenosis per patient was 22%. In conclusion, intravascular ultrasound guided Palmaz-Schatz can be performed without subsequent anticoagulation with a low incidence of stent thrombosis and acceptable clinical and angiographic outcome at 6 month clinical follow-up.
The role of iron deposition in initiating hepatic fibrosis in iron overload disorders is not clearly established, and it is becoming increasingly recognized that iron may be interacting with other potential liver-damaging agents. The authors therefore examined the interplay of iron and alcohol in rats administered subtoxic doses of carbon tetrachloride (CCl4) vapor at 20 ppm in customized chambers. At birth, the offspring of seven pregnant Porton rats were divided into two groups: one group was fed a normal rat chow diet and the other a diet supplemented with 3% (w/w) carbonyl iron for 10 weeks after weaning. In this latter group, the mothers were fed an iron supplement while breastfeeding. At 10 weeks, the animals from the first group (normal chow) were divided into two groups of six animals and fed a Lieber-DeCarli liquid diet with daily exposure to CCl4 vapor: group 1, liquid diet+CCl4; group 2, liquid diet+alcohol 150 kcal/l+CCl4. The animals from the second iron-supplemented group were divided into two groups of six animals and fed a liquid diet with 3% (w/v) carbonyl iron and exposed to CCl4 vapor for 10 weeks: group 3, liquid diet+iron+CCl4; group 4, liquid diet+iron+alcohol supplement+CCl4. Two animals from each group of six had a liver biopsy at 4, 6, and 8 weeks, and all animals were killed after 10 weeks of CCl4 exposure. After the first 10-week iron loading period, the rats fed the carbonyl iron-supplemented diet had a 10-fold elevation in hepatic iron concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
We determined the clinical efficacy of captopril for the prevention of new or stone growth in patients with homozygous cystinuria. Nine patients with a history of multiple cystine stones despite standard fluid and alkalization therapy received 50 mg. captopril, 3 times daily in addition to the standard therapy. Before treatment the rate of new stone formation or stone growth ranged from 0.7 to 2.0 events (mean 1.2) per patient-year for 1 to 3 years of observation (mean 1.9). During treatment the rate ranged from 0 to 3.0 events (mean 1.03) per patient-year for 0.5 to 6 years (mean 2.9). Although statistical significance was not evident for the group as a whole (p = 0.35), our findings suggest that captopril may be clinically efficacious in at least some patients with difficult to control cystinuria. Recommendations regarding its indications in this setting are made.
We present a worldwide analysis of humid tropical forest dynamics and tree species richness. New tree mortality, recruitment, and species richness data include the most dynamic and diverse mature tropical forests known. Twenty-five sites show a strong tendency for the most species-rich forests to be dynamic and aseasonal. Mean annual tree mortality and recruitment-turnover-is the most predictive factor of species richness, implying that small-scale disturbance helps regulate tropical forest diversity. Turnover rates are also closely related to the amount of basal area turnover in mature tropical forests. Therefore the contribution of small-scale disturbance to maintaining tropical forest diversity may ultimately be driven by ecosystem productivity.
The small intestine with its high cell proliferation, well-accepted hierarchy, high radiation susceptibility and low cancer incidence is a useful model for studying the controls of cell replacement. Apoptosis, which represents part of the overall homeostatic process, occurs spontaneously at the stem cell position in the crypts, and very small doses of radiation elevate the levels of apoptosis rapidly in this region. Other cytotoxic agents also target cells in this region including several mutagenic chemicals. Yet other drugs target cells at higher positions in the crypt indicating that all crypt cells possess the programme for apoptosis, but this is normally suppressed in many of the cells. In contrast, high doses of radiation are required to reproductively sterilize the crypts and, using clonal regeneration techniques, the number of clonogenic cells is dependent on the levels of damage induced (dose), i.e. the more injury that is induced the greater number of cells that are recruited into the clonogenic compartment. All doses of radiation trigger rapid changes in proliferation in the stem cell region which suggests that the detection of the induced cell death (even small levels, such as one apoptotic cell per crypt) is efficient and has rapid consequences. p53 may be involved in this damage recognition and apoptosis initiation. The studies to date suggest that apoptosis plays an important role in this tissue in terms of its homeostasis and its protection against carcinogenesis by removal of potentially carcinogenic damaged cells.
We have compared arterial pressures measured by an indwelling radial cannula with those obtained non-invasively by the Finapres 2000 (Ohmeda) during spinal anaesthesia for lower segment Caesarean section. The digital outputs of both pressures were recorded using a computerized system. We studied 20 patients, yielding a total of 18,772 data points after elimination of data recorded during arterial flushing and erroneous results from each source. The data analysis demonstrated a normal distribution for differences between the two methods of measurement, and the correlations between invasive and Finapres readings for systolic, diastolic and mean pressures were 0.78, 0.72 and 0.79, respectively, indicating an overall poor reflection of intra-arterial pressure by the Finapres under these circumstances. Some patients and some periods of readings reflected a high degree of precision and little bias. However, unexplained large differences in pressure and trends of change that were out of phase over time occurred frequently. We conclude that the Finapres cannot be recommended as a monitor of arterial pressure in this group of patients in whom sudden hypotension may be a threat to maternal or fetal outcome.
BACKGROUND: Recent data indicate that the prevalence of genetic haemochromatosis (GH) is greater than previously recognised and suggest that this disease is underdiagnosed. AIMS: To determine the prevalence of GH in rheumatology clinic population. METHODS: Over a 12 month period 339 consecutive patients, mean age 67.0 years, attending a rheumatology clinic were screened for iron overload. RESULTS: Twenty three patients had elevated initial screening tests (transferrin saturation [Tf%] > 55%; ferritin > 500 micrograms/L). Repeat fasting Tf% and ferritin concentrations were obtained in 20 of these patients. Twelve patients had persistently elevated results, and of these patients four had liver biopsy tissue hepatic iron indices consistent with GH. One patient in the group had the diagnosis established by liver biopsy just before the screening commenced. Thus, the prevalence of GH in this population was 1.5%--five times that anticipated for the general population. Three of the patients with GH presented with an arthropathy which was not characteristic of the disease. The increased prevalence of GH in this group of patients with peripheral arthropathy provides an excellent justification for the routine screening of patients with peripheral arthritis for the exclusion of iron overload.
The purpose of this study was to prospectively test the hypothesis that systemic anticoagulation is not needed following coronary stenting when adequate stent expansion is achieved and documented and other flow limitations eliminated. Intravascular ultrasound (IVUS) was used to confirm adequate stent expansion, which was defined as good plaque compression together with the achievement of an intrastent lumen cross-sectional area (CSA) that was greater than 40% of the average reference vessel CSA. In this prospective study, Palmaz-Schatz coronary stenting was performed on 343 lesions in 263 consecutive patients. Primary stenting was successful in 254 patients (96.6%) and 332 lesions (96.8%). All patients with successful primary stenting underwent IVUS imaging except nine patients (13 lesions) that did not have an IVUS evaluation for technical reasons and three patients (4 lesions) in which IVUS was unsuccessful. The initial IVUS performed after achieving an acceptable angiographic result revealed inadequate stent expansion in 191 patients (79%) and 244 lesions (77%). After further dilatation, final adequate stent expansion was accomplished in 230 patients and 301 lesions. These patients were treated with Ticlopidine 250 mg twice per day for 2 months and did not receive postprocedure anticoagulation. There was one acute stent thrombosis (0.3%) that occurred in a lesion with slow flow and an inadequately expanded stent. There was no subacute stent thrombosis and no bleeding or vascular complications. We conclude that when adequate stent expansion is achieved and confirmed and other flow limiting lesions eliminated, that systemic anticoagulation after the stent procedure is not necessary.
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The t(14;18) translocation is found in the majority follicular lymphomas and some high grade B-cell lymphomas. This is results in deregulation of the BCL-2 gene and appears to play a role in oncogenesis. Various numbers of cells from a cell line derived spontaneously from a patient with B-cell lymphoma bearing the t(14;18) translocation and negative for the Epstein-Barr virus (EBV) were injected by IP, IV, and SC routes into SCID mice. The mice developed lymphoma bearing the t(14;18) translocation with as few as 5 x 10(6) cells within 28 days. This was determined by histological examination. The higher the cell inoculation the more rapidly the lymphoma developed. Engraftment of the tumour cells was determined by PCR for the t(14;18) breakpoint region on peripheral blood samples and could be detected prior to development of overt lymphoma. Having established a lymphoma model the cells were treated with antisense oligonucleotides to the first open reading frame of the BCL-2 gene prior to inoculation of the SCID mice. Control treatments with sense and nonsense oligonucleotides was also performed. At 28 days the sense, nonsense and untreated cell SCID mice had developed lymphoma, however, the antisense treated group failed to develop lymphoma. The findings demonstrate the modelling of B-cell lymphoma bearing the t(14;18) translocation and the ability to modify the lymphoma process with the use of antisense oligonucleotides to the BCL-2 gene. Reduction of the BCL2 protein suppresses the oncogenic potential of these lymphoma cells confirming that it plays an essential role in the development of malignancy.
OBJECTIVE: To evaluate the effectiveness of various approaches to follow-up screening of family members after genetic haemochromatosis (GH) has been diagnosed in an individual. DESIGN AND SETTING: Thirty-eight patients diagnosed with GH at the Flinders Medical Centre and Repatriation General Hospital in South Australia over a 16-year period were identified by review of case notes. If possible, a questionnaire and a follow-up interview were used to obtain information about the screening that had been done and any obstacles to screening that were encountered. Patients were asked to outline a family tree, and indicate who had and who had not been screened and reasons for not screening. EVALUATION CRITERION: The number of relatives screened or not screened. RESULTS: The families of 71% of patients diagnosed with haemochromatosis were subject to some degree of screening, although complete screening was achieved in only 13%. Approximately a third (30%) of our GH patients were detected by family screening. However, not all relatives who were at risk were screened. Reasons given for not screening were, for example, ignorance about "genetic disease" and fear of treatment. CONCLUSION: Family screening is an important means of detecting new cases of GH. If these findings reflect practice elsewhere, there is a need for education of medical practitioners regarding those who should be screened. More easily accessible information for patients with GH and their relatives would help to overcome some of the problems surrounding identification of the disease.
BACKGROUND: From the 1920s through the 1950s, radiation therapy was used in Sweden as a treatment for benign breast diseases. It is now known that exposure of the breast to ionizing radiation increases the relative risk of subsequent breast cancer, especially for younger women. However, the degree to which the patient's age contributes to the elevation of risk for subsequent development of breast cancer is not yet completely understood. PURPOSE: The purpose was to study the risk of breast cancer after irradiation of the female breast and, in particular, to analyze the duration of the effect and the risk for women older than 40 years at first exposure. METHODS: In this cohort study, data were obtained through population-based registers. The exposed group consisted of 1216 women (median age, 40 years) who, during the period spanning 1925 through 1954, received radiation therapy for benign breast disease. The reference group consisted of 1874 women (median age, 36 years) who had the same diagnosis during that time period but did not receive radiation therapy. The radiation doses were determined from the original medical records (mean dose, 5.8 Gy; range, 0.003-50.1 Gy). The follow-up lasted up to 60 years after first exposure. The incidence rate ratio was analyzed with Poisson regression models. RESULTS: The total number of breast cancers in the exposed cohort was 198 versus 101 in the unexposed cohort. Overall, the radiation-associated incidence rate ratio was 3.58 (95% confidence interval = 2.77-4.63). The dose-response gradient was statistically significant (P < .001) but leveled off at higher doses. The incidence rate ratios decreased starting about 25 years after first exposure but were at increased levels throughout the entire follow-up period. The incidence rate ratio decreased with age at first exposure but was significantly increased (P < .001) even when the age at time of first exposure was greater than 40 years. CONCLUSIONS: Total dose, age at first exposure, and time since first exposure were all determinants of the incidence rate ratio of breast cancer after exposure of the breast to ionizing radiation. A statistically significant increase in the incidence of breast cancer following radiation treatment of various benign breast diseases was observed even among women older than 40 years at the time of first treatment. IMPLICATIONS: These findings need to be considered when weighing the relative benefits versus risks of generalized screening of younger women for breast cancer by mammography.
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