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Biomedical subjects

P Hall

Publications and source records attributed to P Hall.

At least 19 recordsLinked to original sources

Family history of breast cancer and young age at diagnosis of breast cancer increase risk of second primary malignancies in women: a population-based cohort study.

Among 152 600 breast cancer patients diagnosed during 1958-2000, there was a 22% increased risk of developing a second primary non-breast malignancy (standardised incidence ratio (SIR)=1.22; 95% confidence interval (CI): 1.19-1.24). The highest risk was seen for connective tissue cancer (SIR=1.78; 95% CI: 1.49-2.10). Increased risks were noted among women diagnosed with breast cancer before age 50. Oesophagus cancer and non-Hodgkin's lymphoma showed six- and four-fold higher risks, respectively, in women with a family history of breast cancer compared to those without in the > or =10-year follow-up period.

Aged↗

A novel imaging technique as an adjunct to the in vivo diagnosis of nonmelanoma skin cancer.

BACKGROUND: Spectrophotometric intracutaneous analysis (SIAscopy) is a light-based imaging system capable of producing rapid images of melanin, blood and collagen of the skin. Although the SIAscope has been investigated for melanoma diagnosis, no formal study has been conducted to determine its use in the diagnosis of nonmelanoma skin cancer (NMSC). OBJECTIVES: A prospective study was conducted to investigate the potential for the SIAscope to diagnose NMSC. METHODS: In total, 302 consecutive patients were recruited into the study, 363 lesions being scanned. Logistic regression analysis was used to construct a predictive model for NMSC diagnosis and receiver-operator characteristic curves were used to assess overall accuracy of the model. RESULTS: A sensitivity of 98.0%, specificity of 95.7% and overall accuracy of 98.2% was found for NMSC diagnosis by the SIAscope model. CONCLUSIONS: Results suggest that the SIAscope may be a useful adjunct in the diagnosis of NMSC.

Adolescent↗

Immunohistochemistry detects mismatch repair gene defects in colorectal cancer.

OBJECTIVE: The clinical management of colorectal malignancies that arise via the mismatch repair gene pathway may differ from those that arise from the more common loss of heterozygosity pathway. They respond differently to chemotherapy, have a different prognosis and are associated with a raised incidence of metachronous lesions if a germline mutation is present. Established methods of detecting mismatch repair gene defects require the testing for microsatellite instability. This is expensive and requires specialized molecular biological resources and staff. An immunohistochemical method is attractive because it is far cheaper, and can be performed by most anatomical pathology laboratories. The aim of this study was to determine the incidence of mismatch repair gene defects using immunohistochemistry in a group of patients who were aged < or = 45 years at the time of diagnosis of colorectal cancer and to compare the patient survival and pathological features of tumours with and without mismatch repair gene defects. METHODS: One hundred and four patients with colorectal cancer, diagnosed at 45 years or younger between January 1983 and December 2001, who had been managed at Groote Schuur Hospital, were identified from clinical records. Demographic and clinical data was collected from the clinical notes. The pathological reports were reviewed and the original histopathological slides retrieved. New tissue sections were cut from the original paraffin embedded tissue blocks to obtain both normal colonic mucosa and tumour on the same slide. There was insufficient tissue available or poor staining in 11 patients so 93 were available for the study. RESULTS: The mismatch repair status was detected by antibodies to hMLH1 and hMSH2 gene product using a standard immunohistochemical technique. Fifty-six (60%) of 93 tumours demonstrated normal expression of both hMLH1 and hMSH2 protein. Twenty-five (27%) tumours did not express hMLH1 and 12 (13%) hMSH2 proteins. Comparison of the histopathological features revealed that a greater proportion of tumours with absence of either the hMLH1 or hMSH2 product were right sided, mucinous and poorly differentiated when compared to those that expressed the gene product. There was no detectable difference in overall survival or in survival of patients with Duke's C carcinoma when the groups were separated by the presence or absence of gene product. CONCLUSIONS: This study found that 40% of patients who were < or = 45 years of age at the time of diagnosis of colorectal cancer seen at Groote Schuur Hospital have tumours which are related to the absence of expression of either hMLH1 or hMSH2 genes.

Adaptor Proteins, Signal Transducing↗

Thyroid abnormalities associated with protracted childhood exposure to 131I from atmospheric emissions from the Mayak weapons facility in Russia.

Between 1948 and 1960, the Mayak nuclear weapons facility in Ozyorsk, Russia discharged relatively high levels of radionuclides, primarily (131)I, into the atmosphere, resulting in appreciable exposure to the residents of Ozyorsk. To evaluate the association between thyroid diseases and childhood exposure to radioiodines, we screened 894 Ozyorsk residents born between 1952 and 1953. The study population was comprised of 581 exposed individuals living in Ozyorsk during the years of heaviest exposure and 313 nonexposed individuals who moved to Ozyorsk when radiation exposure from Mayak largely had ended. The screening protocol included a patient interview, palpation of the thyroid, cervical lymph nodes and salivary glands, an ultrasound examination, and measurement of fT4, TSH and TPOAb. Twenty-eight percent of the study group was diagnosed with a thyroid abnormality. The prevalence of nodular disease was significantly higher in the exposed group (20.7%) compared with the nonexposed (14.4%) group (relative risk = 1.4, 95% CI = 1.1; 1.9). Risks were larger for solitary nodules and for nodules > or = 10 mm in diameter. Expansion of the study to increase the number of persons screened as well as detailed dose estimation would offer an unique opportunity to evaluate thyroid disease in relation to chronic exposure to radioiodines during childhood.

Adolescent↗

Ultrasound antenatal diagnosis of cleft palate by a new technique: the 3D "reverse face" view.

OBJECTIVE: To assess the clinical value of a novel three-dimensional (3D) ultrasound technique, the reverse face view (3D RF view), in the antenatal categorization of facial clefting and in particular clefting of the hard palate. METHODS: Eight cases of suspected orofacial clefting were examined by 3D surface rendering. The fetal lips and alveolar ridge were examined in the frontal plane and the face was then rotated through 180 degrees on the vertical axis to examine the secondary palate by the 3D RF view. RESULTS: In each case described, we were able to visualize the fetal face, lips and palate and make an antenatal diagnosis as to whether the palate was affected. In all cases, the antenatal diagnosis was subsequently confirmed. In one case with a left-sided cleft in the lips and alveolar ridge and an intact hard palate, the correct diagnosis was made but a cleft in the soft palate was missed. CONCLUSION: Although clefts of the lips and alveolar ridge are readily diagnosed on high-quality antenatal ultrasound, visualization of the fetal palate using existing techniques is unreliable. In the patients described here, the 3D RF technique allowed relatively straightforward assessment of the fetal palate with a high degree of accuracy.

Cleft Lip↗

Redesigning acute mental health services: an audit into the quality of inpatient care before and after service redesign in Grampian.

Redesigning acute mental health services: an audit into the quality of inpatient care before and after service redesign in Grampian As part of the redesign of adult mental health services in Grampian and in line with the Scottish Framework for Mental Health (1997), the decision was made to close one of the five acute mental health admission wards within Royal Cornhill Hospital. Inpatient services were to be provided within the remaining four admission wards by increasing their bed compliment from 25 to 28 and by increasing the staffing compliment of the community mental health teams serving Aberdeen city and Aberdeenshire. The adult mental health directorate commissioned an audit to measure certain key items in the 6 months leading up to the redesign and in the 6 months post redesign. This audit focused on the number of admissions, the bed occupancy, the number of incidents, the number of days the ward doors were locked, observation levels, sickness levels and the number of bank hours used. These factors were felt to be important indicators in the monitoring of the quality of patient care as any increase in the instance of these factors could be seen as detrimental to patient care. Therefore, a comparison of these factors, pre- and post-ward closure, was seen as a useful method of assessing the effect of the ward closure and the subsequent loss of seven acute inpatient beds. As the results of the audit showed that the rate of these factors had not increased, it was assumed the quality of care in the inpatient service was as at least as good following the redesign as it was before it. Two issues arose from the audit that merit further discussion, that is, the differences in the numbers of observations and in the numbers of times the ward doors were locked. Two G grade community psychiatric nurses were employed on a 0.5 session per week basis to collect and collate the data.

Acute Disease↗

Gene expression profiling for prognosis using Cox regression.

Given the promise of rich biological information in microarray data we will expect an increasing demand for a robust, practical and well-tested methodology to provide patient prognosis based on gene expression data. In standard settings, with few clinical predictors, such a methodology has been provided by the Cox proportional hazard model, but no corresponding methodology is available to deal with the full set of genes in microarray data. Furthermore, we want the procedure to be able to deal with the general survival data that include censored information. Conceptually such a procedure can be constructed quite easily, but its implementation will never be straightforward due to computational problems. We have developed an approach that relies on an extension of the Cox proportional likelihood that allows random effects parameters. In this approach, we use the full set of genes in the analysis and deal with survival data in the most general way. We describe the development of the model and the steps in the implementation, including a fast computational formula based on a subsampling of the risk set and the singular value decomposition. Finally, we illustrate the methodology using a data set obtained from a cohort of breast cancer patients.

Adult↗

Breast cancer prognosis in relation to family history of breast and ovarian cancer.

We linked four nationwide Swedish population-based registries to identify first-degree family history of breast and ovarian cancer among breast cancer cases diagnosed between 1991 and 1998 and followed them until death, emigration or end of follow-up in December 1998. The median follow-up was 36 months. Using Cox proportional hazards models, the hazard ratio of death (HR) due to breast cancer was estimated. Women with a family history of breast or ovarian cancer (n=2175, 12.7%) had a nonsignificantly better prognosis than women without any family history, HR 0.86 (95% CI 0.71-1.05); this appeared unrelated to age at diagnosis either in the index case or in relative(s) with breast and/or ovarian cancer. Our study shows that prognostic outlook is not worse among breast cancer patients with family history.

Breast Neoplasms↗

Preoperative psychological reactions and quality of life among women with an increased risk of breast cancer who are considering a prophylactic mastectomy.

A consecutive sample of 56 women with a familial risk for breast cancer who were considering a prophylactic mastectomy (PM) completed questionnaires preoperatively concerning risk perception, expectations with regard to surgery, anxiety and depressive symptoms (the Hospital Anxiety and Depression Scale (HAD) scale) and quality of life (The Swedish SF-36 Health Survey). 16 had had a previous breast cancer (Group BC) and 40 had not (Group R). They were compared with normative data from an age-matched random sample of the Swedish population and with a reference sample of women with breast cancer. Most women estimated their breast cancer risk accurately. No statistically significant differences were found between Group BC and the normative sample on the HAD scale and SF-36, but Group R reported better physical functioning, emotional role functioning and mental health than the reference sample with breast cancer. Group BC scored closer to them than to the normative sample. Levels of emotional problems and quality of life were comparable to normative values among women considering PM. All women in the present study had previous genetic counselling and our results suggest that their interest in PM was not due to an overestimation of their personal risk.

Adult↗

Risk of non-Hodgkin's lymphoma and skin malignancies in patients diagnosed with cataract.

The rapid increase of non-Hodgkin's lymphoma (NHL) in industrialized countries is yet unexplained. Ultraviolet radiation (UVR) has been suggested as an aetiologic factor due to observed elevated risks of cutaneous malignancies after NHL and vice versa. Cataract, as related to UVR, was tested as a proxy variable to further elucidate this observation. Cataract in-patients (n = 49914) reported to the Swedish Patient Register and later developing NHL and cutaneous malignancies were identified by record linkage to the Swedish Cancer Registry. The observed number of malignancies among cataract patients did not differ significantly from that expected in the general population. In contrast, the risk of cutaneous malignant melanoma was lower than anticipated, based on Swedish background incidence figures. The results did not give support for a causal relationship between NHL and UVR.

Age Distribution↗

Second primary malignancies in thyroid cancer patients.

The late health effects associated with radioiodine ((131)I) given as treatment for thyroid cancer are difficult to assess since the number of thyroid cancer patients treated at each centre is limited. The risk of second primary malignancies (SPMs) was evaluated in a European cohort of thyroid cancer patients. A common database was obtained by pooling the 2-year survivors of the three major Swedish, Italian, and French cohorts of papillary and follicular thyroid cancer patients. A time-dependent analysis using external comparison was performed. The study concerned 6841 thyroid cancer patients, diagnosed during the period 1934-1995, at a mean age of 44 years. In all, 17% were treated with external radiotherapy and 62% received (131)I. In total, 576 patients were diagnosed with a SPM. Compared to the general population of each of the three countries, an overall significantly increased risk of SPM of 27% (95% CI: 15-40) was seen in the European cohort. An increased risk of both solid tumours and leukaemias was found with increasing cumulative activity of (131)I administered, with an excess absolute risk of 14.4 solid cancers and of 0.8 leukaemias per GBq of (131)I and 10(5) person-years of follow-up. A relationship was found between (131)I administration and occurrence of bone and soft tissue, colorectal, and salivary gland cancers. These results strongly highlight the necessity to delineate the indications of (131)I treatment in thyroid cancer patients in order to restrict its use to patients in whom clinical benefits are expected.

Adolescent↗

A biologically based model for liver cancer risk in the Swedish thorotrast patients.

Data on liver tumors among 416 Swedish patients who were exposed to Thorotrast between 1930 and 1950 were analyzed with the biologically based two-step clonal expansion (TSCE) model. For background data, the Swedish Cancer Register for the follow-up period 1958 to 1997 was used. Effects of radiation on the initiating mutation and on the clonal expansion rate explained the observed patterns well. The TSCE model permits the deduction of several kinetic parameters of the postulated tumorigenesis process. Dose rates of 5 mGy/year double the spontaneous initiation rate. The clonal expansion rate is doubled by 80 mGy/year, and for females it reaches a plateau at dose rates beyond 240 mGy/year. For males the plateau is not significant. The magnitude of the estimated promoting effect of radiation can be explained with a moderate increase in the cell replacement probability for the intermediate cells in the liver, which is strikingly similar to the situation in lung tumorigenesis.

Adolescent↗

Cause-of-death registers in radiation-contaminated areas of the Russian Federation and Kazakhstan.

Since the early 1990s, information on radiation-exposed populations other than those exposed from the Chernobyl accident in 1986 has become increasingly available for international scientific research. It is essential to understand how the cohorts of exposed populations have been defined and what mechanisms can be used to study their health outcomes. Different international scientific research collaborations currently investigate four population groups chronically exposed to ionizing radiation during the late 1940s and early 1950s in the Russian Federation and in Kazakhstan. In this framework, collaborations have been established to develop cause-of-death registers in each of these four areas for future mortality follow-up purposes with the aim of studying the health effects of ionizing radiation. The emphasis of this effort is on assessing the information sources available, the mechanisms of data collection and coding, and the data quality and completeness of the information collected. One of the major challenges is the harmonization of all these aspects between the four different centers to the extent possible, taking into account that much of the actual data has been collected over many decades.

Cause of Death↗

Lung cancer risks in women with previous breast cancer.

Evaluation of the adverse effects of breast cancer treatment is becoming increasingly important in light of the earlier detection and prolonged survival of the patients. The beneficial effect of post-surgical radiotherapy has lately been challenged. The Swedish Cancer Registry (SCR) was used to identify approximately 141000 women with breast cancer, diagnosed between 1958 and 1997, followed-up for the occurrence of lung cancer. Standardised incidence ratios and expected number of lung cancers were calculated using incidence rates from the SCR. There were 613 subsequent lung cancers and a statistically significant increased risk of lung cancer was seen >5 years after breast cancer diagnosis, in contrast to a significantly decreased risk the first five years after the breast cancer diagnosis. The latter finding was confined to those >60 years of age when diagnosed with breast cancer. When restricting the analyses to those cases with information on the laterality of breast and lung cancer, an increased risk of a lung cancer on the same side as the breast cancer was seen >10 years after the breast cancer diagnosis. Birth cohorts with a higher smoking prevalence, i.e. 1930-1949, revealed a higher risk of lung cancer, than previous birth cohorts. Women with breast cancer have a significantly increased risk of developing a subsequent lung cancer possibly related to an interaction between radiotherapy and smoking.

Age Distribution↗