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Biomedical subjects

S Campbell

Publications and source records attributed to S Campbell.

At least 235 records · Page 13Linked to original sources

Breast cancer management: is volume related to quality? Clinical Advisory Panel.

A method of carrying out region-wide audit for breast cancer was developed by collaboration between the cancer registry, providers and purchasers as part of work to fulfill the 'Calman-Hine' recommendations. In order to test the audit method, a retrospective audit in North Thames East compared practice in 1992 against current guidelines. The analysis compared care in specialist and non-specialist centres. A stratified random sample comprising 28% of all breast cancer patients diagnosed in 1992 was selected from the population-based Thames Cancer Registry. The data for 309 patients with stage I-III tumours were analysed by hospital type using local guidelines. No difference between specialist (high volume) and non-specialist centres was detected for factors important in survival. Pathological staging was good with over 70% reporting tumour size and grade. A small number of patients were undertreated; after conservative surgery, 10% (19) of women did not receive radiotherapy, and 15% (8) of node-positive premenopausal women did not receive chemotherapy or ovarian ablation. In contrast, a significant trend with hospital volume was found for several quality of life factors. These included access to a specialist breast surgeon and specialist breast nurses, availability of fine-needle aspiration (FNA), which ranged from 84% in high-volume to 42% in low-volume centres, and quality of surgery (axillary clearance rates ranged from 51% to 8% and sampling of less than three nodes from 3% to 25% for high- and very low-volume centres respectively). Confidential feedback of results to surgeons was welcomed and initiated change. The summary information gave purchasers information relevant to the evaluation of cancer services. While the audit applied present standards to past practice, it provided the impetus for prospective audit of current practice (now being implemented in North Thames).

Breast Neoplasms↗

Transvaginal uterine and umbilical artery Doppler examination of 12-16 weeks and the subsequent development of pre-eclampsia and intrauterine growth retardation.

We aimed to determine whether Doppler measurements obtained from the uterine and umbilical arteries in early pregnancy correlate with the subsequent development of pre-eclampsia, or the delivery of a small-for-gestational-age (SGA) baby. A follow-up study was carried out in 652 women with singleton pregnancies who had transvaginal uterine and umbilical artery Doppler examinations performed at 12-16 weeks' gestation. Measurements included: the presence or absence of an early diastolic notch, vessel diameter, resistance index (RI), pulsatility index (PI), time-averaged mean velocity (TAV), maximum systolic velocity and volume flow in the right and left uterine arteries and RI and PI in the umbilical arteries. The main outcome measures were: intrauterine death, birth weight, pre-eclampsia (proteinuric pregnancy-induced hypertension, PPIH) and antepartum hemorrhage. Twelve pregnancies terminated in the second trimester, and in 14 the outcome is unknown. In the remaining 626 women, 44 (7.0%) pregnancies ended in a premature delivery, 30 (4.7%) women developed PPIH, 60 (9.6%) infants were SGA (< 10th centile), of which 19 were < 5th centile and five were < 3rd centile, and 23 (3.7%) women suffered an antepartum hemorrhage. At 12-16 weeks, 205 (32.7%) women had bilateral (right and left) notching of the uterine artery waveforms. When compared to values from women with a normal pregnancy outcome, women who subsequently developed PPIH demonstrated a significant difference in mean uterine artery TAV (24.6 cm/s for PPIH vs. 33.25 cm/s for normal outcome, p < 0.003), volume flow (120.5 ml/min vs. 184.5 ml/min, p < 0.001) and elevated resistance (mean RI = 0.80 vs. 0.695, p < 0.001). In women with bilateral notching, there were significant differences between values for pregnancies with PPIH (odds ratio (OR) 42.02, 95% confidence interval (CI) 5.66, 311.99), being SGA at birth (OR 8.61, 95% CI 4.0, 20.0) or delivering prematurely (OR 2.38, 95% CI 1.19, 4.75), compared with pregnancies with a normal outcome. We conclude that abnormal Doppler values, indicative of a failure to modify the uterine circulation in early pregnancy, are associated with premature delivery, the development of PPIH and the delivery of an SGA baby. This information may be of value in increasing our understanding of the pathophysiological events that lead to the subsequent development of uteroplacental complications such as pre-eclampsia.

Female↗

Sonographic prediction of malignancy in adnexal masses using multivariate logistic regression analysis.

The aim of the study was to assign a probability of malignancy for any patient with an adnexal tumor by the application of multivariate logistic regression analysis to variables recorded at the time of pelvic sonography. Sixty-seven women with known adnexal masses were examined using transvaginal B-mode and color Doppler imaging. For each patient the variables included: (1) age, (2) maximum tumor diameter, (3) tumor volume, (4) unilocularity (presence (0) or absence(1)), (5) papillary projections (presence (1) or absence (0)), (6) random echogenicity (presence (1) or absence (0)), (7) highest peak systolic velocity (PSV), (8) time-averaged maximum velocity (TAMXV), (9) pulsatility index (PI) and (10) resistance index (RI). The TAMXV, PI and RI were those associated with the highest PSV. These ten independent variables and the final histological diagnosis for each patient (the dependent variable) were used for the regression analysis. Approximately 75% of the entire dataset was randomly selected for generating the regression model. The remaining 25% was used as the testing set for cross-validation of the model. In the entire dataset there were 52 women with benign, three with borderline and 12 with invasive ovarian tumors. Regression analysis on the ten variables resulted in the retention of only 'age', 'papillary projection score' and 'TAMXV' as significantly contributing to predicting the presence or absence of malignancy. The probability of malignancy for any patient was given by solving the equation: Probability = 1/(1 + e-z) where e is the base value for natural logarithms and z = (0.1273 x Age) + (0.2794 x TAMXV) + (4.4136 x Papillary projections score) - 14.2046. Cross-validation of the model on the test set of data gave a 100% sensitivity and specificity. However, for the entire dataset the best sensitivity and specificity were 93.3 and 90.4%, respectively, at a cut-off value of 25% probability of malignancy. In conclusion, multivariate logistic regression analysis enables the calculation of probability of malignancy for any patient with a known adnexal mass. The accuracy of this prediction appears to be better than that of morphological or Doppler criteria when the latter are used independently. The value of this model needs to be tested prospectively.

Adult↗

A cross-sectional study of platelet volume in healthy normotensive women with bilateral uterine artery notches.

High uterine artery resistance characterized by bilateral notches seen on Doppler ultrasound in the second half of pregnancy is associated with an increased risk of adverse outcome related to pre-eclampsia and intrauterine growth retardation. We sought to establish whether there was a difference in platelet volume in healthy, normotensive women with high-resistance uterine artery Doppler findings compared to those with normal uterine artery Doppler findings. Forty-seven women were allocated prospectively into 'bilateral notch' and 'no notch' groups at color Doppler imaging of the uterine arteries carried out at a mean of 26 weeks' gestation. The difference in platelet volume between the two groups and the relationship of adverse outcome with raised platelet volume and high-resistance uterine artery Doppler findings was investigated. Twenty-three women had no evidence of uterine artery notches and 24 had bilateral uterine artery notches. Platelet volume in the women with bilateral notches was greater than in those with no notches (8.28 fl vs. 7.46 fl; p = 0.01). However, unlike high-resistance uterine artery Doppler findings, increased platelet volume was not associated with adverse outcome. Uterine artery Doppler flow abnormalities have not previously been studied in combination with hematological or biochemical markers. Our findings show, for the first time, that women with bilateral uterine artery notches have an increased platelet volume compared to those with normal uterine artery Doppler findings many weeks before clinical signs of pre-eclampsia or fetal growth retardation are evident. Women with abnormal uterine artery flow at this gestation may have other cardiovascular and hematological differences compared to those with normal flow.

Arteries↗

Expression of endothelial and inducible nitric oxide synthase in non-pregnant and decidualized human endometrium.

Immunocytochemistry was used to localize endothelial (eNOS) and inducible (iNOS) nitric oxide synthase in human uterine tissues collected at various stages of the menstrual cycle, after exposure to exogenous progestagens, and in early pregnancy. Endothelial NOS-like immunoreactivity was detected in all specimens in endothelial cells lining blood vessels in the myometrium and endometrium, and in endometrial glandular epithelial cells. Inducible NOS-like immunoreactivity was also demonstrated in glandular epithelial cells. For both eNOS and iNOS there was considerable variation in the intensity of epithelial cell staining between samples, which was not related to the stage of the menstrual cycle at which the tissue was collected. Messenger RNA for eNOS and iNOS was detected by reverse transcription-polymerase chain reaction (RT-PCR) using total RNA purified from isolated endometrial gland fragments. Immunoreactivity for eNOS and iNOS was not present in endometrial stroma throughout the menstrual cycle, but iNOS-like immunoreactivity was seen in decidualized stromal cells both following treatment with exogenous progestagen (intrauterine L-norgestrel) and in tissues obtained in the first trimester of pregnancy. The detection of protein and mRNA for eNOS and iNOS in normal human endometrium suggests that NO may play a role in the local control of endometrial function.

Decidua↗

Renal oncocytoma: a clinicopathologic study of 70 cases.

We reviewed 954 primary nonurothelial epithelial renal neoplasms with primary resection at Memorial Sloan-Kettering Cancer Center between the years 1980 and 1995 and classified 70 cases (7%) as renal oncocytomas. The study population was composed of 39 men and 31 women, and the mean age was 65 years (range 25 to 86 years). Fifty-six patients (80%) were asymptomatic at presentation, six (4%) had flank pain, six (4%) presented with a mass, and two (3%) had hematuria. Sixty-one were treated with total or radical nephrectomy, nine with partial nephrectomy. The right kidney was involved in 35 cases (50%), the left kidney in 32 (46%). Three cases (4%) were bilateral. Sixty-one cases (87%) were unifocal, nine (13%) multifocal. All the tumors were well circumscribed but unencapsulated. Forty-five (64%) were described as brown or red, whereas the remainder were variously described as tan to yellow. Central fibrosis or scar was described in 23 cases (33%), and gross areas of hemorrhage or cystic changes in 14 (20%). The mean size was 5.2 cm and median 5.0 cm (range 1.5 cm to 14 cm). Histologically, the tumors were characterized by a mixture of architectural patterns: compact cellular nests and acini embedded in a hyalinized, hypocellular stroma were present in 62 cases (89%), a solid nested architecture in 47 cases (67%), and a variable tubular component in 50 cases (71%). Small papillae, pseudopapillae, and intratubular epithelial tufts were seen in 19 cases (27%). Cytologically, the neoplasms also showed a mixture of cell types, the most common being the classic oncocyte, which consisted of round or polygonal cells with moderate to abundant granular, eosinophilic cytoplasm, and small round nuclei with evenly dispersed granular chromatin. Small basophilic nucleoli were visible in many of these cells in all cases. Thirty-one cases (44%) had a variable number of oncocytic cells with pyknotic nuclei and 20 (30%) contained clusters of small cells with a high nuclear/cytoplasmic ratio and dense hyperchromatic nuclei (so-called oncoblasts). Foci of tubules with clear cells embedded in a hyalinized stroma were present in six cases (9%). Cellular atypia was evident in 42 cases (60%) and was marked in 21 (30%). Eleven cases (16%) exhibited mitotic activity, albeit low. No case had atypical mitoses or necrosis. Twenty-two cases (31%) had areas of calcification within the hyalinized stroma, 12 (17%) had calcospherites, and three (4%) had osseous and myeloid metaplasia. Vascular invasion was present in three cases (4%), and invasion of perinephric fat in 14 (20%). One patient presented with liver metastasis. Fourteen cases (20%) were pT1, 42 (60%) pT2, and 14 (20%) pT3. After a mean follow-up of 58 months (range 1 to 181), 62 patients (89%) were alive with no evidence of tumor, six (9%) had died of other causes, one was alive with stable metastatic disease in the liver 58 months after diagnosis, and one died with metastatic disease to bone and liver. We conclude that renal oncocytomas have a varied morphologic appearance and their pathologic diagnosis should be based on a constellation of architectural and cytologic features. The overwhelming majority of cases behave in a benign fashion, although in rare instances they can metastasize. The presence of atypical morphologic features do not alter the excellent prognosis associated with oncocytomas and do not predict an aggressive clinical course.

Adenoma, Oxyphilic↗

Long-term survival after surgical revascularization for atherosclerotic renal artery disease.

PURPOSE: We analyzed the long-term clinical outcome and survival after surgical revascularization for atherosclerotic renal artery stenosis. MATERIALS AND METHODS: The study group comprised 222 patients who underwent surgical revascularization for atherosclerotic renal artery stenosis between 1974 and 1987. The indications for performing surgical revascularization were treatment of hypertension in 60 patients, preservation of renal function in 12, and control of hypertension and preservation of renal function in 148. Postoperative blood pressure, renal function and survival data were analyzed during a mean followup of 7.4 years. RESULTS: There were 5 operative deaths (2.2%) and postoperative thrombosis or stenosis of the repaired renal artery occurred in 16 patients (7.3%). Long-term cure or improvement of renovascular hypertension was achieved in 72.4% of patients. Preoperative renal function correlated significantly with a favorable blood pressure response to surgical revascularization (p = 0.013). Long-term improvement or stabilization of renal function was achieved in 71.3% of patients. Preoperative renal function (p = 0.034) and bilateral atherosclerotic renal artery stenosis (p = 0.04) correlated significantly with a favorable renal function result after surgical revascularization. Actuarial 5 and 10-year survivals for the entire series from the time of surgical revascularization were 81 and 53%, respectively. The expected 5 and 10-year survivals for a comparable healthy population are 89 and 77%, respectively. Using a multivariate analysis, factors correlating with diminished long-term survival were age older than 60 years (p = 0.002), coronary artery disease (p = 0.031), and previous vascular operations (p = 0.001). CONCLUSIONS: These data support the long-term therapeutic efficacy of surgical revascularization in patients with atherosclerotic renal artery stenosis. The merits of newer forms of therapy, such as percutaneous transluminal angioplasty and endovascular stenting, must ultimately be weighed against these results.

Actuarial Analysis↗

Transvaginal Doppler ultrasound of the uteroplacental circulation in the early prediction of pre-eclampsia and intrauterine growth retardation.

OBJECTIVE: To evaluate the predictive value of transvaginal Doppler ultrasound studies of the uterine and umbilical arteries in early pregnancy, in identifying pregnant women at risk of subsequently developing pre-eclampsia, or the delivery of a small for gestational age infant. DESIGN: A multivariate logistic regression of Z scores of Doppler indices obtained from the uterine and umbilical arteries of 652 women with singleton pregnancies at 12 to 16 weeks of gestation. Measurements included the presence or absence of a notch, bilateral (right and left waveform) notching, vessel diameter, the resistance index, the pulsatility index, time averaged mean velocity (cm/s), maximum systolic velocity (cm/s), and volume flow (mL/min). Stepwise logistic regression and multivariate analysis of all the parameters measured was used to construct several scoring systems. MAIN OUTCOME MEASURES: Pre-eclampsia, birthweight, preterm delivery. RESULTS: In women that developed complications, there was a trend towards increased resistance and reduced velocity and volume flow. If bilateral notches were present there was an increased risk of pre-eclampsia (odds ratio [OR] 21.99, 95% CI 6.55-73.79), premature delivery (OR 2.38, 95% CI 1.19-4.75), and the delivery of a small for gestational age baby (OR 8.63, 95% CI 3.95-18.84). Using multivariate analysis, a seven parameter model was selected (after removal of vessel diameter, uterine and umbilical resistance index). This model produces a scoring system with a sensitivity of 92.9% and a specificity of 85.1% for the prediction of pre-eclampsia. A three parameter model (bilateral notches, uterine resistance index, umbilical pulsatility index) provides similar sensitivities, but lower specificities, when compared with the seven parameter model. CONCLUSION: These data indicate that there are differences in uterine and umbilical artery Doppler blood flow indices at 12 to 16 weeks, in pregnancies with a normal or complicated outcome. Scoring systems derived from multivariate analysis of Doppler indices demonstrate the potential of being able to identify, in early pregnancy, a group of women at increased risk of the subsequent development of pre-eclampsia, premature delivery, or the birth of a small for gestational age baby.

Adolescent↗

Evidence for ethnic tropism of Helicobacter pylori.

Helicobacter pylori infection in humans is linked to gastritis, gastric and duodenal ulcers, and gastric cancer. Peptic ulcer disease, as distinct from chronic asymptomatic infection, is strongly associated with expression of bacterial virulence markers, including a major antigen, CagA, and the vacuolating cytotoxin VacA. We have previously described significant differences in colonization rates, independent of socioeconomic status, among ethnic groups in New Zealand. To evaluate relative risks for peptic ulcer disease, we examined the frequency of two virulence markers in H. pylori strains infecting these ethnic groups. Although these markers occurred significantly more frequently in strains isolated from Polynesians than in strains from Europeans, this frequency was not reflected in the incidence of peptic ulcer disease in the two groups. DNA fingerprinting of the urease gene showed that Polynesians are more frequently infected by a group of strains which are genetically distinct from those affecting European New Zealanders. Our data suggest that separate bacterial lineages may have evolved in parallel with race-specific specialization.

Antigens, Bacterial↗

In vitro assembly of virus-like particles with Rous sarcoma virus Gag deletion mutants: identification of the p10 domain as a morphological determinant in the formation of spherical particles.

Retroviruses are unusual in that expression of a single protein, Gag, leads to budding of virus-like particles into the extracellular space. We have developed conditions under which virus-like particles are formed spontaneously in vitro from fragments of Rous sarcoma virus (RSV) Gag protein purified after expression in Escherichia coli. The CA-NC fragment of Gag was shown previously to assemble into hollow cylinders (S. Campbell and V. M. Vogt, J. Virol. 69:6487-6497, 1995). We have now extended these studies to larger Gag proteins. In every case examined, assembly into regular structures required RNA. A nearly full-length Gag missing only the C-terminal PR domain, as well as similar proteins missing in addition the N-terminal half of MA, the C-terminal half of MA, the entire MA sequence, or the entire p2 sequence, all assembled into spherical particles resembling RSV in size. By contrast, proteins missing p10 assembled into cylindrical particles like those formed by CA-NC alone. Thin section electron microscopy showed that each of these Gag proteins formed in the expressing E. coli cells particles similar in shape to those seen in vitro. We conclude from these results that neither the sequences required for membrane binding in vivo, near the N terminus of Gag, nor the sequences required for a late step in budding, in the p2 portion of Gag, are essential for formation of virus-like particles in this system. Furthermore, we postulate the existence of a shape-determining sequence in p10, which provides or facilitates interactions required for the growing particle to be constrained to a spherical shape.

Avian Sarcoma Viruses↗