The study of haemopoietic stem cells in patients: concepts, approaches and cautionary tales.
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Animals↗
Biomedical subjects
A Weaver
Publications and source records attributed to A Weaver.
A randomised trial investigating the dose intensity of primary chemotherapy in patients with ovarian carcinoma: a comparison of chemotherapy given every four weeks with the same chemotherapy given at three week intervals.
BACKGROUND: The dose intensity of chemotherapy for patients with ovarian carcinoma remains a controversial issue. Few randomised trials have been conducted examining dose intensity using the same total dose of chemotherapy. This study was designed to investigate two schedules of chemotherapy using standard and higher dose intensity with both groups receiving the same total dose. PATIENTS AND METHODS: Patients with FIGO stage IC, II, III and IV epithelial ovarian carcinoma were randomised to receive cycles of cyclophosphamide (600 mg/m2) and carboplatin (300 mg/m2) alternating with doxorubicin (50 mg/ m2) and ifosfamide (5 g/m2) at either four-weekly (n = 47) or three-weekly (n = 97) intervals (1:2 randomisation). At randomisation patients were stratified according to histological grade and amount of post operative residual tumour (greater or less than 2 cm). The two arms of the study were well balanced in terms of the major prognostic features. RESULTS: There was no difference in either progression free survival or overall survival between the two arms. The median overall survival was 730 days for the three-weekly treatment and 740 days in the four-weekly arm (progression-free survival was 500 days and 483 days, respectively). The combined overall response rate (complete and partial response) in the 114 assessable patients was 65.7% (66.7% for the three-weekly treatment and 64% for the four-weekly treatment). These differences were not statistically different. CONCLUSIONS: A modest increase in the dose intensity of chemotherapy (1:3 fold) failed to improve the response rate, progression-free survival and overall survival in patients with ovarian carcinoma.
Adult↗
Attention deficit disorder.
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Attention Deficit Disorder with Hyperactivity↗
Metachronous colon cancer in persons who have had a large adenomatous polyp.
OBJECTIVE: To determine, among persons who have had a large colon polyp, the risk of subsequent colon cancer at a site distant from that polyp. METHODS: Follow-up was done for 226 persons at the Mayo Clinic who had had a > or = 1-cm polyp demonstrated on barium enema between 1965 and 1970 and for whom yearly colon surveillance examination was recommended. Information was collected from Mayo Clinic records and from contact with patients, physicians, and other hospitals regarding the results of surveillance examinations and the development of colon cancer. Colon surveillance was routinely done at the Mayo Clinic using the technique of single contrast barium enema with vigorous manual fluoroscopic examination and proctoscopy. The expected rate of colorectal cancer (CRC) was calculated based on previously published rates for this community. RESULTS: Patients received, on average, four colon examinations in addition to the examination that discovered the index polyp. During 2126 person-years of follow-up, 16 persons developed a colon cancer at a location other than the site of the index polyp, in comparison with 4.0 expected cases, for a standardized incidence ratio of 4.0 (95% CI,2.3, 6.4). The cancers were large (mean 4.5cm) at presentation, and eight of the 16 cancers had been preceded within 3 yr by at least one negative barium enema. CONCLUSIONS: The rate to develop colon cancer in persons who have had a large colon polyp es about 4 times the expected rate, suggesting that such persons should be considered for aggressive colonoscopic surveillance. The failure to detect early cancer or its precursors by surveillance barium enema is probably explained by inherent insensitivity of single contrast barium enema.
Adenomatous Polyps↗
MRSA and its management in the community.
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Community-Acquired Infections↗
Effect of angiotensin-converting enzyme and calcium channel inhibition on progression of IgA nephropathy.
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Aldosterone↗
Patients' perceived control over their health care: an outcome assessment of their psychological adjustment to renal failure.
Previous research has sometimes produced conflicting results regarding patients' psychological adjustment to end-stage renal disease (ESRD). It is generally accepted that treatment outcomes vary across treatment modality, with successful transplant patients reporting a higher subjective quality of life than patients on center hemodialysis. Hemodialysis and transplantation therapies vary in many ways, including the intrusiveness of treatment on all aspects of the patient's life. In the present study, 65 individuals being treated for ESRD with center hemodialysis or a renal transplant were assessed for health locus of control, for generalized control over 11 life dimensions, and for beliefs about control over specific aspects of treatment for ESRD. The study also included indicators of psychological adjustment. The results indicated that control over life dimensions, which includes control over illness, is a significant factor in psychological adjustment. Beliefs that one can comply specifically with diet and fluid restrictions were related to treatment outcome. These data suggest that interventions designed to increase patients' perception of control are likely to have a positive impact on the qualitative aspect of treatment.
Adaptation, Psychological↗
Steroid sparing activity of tenidap in patients with polymyalgia rheumatica: a multicenter double blind randomized placebo controlled study.
OBJECTIVE: To determine whether tenidap treatment would allow reduction or replacement of systemic corticosteroid treatment in patients with polymyalgia rheumatica (PMR). METHODS: A 15-week double blind, randomized, multicenter, placebo-controlled study of tenidap sodium (120 mg/day) in patients with symptomatically controlled PMR receiving 10 mg/day prednisone was conducted. After receiving study drug for 3 weeks, prednisone dose was reduced by 2.5 mg/day every 3 weeks. The lowest clinically effective dose of prednisone was recorded as 10, 7.5, 5, 2.5 or 0 mg/day. RESULTS: Thirty-two patients were randomized to tenidap or placebo. As prednisone was reduced more placebo patients experienced an exacerbation of PMR symptoms, elevation of erythrocyte sedimentation rate and increased serum C-reactive protein. Twice as many placebo patients (10 of 16) as tenidap patients (5 of 16) discontinued due to lack of efficacy. The lowest effective dose of prednisone could be determined in 27 of the 32 patients, 11 receiving tenidap and 16 placebo. A significantly (p = 0.027) greater proportion of patients receiving tenidap (5 of 11) than placebo (1 of 16) were able to discontinue prednisone without experiencing a symptomatic flare. CONCLUSION: As prednisone was reduced, symptoms of PMR were controlled better by tenidap than by placebo. Forty-five percent of evaluable patients receiving tenidap were able to discontinue prednisone without a disease flare compared to 6% for placebo.
Aged↗
The diastrophic dysplasia gene encodes a novel sulfate transporter: positional cloning by fine-structure linkage disequilibrium mapping.
Diastrophic dysplasia (DTD) is a well-characterized autosomal recessive osteochondrodysplasia with clinical features including dwarfism, spinal deformation, and specific joint abnormalities. The disease occurs in most populations, but is particularly prevalent in Finland owing to an apparent founder effect. DTD maps to distal chromosome 5q and, based on linkage disequilibrium studies in the Finnish population, we had previously predicted that the DTD gene should lie about 64 kb away from the CSF1R locus. Here, we report the positional cloning of the DTD gene by fine-structure linkage disequilibrium mapping. The gene lies in the predicted location, approximately 70 kb proximal to CSF1R, and encodes a novel sulfate transporter. Impaired function of its product is likely to lead to undersulfation of proteoglycans in cartilage matrix and thereby to cause the clinical phenotype of the disease. These results demonstrate the power of linkage disequilibrium mapping in isolated populations for positional cloning.
Amino Acid Sequence↗
Diabetes-related end-stage renal disease in Missouri: trends and variations by age and race.
Diabetes-related end-stage renal disease (ESRD-DM) is a major source of morbidity and medical costs. The authors studied patterns of ESRD-DM in Missouri during the period 1985-1992. The incidence of ESRD-DM increased during this period, with the largest increase in older age groups. ESRD-DM is substantially more common among blacks than among whites. Enhanced efforts are needed to improve detection and control of diabetes and its complications, especially in high-risk populations.
Adult↗
A genetic linkage map of the mouse: current applications and future prospects.
Technological advances have made possible the development of high-resolution genetic linkage maps for the mouse. These maps in turn offer exciting prospects for understanding mammalian genome evolution through comparative mapping, for developing mouse models of human disease, and for identifying the function of all genes in the organism.
Animals↗
Surgical management of primary hyperparathyroidism in multiple endocrine neoplasia types 1 and 2.
BACKGROUND: The surgical management of primary hyperparathyroidism in multiple endocrine neoplasia type 1 (MEN 1) remains controversial. In addition, the rarity of MEN 2A-related hyperparathyroidism has not allowed for a separate strategy for this condition. This study examines our surgical experience with MEN 1- and MEN 2A-related hyperparathyroidism and attempts to define a rational therapeutic approach to each. METHODS: Between 1970 and 1991, 124 patients underwent surgery for MEN-related hyperparathyroidism at our institution. Primary cervical explorations were performed in 84 patients with MEN 1 and 18 with MEN 2A. An additional 22 patients with MEN 1 underwent reoperative surgery. All patients with MEN 2A underwent concomitant thyroidectomy for medullary thyroid cancer. RESULTS: Compared with patients with MEN 1, patients with MEN 2A, had a lower preoperative serum Ca2+ level and fewer symptoms or complications of hypercalcemia. Multiple gland disease was evident in 90% and 83%, respectively, of patients with MEN 1 and MEN 2A. Primary explorations in patients with MEN 1 resulted in surgical cure in 94%, persistent hypercalcemia occurring in no patient undergoing subtotal resection compared with 17% of patients in whom more conservative resections were performed (p = 0.005). In patients with MEN 1, 10-year recurrence of hypercalcemia was 16% for primary explorations and 30% for reoperative procedures. In contrast, all patients with MEN 2A, whether treated by total, subtotal, or lesser resections, were cured after surgery and none had recurrence during a median follow-up of 5.8 years. CONCLUSIONS: In MEN 1 the surgical principles should be (1) identification of all four glands, (2) subtotal resection to ensure cure and facilitate possible reoperation, and (3) excision of supernumerary thymic glands. In MEN 2A we should identify and resect all enlarged glands for cure, but routine subtotal resection need not be performed because this condition is readily cured and recurrence is rare.
Adolescent↗
Pheochromocytoma--continuing evolution of surgical therapy.
BACKGROUND: The management of pheochromocytoma has evolved through refinements in diagnosis, localization, and pharmacologic therapy for hemodynamic control both before and during operation. To provide a benchmark for comparison and to assess the feasibility of surgical resection using a posterior or laparoscopic approach, we reviewed the overall management and outcome of 110 patients who underwent primary resection of pheochromocytoma or paraganglioma between 1980 and January 1992 at the Mayo Clinic. METHODS: Patient records were reviewed for demographic information, associated conditions, symptoms, laboratory evaluation, localizing techniques, preoperative adrenergic blockade, intraoperative hemodynamics, tumor location, pathologic conditions, and outcome. RESULTS: The most prominent symptoms included headaches, sweating, and palpitations. Forty-seven percent of patients had sustained hypertension, and classic paroxysmal attacks were present in 72%. The combination of urinary metanephrines and vanillylmandelic acid had a sensitivity of 98% in detecting the disease. The positive and negative predictive values for localization of tumors by computed tomography scan were 95% and 100%, respectively. With routine alpha- and beta-blockade, there were no complications associated with intraoperative hypertension. Perioperative mortality was less than 1% and morbidity was 16%. More than 90% of patients were restored to a condition of normotension; only 20% of these required medication. CONCLUSIONS: Surgical resection of these tumors, via a transabdominal approach, can be accomplished safely and hospitalization usually extends a week. Today the diagnosis, localization, preoperative blockade, intraoperative hemodynamic control, and postoperative management have reached a level sufficient to permit either a posterior or laparoscopic approach, but only if they can be mastered technically.
Adrenal Gland Neoplasms↗
Effect of cadmium and/or selenium on liver mitochondria and rough endoplasmic reticulum in the rat.
This study was conducted to investigate the effect of cadmium (Cd) and/or selenium (Se) on hepatic mitochondria and rough endoplasmic reticulum (RER). Male Sprague Dawley derived rats (150-200 g) received sodium acetate (NaAc; 1.23 mg/kg), Cd (0.84 mg/kg), and/or Se (1.6 mg/kg) intraperitoneally. Livers were perfused with 2% glutaraldehyde at 48 h, 72 h, or 96 h after treatment and prepared for electronmicroscopy. Results indicate that Cd and/or Se are capable of inflicting mitochondrial and RER structural changes, and the damage by Cd alone is more severe than Se alone or with Cd.
Acetates↗
Importance of precise determination of technetium-labeled DISIDA concentrations for in vitro hepatocellular transport studies.
Technetium 99m-labeled diisopropyliminodiacetic (acid [99mTc]DISIDA) has been used extensively in the evaluation of hepatobiliary diseases. As a result of investigation into transport mechanisms of [99mTc]DISIDA, we undertook to determine precise concentrations of this compound in the standard clinical formulation. Calculations based on published formulas were used. These take into account column efficiency, the time since the previous elution of 99mTc from the 99Mo column, and the total quantity of 99mTc eluted. Primary cultures of rat hepatocytes were used to evaluate the transport of Na99mTcO4 and the 99mTc-labeled DISIDA monomer. Pertechnetate was not taken up by the hepatocytes, the amount of [99mTc]DISIDa taken up was not dependent on the concentration of DISIDA but rather on the concentration of technetium, when the DISIDA/99mTc ratio was varied in the culture medium. We conclude that calculation of the total technetium concentration is necessary to determine the amount of compound taken up by the liver, and to interpret kinetic studies of hepatocellular transport mechanisms.
Animals↗
Linkage disequilibrium mapping in isolated founder populations: diastrophic dysplasia in Finland.
Linkage disequilibrium mapping in isolated populations provides a powerful tool for fine structure localization of disease genes. Here, Luria and Delbrück's classical methods for analysing bacterial cultures are adapted to the study of human isolated founder populations in order to estimate (i) the recombination fraction between a disease locus and a marker; (ii) the expected degree of allelic homogeneity in a population; and (iii) the mutation rate of marker loci. Using these methods, we report striking linkage disequilibrium for diastrophic dysplasia (DTD) in Finland indicating that the DTD gene should lie within 0.06 centimorgans (or about 60 kilobases) of the CSF1R gene. Predictions about allelic homogeneity in Finland and mutation rates in simple sequence repeats are confirmed by independent observations.
Base Sequence↗
The effect of cryopreservation on cell viability and hormone secretion in human parathyroid tissue.
BACKGROUND: To explain the decreased success of cryopreserved versus fresh parathyroid autotransplants, we investigated the effect of cryopreservation on parathyroid function. METHODS: Parathyroid cryopreserved tissue from surgical specimens of 18 patients was analyzed in a comparative fashion with 10 fresh abnormal glands. Cell viability was evaluated by a double-fluorescence technique, and parathyroid hormone secretion was detected from individually dispersed parathyroid cells with the reverse hemolytic plaque assay. The plaque area reflected the amount of parathyroid hormone secreted by each cell, and the percentage of plaque-forming cells represented the number of secreting cells. Feedback regulatory mechanisms remained intact for both fresh and cryopreserved tissue as shown over a wide range of calcium concentrations. RESULTS: The percentage of viable cells from fresh and cryopreserved tissue was always in excess of 88%. No significant difference was noted in the percentage of plaque-forming cells nor the amount of hormone released per individual cell comparing fresh and cryopreserved glands (6 months to 2 years). Specifically, at physiologic calcium concentrations no significant differences existed in the secretory behavior between fresh and cryopreserved tissue. CONCLUSIONS: Without showing decreased viability or parathyroid hormone secretion after cryopreservation, the cause of graft failure in cryopreserved tissue still remains unknown.
Calcium↗
Gastric adenocarcinoma and Helicobacter pylori infection.
Helicobacter pylori infection, thought to be causally related to chronic gastritis, may also be associated with an increased risk of gastric cancer. To determine whether an association with gastric cancer does exist, we retrospectively evaluated serum samples from 69 patients with histologically confirmed gastric adenocarcinoma (32 with cancer at the cardia and 37 with cancer at other sites) and from 218 patients with one of three categories of nongastric cancers, with other gastric cancers, or with benign gastric neoplasms. These samples were compared with samples from 252 cancer-free control subjects, a group comprising 76 asymptomatic volunteers and 176 persons with nonmalignant disorders. Serum samples collected from cancer patients prior to surgery and from cancer-free controls were tested for antibodies to H. pylori by using a highly sensitive and specific IgG enzyme-linked immunosorbent assay. The risk of H. pylori infection in the case patients relative to the control subjects was estimated with the use of multivariate logistic regression analysis to adjust for potential confounding variables. Antibodies to H. pylori were detected in 65% of the patients with noncardia gastric cancer but in only 38% of the patients with gastric cancer located at the cardia. A significant association was found between H. pylori infection and noncardia gastric cancer (odds ratio = 2.67; 99% confidence interval = 1.01-7.06). Within the subset of patients with noncardia gastric cancer, a statistically nonsignificant tendency existed for those with the intestinal versus the diffuse histologic type of noncardia gastric cancer to have a higher risk of H. pylori infection. Our results support the hypothesis of a relationship between H. pylori infection and the development of noncardia gastric adenocarcinoma.
Adenocarcinoma↗