Biomedical subjects

R S Brown

Publications and source records attributed to R S Brown.

At least 73 records · Page 4Linked to original sources

PubMed1999

Glucose transporters and FDG uptake in untreated primary human non-small cell lung cancer.

UNLABELLED: PET imaging of malignant tumors with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) as a tracer is a noninvasive diagnostic and prognostic tool that measures tumor metabolism. In this study, we assessed the relationships between FDG uptake and the expression of facilitative glucose transporters, the sizes of populations of proliferating cells and infiltrating macrophages in patients with primary non-small cell lung cancers (NSCLC). METHODS: FDG uptake and the expression of five glucose transporters and the proportions of proliferating cell and macrophage populations were studied in paraffin sections from untreated primary lung cancers by immunohistochemistry. The patients were imaged with FDG PET before surgery. RESULTS: All tumors could be detected by FDG PET. Uptake was correlated with tumor size (P = 0.004). FDG uptake was lower in adenocarcinomas (ACs) than in squamous cell carcinomas (SQCs) (P = 0.03) or large cell carcinomas (P = 0.002) [standardized uptake value corrected for lean body mass (SUL) = 5.42 +/- 2.77, 8.04 +/-3.25 and 10.42 +/- 4.54, respectively]. Glut-1 expression was significantly higher than that of any other transporter. All tumors tested (n = 23) were Glut-1-positive (70.8% +/- 26.1% of tumor cell area was positive and staining intensity was 2.8 +/- 1.2). Glut-1 expression was higher in SQCs (78% +/- 17.8% and 3.5 +/-0.6) than in ACs (47.5% +/- 30.3% and 1.6 +/- 1.1; P = 0.044 for positive tumor cell area and P = 0.005 for staining intensity). Proliferating cells constituted 15.3% +/- 13.1% of the cancer cells, and the average number of macrophages was 7.8% +/- 6.3%; neither correlated with FDG uptake. CONCLUSION: In this population of patients with NSCLC, Glut-1 is the major glucose transporter expressed. Both FDG uptake and Glut-1 expression appear to be associated with tumor size. No association was found between FDG uptake and either macrophage or proliferative cell populations.

Aged↗

PubMed1999

Strategies and pitfalls in quality of life research.

QOL research is an important element of outcomes research and can provide an important adjunct to clinical trials in hepatology. The principles of QOL research are similar to all outcomes research methods. Pitfalls in QOL research include poor study design, choosing the wrong instrument, and inadequate interpretation of design. These pitfalls can be avoided with a well-thought-out strategy including a well-designed hypothesis to test, a validated instrument, careful data collection and analysis, and collaboration with biostatisticians and experts in health-utility research when necessary. QOL research is best suited to questions where survival differences between the two groups studied are modest or to balance economic outcomes, but it can be a useful part of virtually any clinical question.

Health Services Research↗

PubMed1999

Methods to estimate and analyze medical care resource use. An example from liver transplantation.

This paper describes a method to construct a standardized health care resource use database. Billing and clinical data were analyzed for 916 patients who received liver transplantations at three medical centers over a 4-year period. Data were checked for completeness by assessing whether each patient's bill included charges covering specified dates and for specific services, and for accuracy by comparing a sample of bills to medical records. Detailed services were matched to a standardized service list from one of the centers, and a single price list was applied. For certain services, clinical data were used to estimate service use or, if a match was not possible, adjusted charges for the services were used. Twenty-three patients were eliminated from the database because of incomplete resource use data. There was very good correspondence between bills and medical records, except for blood products. Direct matches to the standardized service list accounted for 69.3% of services overall; 9.4% of services could not be matched to the standardized service list and were thus adjusted for center and/or time period. Clinical data were used to estimate resource use for blood products, operating room time, and medications; these estimations accounted for 21.3% of services overall. A database can be constructed that allows comparison of standardized resource use and avoids biases due to accounting, geographic, or temporal factors. Clinical data are essential for the creation of such a database. The methods described are particularly useful in studies of the cost-effectiveness of medical technologies.

Accounting↗

PubMed1999

Case management for high-cost Medicare beneficiaries.

We estimated the effects of three Health Care Financing Administration (HCFA)-funded case management demonstrations for high-cost Medicare beneficiaries in the fee-for-service (FFS) sector. Participating beneficiaries were randomly assigned to receive case management plus regular Medicare benefits or regular benefits only. None of the demonstrations improved self-care or health or reduced Medicare spending. Despite the lack of effects of these interventions, case management might be cost-effective if it includes greater involvement of physicians, is more well-defined and goal-oriented, and incorporates financial incentives to generate savings in Medicare costs. Models incorporating these changes should be investigated before abandoning Medicare case management interventions.

Case Management↗

PubMed1998

Differing roles for zinc fingers in DNA recognition: structure of a six-finger transcription factor IIIA complex.

The crystal structure of the six NH2-terminal zinc fingers of Xenopus laevis transcription factor IIIA (TFIIIA) bound with 31 bp of the 5S rRNA gene promoter has been determined at 3.1 A resolution. Individual zinc fingers are positioned differently in the major groove and across the minor groove of DNA to span the entire length of the duplex. These results show how TFIIIA can recognize several separated DNA sequences by using fewer fingers than necessary for continuous winding in the major groove.

Amino Acid Sequence↗

PubMed1998

Unknown peptide sequencing using matrix-assisted laser desorption/ionization and in-source decay.

The results of a study to determine the utility of in-source decay fragmentation of matrix-assisted laser-desorbed ions for obtaining useful sequence information on unknown peptides are presented. Six peptides were purified by high-performance liquid chromatography and submitted as single blind unknowns. The in-source decay fragment ion data were collected on a linear time-of-flight mass spectrometer equipped with delayed extraction. These fragment ion data were manually interpreted on the basis of known fragmentation pathways to determine a proposed sequence. The proposed sequences for three of the unknowns were essentially correct, with a few minor errors. A fourth unknown had significant errors associated with its proposed sequence due to misinterpretation of the fragmentation data. Two unknowns were found to have undergone significant sample degradation prior to analysis, which compromised the results for these samples. An example of the use of protein database searching of a partial peptide sequence to aid in a sequence determination is also presented.

Amino Acid Sequence↗

PubMed1998

Identifying proteins using matrix-assisted laser desorption/ionization in-source fragmentation data combined with database searching.

Metastable ion decay in matrix-assisted laser desorption/ionization (MALDI) has become a routine method for obtaining primary structures of peptides. Significant fragmentation occurs in the MALDI ion source and can be observed via delayed ion extraction TOF-MS. In-source decay (ISD) can provide C- and N-terminal primary sequence data for even moderate-sized peptides (< 5000 Da). The unique cn series fragmentation that occurs in ISD has been exploited to obtain partial C-terminal sequences for proteins as large as human apotransferrin (75 kDa). Two approaches for combining this ISD MALDI-generated partial sequence information with protein database searching techniques are presented. In one approach, cyanogen bromide is used to cleave relatively large peptide fragments from a sample of human apotransferrin. One of the larger cleavage products (6034.84 Da) was isolated by HPLC and subjected to ISD MALDI analysis. An easily identified cn fragment ion series allowed two noncontiguous segments of the peptide's sequence to be determined (about 55% of the total sequence). This partial sequence information was used to search protein and oligonucleotide sequence databases. In addition to uniquely identifying human apotransferrin in a protein sequence database, an example of the use of this ISD MALDI-determined partial sequence information to search expressed sequence tag databases is presented. Such searches have the potential for rapidly identifying new genes that code for target proteins. An alternate approach for obtaining partial sequence information on proteins is also demonstrated that utilizes ISD MALDI fragmentation of the intact protein to generate partial sequence information. This approach is shown to generate about 5-7% of a protein's sequence, usually near the C-terminus of the protein. Examples of the ISD MALDI fragmentation data obtained from intact (reduced) human apotransferrin and intact (nonreduced) bovine serum albumin (66 kDa) proteins are presented.

Animals↗

PubMed1998

Predictors of the cost of liver transplantation.

BACKGROUND: Orthotopic liver transplantation (OLT) is a highly effective but costly therapy for end-stage liver disease. However, there are limited data on the demographic and clinical variables that affect cost. We undertook a preliminary study using multiple regression techniques to analyze factors that influence the cost of OLT. METHODS: Patient and demographic data, including laboratory values and charges for all liver transplantations performed between June 1992 and June 1993 were analyzed (n = 111). Linear regression with standard and log-transformed values was performed by using STATA software (Stata Corporation College Station, TX). Independent variables included in the analyses were age, sex, United Network for Organ Sharing (UNOS) status, primary versus retransplantation, liver-kidney transplantation, and laboratory parameters of both liver (aspartate aminotransferase, AST; alkaline phosphatase; bilirubin; albumin; and prothrombin time) and kidney (blood urea nitrogen, BUN; creatinine) function. An F-to-remove strategy was employed with a significance level set at P = .05. RESULTS: The full model with 12 variables explained 37% of the total variation in charges. When one excludes variables that did not have a significant impact on cost, the remaining significant variables were BUN and UNOS status 1. The final model was Charges (US$) = 3,407 x BUN + 74,474 x status 1 + 102,662. This model accounted for 29% of the total variability with BUN accounting for the vast majority (26%). CONCLUSIONS: Renal function is the most important predictor of cost of OLT (P < .001). UNOS status 1 further increases cost, but other hospitalized patients have similar costs when one controls for other clinical variables. The degree of liver impairment is less important in predicting cost.

Adolescent↗

PubMed1998

Payer status, but not race, affects the cost of liver transplantation.

Prior studies evaluating the impact of race and payer on cost of liver transplantation did not adjust for clinical factors known to increase cost. We analyzed the impact of race and payer on the cost of liver transplantation after controlling for clinical factors. We analyzed data obtained on patient and graft survival, cost, race, age, sex, payer, and United Network for Organ Sharing (UNOS) status from 153 consecutive liver transplants in 130 patients performed at University of North Carolina Hospitals from September 1991 through December 1996. Race was classified as white or nonwhite, and payer status was classified as commercial or Medicare/Medicaid. Multivariate linear regression was used to compare costs, adjusting for age, sex, race, payer, and UNOS status. For the 130 patients, 1-year patient and graft survival rates were 88% and 82%, respectively. There were no significant differences in patient and graft survival or in the unadjusted average cost of liver transplantation by race or payer. After adjusting for demographic and clinical factors, the cost of transplantation was $28,494 more for Medicare/Medicaid recipients compared with the commercial insurance recipients (P = .02). The Medicare/Medicaid group had higher intensive care unit costs compared with the commercial insurance group ($17,807 and $9,359, respectively; P = .03), and a longer length of stay (41 and 31 days, respectively; P = .04). There was no significant difference in cost between whites and nonwhites adjusting for these factors. Medicare or Medicaid patients had a higher cost of transplantation compared with those with commercial insurance. The cost of liver transplantation was similar for whites and nonwhites.

Adolescent↗

PubMed1998

Early detection of melanoma metastases with radioiodinated methylene blue.

Melanin synthesised in melanoma cells presents a unique target to which the treatment can be selectively addressed, provided the pigment is recognised by a suitable drug. Methylene blue (MTB) possesses a high affinity for melanin and, therefore, accumulates preferentially in melanoma cells. Since not directly toxic to the tumour, MTB serves as a carrier for radioisotopes and, once taken up by melanoma cells, acts as a selectively localised source of radiation. Hence, radioderivatives of the compound can be used for both diagnosis and therapy of disseminated melanoma. Eleven patients with confirmed metastatic melanoma and one with a recent local recurrence were studied using radioiodinated (iodine-123 or iodine-131) MTB and a gamma camera. Biopsies of cutaneous lesions were taken to determine directly the compound uptake in tumours. This first clinical investigation concerning the diagnostic potential of radioiodinated MTB in patients with disseminated melanoma confirmed the existence of approximately 80% of internal lesions previously identified by routine methods and, additionally, enabled detection of unknown secondaries in 6 of 12 patients studied. There were no false-positive gamma camera images regardless of whether 123I or 131I was used. 131I proved to be more suitable than 123I for detecting melanoma metastases with radioiodinated MTB. Hazy images of the lesions treated with external beam radiation and/or some drugs suggest that initial radio- and chemotherapy might affect MTB uptake in melanoma metastases and reduce the clarity of the scintigrams obtained from a gamma camera. However, small, untreated internal lesions that cannot be visualised easily with the standard diagnostic methods are revealed with 131I-MTB regardless of their localisation. It is concluded that use of radioiodinated MTB in conjunction with gamma camera or positron emission tomographic imaging might prove to be a useful and accessible tool for the detection of early melanoma dissemination.

Adult↗

PubMed1998

Successful treatment of massive acute thyroid hormone poisoning with iopanoic acid.

We report a toddler with massive thyroid hormone poisoning in whom the addition of iopanoic acid to the treatment regimen (propylthiouracil and propranolol) resulted in a dramatic clinical and biochemical improvement. Iopanoic acid is a safe and effective drug in the treatment of massive thyroid hormone poisoning in children.

Child, Preschool↗

PubMed1998

Bioassay of thyrotropin receptor antibodies with Chinese hamster ovary cells transfected with recombinant human thyrotropin receptor: clinical utility in children and adolescents with Graves disease.

OBJECTIVE: The objective of this study was to compare the clinical utility of a new bioassay for thyrotropin (TSH) receptor antibodies (Abs) with the conventional radioreceptor assay and with measurement of thyroid peroxidase Abs in the diagnosis of Graves disease in childhood. STUDY DESIGN: Serum samples obtained from 22 children and adolescents with Graves disease (19 hyperthyroid, 3 in remission), 13 children and adolescents with chronic lymphocytic thyroiditis, and 17 normal children in a control group were evaluated. RESULTS: TSH receptor Abs were detected by bioassay in 10 (91%) of 11 patients with active Graves disease but in 0 of 2 patients in remission, 0 of 13 normal members of the control group, and 0 of 11 patients with chronic lymphocytic thyroiditis including 1 with thyrotoxicosis. The sensitivity and specificity of TSH receptor Abs detected by radioreceptor assay studied in the same 11 patients and in an additional 11 patients was similar to bioassay. In contrast, thyroid peroxidase Abs were detected in only 12 (71%) of 17 patients with Graves disease but in 11 of 11 patients with chronic lymphocytic thyroiditis and in 0 of 17 members of the control group. CONCLUSION: Bioassay of TSH receptor Abs is both sensitive and specific for the diagnosis of active Graves disease in the young. When cost and simplicity are considered, however, bioassay offers no advantage over radioreceptor assay for initial diagnostic screening. Rather, bioassay for TSH receptor Abs may be useful in thyrotoxic patients who are negative initially in the radioreceptor assay or in treated patients whose clinical picture is discordant with results in the radioreceptor assay.

Adolescent↗

PubMed1998

The relationship between chronic cocaine or alcohol use and blood pressure in black men during uncomplicated tooth extraction.

PURPOSE: The object of this study was to determine whether a history of cocaine or alcohol use is associated with blood pressure changes in patients undergoing an uncomplicated mandibular molar extraction. PATIENTS AND METHODS: The blood pressure (BP) values of middle-aged (30 to 40 years of age) black men with different chronic drug histories were compared during extraction procedures. The four different groups were 1) no-drug control, (n = 10); 2) alcohol (n = 15); 3) "crack" cocaine (n = 9); and 4) cocaine (n = 22). RESULTS: The cocaine group's blood pressures were significantly different compared with the blood pressures within the no-drug and alcohol groups (P < .05). The cocaine group's BPs decreased throughout the procedure, and the BPs of the no-drug and alcohol groups rose during administration of the local anesthetic and extraction, and then fell. The BPs of the crack group were highly variable and not significantly different when compared with other groups. CONCLUSION: There is a paradoxical effect of chronic cocaine use on blood pressure that needs to be considered when treating such patients.

Adult↗

PubMed1998

Death due to thyroid metastases from renal cell carcinoma.

Renal cell carcinoma is a tumour that is well recognized to metastasize widely and to behave in an unpredictable manner. We report a patient with a renal cell carcinoma that metastasized to the thyroid and resulted in death from associated respiratory compromise. The clinical features of cancers metastasizing to the thyroid are discussed and the apparent over-representation of renal cell carcinoma in symptomatic thyroid metastases is highlighted. The uncertainty about whether metastases arise more frequently in pre-existing abnormal thyroid glands is also reviewed.

Carcinoma, Renal Cell↗

PubMed1998

Pseudo-Meigs' syndrome due to broad ligament leiomyoma: a mimic of metastatic ovarian carcinoma.

Pseudo-Meigs' syndrome is a rare complication of benign leiomyomas of the female genital tract. We report a patient with pseudo-Meigs' syndrome due to a large broad ligament leiomyoma, which also caused bilateral reversible hydronephrosis. This unusual combination of pseudo-Meigs' syndrome, broad ligament leiomyoma and hydronephrosis requiring ureteric stenting does not appear to have been reported previously. Features of the syndrome that led to a diagnostic problem, the mimicking of metastatic ovarian carcinoma, are presented. The little that is known of the pathogenesis of the pleural and ascitic fluids is discussed. An elevated level of serum CA 125 antigen is reported, we believe for the first time in association with pseudo-Meigs' syndrome.

Adult↗

PubMed1998

An audit of antiemetic use with CMF chemotherapy.

A two-stage retrospective audit of the efficacy of antiemetics used with intravenous cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2 and 5-fluorouracil 600 mg/m2 (CMF) chemotherapy for breast cancer has been performed in a single centre. The first audit stage examined emesis rates for 21 patients using a policy of metoclopramide and dexamethasone initially and reserving 5-HT3 antagonists for failure of this combination. Because of high failure rates, the policy was changed so that granisetron and dexamethasone were used in all patients. The second audit stage examined the effectiveness of this new policy in 28 patients. Nine of 21 patients (43%) in the first audit group changed from metoclopramide and dexamethasone because of nausea or vomiting. Emesis occurred in 15 out of 66 (23%) cycles of CMF when metoclopramide and dexmethasone were used. Only eight of 43 patients had emesis episodes with granisetron and dexamethasone (19%). Emesis occurred with only 16 of 206 CMF cycles with granisetron and dexamethasone (8%). The granisetron and dexamethasone combination is superior to metoclopramide and dexamethasone in the prophylaxis of CMF-induced nausea and vomiting, although it is more expensive. A reduced dose of granisetron, 1 mg rather than 3 mg, may allow similar control of emesis at reduced cost.

Antiemetics↗

PubMed1998

Plasmablastic lymphoma: a new subcategory of human immunodeficiency virus-related non-Hodgkin's lymphoma.

A patient with human immunodeficiency virus-related non-Hodgkin's lymphoma arising in the oral cavity is reported. The tumour had an unusual immunohistochemical profile that was negative for leucocyte common antigen and the B-cell antigen CD20 but positive for the plasma cell-reactive antibody VS38c. The features of this type of tumour, which has recently been categorized, are presented and discussed.

Adult↗

PubMed1998

Immunolymphoscintigraphy in breast cancer: evaluation using 131I-labeled monoclonal antibody B72.3.

Noninvasive axillary lymph node staging was investigated using [131I]murine monoclonal antibody B72.3 in 16 patients with breast cancer scheduled for axillary dissection. [131I]B72.3 was injected into ipsilateral finger webs or around the breast biopsy. Scintigraphy to 72 h and gamma-counting/immunohistochemistry of nodes were performed. Specific antibody uptake (%ID/g) and the ratio of specific:nonspecific antibody uptake were not significantly different in tumor-positive versus tumor-negative nodes, suggesting that [131I]B72.3 is unsuitable to discriminate axillary node tumor involvement.

Antibodies, Monoclonal↗