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R S Brown

Publications and source records attributed to R S Brown.

At least 19 recordsLinked to original sources
PubMed2000

Cost-effectiveness analysis of transjugular intrahepatic portosystemic shunt (TIPS) versus endoscopic therapy for the prevention of recurrent esophageal variceal bleeding.

For the prevention of recurrent esophageal variceal bleeding, studies show that patients treated with transjugular intrahepatic portosystemic shunt (TIPS) have lower rebleeding rates compared with endoscopic therapy. However, TIPS is associated with higher rates of portosystemic encephalopathy and possibly higher costs. The aim of this study was to conduct a cost-effectiveness analysis comparing TIPS with endoscopic sclerotherapy and endoscopic ligation for the prevention of recurrent esophageal variceal bleeding. Data for rates of rebleeding, death, complications, and crossover from endoscopy to TIPS were obtained from the literature. Costs for procedures and hospitalizations were obtained from two medical centers. Sensitivity analyses were performed varying probabilities of key variables. The patient population consisted of a hypothetical cohort of cirrhotic patients successfully treated for esophageal variceal bleeding with endoscopic sclerotherapy who received prophylactic sclerotherapy, ligation, or TIPS over 1 year. Endoscopic patients would receive propranolol. Mortality was similar for the three groups. The number of bleeds per patient for sclerotherapy, ligation, and TIPS would be 0.39, 0.32, and 0.07, respectively. The total annual costs per patient for sclerotherapy, ligation, and TIPS were $23,459, $23,111, and $26,275, respectively. The incremental cost per bleed prevented for TIPS compared with sclerotherapy and ligation was $8,803 and $12, 660, respectively. The incremental cost per bleed prevented for TIPS compared with sclerotherapy or ligation was sensitive to the cost of TIPS and the TIPS stenosis rate. Ligation had lower costs and lower recurrent bleeding rates than sclerotherapy. Compared with endoscopic therapy, TIPS leads to lower recurrent variceal bleeding rates and it is more cost effective in the short term for the prevention of recurrent esophageal variceal bleeding.

Cost-Benefit Analysis↗
PubMed2000

Developmental regulation of thyrotropin receptor gene expression in the fetal and neonatal rat thyroid: relation to thyroid morphology and to thyroid-specific gene expression.

The TSH receptor plays a pivotal role in thyroid gland function, growth, and differentiation, but little is known about its role or regulation in the fetus and neonate. To explore these questions, we systematically evaluated TSH receptor gene expression at the level of messenger RNA (mRNA) in thyroid glands obtained from rat fetuses and neonates, from 14 days gestation to day 5 of postnatal life. Results were compared with histological evidence of differentiation and to thyroid-specific gene expression. Northern blot and RT-PCR analysis revealed that TSH mRNA was first detected at low levels on fetal day 15, but it increased 3- to 15-fold on fetal days 17-18. Up-regulation of TSH receptor mRNA on fetal day 17-18 was accompanied by the first appearance of colloid formation and of follicular development on morphological examination. It was also paralleled by increased expression of the thyroid-specific genes thyroglobulin (Tg) and thyroid peroxidase. Unexpectedly, TSH mRNA abundance was 2- to 3-fold higher in pregnant dams than in nonpregnant adult females or adult males. In view of the 8-day lapse between the first appearance of the thyroid diverticulum and up-regulation of TSH receptor gene expression, we conclude that pituitary TSH, acting through its receptor, plays an important role in terminal thyroid maturation, but it is not involved earlier in gestation. Similarly, these data support previous evidence that the weak thyrotropic activity of human CG could not be of significance in early fetal thyroid gland development. The increased TSH receptor mRNA on fetal day 17-18 may be attributable to up-regulation by TSH, which is first secreted into the fetal circulation at this time. The significance of the increased TSH receptor expression during pregnancy remains to be explored.

Animals↗
PubMed1999

Resource utilization in liver transplantation: effects of patient characteristics and clinical practice. NIDDK Liver Transplantation Database Group.

CONTEXT: Liver transplantation is among the most costly of medical services, yet few studies have addressed the relationship between the resources utilized for this procedure and specific patient characteristics and clinical practices. OBJECTIVE: To assess the association of pretransplant patient characteristics and clinical practices with hospital resource utilization. DESIGN: Prospective cohort of patients who received liver transplants between January 1991 and July 1994. SETTING: University of California, San Francisco; Mayo Clinic, Rochester, Minn; and the University of Nebraska, Omaha. PATIENTS: Seven hundred eleven patients who received single-organ liver transplants, were at least 16 years old, and had nonfulminant liver disease. MAIN OUTCOME MEASURE: Standardized resource utilization derived from a database created by matching all services to a single price list. RESULTS: Higher adjusted resource utilization was associated with donor age of 60 years or older (28% [$53813] greater mean resource utilization; P=.005); recipient age of 60 years or older (17% [$32795]; P=.01); alcoholic liver disease (26% [$49596]; P=.002); Child-Pugh class C (41% [$67 658]; P<.001); care from the intensive care unit at time of transplant (42% [$77833]; P<.001); death in the hospital (35% [$67 076]; P<.001); and having multiple liver transplants during the index hospitalization (154% increase [$474 740 vs $186 726 for 1 transplant]; P<.001). Adjusted length of stay and resource utilization also differed significantly among transplant centers. CONCLUSIONS: Clinical, economic, and ethical dilemmas in liver transplantation are highlighted by these findings. Recipients who were older, had alcoholic liver disease, or were severely ill were the most expensive to treat; this suggests that organ allocation criteria may affect transplant costs. Clinical practices and resource utilization varied considerably among transplant centers; methods to reduce variation in practice patterns, such as clinical guidelines, might lower costs while maintaining quality of care.

Adult↗
PubMed1999

Decision-analysis of transjugular intrahepatic portosystemic shunt versus distal splenorenal shunt for portal hypertension.

Transjugular intrahepatic portosystemic shunt (TIPS) and surgical distal splenorenal shunt (DSRS) are treatments for complications of portal hypertension. TIPS is widely used because it is relatively easy to place. Because TIPS may malfunction over time, it is unclear whether TIPS is superior to DSRS in patients with Child's class A cirrhosis who enjoy a longer survival. This study compared the cost-effectiveness of TIPS to DSRS for portal hypertension in Child's class A cirrhosis. A decision analysis model was used to evaluate the number of procedures, life expectancy, and costs over the first 2 years in patients with Child's class A cirrhosis who underwent a TIPS or DSRS. Patients who received TIPS survived 1.96 years, required 1.7 procedures, and incurred $41,685 in costs. Patients who underwent a DSRS survived 1.86 years, required 1.0 procedure, and incurred $26,951 in costs. The cost-effectiveness of TIPS compared with DSRS was $147,340 per life-year saved. Adjusting the rate of TIPS dysfunction, 1-year survival, or the number of ultrasounds to detect TIPS dysfunction did not change the results. In patients with Child's class A cirrhosis, DSRS is a more cost-effective treatment than TIPS. Until the results of a randomized controlled trial comparing TIPS with DSRS are available, TIPS should be regarded as experimental and prohibitively expensive in Child's class A cirrhosis.

Decision Support Techniques↗
PubMed1999

Uptake of positron emission tomography tracers in experimental bacterial infections: a comparative biodistribution study of radiolabeled FDG, thymidine, L-methionine, 67Ga-citrate, and 125I-HSA.

The purpose of this study was to evaluate the localization of positron emission tomography (PET) tracers [2-deoxy-2-fluoro-D-glucose (FDG), thymidine, and L-methionine] in sites of bacterial infection, and to contrast this with that of other tracers. The left calf muscles of rats were infected with a suspension of Escherichia coli and the biodistribution of 18F- or 3H-FDG, 3H-thymidine, L-11C- or 3H-methionine, gallium-67 citrate (67Ga-citrate) and iodine-125 human serum albumin (125I-HSA) was determined in these animals. 3H-FDG uptake in the infectious foci was evaluated by autoradiography of histological sections. Although 18F-FDG, 67Ga-citrate, and 125I-HSA showed comparatively high uptake in the infected muscle [the percentage activity of injected dose (ID) per gram of tissue normalized for rat weight in kilogram (%ID/g)xkg at 2 h postinjection was as follows: 18F-FDG, 0.184+/-0.026 to 0.218+/-0.046; 67Ga-citrate, 0.221+/-0.016; 125I-HSA, 0. 198+/-0.019], the infected muscle to blood ratio was much higher for 18F-FDG than for 67Ga-citrate or 125I-HSA (18F-FDG, 10.31+/-0.76 to 14.89+/-2.26; 67Ga-citrate, 1.24+/-0.67; 125I-HSA, 0.20+/-0.02). The draining reactive lymph nodes also showed higher accumulation of 18F-FDG than of 67Ga-citrate or 125I-HSA. The uptake of 3H-thymidine and L-11C- or 3H-methionine in the infected muscle was lower than that of 18F- or 3H-FDG (at 2 h postinjection, 3H-thymidine = 0. 039+/-0.005 and L-3H-methionine = 0.063+/-0.007 (%ID/g)xkg. Autoradiographs showed that the highest 3H-FDG uptake was seen in the area of inflammatory cell infiltration surrounding the necrotic region. In conclusion, 18F-FDG, which rapidly accumulates in sites of bacterial infection and in reactive lymph nodes with a high target to background ratio, appears to be a promising infection detection agent.

Animals↗
PubMed1999

Papillon-Lefèvre syndrome: neutrophil function in 15 cases fron 4 families in Egypt.

OBJECTIVE: The primary purpose of this study was to investigate the periodontal pathologic cause of Papillon-Lefèvre syndrome by comparing, with respect to neutrophil function, probands with Papillon-Lefèvre syndrome from 4 families in Egypt, unaffected siblings of the probands, and age-matched and gender-matched control subjects. STUDY DESIGN: Family histories and clinical dermal and oral manifestations of Papillon-Lefèvre syndrome were evaluated for 15 affected members of 4 families with the syndrome, 10 siblings of the probands, and 7 age-matched and gender-matched controls. Phagocytic and intracellular killing (lytic activity) of polymorphonuclear neutrophils was evaluated for all subjects according to a modification of the method of Wilkinson; opsonization was evaluated according to a modification of the methods of Cutler et al. Data were analyzed by means of analysis of variance. RESULTS: Family pedigrees were plotted, and consanguinity was noted in 3 of the 4 families with Papillon-Lefèvre syndrome. The means and SDs for phagocytic killing, lytic activity, and opsonization indices were as follows: probands, 4.76+/-1.99, 0.42+/-0.20, and 0.84+/-0.07; unaffected siblings, 10.4+/-1.3, 3.3+/-0.3, and 0.84+/-0.07; controls, 10.8+/-0.8, 3.5+/-0.6, and 0.85+/-0.05. The phagocytic killing and lytic activity indices demonstrated significance between the probands and both siblings and controls (P<.0005), whereas the opsonization index did not demonstrate significance between groups. CONCLUSIONS: Significantly decreased neutrophil function in probands with Papillon-Lefèvre syndrome was demonstrated with respect to neutrophil phagocytotic and lytic activity but not with respect to opsonization. Therefore, specific neutrophil dysfunction appears to be etiologically involved in this disorder.

Adolescent↗
PubMed1999

Complete resolution of angiosarcoma of the scalp with liposomal daunorubicin and radiotherapy.

Angiosarcoma of the head and neck is a rare malignant vascular tumour that predominantly affects elderly men and generally has a poor prognosis. Complete responses to treatment for larger tumours are uncommon. A patient with an extensive tumour that showed a complete response to combination therapy with liposomal daunorubicin and radiotherapy is presented. The rationale for using liposomal chemotherapy agents in the treatment of vascular tumours such as angiosarcoma is discussed.

Aged↗
PubMed1999

Autosomal dominant hypoparathyroidism associated with short stature and premature osteoarthritis.

Familial hypoparathyroidism is an unusual and genetically heterogeneous group of disorders that may be isolated or may be associated with congenital or acquired abnormalities in other organs or glands. We have evaluated a family with a novel syndrome of autosomal dominant hypoparathyroidism, short stature, and premature osteoarthritis. A 74-yr-old female (generation I) presented with hypoparathyroidism, a movement disorder secondary to ectopic calcification of the cerebellum and basal ganglia, and a history of knee and hip replacements for osteoarthritis. Two members of generation II and one member of generation III were also documented with hypoparathyroidism, short stature, and premature osteoarthritis evident as early as 11 yr. Because of the known association between autosomal dominant hypoparathyroidism and activating mutations of the calcium-sensing receptor (CaR) gene, further studies were performed. Sequencing of PCR-amplified genomic DNA revealed a leucine to valine substitution at position 616 in the first transmembrane domain of the CaR, which cosegregated with the disorder. However, this amino acid sequence change did not affect the total accumulation of inositol phosphates as a function of extracellular calcium concentrations in transfected HEK-293 cells. In conclusion, a sequence alteration in the coding region of the CaR gene was identified, but is not conclusively involved in the etiology of this novel syndrome. The cosegregation of hypoparathyroidism, short stature, and osteoarthritis in this kindred does suggest a genetic abnormality involving a common molecular mechanism in parathyroid, bone, and cartilage.

Adolescent↗
PubMed1999

Basonuclin is associated with the ribosomal RNA genes on human keratinocyte mitotic chromosomes.

Basonuclin is a zinc finger protein mainly expressed in keratinocytes of the basal layer of epidermis and the outer root sheath of hair follicles. It is also found in abundance in the germ cells of testis and ovary. In cultured keratinocytes, basonuclin is associated with chromatin in all phases of the cell cycle, including mitosis. By immunocytochemical methods, we demonstrate here that in mitosis basonuclin is associated with the short arms of the acrocentric chromosomes and with other loci on many metaphase chromosomes of human keratinocytes. Using the evolutionarily highly conserved N-terminal pair of zinc fingers in an electrophoresis mobility shift assay, we demonstrate that the DNA target sequences of basonuclin on the acrocentric chromosomes are likely to be within the promoter region of the 45S rRNA gene transcription unit. DNase I footprinting shows that basonuclin zinc fingers interact with the upstream control element of this promoter, which is necessary for the high level of transcription of the rRNA genes. This result suggests that basonuclin may be a tissue-specific transcription factor for the ribosomal RNA genes.

Base Sequence↗
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↗
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↗