Search PubMed⌕ Search

Biomedical subjects

R S Brown

Publications and source records attributed to R S Brown.

At least 55 records · Page 3Linked 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

Variations in dose and dose intensity of adjuvant CMF chemotherapy for breast cancer throughout the UK.

Cyclophosphamide, methotrexate and 5-fluorouracil (CMF) is a commonly prescribed regimen for the adjuvant treatment of early breast cancer in the UK and in other countries with a high incidence of breast carcinoma. A number of variations in dose and scheduling of these drugs have been reported in the literature, with all of these being recognized under the generic term 'CMF'. To investigate the extent of differences in CMF regimens used for the adjuvant treatment of early breast cancer we sent a postal questionnaire to all consultant medical and clinical oncologists in the UK seeking details of their practice. CMF drug doses were then converted into dose intensity parameters for comparison. The results showed a wide variation in the number of CMF schedules (n = 36) and CMF dose intensities (n = 33) used. The potential consequences of such variation and the evidence for and against dose intensity as an important parameter in the adjuvant treatment of early breast cancer are discussed.

Antineoplastic Combined Chemotherapy Protocols↗
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↗
PubMed2000

Recommendations for the outpatient surveillance of renal transplant recipients. American Society of Transplantation.

Many complications after renal transplantation can be prevented if they are detected early. Guidelines have been developed for the prevention of diseases in the general population, but there are no comprehensive guidelines for the prevention of diseases and complications after renal transplantation. Therefore, the Clinical Practice Guidelines Committee of the American Society of Transplantation developed these guidelines to help physicians and other health care workers provide optimal care for renal transplant recipients. The guidelines are also intended to indirectly help patients receive the access to care that they need to ensure long-term allograft survival, by attempting to systematically define what that care encompasses. The guidelines are applicable to all adult and pediatric renal transplant recipients, and they cover the outpatient screening for and prevention of diseases and complications that commonly occur after renal transplantation. They do not cover the diagnosis and treatment of diseases and complications after they become manifest, and they do not cover the pretransplant evaluation of renal transplant candidates. The guidelines are comprehensive, but they do not pretend to cover every aspect of care. As much as possible, the guidelines are evidence-based, and each recommendation has been given a subjective grade to indicate the strength of evidence that supports the recommendation. It is hoped that these guidelines will provide a framework for additional discussion and research that will improve the care of renal transplant recipients.

Ambulatory Care↗
PubMed2000

Evaluation of the early effect of local irradiation on normal rodent bone marrow metabolism using FDG: preclinical PET studies.

UNLABELLED: Our aim was to evaluate the early effect of local irradiation on normal bone marrow glucose metabolism in rodents, assessed by FDG biodistribution measured by tissue excision and gamma counting. METHODS: Sixty-one rats were divided into nine groups (n = 4-11 per group). Eight groups of rats received either local irradiation (10 Gy) or sham irradiation to the right femur on day 0. Irradiation was performed using a 60Co gamma-ray unit under anesthesia. Each group of rats was fasted overnight and then injected with 5.5-7.4 MBq FDG on day 1, 9, 18, or 30 after the local or sham irradiation. A control group of rats that received neither local nor sham irradiation was studied with FDG on day 0. 18F activity in tissue 1 h after injection was measured using a gamma counter. Smear specimens of bone marrow from bilateral femurs were examined by light microscopy. RESULTS: Tracer uptake was relatively stable in marrow from the sham-irradiated rats. By contrast, FDG uptake of the irradiated marrow on day 1 was significantly higher (mean +/- SD, 0.257 +/- 0.036 percentage injected dose [ID] per gram of tissue per kilogram of rat weight [%ID/g/kg]) than that of the sham group on day 1 (0.187 +/- 0.028 %ID/g/kg) and the control group (0.184 +/- 0.009 %ID/g/kg) (P < 0.05). Tracer uptake in the irradiated marrow on day 9 was significantly lower (0.148 +/- 0.023 %ID/g/kg) than that of the sham group on day 9 (0.193 +/- 0.021 %ID/g/kg) and the control group (P < 0.01). In contrast, the nonirradiated contralateral marrow from irradiated rats showed increased FDG uptake on day 18 (0.274 +/- 0.063 %ID/g/kg) that was significantly higher than that of the sham group on day 18 (0.208 +/- 0.030 %ID/g/kg) and the control group (0.183 +/- 0.018 %ID/g/kg) (P < 0.05). The irradiated marrow smear specimens initially revealed increased percentages of neutrophils on day 1 (45% of 500 nucleoid cells examined per slide) compared with that of the sham group (20%), followed by severely decreased overall cellularity on day 9. CONCLUSION: In this experimental system, normal marrow uptake of FDG transiently rose, then fell, and ultimately returned to baseline after external beam irradiation. Knowledge of this biphasic early irradiation effect on normal bone marrow may be important when the efficacy of radiation therapy on bone metastasis is evaluated using FDG PET after irradiation.

Animals↗
PubMed2000

The black and white of dental education in the United States: enrollment and graduation trends.

Data from the American Association of Dental Schools (AADS) and American Dental Association (ADA) were evaluated for trends in dental school enrollment and graduation. In the last 20 years, African-American enrollment has varied from a low of 4.7% (1980-1981) to a high of 6.9% (1988-1989). This figure declined to 5.2% in 1997-1998. African-American graduation percentages in the last 20 years have varied between 3.4% (1979) and 5.4% (1996). The future percentage of graduating African-American dentists is projected to decline. Historically, minority dental education institutions have educated a significant percentage of African Americans and continue to educate approximately 40% of graduating African-American dentists. Strategies to increase recruitment of African Americans include: 1. Greater support for minority primary and secondary education including the establishment of mentoring programs. 2. Dental education outreach programs to minority secondary school and college students. 3. An increase in affirmative action programs. 4. Greater support for minority dental education institutions. 5. Student loan forgiveness programs, which aid recruitment of minority faculty and dental students who either teach or serve minority communities.

Black or African American↗
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↗