Search PubMed⌕ Search

Biomedical subjects

R Day

Publications and source records attributed to R Day.

At least 163 records · Page 9Linked to original sources

An analysis of the cost and revenue of an expanded medical residency.

OBJECTIVE: To analyze the additive costs and revenues resulting from expansion of a medical residency and associated subspecialty programs. METHODS: Direct and indirect costs of the residency program were analyzed as was reimbursement for the costs of the residency. To determine whether expansion of the residency affected cost of care, the authors compared the costs of care on the teaching service and nonteaching services. RESULTS: The number of residents increased from 18 medical resident and subspecialty fellows in the 1988 academic year to 36 medical residents and 12 subspecialty fellows in the 1991 academic year. Total measured costs increased by $2,036,570 to $3,911,196. Reimbursement increased to $5,319,117, of which $2,290,221 was attributed to the increase in the number of residents. Net income from the residency after subtracting costs increased by $815,714 to a total of $1,407,971, excluding any higher costs at the authors' hospital that were an indirect result of the teaching program. Costs for the same diagnosis-related groups (DRGs) were not significantly different on the teaching and nonteaching services. CONCLUSIONS: Expanding the medical residency increased the net income available to offset the higher costs per DRG at the hospital. These costs did not increase in proportion to the increase in resident numbers. Increased revenue came primarily from Medicare indirect cost reimbursement. A reduction in this rate from 7.7% to less than 4.1% would have resulted in a net loss for medical education costs. Present reimbursement policy is not aligned with actual costs or public policy goals. This may have undesired effects both now and in the future.

Costs and Cost Analysis↗

Processing, release and metabolism of cholecystokinin in SK-N-MCIXC cells.

The human cholinergic neuroepithelioma cell line SK-N-MCIXC, which expresses high levels of cholecystokinin (CCK) mRNA and secretes intact CCK into the media, was used to examine CCK processing and metabolism. Our data provide evidence for the existence of specific candidate processing enzymes in SK-N-MCIXC cells which may be involved in processing proCCK in the brain and indicate that SK-N-MCIXC cells provide a model system for studying the regulation of these enzymes. mRNAs for the intracellular processing enzymes, prohormone convertase 1 (PC1), PC2 and furin were present in SK-N-MCIXC cells. PC1 and/or PC2 and/or furin may cleave at the dibasic amino acid pairs Arg-Arg at the C-terminal part of proCCK, and Arg-X-X-Arg at the N-terminal of the CCK-58 sequence in proCCK. The SK-N-MCIXC cell line demonstrated spontaneous and regulated release of CCK and large amounts of CCK-precursors, as measured with region specific radioimmunoassays coupled to high performance liquid chromatography. Storage granules containing glycine-extended CCK were shown in SK-N-MCIXC cells using indirect immunofluorescence. The extracellularly localized CCK-metabolizing enzyme, neutral endopeptidase 24.11 (EC 3.4.24.11), was present in membranes from both SK-N-MCIXC cells and in intact slices of rat cerebral cortex. The rat cerebral cortex is a brain region known to be rich in CCK. The SK-N-MCIXC cell line provides an in vitro model to study the regulation of CCK synthesis and metabolism in neuronal systems since it contains the storage granules, mRNA, intact peptide, and complement of enzymes necessary for biosynthesis and metabolism of CCK.

Amino Acid Sequence↗

Altered ratios of beta-endorphin:beta-lipotropin released from anterior lobe corticotropes with increased secretory drive. II. Repeated stress.

A number of stimuli including acute footshock and electrically-induced seizures lead to release of beta-endorphin immunoreactivity from the anterior pituitary corticotropes. Gel filtration of this beta-endorphin immunoreactivity indicates that approximately 3-fold more beta-endorphin than beta-lipotropin is released into plasma following these acute stressors. A similar preponderance of beta-endorphin over beta-lipotropin is seen in the media of short-term anterior lobe cell suspensions stimulated with ovine corticotropin-releasing hormone. Previous studies indicated that footshock stress, when administered repeatedly, can increase the biosynthesis of anterior lobe proopiomelanocortin (POMC) as indicated by increased steady state adrenocorticotropin/beta-endorphin content as well as increased POMC mRNA levels and increased POMC biosynthesis and rate of processing as measured by pulse-labeling and pulse-chase studies. The goal of the present studies was to determine whether this increased biosynthetic drive results in an alteration in the end products secreted with repeated stress. Acute footshock in a rat which has received 14 days of chronic footshock releases proportionately more beta-lipotropin than is released in a naive rat. Chronic electrically-induced seizures, which also increase anterior lobe POMC derived peptide stores, lead to a similar shift in the ratio of beta-lipotropin:beta-endorphin released following stress. These data suggest that chronic drive and the subsequent changes in POMC peptide stores may lead to a decrease in the proportion of beta-endorphin size immunoreactivity in the releasable pool of the anterior lobe corticotrope, thus altering the hormonal signal from the anterior lobe corticotrope.

Adrenocorticotropic Hormone↗

Detection of Mycobacterium leprae nasal carriers in populations for which leprosy is endemic.

In order to better understand the role of Mycobacterium leprae nasal carriage in the maintenance of infection reservoirs and transmission of leprosy, we applied a polymerase chain reaction (PCR) that detected a 531-bp fragment of the pra gene of M. leprae on nasal swab specimens collected through a total population survey from individuals living in an area in which leprosy is endemic. Among the total tested population of 1,228 people, 7.8% were found to be PCR positive. PCR positivity was shown to be randomly distributed among the population for which leprosy is endemic. No association was observed between PCR positivity, age, or sex. The observed distribution of PCR positivity among households of different sizes confirmed the expected values, with the exception of two households, each with three people with PCR-positive nasal swab specimens. Although nasal carriage does not necessarily imply infection or excretion of bacilli, the finding of nasal carriage supports the theory of a disseminated occurrence of M. leprae in populations for which leprosy is endemic.

Adolescent↗

Increased expression of endothelin-1 gene in blood vessels of deoxycorticosterone acetate-salt hypertensive rats.

We have recently shown that the content of immunoreactive endothelin-1 is increased in acid extracts from blood vessels of deoxycorticosterone acetate (DOCA)-salt hypertensive rats compared with uninephrectomized control rats. We have also found by immunohistochemistry a significant increase in immunoreactive endothelin-1 in endothelial cells of aorta and mesenteric arteries of DOCA-salt hypertensive rats. In the present study, we investigated preproendothelin-1 gene expression in blood vessels of DOCA-salt hypertensive rats and uninephrectomized control rats. Northern blot analysis using a specific 32P-labeled complementary RNA probe for rat preproendothelin-1 of 319 base pairs revealed a fourfold to fivefold increase in abundance of preproendothelin-1 messenger RNA transcripts in both aorta and mesenteric arteries from DOCA-salt hypertensive rats. Thus, increased immunoreactive endothelin-1 content in blood vessels of DOCA-salt hypertensive rats is secondary to increased preproendothelin-1 gene expression. Exaggerated expression of the preproendothelin-1 gene in mineralocorticoid hypertension may contribute to the maintenance of elevated blood pressure.

Animals↗

Prodynorphin gene expression in the rat intermediate pituitary lobe: gender differences and postpartum regulation.

The distribution of prodynorphin (proDyn) messenger RNA (mRNA) was examined in the rat pituitary using Northern and in situ hybridization analysis. Anterior pituitary gonadotrophs are known to express ProDyn, but the present study demonstrated that proDyn mRNA was also expressed in the intermediate lobe melanotrophs and was colocalized with POMC mRNA. The 2.6-kilobase proDyn transcript observed in the intermediate lobe was shown to be translatable by polysome analysis. Immunohistochemical studies showed dynorphin (Dyn)-like immunoreactivity in all intermediate lobe melanotrophs. Intermediate lobe proDyn gene expression was not regulated by dopamine, in contrast to intermediate lobe POMC mRNA levels, which were increased with haloperidol and decreased with bromocriptine treatment, as expected. A gender difference in ProDyn gene expression was noted, since intermediate lobes of male rats had nearly 2-fold higher proDyn mRNA levels than intermediate lobes of female rats. In contrast, no gender difference of intermediate lobe POMC mRNA levels were detected. ProDyn mRNA levels were up-regulated by 3- to 4-fold in the intermediate lobes of postpartum females as compared to pregnant or nonpregnant female rats, whereas POMC mRNA levels were unchanged, suggesting a role for intermediate lobe ProDyn in the postpartum period of the female rat. Although our results demonstrate proDyn and POMC coexpression in the pituitary intermediate lobe melanotrophs and show a differential regulational control for each gene in this tissue, the present data also strengthen the notion that proDyn is a precursor that has a role to play in reproductive functions.

Animals↗

Insights from pharmacokinetic and pharmacodynamic studies of hydroxychloroquine.

There is wide variability between subjects in the pharmacokinetic parameters of hydroxychloroquine. A range of concentrations is achieved by individuals receiving the same dosage. In a cross-sectional study, mean hydroxychloroquine concentrations in patients with shorter duration and lower intensity of morning stiffness and no rheumatoid factor were significantly higher than in patients with worse disease activity. Variable kinetic parameters, causing variable concentrations, are likely to be contributing to the variability in response to hydroxychloroquine in rheumatic diseases.

Adult↗

Gene expression of prohormone and proprotein convertases in the rat CNS: a comparative in situ hybridization analysis.

Posttranslational processing of proproteins and prohormones is an essential step in the formation of bioactive peptides, which is of particular importance in the nervous system. Following a long search for the enzymes responsible for protein precursor cleavage, a family of Kexin/subtilisin-like convertases known as PC1, PC2, and furin have recently been characterized in mammalian species. Their presence in endocrine and neuroendocrine tissues has been demonstrated. This study examines the mRNA distribution of these convertases in the rat CNS and compares their expression with the previously characterized processing enzymes carboxypeptidase E (CPE) and peptidylglycine alpha-amidating monooxygenase (PAM) using in situ hybridization histochemistry. Furin mRNA was ubiquitously distributed and detected both in neurons and non-neuronal tissue throughout the brain with a higher abundance in ependyma, the circumventricular organs, the islands of Calleja, hippocampus, and allocortex. The cellular localization of PC1 and PC2 was exclusively neuronal with highest concentrations in known neuropeptide-rich brain regions. In general, PC2 was more widely expressed than PC1 in the CNS, although many regional variations were detected. The identification of specific combinations of convertase expression together with CPE and PAM expression in neuropeptide-rich brain regions suggests that specific enzymatic pathways are involved in neuropeptide precursor processing, and that these specific combinations are responsible for region-specific differences of posttranslational processing.

Animals↗

The clinical application of the interferons: a review. NSW Therapeutic Assessment Group.

OBJECTIVES: To review the clinical information on the use of alpha, beta and gamma interferons and to classify the use of alpha interferons in Australia according to approved indications, indications for which there is good supporting evidence and indications where therapy is under investigation; and to estimate the cost of therapy with alpha interferons in New South Wales in 1991. DATA SOURCES: Data were obtained from computerised literature searches. DATA EXTRACTION: A position paper was drafted on behalf of the NSW Therapeutic Assessment Group (NSWTAG). This was circulated to clinicians identified as having a particular interest in the use of the interferons in major NSW teaching hospitals, for comment and amendment where necessary. CONCLUSIONS: Two forms of alpha interferon, interferon alfa-2b and interferon alfa-2a have been approved for use in Australia, interferon alfa-2b for use in the management of hairy cell leukaemia and condylomata acuminata and interferon alfa-2a for use in the management of hairy cell leukaemia and human immunodeficiency virus (HIV) related Kaposi's sarcoma. Applications have been lodged for the use of interferon alfa-2b in HIV related Kaposi's sarcoma, cutaneous basal cell carcinoma and hepatitis B and C and for the use of interferon alfa-2a in the management of hepatitis B, cutaneous T-cell lymphoma and metastatic renal cancer. Interferon alfa-n1 is not available in Australia except for use in a clinical trial in patients who are HIV seropositive. The use of the alpha interferons is currently under investigation in a wide variety of other diseases, with the likelihood that other indications will soon be established. However, the alpha interferons are generally not regarded as first line agents. Beta and gamma interferons have been studied less intensively than the alpha interferons, but it is likely that selected applications for their use will also be defined with the passage of time.

Australia↗

Immunological effects of treatment with sequential administration of recombinant interferon gamma and alpha in patients with metastatic renal cell carcinoma during a phase I trial.

Many anticancer mechanisms of the interferons have been proposed but none have been associated with clinical response to date. The biological activities of the interferons in vivo have included effects upon the natural killer cell, T- and B-lymphocytes, and macrophages. This report details a prospective study of the immunological effects on peripheral blood mononuclear cells of sequentially administered recombinant (r) interferon (IFN) gamma and rIFN alpha in 28 patients with metastatic renal cell carcinoma. Natural killer cell activity, T-cell phenotype (CD4, CD8, CD56, CD16, CD4/HLA-DR, CD8/HLA-DR, CD56/HLA-DR) and 2',5'-oligoadenylate synthetase were measured prior to therapy, during therapy, and following completion of treatment. Statistical analysis of all parameters was performed for the entire group, by individual patient, by dosage, by time, and by clinical response. An overall significant depression in natural killer cell activity and in the percentage of circulating CD56, CD16, and CD8+ cells were noted. Significant increases in 2',5'-oligoadenylate synthetase and in the percentage of circulating CD4 cells were also noted. Although an association between the magnitude of change in percentage of CD16+ cells and 2',5'-oligoadenylate synthetase and dosage of rIFN gamma and rIFN alpha, respectively, was observed, optimal biological dose of this sequence of rIFNs could not be determined due to the limited number of patients. A decrease in the percentage of circulating CD8+ cells was observed among patients with objective clinical response (partial and complete). Sequentially administered rIFN gamma and rIFN alpha can modulate immunological parameters in vivo in patients with metastatic renal cell carcinoma. A fall in percentage of circulating CD8+ cell is associated with response and suggests that this sequence of rIFN alpha and rIFN gamma might influence T-cell mediated antitumor activity.

2',5'-Oligoadenylate Synthetase↗

Calculation of lytic units for the expression of cell-mediated cytotoxicity.

Over the past 10 years, the lytic unit has become the most common means by which activity is expressed in cell-mediated cytotoxicity assays. The strengths and weaknesses of the lytic unit as a summary of cytotoxicity are discussed, and computational methods reviewed. The fundamental "assumption of proportional effect" which is implicit in the interpretation of lytic units is described and empirically tested. Based on extensive data from the assay of human natural killer (NK) activity against K562 targets, simplified computational methods are recommended. The proposed methods are easily explained, may be made robust to occasional erratic data, and permit a reasonable interpretation of lytic units even when the assumption of proportional effect breaks down.

Cytotoxicity Tests, Immunologic↗

A comparative ecological study of selected cancers in Kanawha County, West Virginia.

This study compares mortality rates for selected causes of death in Kanawha County, West Virginia, to rates reported in a number of geographically defined populations for 1950-1984. Specific conditions selected for study included cancers of the biliary passages and liver, the bladder and other urinary organs, and the central nervous system (CNS), as well as leukemia and aleukemia, lymphosarcoma and reticulosarcoma, Hodgkin's disease, and cancer of all other lymphopoietic tissue. The analysis made use of several techniques for the investigation of ecological data, including the modeling of rates using Poission regression. The primary findings of this study concern two subgroups of cancers of the lymphatic and hematopoietic tissue: (1) leukemia and aleukemia, and (2) lymphosarcoma and reticulosarcoma. For both subgroups of cancers, white male residents of Kanawha County show evidence of significantly elevated mortality rates over the 35-year period of this study.

Adult↗

The cDNA sequence of the human pro-hormone and pro-protein convertase PC1.

Using a probe consisting of the full-length cDNA sequence of the mouse pro-hormone convertase PC1 (mPC1), we isolated from a lambda gt10 human pituitary cDNA library a number of contiguous clones, of which composite sequence of 3.3-kb defined the complete coding sequence of human PC1 (hPC1). The cDNA sequence of hPC1 encodes a protein containing 753 amino acids and potentially two N-glycosylation sites, one carboxy-terminal amidation site, a cAMP-dependent protein kinase Ser phosphorylation site, a tyrosine kinase phosphorylation site, and an ArgGlyAsp (RGD) sequence. Like mPC1, the carboxy-terminal sequence of hPC1 exhibits an amphipathic domain potentially involved in membrane association. The coding region of hPC1 exhibits an overall 92.6% protein sequence identity to the mouse mPC1 sequence, with the highest homology (98%) found in the catalytic segment of the molecule (residues 84-399). Whereas Northern blot analysis of tissues obtained from mouse, rat and porcine demonstrated the presence of two mRNAs of 3 kb and 5 kb, Northern blots of human tissues and cells demonstrated the presence of a dominant transcript of 6.2 kb and the presence of smaller transcripts in some tissues. The major site of production of hPC1 seems to be the pituitary and brain, although detection was also possible in pancreas and heart.

Amino Acid Sequence↗