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Biomedical subjects

S Moore

Publications and source records attributed to S Moore.

At least 55 records · Page 3Linked to original sources

Renal dysfunction does not alter the pharmacokinetics or LDL-cholesterol reduction of atorvastatin.

The objective of this study was to determine the effects of renal dysfunction on the steady-state pharmacokinetics and pharmacodynamics of atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. Nineteen subjects with calculated creatinine clearances ranging from 13 mL/min to 143 mL/min were administered 10 mg atorvastatin daily for 2 weeks. Pharmacokinetic parameters and lipid responses were analyzed by regression on calculated creatinine clearance. Correlations between steady-state atorvastatin pharmacokinetic or pharmacodynamic parameters and creatinine clearance were weak and, in general, did not achieve statistical significance. Although the elimination rate constant, lambda z (0.579), was significantly correlated with creatinine clearance, neither maximum plasma concentration (Cmax, -0.361) nor oral clearance (Cl/F, 0.306) were; thus, steady-state exposure is not altered. Renal impairment has no significant effect on pharmacodynamics and pharmacokinetics of atorvastatin.

Adult

Surgical treatment for thyroid cancer.

Thyroidectomy procedures are the mainstay treatment for thyroid cancer and are safe and effective when they are performed by experienced surgeons. Preoperative evaluation of patients with suspected thyroid cancer consists of ultrasonography, radioisotope scanning, and computed tomography scans. Postoperative complications of thyroidectomy procedures include hemorrhage, edema of the glottis, muscle rigidity and spasm (ie, tetany), acute thyrotoxicosis, and damage to the laryngeal nerve. Most surgical patients are discharged home within three days after surgery, and many patients require lifelong thyroid hormone replacement to prevent hypothyroidism.

Carcinoma, Papillary

External alkalinization decreases intracellular Ca++ and spontaneous contractions in pregnant rat myometrium.

OBJECTIVES: As plasma pH rises during pregnancy, the effect of raising external pH on spontaneous contractions in pregnant rat myometrium was investigated to test the hypothesis that elevated external pH depresses contraction. STUDY DESIGN: Strips of longitudinal myometrium were loaded with SNARF (seminaphthorhodafluor) or Indo-1 for simultaneous intracellular pH or Ca++ and force measurements. Results were obtained from a minimum of five animals in each group, and significant differences were tested for by paired Student t tests. RESULTS: Raising the external pH significantly reduced spontaneous force and calcium transient in the pregnant uterus. Raising the external pH led to a slow rise in intracellular pH, but this could not account for the functional effect. K+ rubidium 86-labeled efflux rates were unaffected by external pH, suggesting no hyperpolarization. The Ca++ channel agonist Bay K8644 (5 mumol/L) restored contractions abolished by raised external pH. CONCLUSIONS: Raised external pH reduces spontaneous contractions in the pregnant rat uterus, probably by an external effect on Ca++ entry. This effect may contribute to uterine quiescence before term.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy

Expression of syndecan-1 in rabbit neointima following de-endothelialization by a balloon catheter.

Enrichment of proteoglycans is prominent in early atherogenesis, contributing not only to SMC migration and proliferation, but also to low density lipoprotein retention. A family of integral cell membrane proteoglycans termed syndecans has recently been recognized. Among syndecans, syndecan-1, the first isolated member, has received most research attention. In this study, we examined the expression of syndecan-1 in rabbit aorta and aortic neointima, developed in response to a balloon catheter-induced de-endothelialization. The tissues were processed for Northern blot analysis, in situ hybridization, immunohistochemical staining and immunoblotting. Our results indicate that in normal aorta, the signal for syndecan-1 is weak. However, arterial injury induces syndecan-1 expression at both mRNA and protein levels. The presence of syndecan-1 in the neointimal tissue is persistent, prominent even at the 12th week after injury. Syndecan positive cells are distributed in the whole layer of the neointima, but are not visible in the underlying media. The presence of syndecan-1 in arterial neointima suggests a novel means of mediating interactions between neointimal cells and various agents, including extracellular matrix components, growth factors and lipoproteins.

Animals

Home health nurses: stress, self-esteem, social intimacy, and job satisfaction.

A survey of 253 home health care nurses' perceptions of work-related stress, self-esteem, social intimacy, and job satisfaction found that stress has a negative correlation with self-esteem, social intimacy, and job satisfaction. A positive correlation, however, was found between self-esteem and social intimacy and job satisfaction. Health system administrators, owners, and directors had significantly higher levels of self-esteem, nurses with 5 years or more in their home health nursing position had significantly higher levels of self-esteem. The survey found that nurses with less than a baccalaureate degree possessed significantly lower levels of sociability than those with a graduate or baccalaureate degree. Administrators and managers scored significantly higher on sociability than head nurses.

Adult

Peripheral blood is a source of BCR-ABL-negative pre-progenitors in early chronic phase chronic myeloid leukemia.

Manipulation of autologous bone marrow cells (BM) for transplantation in chronic myeloid leukemia (CML) to enrich for normal cells is a novel approach that may improve survival for patients not suitable for allogeneic transplantation. Limitations of this technique include the reported low frequency of normal stem cells in CML and the difficulties in obtaining sufficient BM for manipulation. To address these problems we compared the apheresis product with the diagnostic bone marrow at diagnosis as a source of primitive BCR/ABL-negative progenitors. We analyzed the CD34+ HLA-DR- and CD34+CD38(-) populations in five CML patients to evaluate the frequency of BCR-ABL-negative progenitors and pre-progenitors in these populations. Progenitor analysis was performed by RT-PCR of individual hemopoietic colonies from a standard CFU-GM assay. Analysis of pre-progenitors involved RT-PCR of secondary colonies derived from a stroma-free pre-CFU assay. Our results show variable levels of BCR-ABL-negative progenitors in the 34+DR- population but very low levels of BCR-ABL-negative progenitors in the 34+38- population in blood. Analysis of pre-progenitors from the 34+DR- fraction of peripheral blood (PB) and BM showed 80-100% and 85-100% of colonies were BCR-ABL negative at days 14 and 28, respectively. Analysis of pre-progenitors from the 34+38- fraction of PB and BM showed 23-100% and 42-100% of colonies were BCR-ABL negative at days 14 and 28, respectively. In summary, pre-progenitors from the 34+DR- and 34+38- populations are predominantly BCR-ABL negative in both marrow and blood at diagnosis. Apheresis product collected at diagnosis is a more abundant sources of BCR-ABL-negative pre-progenitors than BM. Thus, apheresis product could potentially be utilized as a source of BCR-ABL-negative stem cells in CML.

ADP-ribosyl Cyclase

Injury-induced alterations in newly synthesized sulphated proteoglycans from rabbit arterial neointima covered by regenerated endothelium.

Proteoglycan (PG) synthesis is a highly regulated, dynamic process that is known to be altered during atherogenesis. Endothelial injury, which may be the primary event in atherosclerosis, has been reported to stimulate PG synthesis and accumulation in the arterial extracellular matrix. The objective of this investigation was to study injury-induced alterations in PG synthesis and accumulation in the neointima, developed in response to a selective balloon catheter de-endothelialization of aortas of normocholesterolaemic rabbits. One group of rabbit aortas was incubated with 35S-Na2SO4 for 8 h, to study in vitro the de novo synthesis of sulphated PG. Another group of rabbit aortas was used to study PG accumulated in aortic neointima vs. PG present in intima-media of normal aortas. Newly synthesized sulphated PG was characterized by light microscopic radioautography and size exclusion chromatography. Purified intimal-medial PG extracts from unlabelled aortas were analysed for protein and glycosaminoglycan (GAG) content and GAG distribution pattern. Results from this study revealed that the neointima of injured aortas synthesized sulphated PG at a significantly higher concentration than the intima of normal aortas. Size exclusion chromatography revealed that neointima synthesized higher molecular weight PG, and in a higher proportion, than its counterpart PG from normal aortas. PG accumulated in neointima of injured aortas showed a significantly altered GAG distribution pattern. These data confirm that neointima developed in response to injury synthesizes and accumulates PG which is altered compared to PG present in the intima-media of normal aorta.

Animals

Microsatellite evolution--a reciprocal study of repeat lengths at homologous loci in cattle and sheep.

The application of microsatellites in evolutionary studies requires an understanding of the patterns governing their evolution in different species. The finding that homologous microsatellite loci are longer, i.e., containing more repeat units, in human and in other primates has been taken as evidence for directional microsatellite evolution and for a difference in the rate of evolution between species. However, it has been argued that this finding is an inevitable consequence of biased selection of longer-than-average microsatellites in human, because cloning procedures are adopted to generate polymorphic and, hence, long markers. As a test of this hypothesis, we conducted a reciprocal comparison of the lengths of microsatellite loci in cattle and sheep using markers derived from the bovine genome as well as the ovine genome. In both cases, amplification products were longer in the focal species, and loci were also more polymorphic in the species from which they were originally cloned. The crossing pattern that we found suggests that interspecific length differences detected at homologous microsatellite loci are the result of biased selection of loci associated with cloning procedures. Hence, comparisons of microsatellite evolution between species are flawed unless they are based on reciprocal analyses or on genuinely random selection of loci with respect to repeat length.

Animals

Prospective study of how students' humanism and psychosocial beliefs relate to specialty matching.

PURPOSE: To determine whether students who match to different specialties are different in their humanistic behaviors and attitudes about the psychosocial aspects of medicine. METHOD: From May 1992 to February 1995 data were collected from 405 students at the Baylor College of Medicine who participated in a required six-week family medicine clerkship. Two instruments were used to collect data: the Humanism Scale and the Physician Belief Scale. The students' humanism was rated by standardized patients (SPs) during the clerkship's objective structured clinical examination; the SPs used an abbreviated scale, consisting of eight items rated on a seven-point scale. The Physician Belief Scale, consisting of 32 items rated on a five-point scale, measures beliefs about the psychosocial aspects of patient care; it was completed by each student prior to the beginning of the clerkship. Specialty match data were based on National Resident Matching Program results at graduation. For statistical analysis, specialties were divided into four groups: primary care, medical, surgical, and support. RESULTS: The students who matched to primary care specialties had significantly higher mean humanism scores than did the students who matched to support specialties. Also, the students who matched to primary care specialties had significantly higher belief-scale scores than did the students who matched to surgery or support specialties. CONCLUSION: The differences between the students matching to various specialties found in this study were only partly consistent with the differences found in another study of resident physicians in the same specialties. The postgraduate residency experience may thus be an important factor accounting for this difference between students and physicians.

Career Choice

Isoprostanes: free radical-generated prostaglandins with constrictor effects on cerebral arterioles.

BACKGROUND AND PURPOSE: Isoprostanes are generated by cyclooxygenase-independent free radical attack of arachidonic acid and are potent constrictors of the peripheral vasculature. Traumatic brain injury stimulates oxygen radical production and is associated with cerebral blood flow reduction. However, no specific vasoconstrictor has been identified as the cause of posttraumatic blood flow reduction. The purpose of this study was to determine whether isoprostanes constrict cerebral arterioles. METHODS: The effects of 10(-9) to 10(-5) mol/L 8-iso-prostaglandin F2 alpha (8-iso-PGF2 alpha), 8-iso-prostaglandin E2 (8-iso-PGE2), and prostaglandin F2 alpha (PGF2 alpha) on pial arteriolar diameter were measured in anesthetized rats using a closed cranial window and in vivo microscopy. RESULTS: All prostanoids produced vasoconstriction. Of these, 8-iso-PGF2 alpha produced the greatest vasoconstriction (34% +/- 2), followed by 8-iso-PGE2 (25% +/- 4) and PGF2 alpha (20% +/- 2). After six cerebrospinal fluid washouts of the cranial window, both 8-iso-PGF2 alpha- and 8-iso-PGE2-treated vessels remained slightly constricted, whereas the PGF2 alpha-treated vessels returned to control diameter. Coapplication of the semiselective thromboxane A2/prostaglandin H2 receptor antagonist SQ29548 completely blocked the vasoconstriction induced by 8-iso-PGF2 alpha and 8-iso-PGE2. CONCLUSIONS: Isoprostanes are potent constrictors of cerebral arterioles and appear to act at a receptor that is similar to the thromboxane A2/prostaglandin H2 receptor. Isoprostanes may play a role in the reduction of cerebral blood flow that occurs after brain injury and subsequent oxygen radical production.

Animals

Cognitive test performance and background music.

This study examined the effects of background music on test performance. In a repeated-measures design 30 undergraduates completed two cognitive tests, one in silence and the other with background music. Analysis suggested that music facilitated cognitive performance compared with the control condition of no music: more questions were completed and more answers were correct. There was no difference in heart rate under the two conditions. The improved performance under the music condition might be directly related to the type of music used.

Acoustic Stimulation

Synthesis of tissue inhibitor of metalloproteinase-1 (TIMP-1) in rabbit aortic neointima after selective de-endothelialization.

Altered TIMP-1 synthesis in the arterial wall may be important for the balance between metalloproteinases and their inhibitors, and thus contribute to dysregulated extracellular matrix metabolism in atherosclerotic lesions. To examine this, we cloned the rabbit TIMP-1 gene from aortic neointima, developed in response to a balloon-catheter induced de-endothelialization. The apparent homology of cDNA with TIMP-1 genes from several sources suggested that it is a rabbit form of TIMP-1. We examined the recombinant rabbit TIMP-1 expression in Escherichia coli using the pTrxFus expression system and the synthesis of the resulting soluble protein was confirmed by immunostaining with anti-TIMP-1. The TIMP-1 concentration in normal and de-endothelialized rabbit aortas was compared using Northern blot, Western blot and mRNA in situ hybridization techniques. We observed a significant increase of TIMP-1 expression in neointimal SMCs at both nucleic acid and protein levels, suggesting a role of TIMP-1 in injury-induced atherogenesis.

Amino Acid Sequence

Differential increases in rat retinal ganglion cell size with various methods of optic nerve lesion.

Optic nerve injury is a well established paradigm for studying a variety of neuronal responses, although the actual method of nerve severance is rarely taken into account. This study assessed changes to ganglion cell size in three different methods of optic nerve lesions. Adult rats underwent either one of two types of mechanical nerve crush, or an axotomy. Ganglion cells were visualised by retrograde labelling from the optic nerve with 4Di-10ASP, and soma size measured. Two weeks after lesion, mean soma size was increased in all groups. However, at 4 weeks, the crush groups continued to show an increase (60.5% larger than normal), while the mean cell size in the axotomy group was almost at normal levels (0.2% smaller than normal). This study supports the hypothesis that axotomy, and not simple crush, deprives ganglion cells of substances beneficial to cell survival.

Animals

The expression and characterization of five recombinant murine alpha 1-protease inhibitor proteins.

The Mus musculus alpha 1-protease inhibitor gene cluster encodes five highly related proteins. The most significant amino acid polymorphisms lie within the reactive-site loop which is important in determining serpin substrate specificity. All five genes are transcribed in M. musculus adult liver and presumably secreted into plasma. In an attempt to characterize their protein products all five cDNAs were expressed in recombinant mammalian cells and the protease inhibition activity of each determined. Only two of the proteins were efficient inhibitors of neutrophil elastase, the major physiological target of the sole human alpha 1-protease inhibitor (antitrypsin). Four of the proteins were active against chymotrypsin, while no substrate could be identified for the fifth.

Amino Acid Sequence

Surgical treatment of patients with open tibial fractures.

Open tibial fractures are true surgical emergencies because of the risk of extensive infection to bone and devitalized soft tissue. The most serious consequence of open tibial fractures is osteomyelitis, which usually can be prevented by prompt surgical intervention within six to eight hours after injuries occur. Open tibial fractures often are the result of trauma from motor vehicle collisions, farm accidents, falls from heights, or gunshot wounds. Initial management of patients with multiple trauma injuries focuses on their life-threatening injuries before or during orthopedic surgical intervention for open tibial fractures. Orthopedic surgeons often work in collaboration with general, vascular, and plastic surgeons and perform multiple surgical procedures (eg, fasciotomy procedures for compartment syndromes, irrigation and debridement of wounds, application of external fixation devices, placement of intramedullary nails, possible limb amputations). The type and extent of open tibial fractures and soft tissue injuries determine the best treatment options for patients. Perioperative nurses should help patients focus on treatment choices for their open tibial fractures that ensure optimal surgical outcomes and maintain their quality of life.

Accidents

Colonization with antibiotic-resistant Streptococcus pneumoniae in children with sickle cell disease.

OBJECTIVE: Because of susceptibility to severe pneumococcal infection, children with sickle cell disease (SCD) routinely receive penicillin prophylaxis. Increasing rates of penicillin resistance have been reported throughout the world. Our objective was to assess the prevalence of nasopharyngeal colonization with Streptococcus pneumoniae and to assess the antimicrobial susceptibility of the organisms in children with SCD. STUDY DESIGN: Nasopharyngeal cultures for S. pneumoniae were obtained from all children with SCD attending clinics in a statewide university-based network. Background colonization rates were determined in children attending day care centers in some of the same locations. All recovered S. pneumoniae organisms were tested for susceptibility to penicillin, and all resistant strains were examined for susceptibility to other antibiotics. RESULTS: Overall nasopharyngeal pneumococcal colonization rates among children with SCD were 12%. Colonization was associated with age less than 2 years (p <0.001) and day care attendance for more than 20 hr/wk (p = 0.00005). More than half of these strains (62%) were resistant to penicillin, 33% having intermediate resistance (minimal inhibitory concentration 0.06 to 1 microgram/ml) and 29%, high level resistance (minimal inhibitory concentration > or = 2.0 microgram/ml). Penicillin resistance was associated with penicillin prophylaxis (p <0.01). Many of these organisms were also resistant to other classes of antibiotics. CONCLUSIONS: Although penicillin prophylaxis and pneumococcal vaccine for patients with SCD have reduced overall nasopharyngeal colonization and disease caused by S. pneumoniae (p <0.001), a higher percentage of colonizing strains are now resistant both to penicillin and to other antimicrobial agents (p <0.01). Newer strategies for preventing disease and early management of suspected pneumococcal infection in these children must be developed.

Anemia, Sickle Cell