Search PubMed⌕ Search

Biomedical subjects

R E Smith

Publications and source records attributed to R E Smith.

At least 91 records · Page 5Linked to original sources
PubMed1997

Presumed multifocal cryptococcol choroidopathy prior to specific systemic manifestation.

PURPOSE: Disseminated cryptococcosis is a major cause of morbidity and mortality in immunocompromised individuals, especially those with the acquired immunodeficiency syndrome (AIDS). Early diagnosis and treatment greatly improves the outcome, so clinical clues that lead to prompt diagnosis are important. METHODS: Three patients with AIDS in whom multifocal choroiditis and choroidal lesions were the initial signs of disseminated cryptococcosis were treated with systemic amphotericin B and flucytosine. All of the patients had a systemic work-up that included evaluation of the cerebral spinal fluid (CSF). RESULTS: All three patients who were seen with the choroidal lesions as the presenting sign were noted to have either positive titers for cryptococcus or cultures that grew cryptococcus in the CSF. The choroidal lesions are presumed to be due to cryptococcus as no histopathologic or microscopic studies were available for ocular tissues. The choroidal lesions started to resolve one to three months after systemic treatment with amphotericin B and flucytosine. CONCLUSION: Primary choroidal lesions in patients with AIDS may herald severe systemic disseminated disease. Funduscopic examination, however, may detect disseminated cryptococcal disease before other overt clinical manifestations, thereby allowing prompt institution of effective therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Facilitating and debilitating trait anxiety, situational anxiety, and coping with an anticipated stressor: a process analysis.

Participants completed anxiety and coping diaries during 10 periods that began 7 days before an academic stressor and continued through the evening after the stressor. Profile analysis was used to examine the anxiety and coping processes in relation to 2 trait anxiety grouping variables: debilitating and facilitating test anxiety (D-TA and F-TA). Anxiety and coping changed over time, and high and low levels of D-TA and F-TA were associated with different daily patterns of anxiety and coping. Participants with a debilitative, as opposed to facilitative, trait anxiety style had lower examination scores, higher anxiety, and less problem-solving coping. Covarying F-TA, high D-TA was associated with a pattern of higher levels of tension, worry, distraction, and avoidant coping, as well as lower levels of proactive coping. Covarying D-TA, high F-TA was associated with higher levels of tension (but not worry or distraction), support seeking, proactive and problem-solving coping.

Adaptation, Psychological↗
PubMed1997

Aging and prospective memory: the influence of increased task demands at encoding and retrieval.

A feature of prospective memory tasks is that they tend to be embedded into other background activities. Two experiments examined how the demands of these background activities affect age differences in prospective memory. The first experiment showed that increasing the demands of the background activities (by adding a digit-monitoring task) significantly reduced prospective memory performance. Planned comparisons revealed that age differences in prospective memory were reliable only in the more demanding background condition. The second experiment revealed significant prospective memory declines when the demands were selectively increased at encoding for both younger and older adults. When the demands were selectively increased at retrieval, older adults were particularly affected. The authors propose a model that relies on both automatic retrieval processes and working memory resources to explain prospective memory remembering.

Adult↗
PubMed1997

The INR: a perspective.

The use of oral anticoagulants to treat and prevent thromboembolic disease has been a major medical development and has largely been made practicable by the introduction of the prothrombin time as a method for monitoring patients during therapy. Unfortunately, despite many years of application, the administration of oral anticoagulants is still fraught with complications. This has been partly a consequence of the absence of a uniform method of performing and comparing prothrombin times from one laboratory to another. One attempt to solve this problem has been the introduction of the International Sensitivity Index (ISI) and the International Normalized Ratio (INR) as applied to the prothrombin time. The objectives of this article are to (1) explain the need for and development of the INR, (2) discuss shortcomings of the INR and common misinterpretations, and (3) present easy ways to correct for the identified shortcomings.

Administration, Oral↗
PubMed1997

Determining optimal atrial sensitivity settings for single lead VDD pacing: the importance of the P wave histogram.

In order to provide atrioventricular synchrony, VDD pacing systems require reliable atrial sensing. Variations in atrial signals with exercise and daily activities may lead to undersensing, with loss of physiological pacing. The aim of this study was to determine, for a single lead VDD pacing system, the maximal variation in atrial signals in order to facilitate optimal programming of atrial sensitivity. Fifteen patients underwent implantation of a Vitatron Saphir VDD pacemaker with a Vitatron Brilliant electrode. At a mean (+/-SD) follow-up of 67.3 +/- 38.8 days, resting P wave amplitude was compared with the P wave amplitude histogram obtained from the pacemaker, which recorded atrial signals over the preceding 30 days. Resting P wave amplitude was also compared with P wave amplitudes during variations in posture, respiration, and during exercise. P wave amplitude showed great variation with changes in posture and respiration, but there was no consistent increase or reduction. During exercise, the mean P wave amplitude fell by 36.6% +/- 31.3% compared with the resting value (P < 0.05). During daily activities, 22.6% of P wave amplitudes recorded on the P wave histogram were < 0.5 mV. The smallest P wave amplitudes were detected by the P wave histogram in 11 (79%) of 14 patients. These data suggest that atrial sensitivity may need to be programmed higher than that indicated by single readings or exercise. The P wave amplitude histogram is the most reliable indicator of the smallest atrial signal and should be used to optimize atrial sensitivity settings.

Aged↗
PubMed1997

Genetic determinant of rapid-onset B-cell lymphoma by avian leukosis virus.

Infection of 10 day-old chicken embryos with the recombinant avian leukosis virus (ALV) EU-8 induces a high incidence of rapid-onset B-cell lymphoma by insertional activation of the c-myb gene. LR-9, a related ALV with differences from EU-8 in the gag and pol genes, induces rapid-onset lymphoma at only a low incidence. To localize the viral determinant(s) responsible for this biologic difference, we constructed and tested a series of reciprocal chimeras between EU-8 and LR-9 ALVs. The ability to induce rapid-onset lymphoma efficiently was localized to a 925-nucleotide (nt) region of the EU-8 gag gene. Sequence analysis of the region revealed a 42-nt deletion in EU-8 relative to LR-9, as well as some single-nucleotide changes. A mutant virus, delta LR-9, constructed by deleting these 42 nt from LR-9, also induced rapid-onset lymphoma at a high frequency, confirming the biologic significance of this deletion. This deletion removed nt 735 to 776, which lies within a cis-acting RNA element that negatively regulates splicing (NRS). The deletion was shown to cause an increase in splicing efficiency, which may lead to increased production of a truncated myb gene product from an ALV-myb readthrough RNA.

Animals↗
PubMed1997

Induction and role of NO synthase in hypotensive hepatic failure.

Nitric oxide (NO) plays an important role in the physiological and pathophysiological control of the vascular system. NO is synthesized by isoforms of the enzyme NO synthase (NOS). Hepatic failure is complicated by hypotension, low systemic vascular resistance, and resistance to vasoconstrictor drugs. The potential role of NO in these abnormalities was investigated by using in vitro pharmacological interventions on hepatic arteries obtained from both donor and recipient patients at the time of liver transplantation. The presence of NOS mRNA was investigated by reverse transcription polymerase chain reaction (RT-PCR) with primers designed from human endothelial NOS (eNOS) and inducible NOS (iNOS) cDNA sequences. Arteries from patients with hepatic failure had an impaired constrictor response to phenylephrine compared with those of donor arteries. The constrictor effect of phenylephrine was potentiated by NG-monomethyl-L-arginine, an inhibitor of NOS, which had no effect in donor control arteries. RT-PCR identified human eNOS mRNA in donor and recipient arteries and human iNOS mRNA in recipient arteries only. Induction of NOS in the vasculature with subsequent NO-induced vasodilatation may therefore contribute to the hemodynamic abnormalities observed in hepatic failure and potentially in other pathologies associated with endotoxemia. Whether selective inhibitors of iNOS will improve hemodynamic control or clinical outcome in these conditions requires further study.

Acetylcholine↗
PubMed1997

Reevaluation of a weight-based heparin dosing nomogram: is institution-specific modification necessary?

OBJECTIVE: To compare a heparin dosing nomogram using an initial infusion rate of 18 units/kg/h with physician-directed heparin prescribing and with a modified version of the nomogram adjusted for institution-specific data. METHODS: During consecutive phases of this cohort study, patients' intravenous heparin therapies were initiated and adjusted by using one of the following three methods: (1) physician-directed dosing, (2) a body weight-based dosing nomogram with an initial infusion rate of 18 units/kg/h, and (3) a body weight-based dosing nomogram with an initial infusion rate determined by the median dose of heparin (in units/kg/h) required to achieve therapeutic activated partial thromboplastin times (aPTTs) during the first two phases. The time required to achieve therapeutic aPTTs as well as the percentage of initial aPTTs in the therapeutic range were compared for the three phases. RESULTS: The heparin dosing nomogram in which the initial infusion rate was adjusted for our individual institution resulted in a statistically shorter median time until aPTTs were in the therapeutic range than did either the physician-directed dosing or unmodified nomogram groups (6.1 h in the modified nomogram group, 10.5 h in the physician-directed group, 21.5 h in the unmodified nomogram group; p < 0.05 for all differences). Use of the institution-specific nomogram resulted in the greatest percentage of initial aPTTs in the therapeutic range (84% in the 13 units/kg/h nomogram group vs. 47% in the physician-directed group and 18% in the 18 units/kg/h nomogram group; p < 0.05 for all differences). CONCLUSIONS: Use of a heparin dosing nomogram with an initial infusion rate of 18 units/kg/h resulted in prolongation of the time to reach therapeutic aPTTs. By modifying the nomogram for use at an individual institution, we reduced the time to achieve therapeutic range of aPTTs while still reducing the likelihood of excessive anticoagulation of patients.

Aged↗
PubMed1997

Immunohistochemical and molecular characterization of the rat 11 beta-hydroxysteroid dehydrogenase type II enzyme.

Mineralocorticoid action is facilitated by 11 beta-hydroxysteroid dehydrogenase type II (11 beta HSD2), which metabolizes glucocorticoids and allows aldosterone to bind to the nonselective mineralocorticoid receptor. We have recently demonstrated the presence of the 11 beta HSD2 protein in a wide range of human epithelia, suggesting that it is the sole isoform endowing specificity in man. In the present study we have used an immunopurified polyclonal antibody (RAH23) raised against a C-terminal peptide derived from the cloned rat 11 beta HSD2 protein to perform immunohistochemical and molecular analysis in rat tissues. In frozen sections of rat kidney, strong staining was seen with the RAH23 antibody in the distal tubule; weaker staining was observed in the thick ascending loop of Henle and the medullary and papillary collecting ducts. Punctate cortical staining was observed in the fetus at 20 days gestation and in 8-day-old rats, with a noticeable increase in the staining pattern at 16 days of age. The kidney did not attain the adult pattern of staining until 28 days of age. Epithelia of ileum and colon also stained with RAH23, as did excretory ducts of the submandibular gland. Intrahepatic and excretory bile ducts displayed strong immunoreactivity in the epithelial lining. Rat adrenal glands showed evidence of the 11 beta HSD2 antigen in the zona fasciculata and zona reticularis, but not in the zona glomerulosa or medulla. Western blot analysis with the RAH23 antibody revealed strong bands in the kidney, colon, adrenal gland, and submandibular gland at 40 kDa, colinear with the migration of the cloned 11 beta HSD2 enzyme. A band of medium intensity was also seen at this size in the pancreas, whereas a band of moderate intensity was seen in the bile duct, and weaker bands were noticed in the stomach, small intestine, and liver, with a diffuse band at 36-42 kDa in the prostate. Strong bands were seen in the pancreas and prostate at 78 kDa, with weaker signals in the colon, adrenal, stomach, and bile duct. A number of tissues also displayed multiple bands at about 30 kDa. Enzymatic assays on tissue homogenates showed extensive conversion of corticosterone to its 11-dehydro product in an NAD-dependent manner in the submandibular gland, adrenal gland, and kidney, but not in the pancreas or prostate. This study confirms the ubiquitous presence of 11 beta HSD2 in sodium-transporting epithelia, demonstrates the high level of 11 beta HSD2 protein and enzyme activity in the rat adrenal, and suggests a possible role for the enzyme in the biliary system. Further studies are required to determine the relevance of the various molecular species to the activity, latency, and processing of the enzyme.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1997

11 beta-Hydroxysteroid dehydrogenase type II in the human endometrium: localization and activity during the menstrual cycle.

The 11 beta-hydroxysteroid dehydrogenase type II enzyme (11 beta HSD2) is a potent inactivator of glucocorticoids and is present in high amounts in the placental syncytiotrophoblast and sodium-transporting epithelia. Placental 11 beta HSD2 is thought to protect the fetus from high circulating levels of maternal glucocorticoids, whereas the renal enzyme is important in conferring aldosterone specificity on the mineralocorticoid receptor. An isoform of 11 beta HSD (11 beta HSD1) is also present in a wide range of tissues, but usually acts as an oxoreductase, converting the biologically inactive cortisone to cortisol. In the present study we have used an immunopurified antibody to the carboxy-terminus of human 11 beta HSD2 (HUH23) to demonstrate localization of the enzyme in luminal and glandular epithelia of human endometrium. In some specimens staining was uniformly distributed, but in others there was clear evidence of heterogeneity both between and within epithelia. Although 11 beta HSD2 was found mainly in the cytoplasm, some cells showed evidence of nuclear staining only. Western blot analysis showed a band at 41 kDa in endometrium and myometrium, confirming the presence of 11 beta HSD2. Measurement of activity throughout the menstrual cycle showed that mean levels (+/- SEM) of activity were 156 +/- 17 and 6.1 +/- 1.1 pmol product/min.g homogenate protein for 11 beta HSD2 and 11 beta HSD1, respectively. Patients taking combined estrogen/progesterone contraceptives had significantly lower activities of both enzymes (76 +/- 19 and 1.9 +/- 0.4; both P < 0.01) compared with the control group. 11 beta HSD2 activity was significantly higher in the secretory than in the proliferative phase of the cycle in controls (193 +/- 22 vs. 120 +/- 23; P < 0.05). All groups contained outliers with elevated enzyme activities, with some patients displaying 11 beta HSD2 levels comparable to those observed in human kidney (> 1000 pmol/min.g). Further analysis showed that there was a statistically significant correlation (r = 0.43; P < 0.001) between the levels of 11 beta HSD1 and 11 beta HSD2. There was no detectable mineralocorticoid receptor binding in endometrial cytosols prepared from patients with a range of 11 beta HSD2 activities. It remains to be determined whether elevated or suppressed levels of either isoform are associated with fertility or endometrial pathology.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1997

Teaching diagnostic reasoning: using a classroom-as-clinic methodology with videotapes.

OBJECTIVES: The purpose of this study was to examine the effect of a "classroom-as-clinic" format, using videotaped occupational therapy evaluations, on students' diagnostic reasoning skills. In the classroom-as-clinic format, students write a problem list on the basis of preliminary client information before viewing the videotape. METHOD: A post-hoc experimental design was used to compare the accuracy of treatment plan problem lists for two groups of senior occupational therapy students--one group viewed two videotapes of client-therapist interactions without a classroom-as-clinic format (n = 82), and one group viewed the same videotapes within the context of a classroom-as-clinic format (n = 45). Both groups viewed the same two videotapes. Videotape 1 was of a client with a brain stem infarct, and Videotape 2 was of a client with traumatic brain injury. RESULTS: Subjects experiencing a classroom-as-clinic format identified significantly more occupational therapy problems for Videotape 1 than those who did not have preevaluation information. There was no significant difference between the two subject groups in the accuracy of their problem lists for Videotape 2. Only subjects in the non-classroom-as-clinic group showed a significant improvement from Videotape 1 to Videotape 2 in occupational therapy problem identification. CONCLUSION: This study suggests that to be truly effective when used videotapes, the classroom-as-clinic methodology needs to be combined with explicit coaching in problem sensing and problem definition.

Adult↗
PubMed1997

Anterior segment prosthesis development: retinal function following anterior segment removal.

Replacement of the entire anterior segment of the eye is a very ambitious and complex endeavor and it is not known whether the retina remains functional when the anterior structures have been removed. We used routine histo-pathologic evaluation and electroretinographic measurements to determine the structural and functional status of rabbit retinas following surgical removal of the internal anterior structures (iris, ciliary body, and lens) and replacement of the vitreous with silicone oil. In some cases, we were able to record both a scotopic and a photopic electroretinographic response as long as 15 weeks after complete removal of the internal anterior segment structures. Although many hurdles remain and more efficacious surgical techniques and biomaterials need to be developed, our results suggest that, in the rabbit, the retina may continue to function in the absence of critical anterior segment structures.

Animals↗
PubMed1997

Rapid induction of B-cell lymphomas by avian leukosis virus.

Avian leukosis viruses (ALVs) that induce rapid B-cell lymphomas integrate into the c-myb gene and produce an ALV-myb read-through RNA, which is spliced to produce a truncated Myb protein. The genetic determinants of such recombinant ALVs have been mapped to a 42-nt deletion within the gag gene. This deletion increases splicing efficiency since it is located within a negative regulator of splicing. We propose that the deletion leads to increased production of Myb protein by increasing splicing of an ALV-myb pre-mRNA.

Animals↗
PubMed1996

Rat 11 beta-hydroxysteroid dehydrogenase type 2 enzyme is expressed at low levels in the placenta and is modulated by adrenal steroids in the kidney.

The 11 beta-hydroxysteroid dehydrogenase type II enzyme (11 beta HSD2) protects the non-discriminating mineralocorticoid receptor from occupation by glucocorticoids. In man the enzyme is also highly expressed in the placenta where it is thought to also protect the fetus from the high circulating levels of maternal glucocorticoids. Mutations in the HSD11B2 gene have recently been shown to account for the syndrome of apparent mineralocorticoid excess. In the present study we have used a rat 11 beta HSD2 cDNA to study the distribution and regulation of this enzyme. The rat protein is highly homologous to the mouse, rabbit and human enzymes, except for the carboxy-terminal region which displays extensive divergence between species beyond residue 382. Northern blot analysis of rat total RNA showed that the single copy gene is highly expressed in kidney and adrenal with lower levels in the colon; surprisingly, there was no detectable signal in the placenta. There was also no detectable mRNA in the liver, heart, hippocampus, testis, thymus and pancreas. Nuclease protection analysis revealed the presence of moderate 11 beta HSD2 message levels in the parotid and exceedingly low levels in the placenta. Regulation studies showed that administration of dexamethasone, deoxycorticosterone and 9 alpha-fluorocortisol to adrenalectomized rats for 7 days increased renal enzyme activity 33%-50%, while message levels decreased 35%-70%, suggesting that the increased enzyme activity may represent activation of latent enzyme.

11-beta-Hydroxysteroid Dehydrogenases↗