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Biomedical subjects

R Nelson

Publications and source records attributed to R Nelson.

At least 109 records · Page 6Linked to original sources
PubMed1997

Organizational diagnosis of computer and information learning needs: the process and product.

Organizational diagnosis views the organization as a single entity with problems and challenges that are unique to the organization as a whole. This paper describes the process of establishing organizational diagnoses related to computer and information learning needs within a clinical or academic health care institution. The assessment of a college within a state-owned university in the U.S.A. is used to demonstrate the process of organizational diagnosis. The diagnoses identified include the need to improve information seeking skills and the information presentation skills of faculty.

Computer User Training↗
PubMed1997

Successful detection of small acoustic tumors using the stacked derived-band auditory brain stem response amplitude.

HYPOTHESIS: The aim of this study was to show that a new auditory brain stem response (ABR) measure, the stacked derived-band ABR amplitude, can detect small acoustic intracanalicular tumors missed by standard ABR measures. BACKGROUND: Recent studies clearly have shown that standard ABR latency measures have inadequate sensitivity to detection of small intracanalicular acoustic tumors. Consequently, despite its relatively low cost and wide availability, the standard ABR test has been replaced as a diagnostic screening tool by magnetic resonance imaging (MRI) with gadolinium (GdDTPA) contrast. However, screening with MRIs can be problematic because of their high cost, limited availability, and impact on patient comfort. Thus, an ABR method capable of detecting small tumors with good specificity would be an invaluable cost-effective screening tool for reducing the number of patients without tumor imaged. METHODS: Derived-band ABRs were obtained to 63-dB normal hearing level (nHL) clicks using high-pass noise-masking procedures. The new measure is the wave V amplitude of a stacked ABR constructed by temporally aligning wave V of each derived-band ABR and then summing the time-shifted responses. RESULTS: In a series of 25 tumor cases, 5 small (< or = 1 cm) intracanalicular tumors, missed by standard ABR latency measures, were detected by this new stacked ABR method. The stacked wave V ABR amplitudes in all five cases were significantly lower than those obtained in a group of normal-hearing individuals without tumors. CONCLUSIONS: A new ABR measure, the stacked derived-band ABR amplitude, is sensitive to the presence of small intracanalicular tumors in patients and has excellent specificity for the absence of tumors in normal-hearing individuals. This method, in combination with standard ABR measures, appears promising both as a cost-effective approach to reducing the number of patients without tumors imaged and as a method for acoustic tumor screening when MRI scans: 1) are unavailable; 2) are not appropriate because of patient comfort; and 3) need to be justified because of their cost.

Evoked Potentials, Auditory, Brain Stem↗
PubMed1996

Hyperpolarizing, small-field, amacrine cells in cone pathways of cat retina.

Intracellular recording and horseradish peroxidase (HRP) staining of amacrine cells in the isolated arterially perfused cat retina have revealed examples of small-field cells that hyperpolarize to light. Two were examined in detailed electron microscopic reconstructions to determine patterns of synaptic relationships within the inner plexiform layer (IPL). The cells were morphologically similar to A8 and A13 types as described in Golgi-impregnated material (Kolb et al. [1981] Vision Res. 21:1081-1114). Both types received ribbon synaptic input from rod and cone bipolar cells. The latter input was numerically predominant, occurred in both a and b sublaminae of the IPL, and arose from at least three cone bipolar types. Reciprocal synapses were evident between A13 cells and cone bipolar cells. Amacrine input occurred throughout the dendritic tree of both A8 and A13 types, and numerically exceeded bipolar cell input for A13. Gap junctions between stained, and similar-appearing unstained dendritic profiles were observed for both amacrine types. In addition, A8 engaged in gap junctions with cone bipolar profiles in sublamina b which also provided ribbon input. Synaptic output for both amacrine types occurred primarily upon amacrine and ganglion cells in sublamina a. Both cells were presynaptic upon single OFF-center beta ganglion cells running through the middle of their dendritic trees. Mixtures of rod and cone signals were found in the centrally evoked hyperpolarizations of each type. Center mechanism space constants of such types ranged from 100 to 400 microns, with antagonistic surround in 1 of 5 cases. Dopamine (250 microM) reduced receptive field space constants by one-third in one case. The synaptic organization and potential circuitry implications of these cone system-dominated amacrine types are compared and contrasted to the better-known AII and A17 types previously described for the rod system.

Animals↗
PubMed1996

ON-OFF amacrine cells in cat retina.

We studied the morphology, photic responses, and synaptic connections of ON-OFF amacrine cells in the cat retina by penetrating them with intracellular electrodes, staining them with horseradish peroxidase, and examining them with the electron microscope. In a sample of seven cells, we found two different morphological types: the A19, which ramifies narrowly in stratum 2 (sublamina a) of the inner plexiform layer, and the A22, which ramifies mostly in stratum 4 (sublamina b) but extends some dendrites to sublamina a. Both of these cell types have axon-like processes that extend > 800 microns from the conventional dendritic arbor. ON-OFF amacrine cells in our sample had receptive fields (1.7 +/- 0.3 mm diameter) that were broader than their dendritic arbors (425 +/- 35 microns diameter) and that extended over the region of axon-like processes. In addition, we found many features in common with ON-OFF amacrine cells in poikilotherm vertebrates: a broad receptive field without surround antagonism, two sizes of spike-like events, narrow dynamic range (1 log unit intensity), and excitatory postsynaptic potentials at light on and light off. Two A19 amacrine cells were examined in the electron microscope: most synaptic inputs (93 and 76%, respectively) to either cell were from amacrine cells, with minor inputs from cone bipolar cells. Synaptic outputs were to bipolar, amacrine, and ganglion cells, including the OFF-alpha cell.

Animals↗
PubMed1996

Lisofylline inhibits transforming growth factor beta release and enhances trilineage hematopoietic recovery after 5-fluorouracil treatment in mice.

The effectiveness of endogenous or exogenously administered colony-stimulating factors may be modulated by the presence of hematopoietic inhibitory molecules. Cytotoxic therapy may result in the induction of hematopoietic inhibitors contributing to prolonged myelosuppression, whereas preventing the induction of such inhibitors may accelerate multilineage recovery. Lisofylline [LSF; (R)-1-(5-hydroxyhexyl)-3,7, dimethyl-xanthine], inhibits the signaling and/or release of certain hematopoietic inhibitory molecules such as tumor necrosis factor alpha, macrophage inflammatory protein 1 alpha, transforming growth factor beta, and IFN-gamma. Treatment of murine bone marrow cells with the cytotoxic agent 5-fluorouracil (5-FU) results in the release of a nondialyzable inhibitor of progenitor (colony-forming unit-granulocyte macrophage; CFU-GM) proliferation. When murine bone marrow cells were treated with 5-FU plus LSF, release of this inhibitor of CFU-GM proliferation was blocked. Neutralizing antibody and Western blot analysis indicated that the inhibitor was TGF-beta. We tested the effect of LSF (100 mg/kg i.p., b.i.d.) on multilineage regeneration after high-dose 5-FU or thiotepa treatment in BALB/c mice. In 4 of 5 experiments, LSF significantly accelerated neutrophil recovery (P < or = 0.05, Wilcoxon paired-signed test). In addition, platelet, reticulocyte, and CFU-GM regeneration were significantly accelerated in mice treated with LSF compared to control mice (P < or = 0.05). LSF had no significant effects on the ability of 5-FU to kill hematopoietic progenitor cells, nor did LSF stimulate or inhibit proliferation of CFU-GM. LSF had no effect on chemotherapy-induced killing of tumor cells in vitro, nor on the antitumor activity of 5-FU or thiotepa in BALB/c mice implanted with P388 leukemia cells. Inhibition of hematopoietic inhibitor release may accelerate multilineage recovery after cytotoxic therapy and, as such, may represent an alternative or additional therapy to the use of positively acting lineage specific colony-stimulating factors.

Animals↗
PubMed1996

Real-time evaluation of somatostatin subtype 2 receptor activity employing the technique of cytosensor microphysiometry.

Five types of somatostatin (SS) receptors (sst1-5) have been cloned and are widely distributed in the central nervous system and variably expressed in target tissues of the periphery. At the cellular level, adenylate cyclase inhibition has been classically described in native and transfected cells expressing sst subtypes. In addition, ion channel modulation (K+, Ca2+), phospholipase C, phospholipase A2, and tyrosine phosphatase activation have also been reported. The present study describes a novel in vitro approach based on quantifying receptor-activated metabolic rate changes to evaluate SS biological activity in cells (CHO-K1) stably expressing the human (h) sst2 receptors. Real-time metabolic rate changes were evaluated by determining the rate of extracellular acidification (microphysiometry). The metabolic rate was transiently and potently (EC50 1 nM) increased in response to natural SS ligands, SS-14 and SS-28. The peak activation time was approximately 2 min. Pharmacological analysis for the sst2 receptor yielded rank order of potency for SS analogues of: MK-678 > BIM-23027 > octreotide > BIM-23014C << L-362,855 > BIM-23052 << BIM-23056. Similar rank orders were obtained from in vitro receptor binding studies in the same cell line. These results demonstrate that microphysiometry is a rapid and valid technique to evaluate the pharmacology SS receptor activation.

Animals↗
PubMed1996

A full genome search in multiple sclerosis.

The aetiology of multiple sclerosis (MS) is uncertain. There is strong circumstantial evidence to indicate it is an autoimmune complex trait. Risks for first degree relatives are increased some 20 fold over the general population. Twin studies have shown monozygotic concordance rates of 25-30% compared to 4% for dizygotic twins and siblings. Studies of adoptees and half sibs show that familial risk is determined by genes, but environmental factors strongly influence observed geographic differences. Studies of candidate genes have been largely unrewarding. We report a genome search using 257 microsatellite markers with average spacing of 15.2 cM in 100 sibling pairs (Table 1, data set 1 - DS1). A locus of lambda>3 was excluded from 88% of the genome. Five loci with maximum lod scores (MLS) of >1 were identified on chromosomes 2, 3, 5, 11 and X. Two additional data sets containing 44 (Table 1, DS2) and 78 sib pairs (Table 1, DS3) respectively, were used to further evaluate the HLA region on 6p21 and a locus on chromosome 5 with an MLS of 4.24. Markers within 6p21 gave MLS of 0.65 (non-significant, NS). However, D6S461, just outside the HLA region, showed significant evidence for linkage disequilibrium by the transmission disequilibrium test (TDT), in all three data sets (for DS1 chi2 = 10.8, adjusted P < 0.01)(DS2 and DS3 chi2 = 10.9, P < 0.0005), suggesting a modest susceptibility locus in this region. On chromosome 5p results from all three data sets (222 sib pairs) yielded a multipoint MLS of 1.6. The results support genetic epidemiological evidence that several genes interact epistatically to determine heritable susceptibility.

Chromosome Mapping↗
PubMed1996

Biochemical cure of recurrent acromegaly by resection of cervical spinal canal metastases.

Pituitary carcinoma with metastatic endocrine secreting tissue is rare. Eight cases of malignant, growth hormone-secreting tumours, all metastatic within the central nervous system have been previously described. Complete surgical resection was not possible and the patients died within 4 years of presentation with distant spread. Here we describe the first case of an apparent surgical cure of a somatotroph carcinoma metastatic to the cervical spine, documented by biochemical assessment and magnetic resonance and radioligand imaging. The possibility that intrathecal metastasis of somatotroph tumours may be responsible for some cases of treatment resistant acromegaly is discussed.

Acromegaly↗
PubMed1995

Community-based prevalence of anal incontinence.

OBJECTIVE: To determine the prevalence of and characteristics associated with anal incontinence in the general community. SETTING: Community survey. PARTICIPANTS: The population of the state of Wisconsin sampled in the Wisconsin Family Health Survey. Subjects were identified by random digit dialing with telephone interview. The individual within each household identified as most knowledgeable about the health status of all other members of the household was asked about the health status of each member of the household. Approximately 200 households were surveyed each month. MAIN OUTCOME MEASURES: The presence of anal incontinence to solid or liquid feces or gas, who suffered from it, the frequency of anal incontinence, and how the incontinent person coped with it. RESULTS: A total of 2570 households comprising 6959 individuals were surveyed, and 153 individuals were reported to have anal incontinence, representing 2.2% of the population (95% confidence interval [Cl], +/- 0.3%). Thirty percent of the incontinent subjects were older than 65 years, and 63% were women. Of those with anal incontinence, 36% were incontinent to solid feces, 54% to liquid feces, and 60% to gas. In a multivariate analysis, independent associations of the following risk factors with anal incontinence were found: female sex (odds ratio [OR], 1.5; Cl, 1.1 to 2.1), age (continuously adjusted) (OR, 1.01; Cl, 1.01 to 1.02), physical limitations (OR, 1.8; Cl, 1.2 to 2.7), and poor general health (OR, 1.6; Cl, 1.4 to 1.9). CONCLUSIONS: Anal incontinence was reported in 2.2% of the general population. Independent risk factors for incontinence include female sex, advancing age, poor general health, and physical limitations.

Adult↗
PubMed1995

Attenuation of isoproterenol-mediated vasodilatation in blacks.

BACKGROUND: The mechanism of enhanced vascular reactivity in young blacks, which may play a part in the development of hypertension, has not been defined. To determine the contribution of blunted vasodilatation mediated by beta 2-adrenergic receptors to this phenomenon, we compared forearm blood-flow responses to isoproterenol in young black and white normotensive men. METHODS: We used venous-occlusion plethysmography to measure the responses of blood flow in the forearm to the intraarterial administration of isoproterenol (10 to 400 ng per minute) in 9 normotensive black men (mean [+/- SD] age, 31.3 +/- 8.0 years) and 13 normotensive white men (mean age, 32.9 +/- 5.6 years). Sympathetic activity in the forearm was measured simultaneously by isotope-dilution techniques. RESULTS: Base-line blood flow in the forearm was similar in blacks and whites, but the degree of vasodilatation in response to isoproterenol was markedly lower in blacks. Isoproterenol at an infusion rate of 400 ng per minute produced a 9-fold increase in blood flow in whites but only a 3.5-fold increase in blacks (P < 0.001). The base-line rate of norepinephrine spillover in the forearm was higher in blacks (2.0 +/- 1.3 ng per minute [11.8 +/- 7.7 nmol per minute]) than in whites (0.6 +/- 0.5 ng per minute [3.5 +/- 3.0 nmol per minute], P = 0.002), but there was no difference between the groups after isoproterenol stimulation. CONCLUSIONS: Forearm blood-flow responses to isoproterenol were markedly attenuated in normotensive blacks, indicating a blunting of vasodilatation mediated by beta 2-adrenergic receptors. Sympathetic activity in the forearm was greater in blacks than in whites, but isoproterenol-stimulated presynaptic beta 2-adrenergic responses (which facilitated norepinephrine release) did not differ significantly between blacks and whites. Our findings suggest that the mechanisms responsible for blunted vasodilatation in response to the administration of isoproterenol may contribute to enhanced vascular reactivity in blacks and may play a part in the pathogenesis of hypertension in blacks.

Adult↗
PubMed1995

[In vitro synergic lymphocyte stimulation in HIV-1 infected patients using inosine derivatives and radio-detoxified endotoxin].

Restoration of immune functions through promoting cell cycle might delay acquired immunodeficiency syndrome development. Therefore, stimulation of peripheral lymphocytes of human immunodeficiency virus-1 infected patients in successive clinical stages was studied by phytohaemagglutinin and other stimulants. In vitro blastogenesis was quantitated by 3H-thymidine uptake. Stimulation by phytohaemagglutinin decreased in patients with AIDS related complex to 63.1%, with AIDS to 13.6% of control values. Small amount of recombinant interleukin-2 or indomethacin solely not promoting lymphocytes, increased response to phytohaemagglutinin minimally. Alone ineffective methyl-ester and methyl-phosphonate inosine derivatives augmented phytohaemagglutinin-response of controls and patients with AIDS related complex by approx. 1.5-fold, but the effect in the case of AIDS patients was minimal. Radio-detoxified endotoxin alone or in combination with phytohaemagglutinin stimulated lymphocytes of both controls and patients with AIDS related complex slightly. Lymphocyte stimulation of patients with AIDS related complex was augmented in concentration-dependent manner, and by synergic effect it approached phytohaemagglutinin-stimulated blastogenesis of controls. Anergy due to human immunodeficiency virus-1 infection damages synchronisation of secondary messenger systems induced on cell surface receptors, therefore their selective influence by recombinant interleukin-2 or indomethacin is less efficient. Inosine derivatives promote cell cycle by inhibiting cyclic adenosine 3',5'-monophosphate production. In the early stage of virus infection, radio-detoxified endotoxin might bind to receptors of immature T cells and facilitate cell cycle through cyclic guanosine 3',5'-monophosphate stimulation. The clinical trials of radio-detoxified endotoxin (Tolerin) have already been launched.

AIDS-Related Complex↗
PubMed1995

Validated assays for the determination of gemcitabine in human plasma and urine using high-performance liquid chromatography with ultraviolet detection.

Procedures are described for the determination of gemcitabine, a new anti-tumor agent, and its uridine metabolite in human plasma and in human urine. The sample preparation for the plasma assay involves precipitation of plasma proteins with isopropanol and ethyl acetate. Following this, the solids are discarded and the supernatant is evaporated to dryness. For the urine assay, the sample is diluted with methanol and evaporated to dryness. For both procedures, the residue is reconstituted in mobile phase prior to injection into a normal-phase (amino column) liquid chromatographic system followed by UV detection at 272 nm. The limits of quantitation for both compounds are 50 ng/ml in plasma and 20 micrograms/ml in urine. The procedures were used to provide pharmacokinetic data for both compounds in man following the intravenous administration of a 1000 mg/m2 dose of gemcitabine.

Antimetabolites, Antineoplastic↗