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Biomedical subjects

R Nelson

Publications and source records attributed to R Nelson.

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

Immunopharmacology: immunomodulation and immunotherapy.

Immunopharmacology has changed dramatically over the past 25 years. Although a variety of traditional nonspecific immunosuppressive drug therapies are available for the treatment of autoimmune disease and organ transplantation rejection, with advances in cell biology and monoclonal antibody technology, a highly specific antibody can be engineered to cell surface determinants on immune cells or tumors or to neutralize inflammatory and immune mediators from an immune response. Many of these modalities are still in early phases of study for the treatment of autoimmune disease. In addition to therapies that suppress immune responses, advances in molecular biology have led to new agents and methods to enhance immune responses and correct immune deficits, such as growth factor replacement and cytokine therapies. Finally, gene therapy is a method for the long-term treatment of disorders in which a defective gene leads to disease.

Adjuvants, Immunologic↗
PubMed1997

Bat bite?

Explore the source record for details and available documents.

Adolescent↗
PubMed1997

Proton-induced cation current in embryonic rat spinal cord neurons changes ion dependency over time in vitro.

A rapid increase in proton concentration [H+]0 induces Na+ conductance in a variety of cell types. Here we report that H+ trigger a cation-selective channel whose ion dependency changes over time in culture. Whole-cell recordings of ventral spinal cord neurons dissociated at E15 and cultured for up to 14 days revealed that more than 80% had H(+)-induced inward current responses exhibiting a rapid decay phase. The current response was activated beginning about pH 6.8. Following decay, several minutes were required for complete recovery. More modest decreases in pH, which by themselves failed to activate this current, depressed those triggered by effective changes in pH. The currents recorded from cells in culture for less than 7 days could be abolished completely in the absence of Ca2+ and persisted in Na(+)-free and Ba(2+)-containing solutions. Ensemble analysis of current fluctuations recorded at the peak of the current allowed us to estimate a unitary channel conductance of 7.0 pS and a mean open time of 4.1 ms. In neurons cultured 2 weeks or more, protons induced an inward current response with similar kinetic properties, but with [Na+]0 dependency. Thus, proton-activated cation conductance in embryonic rat spinal cord neurons is self-limiting and involves brief openings of cation-selective channels whose ion dependency changes over time in culture.

Animals↗
PubMed1997

Ectopic induction of tendon and ligament in rats by growth and differentiation factors 5, 6, and 7, members of the TGF-beta gene family.

Little is known about the regulatory signals involved in tendon and ligament formation, and this lack of understanding has hindered attempts to develop biologically based therapies for tendon and ligament repair. Here we report that growth and differentiation factors (GDFs) 5, 6, and 7, members of the TGF-beta gene superfamily that are most related to the bone morphogenetic proteins, induce neotendon/ligament formation when implanted at ectopic sites in vivo. Analysis of tissue induced by GDF-5, 6, or 7, containing implants by currently available morphological and molecular criteria used to characterize tendon and ligament, adds further evidence to the idea that these GDFs act as signaling molecules during embryonic tendon/ligament formation. In addition, comparative in situ localizations of the GDF-5, 6, and 7 mRNAs suggest that these molecules are important regulatory components of synovial joint morphogenesis.

Amino Acid Sequence↗
PubMed1997

Use of the urine cortisol: creatinine ratio to monitor treatment response in dogs with pituitary-dependent hyperadrenocorticism.

OBJECTIVE: To determine the usefulness of measuring urine cortisol:creatinine ratio (UCCR) as a means of monitoring response to mitotane treatment in dogs with pituitary-dependent hyperadrenocorticism (PDH). DESIGN: Case series. ANIMALS: 51 clinically normal dogs and 21 dogs with PDH. PROCEDURE: The reference range for the UCCR was determined by measuring the ratio in 51 clinically normal dogs. The usefulness of measuring UCCR in evaluating response of 21 dogs with PDH to treatment with mitotane was evaluated by comparing ACTH-stimulated blood cortisol concentrations with UCCR at the end of the induction phase of treatment (13 dogs) and during the maintenance phase of treatment (21). RESULTS: UCCR was not useful for identifying dogs with inadequate adrenal reserves at the end of the induction phase of treatment or during the maintenance phase. The UCCR was useful for identifying dogs in which control of cortisol secretion was not adequate. CLINICAL IMPLICATIONS: UCCR should not be used for evaluation of dogs during the induction phase of treatment, because the potential consequences of not identifying dogs with inadequate adrenal reserves are great. The UCCR may be useful as an adjunct means of monitoring treatment response during the maintenance phase of treatment. However, the ACTH stimulation test remains a necessary component when monitoring response to treatment in dogs with PDH receiving mitotane.

Adrenocortical Hyperfunction↗
PubMed1997

Vasodilation in black Americans: attenuated nitric oxide-mediated responses.

BACKGROUND: Attenuated vasodilation in response to the intra-arterial administration of the beta-adrenergic agonist isoproterenol (INN, isoprenaline), an endothelium-independent vasodilator, has previously been observed in normotensive black Americans. To determine whether this reflected a more generalized attenuation of responses to vasodilators, we compared forearm blood flow responses to the endothelium-dependent vasodilator methacholine and the endothelium-independent vasodilator sodium nitroprusside in young normotensive black men and white men. METHODS: Forearm blood flow responses to the intra-arterial administration of isoproterenol (10 to 400 ng/min), methacholine (0.25 to 8 micrograms/min), and sodium nitroprusside (0.25 to 8 micrograms/min) were measured with use of venous occlusion plethysmography in 11 normotensive black men (mean +/- SE age, 30.5 +/- 2.2 years) and nine normotensive white men (mean age, 28.0 +/- 3.2 years). RESULTS: Baseline characteristics, including baseline forearm blood flow, were similar in the black and the white subjects. Vasodilation in response to isoproterenol, sodium nitroprusside, and methacholine was significantly attenuated in black subjects, resulting respectively in a 3.7-fold, 3.6-fold, and 5.0-fold increase in forearm blood flow in black subjects and a 7.5-fold, 5.2-fold, and 6.9-fold increase in forearm blood flow in white subjects (ANOVA; isoproterenol, p < 0.0001; sodium nitroprusside, p < 0.0001; methacholine, p = 0.01). CONCLUSIONS: Our finding of attenuated nitric oxide-mediated vasodilation in response to methacholine and sodium nitroprusside in healthy black American men suggests that attenuated vasodilation in black subjects is a relatively generalized phenomenon, resulting in attenuated responses to multiple vasodilators that act through different receptor- and nonreceptor-mediated mechanisms.

Adrenergic beta-Agonists↗
PubMed1997

Lung transplantation for treatment of infants with surfactant protein B deficiency.

OBJECTIVE: To evaluate lung transplantation for treatment of surfactant protein B (SP-B) deficiency. STUDY DESIGN: We compared surfactant composition and function from pretransplantation and posttransplantation samples of bronchoalveolar lavage fluid, somatic and lung growth, neurodevelopmental progress, pulmonary function, and pulmonary immunohistology in 3 infants with SP-B deficiency who underwent bilateral lung transplantation at 2 months of age and 3 infants who underwent lung transplantation for other reasons. RESULTS: Two years after transplantation, the 2 surviving infants with SP-B deficiency exhibited comparable somatic growth and cognitive development to the comparison infants. All infants had delays in gross motor development that improved with time. Both groups have exhibited normal gas exchange, lung growth, and pulmonary function. The SP-B-deficient infants have also exhibited normal SP-B expression and pulmonary surfactant function after lung transplantation. In two SP-B-deficient infants antibody to SP-B developed. No pathologic consequences of this antibody were identified. CONCLUSIONS: Apart from the development of anti-SP-B antibody, the outcomes for SP-B-deficient infants after lung transplantation are similar to those of infants who undergo lung transplantation for other reasons. Lung transplantation offers a successful interim therapy until gene replacement for this disease is available.

Antibodies↗
PubMed1997

A comparison of the nasal cross-sectional areas and volumes obtained with acoustic rhinometry and magnetic resonance imaging.

Acoustic rhinometry (AR) evaluates the geometry of the nasal cavity with acoustic reflections and provides information about nasal cross-sectional areas (CSA) and nasal volume within a given distance. The accuracy of the information obtained by AR was compared with that of magnetic resonance imaging (MRI) of the nasal cavity. Five healthy subjects were evaluated with AR and the MRI before and after the application of a long-acting nasal decongestant spray, to eliminate possible interference of the nasal cycle with both measurement techniques. The MRI images of 2 mm coronal sections of the nasal cavity were traced by three independent observers and the CSAs were calculated by computer-aided imaging digitization, to be compared with the calculated CSAs obtained with the AR at the corresponding distance from the nasal tip. Digitized data from the MRI images were also used to calculate the nasal volume within the first 6 cm from the nasal tip and compared with the AR volume measurements. The interobserver variation of digitized MRI data predecongestant and postdecongestant was not significant. The correlations of CSA and volume measurements between the AR and MRI were high (0.969) after the application of the decongestant. The correlation between the AR and MRI measurements before the decongestant was low (0.345). This may have been the result of interference of the nasal cycle during the long MRI measurements (1 hour) or other unknown factors. We conclude that AR measurements of nasal CSAs and volumes provide accurate information when compared with the MRI of the decongested nasal airway.

Acoustics↗
PubMed1997

Evaluation of the nasal cavity by acoustic rhinometry in normal and allergic subjects.

With acoustic rhinometry, one can detect a difference in response to a topical decongestant between normal and allergic subjects at the minimal cross-sectional area. The minimal cross-sectional area corresponds in most cases to the anterior end of the inferior turbinate or the first valley, which occurs after the nose piece of the acoustic rhinometer on the acoustic rhinometry graph. Allergic patients typically have an increase in nasal mucosal swelling, which leads to a decrease in the nasal volume and area and, subsequently, to an increase in congestion. In this study acoustic rhinometry was used to test normal and allergic subjects before and after the application of a topical decongestant (1% phenylephrine (Neo-Synephrine)). Symptoms were measured by a five-point scale. Results showed that increasing symptom scores demonstrated a trend toward being related to decreasing area as measured at the minimal cross-sectional area or nasal valve. The average total percent change at the minimal cross-sectional area was calculated for both groups and compared. The normal subjects had an average total percent area change at the minimal cross-sectional area of 15.6% +/- 14.8%, and the allergic subjects had a percent change of 24.6% +/- 20.8%. This represents a significant difference between the normal and allergic subjects in response to the topical decongestant at the minimal cross-sectional area (p = 0.04). However, the average total percent change was not significantly different between the two groups at the second and third valleys. At the second valley, the normal subjects had a percent change of 40% +/- 17.5%, and the allergic subjects had a percent change of 36% +/- 18.5%. At the third valley, the normal subjects had a percent change of 35% +/- 15.4%, and the allergic subjects had a percent change of 32% +/- 20.6% (p = 0.4 and 0.5, respectively). The total area was calculated by adding measurements from both right and left nasal cavities for each subject in an attempt to control the effect of the nasal cycle. Acoustic rhinometry makes it possible to detect a trend in the relationship between either a decrease in area at the minimal cross-sectional area or a decrease in the total volume from 0 to 7 cm into the nasal cavity and congestion. A statistically significant difference between normal and allergic subjects in their response to a topical decongestant at the minimal cross-sectional area was detected by acoustic rhinometry at the nasal valve.

Acoustics↗
PubMed1997

A new X linked recessive syndrome of mental retardation and mild dysmorphism maps to Xq28.

Efforts to understand the genetic basis of mental retardation are greatly assisted by the identification of families with multiple relatives with mental retardation that clinical geneticists encounter in the routine practice of their profession. Here we describe a linkage study of a four generation family in which X linked recessive mental retardation (XLMR) is associated with minor dysmorphism and premature death of the affected males. Microsatellite based polymorphic loci evenly spaced over the entire X chromosome were used initially to detect linkage to Xq28. Further analysis identified a haplotype of Xq28 markers bounded proximally by locus DXS1113 and distally by DXS1108 that cosegregated with XLMR in this family. Two point lod scores > 3.0 provided strong evidence that the gene locus responsible for XLMR in this family is within this 7 Mb region of Xq28. The minor anomalies noted in some affected males were not distinctive enough to suggest a unique syndrome. None of our patients had features of the Waisman-Laxova syndrome or the PPM-X syndrome. The possibility of allelism with any of the five other non-specific XLMR syndromes (MRX3, MRX16, MRX25, MRX28, and MRX41) mapped to Xq28 could not be excluded. While the recognition of a gene responsible for this disorder needs much additional work, multiple female relatives at risk in this family benefit immediately from knowing their genotype and heterozygotes will have the opportunity to undergo prenatal diagnosis.

Adult↗
PubMed1997

Liver metastases: improved detection with dynamic gadolinium-enhanced MR imaging?

PURPOSE: To compare dynamic gadolinium-enhanced with unenhanced magnetic resonance (MR) imaging in detection of liver metastases. MATERIALS AND METHODS: Two groups of patients were prospectively examined with unenhanced and dynamic gadolinium-enhanced MR imaging. The first group (n = 48) had proved liver metastases; the second group (n = 49) did not. One set of unenhanced and one set of gadolinium-enhanced MR images were selected per patient. Three independent, blinded readers assessed the images for presence, number, location, and conspicuity of lesions. Data were analyzed with receiver operating characteristic curves, and contrast-to-noise ratios were calculated for the images. RESULTS: There was no statistically significant difference between the use of unenhanced and gadolinium-enhanced MR images in the differentiation of patients with from patients without metastases. The numbers of false-positive and false-negative diagnoses of individual lesions were higher (not statistically significant) with dynamic MR images than with unenhanced MR images. At dynamic MR imaging, contrast-to-noise ratio was highest in the early phase (30 seconds after injection of the contrast agent) but was not significantly different from the contrast-to noise ratio of the T2-weighted images. CONCLUSION: Dynamic gadolinium-enhanced MR imaging showed no improvement over unenhanced MR imaging in detectability of liver metastases.

Adult↗
PubMed1997

Norepinephrine release in the human forearm: effects of epinephrine.

It has been postulated that delayed facilitation of norepinephrine release by epinephrine is causally related to the development of hypertension. It has been proposed that a brief increase in epinephrine concentrations results in the uptake of epinephrine into the sympathetic nerve terminal. Subsequent rerelease of epinephrine stimulates presynaptic beta-adrenergic receptors, resulting in a prolonged increase in plasma norepinephrine (NE) concentrations, with amplified sympathetic responses and vasoconstriction. To determine whether such epinephrine-induced, delayed facilitation of NE release occurs in a vascular bed draining resistance vessels and, if it occurs, whether that facilitation differs in hypertension, we used a radioisotope dilution method to measure unstimulated and isoproterenol-stimulated forearm NE spillover before, during, and after a 50 ng/min infusion of epinephrine for 30 minutes directly into the brachial artery. No delayed facilitatory effects of epinephrine on forearm NE spillover were observed in either 6 normotensive (NT) or 8 borderline hypertensive (BHT) subjects (NT unstimulated forearm NE spillover preepinephrine 1.79+/-0.41 ng/min versus postepinephrine 2.36+/-0.65 ng/min, P=.38; BHT preepinephrine 2.24+/-0.70 ng/min versus postepinephrine 1.93+/-0.46 ng/min, P=.51; NT isoproterenol-stimulated forearm NE spillover preepinephrine 4.61+/-1.01 ng/min versus postepinephrine 4.4+/-0.98 ng/min, P=.9; BHT preepinephrine 4.04+/-1.36 ng/min versus postepinephrine 4.69+/-1.49 ng/min P=.5). We conclude that the short-term local infusion of epinephrine does not have a delayed facilitatory effect on forearm NE spillover in NT or BHT subjects. Therefore, the prolonged increase in NE concentrations after epinephrine infusion previously shown systemically, and not seen locally in the forearm, suggests that the delayed facilitatory response to epinephrine may occur in other organs.

Adult↗
PubMed1997

Posttraumatic stress disorder in patients with traumatic brain injury and amnesia for the event?

Frequency of DSM-III-R posttraumatic stress disorder (PTSD) was studied in 47 active-duty service members (46 male, 1 female; mean age 27 = 7) with moderate traumatic brain injury and neurogenic amnesia for the event. Patients had attained "oriented and cooperative" recovery level. When evaluated with a modified Present State Examination and other questions at various points from study entry to 24-month follow-up, no patients met full criteria for PTSD or met criterion B (reexperience); 6 (13%) met both C (avoidance) and D (arousal) criteria. Five of these 6 also had organic mood disorder, depressed type, and/or organic anxiety disorder. Posttraumatic amnesia following moderate head injury may protect against recurring memories and the development of PTSD. Some patients with neurogenic amnesia may develop a form of PTSD without the reexperiencing symptoms.

Adult↗
PubMed1997

Underdiagnosis of PTSD and substance use disorders in hospitalized female veterans.

Discharge diagnoses of 31 female veterans and 31 male veterans hospitalized at a large urban VA medical center were examined to elucidate possible biases in clinicians' diagnostic practices. Only one woman in the sample was diagnosed as having posttraumatic stress disorder, compared with seven men. All men given this diagnosis were combat veterans. Although about half of each group had a drug-positive urine screen on admission, only 11 women received a diagnosis of a substance use disorder, compared with 24 men. VA clinicians may need further training and experience assessing the presentation of PTSD and substance use disorders in women.

Adult↗
PubMed1997

Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial.

PURPOSE: Most patients with advanced pancreas cancer experience pain and must limit their daily activities because of tumor-related symptoms. To date, no treatment has had a significant impact on the disease. In early studies with gemcitabine, patients with pancreas cancer experienced an improvement in disease-related symptoms. Based on those findings, a definitive trial was performed to assess the effectiveness of gemcitabine in patients with newly diagnosed advanced pancreas cancer. PATIENTS AND METHODS: One hundred twenty-six patients with advanced symptomatic pancreas cancer completed a lead-in period to characterize and stabilize pain and were randomized to receive either gemcitabine 1,000 mg/m2 weekly x 7 followed by 1 week of rest, then weekly x 3 every 4 weeks thereafter (63 patients), or to fluorouracil (5-FU) 600 mg/m2 once weekly (63 patients). The primary efficacy measure was clinical benefit response, which was a composite of measurements of pain (analgesic consumption and pain intensity), Karnofsky performance status, and weight. Clinical benefit required a sustained (> or = 4 weeks) improvement in at least one parameter without worsening in any others. Other measures of efficacy included response rate, time to progressive disease, and survival. RESULTS: Clinical benefit response was experienced by 23.8% of gemcitabine-treated patients compared with 4.8% of 5-FU-treated patients (P = .0022). The median survival durations were 5.65 and 4.41 months for gemcitabine-treated and 5-FU-treated patients, respectively (P = .0025). The survival rate at 12 months was 18% for gemcitabine patients and 2% for 5-FU patients. Treatment was well tolerated. CONCLUSION: This study demonstrates that gemcitabine is more effective than 5-FU in alleviation of some disease-related symptoms in patients with advanced, symptomatic pancreas cancer. Gemcitabine also confers a modest survival advantage over treatment with 5-FU.

Adult↗