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Biomedical subjects

S Jordan

Publications and source records attributed to S Jordan.

At least 73 records · Page 4Linked to original sources
PubMed1997

PET studies of functional compensation in a primate model of Parkinson's disease.

MPTP 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine is a neurotoxin that produces degeneration of nigrostriatal dopaminergic neurons and a chronic parkinsonian condition in primates. Positron emission tomography (PET) studies of rhesus macaques at various time points following unilateral MPTP administration demonstrated a different time course of degeneration in the dopaminergic terminals in the putamen and in the cell bodies in the substantia nigra, consistent with other evidence of retrograde degeneration. In addition, the substantia nigra showed a transient upregulation in dopaminergic function in the lesioned hemisphere indicating functional compensation. This plasticity has important implications for the therapeutic effects of growth factors and other potential treatments for neurodegenerative diseases.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1997

6-[18F]fluoro-L-m-tyrosine: metabolism, positron emission tomography kinetics, and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine lesions in primates.

The tracer 6-[18F]fluoro-L-m-tyrosine (FMT) was studied with regard to its biochemistry and kinetics, as well as its utility in evaluating brain dopaminergic function in primates before and after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment using positron emission tomography (PET). Plasma analysis of FMT and its F18-labeled metabolites 6-fluoro-3-hydroxyphenylacetic acid (FPAC) and 6-fluoro-3-hydroxyphenylethylamine (FMA) during PET scanning enabled kinetic analysis of FMT uptake. A separate study examined brain FMT metabolism in MPTP-naive monkeys euthanized 60 or 120 min after FMT injection. Almost 60% of total plasma F-18 activity was associated with FPAC and FMA 120 min after FMT injection. The FMT signal accumulated preferentially in dopaminergic areas such as caudate and putamen. This bilateral FMT signal was disrupted after unilateral intracarotid artery (ICA) MPTP infusion which reduced ipsilateral striatal activity. A three compartment three kinetic rate constant model for FMT uptake revealed reduced FMT decarboxylation (k3) in ipsilateral caudate and putamen after unilateral MPTP although a further decrease was not evident after intravenous MPTP. FPAC was the major F-18 species in all brain regions except in cerebellum where FMT was predominant 60 min post-mortem. FPAC was most concentrated in dopaminergic areas whereas lower levels occurred in areas containing few dopamine terminals. These data demonstrate preferential FMT metabolism and F-18 retention in dopaminergic tissue and support the use of FMT to evaluate normal and abnormal dopaminergic function.

Animals↗
PubMed1997

Abnormal immunoreactivity of the E-cadherin-catenin complex in gastric carcinoma: relationship with patient survival.

BACKGROUND & AIMS: The E-cadherin-catenin complex plays a critical role in the maintenance of normal tissue architecture. Mutation of any of its components is believed to result in loss of cell-cell adhesion and contribute to neoplasia. The aim of this study was to examine the expression of E-cadherin and alpha-, beta-, and gamma-catenin in gastric carcinoma and dysplasia and determine any relationship with tumor characteristics and survival. METHODS: Immunoperoxidase staining of E-cadherin and alpha-, beta-, and gamma-catenin was performed using 89 gastric carcinomas, lymph node metastases, and gastric biopsy specimens from 14 patients with dysplasia and 10 healthy controls. RESULTS: Membranous staining was observed in control biopsy specimens for all components of the complex. Up to 57% of gastric dysplasia and 90% of tumors stained abnormally for one or more components of the cadherin-catenin complex. Abnormal E-cadherin and gamma-catenin staining occurred more frequently in diffuse than intestinal tumors (P < 0.0005 and < 0.05, respectively). No association with tumor grade or stage was found. A survival advantage was noted in intestinal and diffuse tumors retaining membranous expression of beta-catenin, independent of tumor type, grade, or stage (P < 0.005). CONCLUSIONS: Abnormal expression of the E-cadherin-catenin complex occurs frequently in gastric carcinoma. The close correlation with poor survival suggests that abnormal beta-catenin may be a useful prognostic marker.

Adult↗
PubMed1997

Teaching pharmacology by case study.

This paper describes why case studies deserve a place in the centre of the bioscience curriculum, and how they have been used as a vehicle to improve care and save lives. A knowledge of drugs, their side-effects and interactions is becoming increasingly important to nurses. One powerful way to convey this information is the case study, which, despite its limitations, has the potential to endow difficult topics in therapeutics with the power of the narrative. The author suggests that case study projects encourage students to forge theory-practice links, related to their own specialist areas. When shared with their colleagues, these encourage the class by illustrating 'bioscience in action' and endowing the subject with the 'reality factor'. They also provide rich qualitative data for evaluating and delineating the curriculum. These case studies demonstrate the value of evidence-based practice; although case data is part of the evidence, it can never substitute for evidence-based practice. This paper builds on the findings of the author's PhD in postregistration nurse education; the examples described here are typical of 151 such cases in the research project.

Aged↗
PubMed1997

Benzodiazepine prevention of swim stress-induced sensitization of cortical biogenic amines: an in vivo microdialysis study.

In vivo microdialysis was used to determine the effect of diazepam, flumazenil and FG-7142 upon the biogenic amine response to acute and repeated swim stress in the medial prefrontal cortex of the rat. Acute swim stress increased norepinephrine levels, although dopamine and serotonin levels remained stable. Upon re-exposure to swim stress twenty-four hours later, sustained increases (200-300% of baseline) in all three biogenic amines were detected. This enhanced response to re-stress was not seen in rats pretreated with either a benzodiazepine: agonist (diazepam, 2 mg/kg), an antagonist (flumazenil, 10 mg/kg), or an inverse agonist (FG-7142, 10 mg/kg) given prior to the first swim stress. Therefore, the sensitization of biogenic amine response to re-stress may be prevented by compounds which differ in their activity at the benzodiazepine receptor.

Animals↗
PubMed1997

The biological sciences in nursing: an empirical paper reporting on the applications of physiology to nursing care.

This action research study was undertaken to address practical concerns over curriculum development in nursing. The applied physiology component of a post-registration nursing diploma was evaluated in terms of its impact on patients rather than on the nurses themselves. The reported data were triangulated, all the findings indicated that patient care could be enhanced when nurses applied their knowledge of physiology to practice. Despite its limitations of scale, this study contributes to the curriculum debate in nurse education.

Biological Science Disciplines↗
PubMed1997

Oxyntomodulin stimulates intestinal glucose uptake in rats.

BACKGROUND & AIMS: Enteroglucagon peptides have long been proposed as mediators of intestinal adaptation, including mucosal growth and nutrient absorptive capacity. The hypothesis that infusions of oxyntomodulin, a bioactive form of enteroglucagon, would stimulate glucose and amino acid uptake was tested and its effects were compared with those of glucagon. METHODS: Rats were infused intravenously via minipumps with either saline, rat oxyntomodulin (0.47 nmol x kg(-1) x h[-1]), or glucagon (0.88 nmol x kg(-1) x h[-1]) for 7 days, and plasma hormone levels were measured. At death, intestinal dimensions and brush border uptake of D-glucose and L-proline were measured using an in vitro everted sleeve technique. RESULTS: Plasma enteroglucagon and glucagon levels were increased 4- and 12-fold, respectively, but there were no effects on food intake, body weight, or intestinal dimensions. In contrast, oxyntomodulin and glucagon significantly stimulated total intestinal glucose uptake capacity by 44% and 53%, respectively, over controls. Oxyntomodulin most potently enhanced glucose uptake in the ileum (215%), whereas glucagon's greatest effect was in the jejunum (63%-85%). However, neither peptide affected proline uptake. CONCLUSIONS: These results support a new, specific action for oxyntomodulin in intestinal adaptation as a glucose uptake stimulator and confirm glucagon's role as a regulator of glucose uptake.

Animals↗
PubMed1997

Effects of theophylline on renal function in premature infants.

Xanthines are frequently being used in the management of premature babies. Studies in adult subjects have demonstrated a diuretic effect of aminophylline due to the inhibition of solute reabsorption in various segments of the nephron. We evaluated the effects of aminophylline on the developing kidney. Nineteen premature infants, with a mean +/- SD gestational age of 31.1 +/- 2.8 weeks and mean birth weight of 1481 +/- 454 g were studied at mean age of 4.5 +/- 4.0 days before and after a 20-minute loading infusion of 6 mg/kg aminophylline, followed by maintenance therapy at a dose of 2 mg/kg every 12 hours. A marked diuresis occurred immediately after the loading dose, the ratio of urinary output to water intake increased from 0.58 +/- 0.36 to 1.19 +/- 0.65. Concomitantly, the fractional excretion of sodium increased from 2.7 +/- 2.6% to 5.7 +/- 4.4% and that of potassium rose from 21 +/- 19% to 31 +/- 21%. Urinary calcium and uric acid excretion were also enhanced: calcium to creatinine ratio rose from 0.31 +/- 0.29 to 0.60 +/- 0.54 and uric acid to creatinine ratio increased from 2.5 +/- 1.5 to 3.8 +/- 2.0. Tubular reabsorption of phosphorus (TRP) was not affected. Most of the effects were no longer evident after 24 hours, despite continuing aminophylline maintenance therapy. In premature infants the aminophylline loading dose, but not maintenance therapy, affected renal functions. Because heart rate, blood pressure, and creatinine clearance did not change, it appears that aminophylline acts directly on tubular reabsorptive functions.

Absorption↗
PubMed1997

Doctor in the process. The engagement of clinical directors in hospital management.

Aims to examine medical involvement in hospital management processes, and to consider the implications of current experience for the next generation of clinical directors. Doctors who move into a formal management role often find themselves unprepared for their new responsibilities. Research has thus concentrated on identifying the management competences which doctors lack, and with designing ways to remedy the deficit. Seeks to move beyond this deficit model by adopting a perspective which focuses on the engagement of doctors in the management process. Draws data from in-depth interviews with six clinical directors and 19 other members of the hospital management team at Leicester General Hospital NHS Trust (LGH). Content analysis of interviews suggest that the engagement of clinical directors in the hospital management process at this site can be described as reluctant, transient, service-driven, power-pulled and pressured. This negative portrayal of the role, however, must be set in the context of the "management expectation" held of clinical directors by other hospital managers and staff--an expectation that is not currently fulfilled.

Clinical Medicine↗
PubMed1997

Using participatory action research to understand the meanings aboriginal Canadians attribute to the rising incidence of diabetes.

This paper discusses the advantages of adopting forms of participatory action research with aboriginal Canadians. Using a recent qualitative study of non-insulin-dependent diabetes mellitus among the James Bay Cree, it outlines and discusses the methodology used to construct a form of action research that focused on what meaning the Cree gave to the rising incidence and prevalence of diabetes. In order to understand this perspective, the researchers recruited members of the Cree community as co-researchers in the study. This facilitated the development of a Cree perspective on diabetes and also allowed the Cree members of the study to acquire a grounding in the knowledge and skills necessary for forms of qualitative research that can inform both policy and practice in health care and related areas. In particular, the paper discusses how the study was constructed and what lessons can be drawn from this form of collaborative inquiry.

American Indian or Alaska Native↗
PubMed1996

The side effect profile of sirolimus: a phase I study in quiescent cyclosporine-prednisone-treated renal transplant patients.

A 14-day ascending dose course of sirolimus (rapamycin, RAPA) was administered to quiescent renal transplant patients receiving a double-drug cyclosporine (CsA)/corticosteroid regimen in a double-blinded randomized study. Oral sirolimus or placebo was delivered twice daily in divided doses for 13 days and a final dose was administered on the morning of study day 14. In addition, patients in the sirolimus- and placebo-treated groups were compared with a demographically matched, concurrently treated control cohort of 30 patients who received the same concentration-controlled CsA/corticosteroid regimen. The study cohort was partitioned into four sirolimus dose level groups: placebo (0 mg/m2/day, N = 10), low dose (1 to 3 mg/m2/day, N = 9), medium dose (5 to 6 mg/m2/day, N = 9), and high dose (7 to 13 mg/m2/day, N = 12). the primary side effect of sirolimus was a reversible decrease in platelet (PLT) and white blood cell (WBC) counts. Cholesterol values increased statistically significantly in the sirolimus-treated patients when compared with those of the placebo patients, but not when compared with those of the control group patients. There were no statistically significant differences in the steady-state average concentrations of CsA among sirolimus dose groups (including placebo). No differences were observed between the pre- and post-sirolimus treatment values of systolic and diastolic blood pressure values, glomerular filtration rates (GFR), serum creatinine values (SCr), and serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) or triglyceride levels. Because the principal side effects of sirolimus are distinct from the principal nephrotoxic properties of CsA, this drug combination may display potent immunosuppression without exacerbated toxicity.

Adult↗
PubMed1996

Bronchial inflammation and the common cold: a comparison of atopic and non-atopic individuals.

BACKGROUND: Cold virus infections are associated with asthma attacks and with increased bronchial responsiveness even in normal subjects. Possible mechanisms include epithelial damage, interaction with adhesion molecules or with T-helper cell subsets. OBJECTIVE: To determine whether colds increase lower airway inflammation, comparing atopic with non-atopic normal subjects. METHODS: Thirty healthy volunteers (15 atopic) took part. Baseline tests included viral serology, microbiological culture and polymerase chain reaction for rhinovirus infection (HRV-PCR), histamine bronchial provocation and bronchoscopy. Twenty subjects (eight atopic) underwent repeat tests when they developed a cold. RESULTS: Forced expiratory volume in one second (FEV1) was significantly lower during colds (-0.19 L [95% confidence interval -0.10, -0.29], P = 0.0004) and there was a significant increase in bronchial responsiveness (+0.62 doublings of the dose-response slope [+0.24, +1.00], P = 0.003). Eight subjects (two atopic) had a diagnosed viral infection: two HRV, three coronavirus (HCV), one HRV + HCV, one parainfluenza III (PI) and one respiratory syncytial virus (RSV) (also Haemophilus influenzae). In biopsies, during colds, total eosinophils (EGI+) increased significantly (geometric mean 6.73-fold [1.12,40.46], P = 0.04). Activated eosinophils (EG2+) only increased significantly in the subgroup without diagnosed viral infection and particularly in atopic rhinitics. T-suppressor (CD8+) cells also increased significantly (median + 178.3 cells mm2, P = 0.004). Epithelial expression of intercellular adhesion molecule-1 (ICAM-1) expression increased in four atopic rhinitics during colds. Bronchial washings showed a significant increase in neutrophils (GM 1.53-fold [1.04,2.25], P = 0.02). CONCLUSION: Lower airway inflammation was present in atopic and non-atopic normal subjects with colds. Atopic subjects differed in that they were less likely to have positive virological tests and were more likely to show activated eosinophilia in the lower airway, despite a similar spectrum of symptoms.

Adolescent↗
PubMed1996

Iodine-123-5-iodo-6-nitroquipazine: SPECT radiotracer to image the serotonin transporter.

UNLABELLED: Because serotonergic function has been implicated in the pathophysiology of a number of diseases of the nervous system, efforts to image this system in vivo have received considerable recent attention. Promising preliminary results with the tracer 5-iodo-6-nitroquipazine (INQUIP) have prompted us to perform further studies designed to validate the use of the tracer as an in vivo ligand for the serotonin transporter. METHODS: We studied six adult macaca mulatta in eight experiments which involved SPECT imaging at 17 to 24 hr post-tracer injection, including three experiments with coinjection of the 123I-and 125I-radiolabeled tracer for direct comparison of autoradiography and SPECT, and three experiments in which animals were lesioned with the serotonergic neurotoxin (+/-)3,4-methyl-enedioxymethamphetamine (MDMA). In addition, we evaluated the metabolism of the tracer in the brain and periphery. RESULTS: SPECT images obtained at 17 and 24 hr reflected the known pattern of distribution of serotonin transporters and also showed close correspondence to the autoradiograms. Ratios of binding in the brain-stem to binding in the cerebellum were close to 3 at 17 hr. autoradiograms from an MDMA-treated animal showed up to 95% reductions of binding, while the SPECT data showed smaller reductions. Virtually all of the tracer in the brain stem was in the form of unmetabolized parent compound, but plasma showed rapid peripheral metabolism of the tracer. CONCLUSION: These results demonstrate that INQUIP SPECT images are sensitive measures of in vivo binding to the serotonin transporter, and support the further development of the tracer as a method for the in vivo study of serotonergic neurons in humans.

Animals↗
PubMed1995

Integrin expression in primary breast cancer and its relation to axillary nodal status.

BACKGROUND: Integrins are transmembrane receptors that modulate cell adhesion. Each is a heterodimer of varying alpha and beta subunits. In malignancy, loss of integrin expression may result in less adhesive cells more likely to metastasize. Our aim was to characterize the integrins in human breast tissue and to examine the relationship between integrin expression and nodal metastasis in breast cancer. METHODS: Cryostat sections from 12 benign and 61 malignant (50 ductal and 11 lobular) samples were stained by the avidin-biotin complex method with monoclonal antibodies to the beta 1, beta 3, beta 4, and beta 5 subfamilies. All slides were read by two independent assessors with consensus agreement. Integrin expression was compared to variables by using the chi-squared test with Yates' correction and multivariate analysis based on logistic regression. RESULTS: All integrin subunits studied were significantly reduced on breast cancer compared with benign cells (chi-squared test) but were not related to tumor differentiation. Loss of alpha 1 beta 1, alpha 2 beta 1, alpha 3 beta 1, alpha 6 beta 1, alpha v beta 1, and alpha v beta 5 were related to the presence of axillary metastasis. Independently the integrins were of limited clinical value as predictors of axillary spread. However, on multivariate analysis the combination of beta 1, alpha v, alpha 1, tumor size, and vascular invasion gave a cumulative overall accuracy in predicting nodal disease of 97%. CONCLUSIONS: Integrin expression is reduced in breast cancer and may explain tumor progression. Measuring the integrins might thus provide a means of selection for aggressive axillary treatment.

Adult↗
PubMed1995

Serotonergic modulation of swimming speed in the pteropod mollusc Clione limacina. I. Serotonin immunoreactivity in the central nervous system and wings.

Serotonin-immunoreactive somata in the pteropod mollusc Clione limacina were restricted to the cerebral and pedal ganglia. 10-14 pairs of cells were consistently found in the cerebral ganglia, including one large pair that had soma positions and axon branching patterns reminiscent of those of the metacerebral cells of other molluscs. Two clusters of somata were found on the midline near the cerebral commissure, one on the anterior-lateral margin and one posterior-laterally. A distinct paired cluster of up to nine somata was found on the dorso-lateral margin of the pedal ganglia, near the emergence of the pedal commissure. Up to five of these cells innervated the ipsilateral wing via the wing nerve. Dye-fills of these cells showed that they branch repeatedly in the ipsilateral wing and innervate the swim musculature. Double-labelling experiments indicated that the filled neurons were also serotonin-immunoreactive. Neurobiotin fills that were processed for electron microscopy revealed two types of terminals associated with the swim musculature: direct contacts and reactive terminals adjacent to non-labelled presynaptic terminals. Additional immunoreactive neurons in the pedal ganglia included the asymmetrical heart excitor neuron of the left pedal ganglion and up to nine ventral somata.

Animals↗