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Biomedical subjects

D Russell

Publications and source records attributed to D Russell.

At least 109 records · Page 6Linked to original sources
PubMed1996

Increased basal REM sleep but no difference in dark induction or light suppression of REM sleep in flinders rats with cholinergic supersensitivity.

Increased cholinergic sensitivity in the central nervous system has been postulated to account for some of the neuroendocrine abnormalities and sleep disturbances seen in human depressives. The Flinders Sensitive Line (FSL) rats, which exhibit increased sensitivity to cholinergic agents, have been shown to have REM sleep patterns similar to those seen in depressives, including shorter REM sleep latency and increased daily percentage of REM sleep. We studied the response of FSL and control rats to brief dark pulses administered during the normal light period (which are known to stimulate REM sleep in albino rats) and to brief light pulses during the normal dark period (which suppress REM sleep in albino rats) to determine whether these responses are affected by central cholinergic hypersensitivity. FSL rats showed REM sleep patterns indistinguishable from controls during light or dark pulses, which does not support the primary involvement of cholinergic systems in this mechanism of REM sleep regulation. We also examined REM and non-REM (NREM) sleep patterns in FSL rats and their controls to determine whether they show sleep continuity disturbances or decreased sleep intensity as seen in depression. In agreement with an earlier study, we found that FSL rats had more daily REM sleep and accumulated less NREM sleep between REM bouts than controls. Duration of NREM sleep bouts, total daily NREM sleep time, and EEG amplitude of NREM sleep did not differ between FSL and control rats, suggesting that the cholinergic abnormalities in FSL rats do not produce substantial NREM sleep changes.

Animals↗
PubMed1996

The targeting of Lamp1 to lysosomes is dependent on the spacing of its cytoplasmic tail tyrosine sorting motif relative to the membrane.

Lamp1 is a type I transmembrane glycoprotein that is localized primarily in lysosomes and late endosomes. Newly synthesized molecules are mostly transported from the trans-Golgi network directly to endosomes and then to lysosomes. A minor pathway involves transport via the plasma membrane. The 11-amino acid cytoplasmic tail of lamp1 contains a tyrosine-based motif that has been previously shown to mediate sorting in the trans-Golgi network and rapid internalization at the plasma membrane. We studied whether this motif also mediates sorting in endosomes. We found that mutant forms of lamp1 in which all the amino acids of the cytoplasmic tail were modified except for the RKR membrane anchor and the YXXI sorting motif still localized to dense lysosomes, indicating that the YXXI motif is sufficient to confer proper intracellular targeting. However, when the spacing of the YXXI motif relative to the membrane was changed by deleting one amino acid or adding five amino acids, lysosomal targeting was almost completely abolished. Kinetic studies showed that these mutants were trapped in a recycling pathway, involving trafficking between the plasma membrane and early endocytic compartments. These findings indicate that the YXXI signal of lamp1 is recognized at several sorting sites, including the trans-Golgi network, the plasma membrane, and the early/sorting endosomes. Small changes in the spacing of this motif relative to the membrane dramatically impair sorting in the early/sorting endosomes but have only a modest effect on internalization at the plasma membrane. The spacing of sorting signals relative to the membrane may prove to be an important determinant in the functioning of these signals.

Amino Acid Sequence↗
PubMed1996

Spinal anaesthesia for Caesarean section: effect of Sprotte needle orientation.

We induced spinal anaesthesia in 100 women presenting for elective Caesarean section with the mother in the right lateral position. Patients were allocated randomly to have the side eye of the 24-gauge Sprotte spinal needle pointing in one of four directions: group A, cephalad; group B, right lateral; group C, left lateral; group D, caudad. Isobaric bupivacaine 0.5% (2.5 ml) was injected over 30 s before the mother was placed supine with a 15 degree left lateral tilt. Onset time and height of the subsequent analgesic and anaesthetic blocks were assessed by a blinded observer. Onset of sensory block to T4 was significantly faster in group A (P = 0.001). There were no differences in final block height, incidence of hypotension, nausea and vomiting or ephedrine requirements.

Adult↗
PubMed1996

Patient-controlled analgesia with morphine and droperidol following caesarean section under spinal anaesthesia.

BACKGROUND: The addition of droperidol to morphine for patient-controlled analgesia reduces the incidence of nausea and vomiting, but may result in unwanted side effects. METHOD: We studied 40 women randomised to receive morphine sulphate with or without added droperidol (10mg droperidol/60 mg morphine) by patient-controlled analgesia following elective caesarean section under spinal anaesthesia. RESULTS: Median morphine demand in the 20 h after surgery was 74 mg with morphine alone, and 53 mg with added droperidol, the median consumption of which was 8.8 mg. The incidence of nausea was reduced from 80% to 38.8% (P < 0.01), and that of emesis from 55% to 16.7% (P < 0.05) by the addition of droperidol. Psychomotor function was significantly impaired to a similar degree in both groups and there was no significant difference in sedation scores or pain scores. Subjective drowsiness which resulted in withdrawal from the study occurred in two patients, both of whom were receiving droperidol, and though all patients who completed the study were satisfied with their analgesia overall, significantly more of those receiving unsupplemented morphine (11/19 compared with 4/18, P < 0.05) described it as excellent. CONCLUSION: The addition of droperidol 10 mg to morphine 60 mg for PCA following caesarean section under spinal anaesthesia reduces the incidence of nausea and emesis, but may result in drowsiness, limiting the usefulness of the technique.

Analgesia, Obstetrical↗
PubMed1996

Glial cell line-derived neurotrophic factor: the lateral cerebral ventricle as a site of administration for stimulation of the substantia nigra dopamine system in rats.

The direct application of recombinant human glial cell line-derived neurotrophic factor (rhGDNF) to the deep structures of the nigrostriatum has been shown previously to augment dopamine function and inhibit loss of substantia nigra neurons in rodent models of Parkinson's disease. The present studies were designed to determine whether administration of rhGDNF into the lateral ventricle, a more clinically accessible intracranial target, is capable of augmenting dopamine function of the nigrostriatal pathway in normal rats. Single bolus intracerebroventricular (i.c.v) injections of rhGDNF increased locomotor activity and decreased food and water consumption and body weight gain in a dose-dependent manner. rhGDNF increased concentrations of dopamine and dopamine metabolites in the substantia nigra, ventral tegmental area and hypothalamus, but had no significant effects in the striatum. rhGDNF had no effect on striatal or substantia nigral serotonin (5-HT) and 5-hydroxyindoleacetic acid levels, but these levels were significantly increased in the ventral tegmental area and hypothalamus respectively. The augmentation of the dopamine and 5-HT systems was detected 2 weeks but not 3 days or 6 weeks after rhGDNF administration. After a repeat injection of i.c.v rhGDNF (6 weeks after the initial injection), substantia nigral dopamine, 5-HIAA and noradrenalin levels were increased. These results indicate that i.c. v administration of rhGDNF has an influence on adult rat dopamine neurons. This route of administration may be useful for stimulating dopamine neurons in Parkinson's disease.

Animals↗
PubMed1996

A population based survey of women's experience of the menopause.

OBJECTIVES: To describe the prevalence of, and degree of distress caused by, 15 symptoms commonly attributed to the menopause among a random sample of women aged 45 to 54, selected from the total population of a geographically defined area. DESIGN: Postal questionnaire survey. SETTING: Grampian Health Board area. PARTICIPANTS: Eight thousand women, aged 45 to 54, randomly selected from the Grampian Community Health Index. MAIN OUTCOME MEASURES: Self-reported symptoms, including depression, and use of hormone replacement therapy (HRT) among women of differing menopausal status. RESULTS: The response rate was 78%; 57% of respondents had experienced one or more of the 15 symptoms listed, but only 22% had found such symptoms a problem. Women's experience of classic vasomotor and atrophic symptoms varied according to menopausal status but experience of general somatic and psychological symptoms did not. Users of HRT and women whose menopause was iatrogenic found more symptoms a problem. CONCLUSIONS: Symptoms attributed to the menopause are common among women in the age group studied but often are not perceived as a problem. Among nonusers of HRT, only vasomotor and atrophic symptoms vary with menopausal status. Other somatic and psychological symptoms experienced by middle-aged women cannot be regarded as part of the same "menopausal syndrome'.

Anxiety↗
PubMed1996

Assessment of the ophthalmic artery as a collateral to the cerebral circulation. A comparison of transorbital Doppler ultrasonography and regional cerebral blood flow measurements.

The role of the ophthalmic artery (OA) as a collateral to the cerebral circulation in carotid occlusive disease is somewhat controversial. The aim of this study was to assess the importance of this collateral by comparing the results of transorbital Doppler ultrasonography and regional cerebral blood flow measurements using SPECT and Xenon-133 inhalation in 41 patients with unilateral high-grade internal carotid artery occlusive disease. Both measurements were performed under basal conditions and after the intravenous administration of 1 g acetazolamide to test cerebral vasoreactivity. Based on the direction of OA flow, the patients could be divided into three groups. In Group 1 (n = 16) with anterograde OA flow before and after acetazolamide, baseline rCBF values did not differ significantly between the two sides, or from those of the controls. The side-to-side asymmetry of the response to acetazolamide was also normal. In Group 2 (n = 11) where the OA flow was anterograde or "0 flow" before, but became retrograde after acetazolamide, rCBF was significantly reduced on the symptomatic compared to the non-symptomatic side under basal conditions. However, the increase in rCBF after acetazolamide was within normal limits. In Group 3 (n = 14) the OA flow was reversed both under basal conditions and after the vasodilatory stimulus. Baseline rCBF was significantly lower (p < 0.05) on the symptomatic side compared to the non-symptomatic, and the asymmetry became even greater (p < 0.001) after acetazolamide. Our findings demonstrate that the OA may be an important collateral pathway in patients with ICA occlusive disease, and contribute to the cerebral perfusion reserve in the case of compromised blood supply.

Acetazolamide↗
PubMed1996

Risk factors related to carotid intima-media thickness and plaque in children with familial hypercholesterolemia and control subjects.

To assess the relationship between risk factors for cardiovascular disease and early atherosclerotic changes in the carotid artery, we measured carotid intima-media thickness by B-mode ultrasonography in 61 boys and 29 girls 10 to 19 years old with familial hypercholesterolemia (FH) and 30 control subjects matched for age and sex. All were nonsmokers, and all the FH adolescents had a known mutation in the LDL receptor gene. Mean intima-media thickness in the far wall of the carotid bulb was greater (P = .03) in the FH group than in the control subjects: 0.54 mm (95% confidence interval [CI], 0.52 to 0.56) versus 0.50 mm (95% CI, 0.47 to 0.52). In the entire group, mean and maximum intima-media thicknesses in the carotid bulb were positively associated with levels of apolipoprotein B and fibrinogen after control for pubertal stage (r = .19 to .24; P < .05), as was male sex. Plasma total homocysteine was similar in the FH and control groups and was associated with mean and maximum intima-media thicknesses in the far wall of the common carotid artery and carotid bulb after control for pubertal stage (r = .22 to .28; P < .05). With the exception of the relation between plasma fibrinogen level and mean carotid bulb intima-media thickness, these associations were essentially unchanged in stepwise multiple linear regression analyses, allowing for the entry of BMI and level of HDL cholesterol into the analysis. Carotid artery plaque was present in 10% of the children with FH versus none of the control subjects. Children with plaque had a higher mean cholesterol-years score than children without plaque. These findings suggest that the classic lipid and hemostatic risk factors as well as plasma total homocysteine are associated with markers of early carotid atherosclerosis from the second decade of life. B-mode ultrasonography may prove to be a useful tool in risk stratification of children with FH.

Adolescent↗
PubMed1996

Lipoprotein changes in relation to body mass index in Native American adolescents.

In view of their known high incidence of noninsulin dependent diabetes (NIDDM), we sought to determine whether Native American (Plains Indian) children and adolescents show evidence of risk factors for both NIDDM and cardiovascular disease. Children and adolescents between the ages of 4 and 19 y were recruited, and field days were organized for data collection, which included height, weight [to compute body mass index (BMI)], waist and hip circumference, family histories, quantum of Native American ancestry, and blood sampling for fasting lipids, apolipoproteins, insulin, and glucose. BMI increased with age in boys and girls and tended to be higher than in Caucasian children. The difference was significant in 5-9-y-old (p < 0.05) and 10-14-y-old (p < 0.05) boys and 10-14-y-old girls (p < 0.001). Ten- to 14-y-old girls in the highest quartile for BMI had higher triglyceride levels (p < 0.05) and lower HDL cholesterol (p < 0.001) when compared with those in the lower quartiles. In contrast, 15-19 y olds in the highest quartile for BMI had higher cholesterol, LDL cholesterol, and apolipoprotein B (p < 0.001). The mean fasting insulin levels were not related to BMI. The data suggest that, within this Plains Indian population, obesity associated with elevated lipid levels tends to begin at an early age in Native American children. Insulin levels do not appear to be related to BMI, a putative index of adiposity, in this population of children known to be prone to NIDDM in adult life.

Adolescent↗
PubMed1996

Reduced Global Cerebral Blood Flow in Non-Demented HIV Positive Patients.

Twelve non-demented HIV positive men with different degrees of immunodeficiency were examined with single photon emission computed tomography (SPECT). Reduction in relative global cerebral blood flow was found in HIV positive patients compared to healthy HIV negative controls (p = 0.014). In the patients there was also a change in cerebral flow distribution, with lower global flow compared to central flow (p = 0.01), most pronounced in patients with early disease. In the patients with advanced HIV disease the relative cerebral blood flow was lower than in the controls in 108 of 116 (93%) regions investigated.

Cerebrovascular Circulation↗
PubMed1995

Morphological and functional effects of intranigrally administered GDNF in normal rhesus monkeys.

Effects of a single injection of either 150 micrograms human recombinant glial cell line-derived neurotrophic factor (rGDNF) or vehicle into the right substantia nigra were analyzed in 12 normal adult female rhesus monkeys. The studies included evaluating whole animal behavior, electrochemical recordings of striatal dopamine release, neurochemical determinations of basal ganglia and nigral monoamine levels, and immunohistochemical staining of the nigrostriatal dopamine system. The behavioral effects over the 3-week observation period following trophic factor administration were small, with blinded observers unable to distinguish between GDNF- and vehicle-treated animals. Quantitative measurements did show that five of six trophic factor recipients experienced some weight loss and four of the six GDNF recipients displayed small, but significant, increases in daytime activity levels. In vivo electrochemical recordings in the ipsilateral caudate and putamen 3 weeks after GDNF administration revealed increased potassium-evoked release of dopamine in trophic factor recipients. In a second series of animals killed at the same time, dopamine levels in the substantia nigra and ventral tegmental area of GDNF recipients were significantly increased, with ipsilateral values more than 200% higher than contralateral and control levels. Levels of the dopamine metabolite HVA were significantly elevated in the substantia nigra, ventral tegmental area, and caudate nucleus ipsilateral to the trophic factor injection. There was a trend toward increased HVA levels in the ipsilateral putamen, nucleus accumbens, and globus pallidus in GDNF-treated animals, but the ratios of HVA to dopamine were not significantly different between vehicle- and GDNF-treated recipients. Although some tissue damage from the delivery of concentrated trophic factor was evident, dopamine neurons remained in an adjacent to the injection site. In the substantia nigra ipsilateral to GDNF administration, dopamine-neuron perikaryal size was significantly increased, along with a significant increase in tyrosine hydroxylase-positive axons and dendrites. We conclude that, in the adult rhesus monkey, a single intranigral GDNF injection induces a significant upregulation of mesencephalic dopamine neurons which lasts for weeks.

Animals↗
PubMed1995

Vesicle membrane association of nitric oxide synthase in primary mouse macrophages.

The isoform of nitric oxide synthase (NOS) whose activity is independent of elevated Ca2+ and exogenous calmodulin (iNOS; NOS type II) is inducible in a wide variety of cells and plays a major role in pathophysiology. The notion that iNOS is predominantly cytosolic is based on studies of a transformed cell line; almost nothing is known about the subcellular localization of iNOS in primary cells. Accordingly, we undertook a combined immunoelectron microscopic and biochemical analysis of iNOS in primary mouse macrophages. Approximately one-half of their iNOS activity and protein could be sedimented from 1 M KCl at 100,000 x g. The morphologic counterpart of particulate iNOS was a population of 50 to 80 nm vesicles that did not correspond to lysosomes nor peroxisomes. Vesicular iNOS arose from cytosolic iNOS by undergoing a post-translational modification that increased its apparent molecular mass by 4.5 kDa and promoted its salt-, detergent-, acid- and urea-resistant association with membranes, in the absence of detectable alternative splicing, myristoylation, palmitoylation, acetylation, glycosylation, or COOH-terminal truncation. Although primary macrophage iNOS underwent phosphorylation, ubiquitinylation, and binding of calmodulin tightly enough to resist boiling in SDS, these modifications did not allow us to distinguish between the cytosolic and particulate variants. The apparently novel iNOS-positive vesicles may translocate to phagosomes containing appropriately opsonized particles.

Amino Acid Oxidoreductases↗
PubMed1995

PEG-BP-30 monotherapy attenuates the cytokine-mediated inflammatory cascade in baboon Escherichia coli septic shock.

Septic shock following gram-negative infection is a leading cause of mortality in critically ill patients, accounting for nearly 200,000 deaths a year. The exaggerated production of tumor necrosis factor-alpha (TNF alpha) is known to contribute to hemodynamic collapse and the hematological dyscrasia associated with gram-negative sepsis. Although previous studies have shown TNF alpha antibodies and TNF immunoadhesins to be effective in experimental gram-negative sepsis, we postulated that administration of a novel construct of two modified soluble p55 receptors linked to polyethylene glycol (PEG-BP-30) would also attenuate the hemodynamic and hematologic alterations to lethal Escherichia coli septic shock in non-human primates. Nine adult female and male baboons (Papio anubis), weighing 10-17 kg, were anesthetized and invasively monitored. The nine animals were randomized to receive either 0.2 mg/kg body wt PEG-BP-30 (n = 3), 5.0 mg/kg body wt PEG-BP-30 (n = 3), or placebo (n = 3). One hour after pretreatment, animals were infused with 5-10 x 10(10) CFU/kg of live E. coli iv and vital signs were recorded for the next 8 hr. Arterial blood was drawn for baseline parameters and throughout the study to obtain total and differential white blood cell and platelet counts and cytokine levels (TNF alpha, IL-1 beta, IL-6, IL-8). E. coli bacteremic baboons receiving only placebo demonstrated a significant fall in mean blood pressure and leukopenia. Two of the three animals expired. In contrast, five of the six baboons receiving the PEG-BP-30 survived and these animals exhibited markedly attenuated declines in blood pressure and leukocyte numbers.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

The effect of glial cell line-derived neurotrophic factor in fibrin glue on developing dopamine neurons.

Glial cell line-derived neurotrophic factor (GDNF), a member of the transforming growth factor-beta superfamily, promotes the survival, morphological differentiation, and high-affinity dopamine (DA) uptake of cultured nigral DA neurons. In order to test potential methodology for peptide delivery in vivo, GDNF-containing fibrin glue balls (8 micrograms/ball) were incorporated with pieces of fetal ventral mesencephalon (E15) and transplanted into the anterior chambers of sympathetically denervated adult rats. Five weeks after grafting, the numbers of TH-positive neurons and the nerve fiber density were significantly higher in the ventral mesencephalic grafts treated with GDNF-containing glue balls than in those treated with vehicle. In addition, the laminin and GFAP immunoreactivities were similar between the two groups. These data support the concept that GDNF is a potent trophic factor for DA neurons in vivo and suggest that fibrin glue may provide a unique and safe means to permit prolonged delivery of trophic molecules to CNS tissues.

Animals↗
PubMed1995

Impact of attitudes on maternal decisions regarding infant feeding.

It is essential that physicians and other health care professionals seeking to increase the rate of initiation and duration of breast-feeding build on the body of information concerning factors that influence a woman's attitudes about breast-feeding. The relation between positive attitudes concerning breast-feeding and its initiation is important to the development of programs targeting women before they become pregnant, and to the provision of active support for breast-feeding throughout the pregnancy, perinatal, and postnatal period. However, it is not sufficient for these programs to target only the mother or potential mother; members of a woman's social network must be considered as information targets. Educational programs must also be directed to the appropriate racial or ethnic group to develop programs that reach the individuals (father, female relative, or friend) most likely to influence the mother's breast-feeding decision. Physicians may be very knowledgeable about the nutritional and immune properties of human milk and yet not be supportive of the act of breast-feeding. This lack of support may be manifested by the lack of verbal support for women who intend to or are in the process of breast-feeding, the provision of infant formula before or at the time of birth of the baby, or encouragement to terminate breast-feeding should the mother encounter any difficulties with lactation. To increase physician awareness of the process of breast-feeding and the properties of human milk, information about the benefits should be integrated in both the basic science and the clinical curricula of medical schools. Primary care training programs, including obstetrics, should actively involve trainees in the management of breast-feeding women so that trainees become aware of the spectrum of circumstances that confront women seeking to establish and maintain successful breast-feeding. This type of involvement would provide a contextual base for physicians' understanding the attitudes and behaviors supportive of breast-feeding. Attitudes and behavior of women, although more complex then demographic factors, provide a powerful tool for meeting the Healthy People 2000 goals for the initiation and duration of breast-feeding. It is important to build on the base of research reviewed here to develop new and and more powerful interventions. Thus the emphasis on the known health advantages of human milk or the discovery of additional health benefits of breast-feeding should continue to be discussed because they may tip the balance in favor of breast-feeding for some women. Nevertheless, it may ultimately be more important to increase the amount of information provided to women (and girls and boys) about the practical aspects of the breast feeding process (e.g., ease of night feeding, fathers ability to feed mother's milk by bottle, lower cost, strategies to control leaking) then to rely solely on the positive health outcomes related to breast-feeding.

Adult↗