PubMed Health⌕ Search

Biomedical subjects

N Hill

Publications and source records attributed to N Hill.

At least 37 records · Page 2Linked to original sources
PubMed1998

Immunologic parameters in chronic fatigue syndrome, major depression, and multiple sclerosis.

The purpose of this study was to evaluate the immune dysfunction hypothesis of chronic fatigue syndrome (CFS) by comparing immunologic data from patients with CFS with data from patients with other fatiguing illnesses--major depression and multiple sclerosis (MS)--and with data from healthy sedentary controls. The subjects were 65 healthy sedentary controls, 71 CFS patients (41 with no axis-I diagnosis), 23 patients with mild MS, and 21 patients with major depression. Blood was sampled and assayed for the following: (1) immunologic serologic variables--circulating immune complexes (i.e., Raji cell and C1q binding), immunoglobulins A, E, G, and M, and IgG subclasses; (2) cell surface activation markers--the proportion of CD4+ cells expressing CD45RA+ and CD45RO+ and the proportion of CD8+ cells expressing CD38+, CD11b-, HLA-DR+ and CD28+; and (3) natural killer (NK) total cell count as well as the proportion of lymphocytes expressing NK cell surface markers (i.e., CD3-/CD16+ and CD56+. Of the 18 variables studied, differences between CFS patients and controls were found only for IgG1 and IgG3. When CFS patients were stratified by the presence or absence of concurrent axis-I disease, it was the group with axis-I disorder that had the lowest IgG1 values-contrary to expectation. When data from patients with MS and major depression were also evaluated, the subclass deficiency was no longer significant. The one group to show evidence for immune activation (i.e., an elevated proportion of CD4+ cells expressing the CD45RA+ activation marker) was the group with mild MS. These data support neither immune dysfunction nor immune activation in CFS or in major depression, for the variables studied. The reductions in IgG subclasses may be an epiphenomenon of patient or control subject composition. In contrast, MS, even in the mild and early stages, as in the patients studied here, is associated with immune activation.

Adult↗
PubMed1998

Effect of serum on vascular smooth muscle function.

Serum contains many biologically active factors influencing cell growth and is commonly used as a culture medium supplement. It has not generally been appreciated that serum can affect vascular tone. We have observed that the contractile response of aortic rings previously exposed to 10% fetal bovine serum (FBS) for 24 hours and then stimulated with phenylephrine (0.01-1microM) or angiotensin II (1microM) is significantly diminished compared to 1) rings incubated in FBS for only 6 hours, 2) aortic rings previously incubated in 1% FBS or 3) aortic rings incubated in 10% bovine serum albumin for 24 hours. A similar attenuated response was also seen when the vascular aortic rings were incubated in heat inactivated adult bovine serum. To test whether prostaglandins might be induced by factors contained in serum and account for the diminished stimulated contractile response, rings were incubated for 24 hours in media containing 10% FBS with either indomethacin 10microM, corticosterone 100nM or 11-dehydrocorticosterone 100nM. These agents are known to affect prostaglandin synthesis. Contractile responses were then measured accordingly. In each series, the previously attenuated contractile response to phenylephrine and to angiotensin II was fully restored with prostaglandin synthesis inhibition. Thus, factors contained in serum are capable of blunting the stimulated contractile response of rat aortic vessels. These serum factors appear to act by inducing prostaglandin synthesis in vascular tissue.

Animals↗
PubMed1998

Does the Child Health Computing System adequately identify children with cerebral palsy?

BACKGROUND: This paper assesses the usefulness of the Child Health Computing System as a source of information about children with cerebral palsy. METHODS: A comparative survey of information held on the Child Health Computing System (CHCS) and the Northern Ireland Cerebral Palsy Register (NICPR) in one Health and Social Services Board in Northern Ireland was carried out. The sample comprised children with cerebral palsy aged 5-9 years. RESULTS: Of the 135 cases recorded on the NICPR, 47 per cent were not found on the CHCS; the majority of these children had no computer record of any medical diagnosis. Of the 82 cases recorded on the CHCS, 10 (12 per cent) were not found on the NICPR; five of these cases (6 per cent) were found on follow-up not to have CP. CONCLUSIONS: Unless improvements are made in case ascertainment, case validation and recording activities, the evidence suggests that the CHCS will not be able to provide the same quality of information for needs assessment and surveillance of very low birthweight infants in relation to cerebral palsy as is provided by a specialist case register.

Cerebral Palsy↗
PubMed1998

Single-blind, placebo phase-in trial of two escalating doses of selegiline in the chronic fatigue syndrome.

AIM: To perform a clinical trial of selegiline in 25 patients with chronic fatigue syndrome (CFS) where patients were told they would receive placebo or active agent at different times during the 6-week trial. We chose selegiline, a specific monoamine oxidase (MAO) B receptor inhibitor, because a prior trial of lowdose phenelzine, a nonspecific MAO inhibitor, showed a small but significant therapeutic effect. METHODS: Questionnaires comprised of 19 tests of mood, fatigue, functional status and symptom severity were collected at the start and end of the trial as well as 2 weeks after its start. The trial was done in three 2-week blocks: in the first, 2 placebo pills were given per day; in the next, one 5-mg tablet of agent and one placebo were given per day, and in the last, a 5-mg tablet of agent was given twice a day. The plan was to compare the changes in the 19 tests during the placebo phase to those found in the active treatment phase in 19 patients completing the trial. FINDINGS: Significant improvement in 3 variables-tension/anxiety, vigor and sexual relations-was found. A significant pattern of improvement compared to worsening was found for the 19 self-report vehicles during active treatment as compared with placebo treatment. Evidence for an antidepressant effect of the drug was not found. CONCLUSIONS: Selegiline has a small but significant therapeutic effect in CFS which appears independent of an antidepressant effect.

Activities of Daily Living↗
PubMed1997

Effects of licorice derivatives on vascular smooth muscle function.

Vascular smooth muscle contains a bidirectional form of the enzyme 11beta-hydroxysteroid dehydrogenase (11beta-HSD) which can inactivate (dehydrogenase) endogenous circulating glucocorticoids (GCs) or activate (oxo-reductase) 11-dehydro-metabolites by their conversion back to the parent steroid. Enzyme direction in vascular smooth muscle (VSM) has potential physiological consequences since GCs may enhance the response to known vasoconstrictors. We determined that carbenoxolone is a competitive inhibitor of 11beta-HSD contained in VSM cells with a lower Ki for forward dehydrogenase reaction (0.02 microM) compared to the oxo-reductase reaction (0.41 microM). To test whether changes in enzyme directional activity can affect the contractile response, aortae from adrenally intact Sprague Dawley rats were removed and sectioned into 2.5 mm rings. Rings were incubated with corticosterone 10 nM plus carbenoxolone (CBX) 10 microM (a concentration well above the Ki for both the dehydrogenase and oxo-reductase reaction) for 24 hrs. These rings showed an enhanced dose dependent contractile response to phenylephrine (PE) 0.01 microM(-1) microM and to angiotensin II 1 microM compared to rings incubated with corticosterone alone, CBX alone, or controls: [e.g. response to PE 1 microM in mg of contractile force, mean +/- SE: corticosterone plus CBX 1495 +/- 162 (n=10) vs corticosterone 1039 +/- 64 (n=9), p<0.05]. Aortic rings preincubated with 11-dehydrocorticosterone 10(-7)M and CBX 10 microM displayed a decreased contractile response compared to 11-dehydrocorticosterone alone. Thus in situ glucocorticoid metabolism is important in mediating the constrictor responses of vascular tissue.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1997

Exaggerated pulmonary hypertension with monocrotaline in rats susceptible to chronic mountain sickness.

Hilltop (H) strain Sprague-Dawley rats are more susceptible to chronic mountain sickness than are the Madison (M) strain rats. It is unclear what role pulmonary vascular remodeling, polycythemia, and hypoxia-induced vasoconstriction play in mediating the more severe pulmonary hypertension that develops in the H rats during chronic hypoxia. It is also unclear whether the increased sensitivity of the H rats to chronic mountain sickness is specific for a hypoxia effect or, instead, reflects a general propensity toward the development of pulmonary hypertension. Monocrotaline (MCT) causes pulmonary vascular remodeling and pulmonary hypertension. We hypothesized that the difference in the pulmonary vascular response to chronic hypoxia between H and M rats reflects an increased sensitivity of the H rats to any pulmonary hypertensive stimuli. Consequently, we expected the two strains to also differ in their susceptibility to MCT-induced pulmonary hypertension. Pulmonary arterial pressures in conscious H and M rats were measured 3 wk after a single dose of MCT, exposure to a simulated high altitude of 18,000 ft (barometric pressure = 380 mmHg), and administration of a single dose of saline as a placebo. The H rats had significantly higher pulmonary arterial pressures and right ventricular weights after MCT and chronic hypoxia than did the M rats. The H rats also had more pulmonary vascular remodeling, i.e., greater wall thickness as a percentage of vessel diameter, after MCT and chronic hypoxia than did the M rats. The H rats had significantly lower arterial PO2 than did the M rats after MCT, but the degree of hypoxemia was mild [arterial PO2 of 72.5 +/- 0.8 (SE) Torr for H rats vs. 77.4 +/- 0.8 Torr for M rats after MCT]. The H rats had lower arterial PCO2 and larger minute ventilation values than did the M rats after MCT. These ventilatory differences suggest that MCT caused more severe pulmonary vascular damage in the H rats than in the M rats. These data support the hypothesis that the H rats have a general propensity to develop pulmonary hypertension and suggest that differences in pulmonary vascular remodeling account for the increased susceptibility of H rats, compared with M rats, to both MCT and chronic hypoxia-induced pulmonary hypertension.

Altitude↗
PubMed1997

Wavelengths of bioconvection patterns

Bioconvection occurs as the result of the collective behaviour of many micro-organisms swimming in a fluid and is realised as patterns similar to those of thermal convection which occur when a layer of water is heated from below. A methodology is developed to record the bioconvection patterns that are formed by aqueous cultures of the single-celled alga Chlamydomonas nivalis. The analysis that is used to quantify the patterns as a function of cell concentration, suspension depth and time is described and experimental results are presented.

Journal Article↗
PubMed1996

The efficacy of Prrrikweg gel in the treatment of insect bites: a double-blind, placebo-controlled clinical trial.

OBJECTIVE: This study was conducted to examine the efficacy of Prrikweg gel, a homeopathic after-bite gel, in relieving the effects of mosquito bites, in particular itching and erythema. DESIGN: A double-blind, randomized, placebo-controlled clinical trial. SETTING: London School of Hygiene and Tropical Medicine. SUBJECTS: 100 healthy volunteers. METHODS: All subjects were bitten under laboratory conditions by Aedes aegypti mosquitoes at one spot on the ventral aspect of the left forearm and another on a corresponding position on the right forearm. One spot was treated with the homeopathic after-bite gel and the other with a placebo gel. MAIN OUTCOME MEASURES: Itching was assessed on a 5-point discrete rating scale at 0, 0.5, 1, 26.5, and 48 h post-bite to compare the itch-relieving efficacy of the two treatments. Erythema development was assessed by photographing the bite sites, measuring length and width of the erythema with a calliper, and comparing the ratio of the erythema surface at baseline T(0) to the mean erythema surface at 0.5, 1, 26.5, and 48 h post-bite (T mean) for the two treatments. RESULTS: Testing erythema development by comparing the ratio T(0)/T (mean, after-bite gel) and the ratio T(0)/T (mean, placebo gel) gave a two-tailed p = 0.098(95% Cl, -0.031-0.361) in favour of the after-bite gel. There was not a statistically significant difference between the itch relief provided by the two treatments (two-tailed p = 0.424; 95 percent Cl, -0.541-0.191). The correlation between itching and erythema was significant (r = 0.46; p < 0.001). CONCLUSIONS. There are strong indications that the homeopathic after-bite gel reduces erythema development following mosquito bites. The homeopathic mother tinctures of Echinacea angustifolia DC., Ledum palustre L., Urtica urens L. as well as the Hamamelis extract in this gel, whether alone or in combination, are the biologically active ingredients. The homeopathic after-bite gel was not demonstrated to relieve itching; however, based on the correlation between erythema and itching, an effect on itching is not inconceivable.

Adult↗
PubMed1995

A placebo controlled clinical trial investigating the efficacy of a homeopathic after-bite gel in reducing mosquito bite induced erythema.

A randomised, placebo controlled clinical trial was conducted to examine the efficacy of a homeopathic after-bite gel in the symptomatic relief of mosquito bites. Sixty eight healthy volunteers were bitten under laboratory conditions by Aedes aegypti mosquitoes at three spots, on the ventral aspect of the forearm. One bite was treated with the homeopathic after-bite gel, another bite with a placebo gel which was identical in appearance and smell to the homeopathic after-bite gel, and the third bite remained untreated. Immediately after the bites and 1, 3, 6, 26 and 31 hours post-bite, the length and width of the erythema were measured with a calliper, and photographs were taken of the bite sites from which the size of the erythema was subsequently determined. This was followed by assessment of the extent of itching with a verbal analogue scale, and finally treatment took place. For each spot the total erythema was calculated as the area under the plotted curve of the erythema at different time points (mm2*h) and the total sum of the itch scores was determined. For the bites treated with the homeopathic after-bite gel the median total erythema was 10.500 mm2*h. For the spots treated with the placebo gel and the untreated spots the median total erythema was 12.900 mm2*h and 13.300 mm2*h, respectively. The difference between the spots treated with the homeopathic after-bite gel and the untreated spots came close to significance (two-tailed P = 0.06), which was not the case for the difference between the spots treated with the homeopathic after-bite gel and the spots treated with placebo gel (P = 0.13). After pooling the data of a very similar previous pilot study and the present study (ntotal = 83), the homeopathic after-bite gel was significantly superior to no treatment (two-tailed P = 0.003) as well as to placebo gel (two-tailed P = 0.03). Comparing itching after the three treatments, no significant differences could be demonstrated. The extent of itching was positively correlated with the area of the erythema (r = 0.63). Treatment of mosquito bites with the homeopathic after-bite gel will reduce the erythema compared to no treatment. Comparison with the placebo gel suggests it is the plant extracts which are the active components of this gel.

Adult↗
PubMed1995

Reducing heterogeneity in chronic fatigue syndrome: a comparison with depression and multiple sclerosis.

Chronic fatigue syndrome (CFS) is a heterogeneous illness characterized by a high prevalence of psychiatric problems. We reasoned that we could reduce heterogeneity by excluding patients with psychiatric problems preceding CFS. We compared the functional status, mood, fatigue level, and psychiatric status of this more homogeneous group of CFS patients with the same parameters in patients with mild multiple sclerosis and in patients with major depression or dysthymia. Patients with CFS and those with multiple sclerosis were similar in terms of level of anger, severity of depression, level of anxiety, and frequency of current psychiatric diagnoses. Patients with CFS resembled depressed patients in having impaired vigor and experiencing substantial fatigue and confusion--problems constituting part of the case definition of CFS. The group with CFS was not psychologically vulnerable before the development of this condition and maintained adequate networks of social support despite disabling illness. Stratification to exclude patients with prior psychiatric disease and those with mild CFS allowed us to define a group of patients with CFS who more resembled patients with mild MS than patients with major depression or dysthymia and thus were more likely to have illness with an infectious or immunologic cause. Use of such a stratification strategy should prove important in testing of the viral/immunologic hypothesis of the etiology of CFS.

Adolescent↗
PubMed1994

The role of endogenous nitric oxide and platelet-activating factor in hypoxia-induced intestinal injury in rats.

BACKGROUND/AIMS: Nitric oxide is an endothelium-derived relaxing factor that promotes capillary integrity, inhibits leukocyte adherence and activation, and scavenges oxygen radicals. Because these effects are important in experimental intestinal injury, we studied the role of NO inhibition on hypoxia-induced bowel necrosis in the rat and investigated the interaction between platelet-activating factor (PAF) and NO in this model. METHODS: Sprague-Dawley rats were treated with either hypoxia, NO synthase inhibition (NG-methyl-L-arginine [LNMA] or NG-nitro-L-arginine methyl ester [L-NAME]), hypoxia+LNMA, hypoxia+LNMA+NO donors, or hypoxia+LNMA+PAF receptor inhibition. Evaluations included blood pressure, superior mesenteric artery blood flow, arterial blood gases, histological intestinal injury, intestinal myeloperoxidase activity, and intestinal PAF activity. RESULTS: We found that hypoxia alone for 90 minutes (10% O2, partial O2 pressure = 45 mm Hg) or LNMA alone had no detrimental effects. However, hypoxia+LNMA together caused hypotension, metabolic acidosis, intestinal injury, increased intestinal myeloperoxidase activity, and elevated intestinal PAF concentrations that were prevented by exogenous L-arginine. Furthermore, the hypotension and intestinal injury was prevented by PAF receptor blockade. CONCLUSIONS: We conclude that endogenous NO protects the intestine from hypoxia-induced inflammation and injury, and the balance between local PAF and NO modulates the outcome of hypoxia-stressed intestine.

Animals↗
PubMed1994

Fractures and dislocations of the foot and ankle in diabetics associated with Charcot joint changes.

This study was undertaken to evaluate the occurrence of Charcot joint changes in diabetic patients after fractures and/or dislocations of the foot and ankle. There were 20 fracture/dislocations of the foot and ankle in 18 patients, with an average follow-up of 27 months (range 14-70 months). There were eight fractures of the midfoot, six fractures of the ankle, four fractures of the hindfoot, and two fractures of the forefoot. Eight fractures were followed by the development of Charcot changes: five in the midfoot and one each in the forefoot, hindfoot, and ankle. Of nine fractures recognized early and initially treated by early immobilization or ORIF, seven healed uneventfully. Two fractures, both open injuries, developed soft tissue infection and osteomyelitis, respectively. Of the 11 fractures in which there was a delay in diagnosis and treatment, eight developed Charcot changes. The early recognition and appropriate treatment of fractures in diabetic patients appears to be important in the prevention of Charcot joint changes.

Adult↗
PubMed1994

Postreceptor signal transduction mechanisms involved in octreotide-induced inhibition of angiogenesis.

BACKGROUND: Somatostatin analogues inhibit peptide release and cell growth through multiple postreceptor signal transduction mechanisms (PRSTM), including G proteins (GP), cyclic adenosine monophosphate (cAMP), calcium, protein kinase C (PKC), and tyrosine phosphatase (TP). Octreotide acetate (OA), a somatostatin analogue, has been shown to inhibit angiogenesis; however, the PRSTM involved are unknown. METHODS: Fertilized chicken eggs were obtained and incubated. On day 3, embryos were removed and placed in plastic wrap hammocks. On day 7, disks containing OA, test substances that interfere with PRSTM, or combinations of OA plus a test substance were placed on the developing chorioallantoic membrane. Blood vessel growth under each disk was assessed at 24 hours. Data were evaluated by chi-squared analysis. RESULTS: OA's ability to inhibit angiogenesis is significantly diminished when combined with calcium, bradykinin (increases calcium), pertussis toxin (inhibits GP), or 3-isobutyl-1-methylxanthine (increases cAMP). In contrast, no significant decrease is noted in OA's ability to inhibit angiogenesis when combined with phorbol ester (activates PKC) or vanadate (inhibits TP). CONCLUSIONS: OA-induced inhibition of angiogenesis is GP, calcium, and cAMP dependent and is PKC and TP independent. Better understanding of the PRSTM involved with OA-induced inhibition of angiogenesis may lead to enhancement of OA's effect on angiogenesis.

Animals↗
PubMed1993

Increase in plasma platelet-activating factor levels in enterally fed preterm infants.

Because platelet-activating factor (PAF) has been implicated in the pathogenesis of neonatal necrotizing enterocolitis (NEC), we designed a prospective study to examine plasma PAF levels during the first 14 days of feeding in a population of neonates of less than 32 weeks gestation. We found that significantly more patients had detectable plasma PAF levels on days 3 and 14 of feeding when compared to their prefeeding levels (7% on day 0 vs. 26% at day 3, p = 0.04; none on day 0 vs. 18.5% at day 14, p = 0.01). This finding could not be explained by decreased plasma activity of acetylhydrolase, the PAF breakdown enzyme, spontaneous endotoxinemia or a maturational effect. None of the infants who developed detectable PAF levels after feedings were begun went on to develop NEC. We conclude that our findings may reflect increased intestinal PAF production with the provision of feedings to some premature infants. However, this phenomenon by itself does not appear to be a sufficient condition for the subsequent development of NEC.

Acetyltransferases↗