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Biomedical subjects

S Morton

Publications and source records attributed to S Morton.

At least 19 recordsLinked to original sources
PubMed1999

N-Substituted analogues of S-nitroso-N-acetyl-D,L-penicillamine: chemical stability and prolonged nitric oxide mediated vasodilatation in isolated rat femoral arteries.

Previous studies show that linking acetylated glucosamine to S-nitroso-N-acetyl-D,L-penicillamine (SNAP) stabilizes the molecule and causes it to elicit unusually prolonged vasodilator effects in endothelium-denuded, isolated rat femoral arteries. Here we studied the propanoyl (SNPP; 3 carbon side-chain), valeryl (SNVP; 5C) and heptanoyl (SNHP; 7C) N-substituted analogues of SNAP (2C), to further investigate other molecular characteristics that might influence chemical stability and duration of vascular action of S-nitrosothiols. Spectrophotometric analysis revealed that SNVP was the most stable analogue in solution. Decomposition of all four compounds was accelerated by Cu(II) and cysteine, and neocuproine, a specific Cu(I) chelator, slowed decomposition of SNHP. Generation of NO from the compounds was confirmed by electrochemical detection at 37 degrees C. Bolus injections of SNAP (10 microl; 10(-8)-10(-3) M) into the perfusate of precontracted, isolated rat femoral arteries taken from adult male Wistar rats (400-500 g), caused concentration-dependent, transient vasodilatations irrespective of endothelial integrity. Equivalent vasodilatations induced by SNVP and SNHP were transient in endothelium-intact vessels but failed to recover to pre-injection pressures at moderate and high concentrations (10(-6)-10(-3) M) in those denuded of endothelium. This sustained effect (> 1 h) was most prevalent with SNHP and was largely reversed by the NO scavenger, haemoglobin. We suggest that increased lipophilicity of SNAP analogues with longer sidechains facilitates their retention by endothelium-denuded vessels; subsequent slow decomposition within the tissue generates sufficient NO to cause prolonged vasodilatation. This is a potentially useful characteristic for targeting NO delivery to areas of endothelial damage.

1-Octanol↗
PubMed1998

IgE and non-IgE mediated allergic disorders in systemic lupus erythematosus.

OBJECTIVE: To ascertain the prevalence of IgE and non-IgE mediated allergic disorders in patients with systemic lupus erythematosus (SLE). METHODS: 49 SLE cases (all satisfying at least four "Revised ARA Criteria") and 98 healthy, age, and sex matched controls (randomly selected through two urban general practices and one rural general practice) were interviewed by telephone to screen for a history of allergy. Subjects with a history of allergic rhinitis, asthma or atopic eczema then underwent skin prick testing to confirm underlying IgE mediated disease. RESULTS: Analysis of the data by conditional logistic regression revealed no significant difference in frequency of allergic disorders in SLE cases and controls (odds ratio (OR) 0.92, 95% confidence intervals (CI) 0.45, 1.86). In addition a subgroup analysis of subjects with IgE mediated/associated atopic disorders, showed that cases and controls were at a similar risk of having these conditions (OR 0.90, 95% CI 0.41, 1.96). CONCLUSIONS: This study suggests that people with SLE are not at an increased risk of IgE mediated/associated allergic disorders, in contrast with previous reports.

Adult↗
PubMed1998

Basaloid follicular hamartoma, total body hair loss and SLE.

We describe a patient with systemic lupus erythematosus (SLE) and antiphospholipid antibody syndrome (APLS) who developed a plaque-like lesion around the mouth and lost all body hair. Biopsies of the circumoral lesion and scalp, were originally reported as containing extensive basal cell carcinoma, but on review, both showed the typical appearance of a benign malformation of the hair follicle known as basaloid follicular hamartoma. Regrowth of hair and partial resolution of the peri-oral plaque occurred with more aggressive treatment of her SLE, but the basaloid follicular hamartomas in her scalp skin persisted. There is a known, but rare, association between this pattern of basaloid follicular hamartoma, alopecia and myasthenia gravis, but only two cases have been described in association with SLE and none with APLS.

Adult↗
PubMed1997

A community outbreak of Vero cytotoxin producing Escherichia coli O157 infection linked to a small farm dairy.

A community outbreak of infection with Vero cytotoxin producing Escherichia coli O157 (VTEC 0157) occurred in a small area of north west England in 1996. An outbreak control team was established to investigate the outbreak and implement control measures. Nine people developed symptomatic infections with VTEC O157, and a further three were found to be excreting the bacteria. All were infected with the same genotype of VTEC O157. Three children under 5 years of age and one adult were admitted to hospital. One child developed haemolytic uraemic syndrome. All cases recovered. All primary cases had consumed milk from a particular farm dairy. No other common foods were identified. The farm dairy had a faulty pasteuriser and the potential for post pasteurisation contamination existed. VTEC O157 was isolated from a milk sock specimen and from two cows, but these strains differed from that infecting the cases. All local doctors and the public were alerted and advised about preventative measures. Distribution of unpasteurised milk from the farm was discontinued as was the sale of pasteurised milk when the faulty pasteuriser was discovered. A replacement pasteuriser was installed and checked before milk was released for human consumption. No conclusive evidence of the origin of this outbreak was found, but the farm was the most probable source. The investigations raised concerns about the distribution of VTEC O157 colonised dairy cattle, the natural history of such colonisation, the effectiveness of pasteurisation with respect to the elimination of VTEC O157, and the effectiveness of current legislation for the prevention and control of milkborne infection.

Adult↗
PubMed1997

Inability of histamine to regulate TNF-alpha production by human alveolar macrophages.

Tumor necrosis factor alpha (TNF-alpha), a major product of alveolar macrophages (AM), has been implicated in many pulmonary diseases. Histamine, a mediator important in pulmonary inflammation, has been demonstrated to regulate the production of TNF-alpha by monocytes. In this study, we show that human AM and monocytes differ in their responses to histamine. Whereas histamine suppressed lipopolysaccharide (LPS)-stimulated TNF-alpha production by monocytes through a cAMP-dependent mechanism, it had no effect on either cAMP levels or TNF-alpha production by AM. In contrast, both PGE2 and IL-10 suppressed LPS-stimulated TNF-alpha production by AM and monocytes. The lack of response of AM to histamine appears unique, as histamine suppressed LPS-stimulated TNF-alpha production by mononuclear cells isolated from sites of acute and chronic inflammation, as well as from noninflammatory tissues, and by macrophages differentiated in vitro. In the presence of the phosphodiesterase (PDE) inhibitor 3-isobutyl-1-methylxanthine, histamine increased cAMP levels in AM. Freshly isolated monocytes and AM did not differ in PDE activity. However, PDE activity in AM, but not in monocytes, was increased 15 min after culture with histamine and may, in part, be responsible for the inability of histamine to suppress TNF-alpha production by AM. However, this increase was small and we hypothesize that additional mechanisms may contribute to the unresponsiveness of AM to histamine. We suggest that the lack of response of AM to histamine may be important in the host defense function of AM in the distal lung.

Adult↗
PubMed1996

Two critical periods of Sonic Hedgehog signaling required for the specification of motor neuron identity.

Antibodies that block Sonic Hedgehog (SHH) signaling have been used to show that SHH activity is required for the induction of floor plate differentiation by the notochord and independently for the induction of motor neurons by both the notochord and midline neural cells. Motor neuron generation depends on two critical periods of SHH signaling: an early period during which naive neural plate cells are converted into ventralized progenitors and a late period that extends well into S phase of the final progenitor cell division, during which SHH drives the differentiation of ventralized progenitors into motor neurons. The ambient SHH concentration during the late period determines whether ventralized progenitors differentiate into motor neurons or interneurons, thus defining the pattern of neuronal cell types generated in the neural tube.

Animals↗
PubMed1994

Cryptogenic organizing pneumonia with atypical histopathological features.

A case report of cryptogenic organizing pneumonia (COP); also known as bronchiolitis obliterans organizing pneumonia (BOOP) is presented. The histopathologic findings of COP are well documented in the literature and typically consist of organizing pneumonia of uniform appearance. This case report describes, in addition to the classic findings, more acute exudative inflammation not usually associated with this condition. Variation in the evolution of the pneumonic process is one of the reasons for reporting this case. The promotion of awareness of this treatable condition is the other reason for reporting this case. When multifocal areas of consolidation are demonstrated radiologically, particularly when peripheral and basal, and in the correct clinical setting, the possibility of COP should be entertained. This condition responds dramatically to steroid therapy, and has a good prognosis.

Bronchiolitis Obliterans↗
PubMed1993

A comparison of alpidem and placebo in relieving benzodiazepine withdrawal symptoms.

Chronic normal-dose benzodiazepine users requesting drug withdrawal were allocated to substitution with either the new anxiolytic alpidem (n = 13) or placebo (n = 12). During the first 2 weeks of the tapering programme, the dose of benzodiazepine was kept constant; for the next 2 weeks it was halved and half-dose alpidem (25 mg twice daily) or placebo substituted; for weeks 5 and 6, the benzodiazepine was discontinued and full-dose alpidem or placebo given; next alpidem or placebo were tapered to half-dose and then finally discontinued. Regular anxiety and tranquillizer withdrawal ratings were made. Nine of 12 patients given placebo withdrew successfully compared with four of 13 alpidem-treated patients. Anxiety and other symptom levels increased in the alpidem but not the placebo patients. It was concluded that alpidem is not helpful in helping patients withdrawing from a benzodiazepine withdrawal perhaps because of partial agonist properties. These actions may imply a lesser propensity to induce dependence on long-term use.

Adult↗
PubMed1992

Alpidem and lorazepam in the treatment of patients with anxiety disorders: comparison of physiological and psychological effects.

The physiologcal and psychological effects of the novel imidazo-pyridine alpidem were compared with those of the benzodiazepine lorazepam in the context of a clinical trial. Twenty-three psychiatric out-patients with generalised anxiety disorder received alpidem (mean dose 112.5 mg daily) or lorazepam (mean 3.5 mg daily) in doses adjusted to clinical need under double-blind conditions. A battery of tests was performed before and after four weeks treatment. Anxiety scores improved very significantly in both groups with no subjective sedation nor other particular side-effects noted in either group. However, lorazepam reduced the EEG averaged evoked response and produced significant impairment in the reaction time and memory tests whereas alpidem had no such effects. Alpidem therefore shows promise as an effective anxiolytic devoid of the adverse psychomotor and cognitive effects often associated with the benzodiazepines.

Adult↗
PubMed1991

Benzodiazepine problems.

Benzodiazepines present problems related to both unwanted and withdrawal effects. Dosage adjustments usually obviate unwanted effects except for paradoxical reactions such as hostility. Patients with apparent benzodiazepine dependence need careful assessment with respect to personality, social situation and psychiatric disorder. The patient must be motivated and carefully prepared for withdrawal and taught anxiety management techniques. Withdrawal must always be gradual over at least 6 weeks but very prolonged schedules are counter-productive. Substituting a long-acting for a medium-acting benzodiazepine may be helpful in the more intractable cases. An antidepressant may be needed if a depressive disorder supervenes, but other adjunctive therapies are usually unhelpful.

Anti-Anxiety Agents↗
PubMed1990

Studies with alpidem in normal volunteers and anxious patients.

Alpidem, an imidazo-pyridine compound, has been evaluated as an anxiolytic in comparison with placebo and lorazepam. In the first of our normal volunteer studies, we compared single doses of alpidem, 25, 50 and 100 mg with lorazepam 2 mg and placebo on a range of cognitive, psychomotor and EEG variables. Lorazepam and the highest (100 mg) dose of alpidem impaired performance on a range of psychomotor tasks, the effects of the benzodiazepine being more severe and more prolonged. No impairment of performance was observed with the 25 and 50 mg doses. In the second study, the focus was on memory functions. Lorazepam, 2 mg, caused anterograde amnesia which was most apparent 1 h post-drug but persisted until 4 h: sedation was marked. By contrast, single doses (25, 50 mg) of alpidem had little effect on either memory or alertness. The third study compared the effects of alpidem (25, 50 mg) and lorazepam (1 mg) with placebo, each given twice-daily for 8 days to normal volunteers. On the final day, a test dose of ethanol was given. Lorazepam impaired many tests of cognitive and psychomotor function, and this impairment was enhanced by ethanol. By contrast, alpidem produced less impairment with less interaction with alcohol. In a fourth, clinical, study, 24 patients with a DSM III primary diagnosis of generalised anxiety disorder were treated, under double blind conditions, with doses adjusted according to clinical need of either alpidem 25-150 mg daily or lorazepam 1-6 mg daily.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Anxiety Agents↗
PubMed1988

Sequential intrahepatic metabolic effects of enteric galactose alimentation in newborn rats.

We determined metabolic responses after enteric galactose alimentation in 5- to 7-day-old newborn rats fasted for 24 h. The glycemic response was attenuated after enteric galactose feeding compared with the response after enteric glucose-fed rat pups. 14C radioactivity in blood from galactose-fed pups was reduced as counts in blood galactose were lower than counts in blood glucose in glucose-fed pups. Nonetheless within 15 min, [14C] from galactose appeared in blood glucose suggesting rapid conversion of galactose to glucose. The plasma insulin response was also attenuated after galactose feeding compared with the insulin response after enteric glucose. Hepatic glycogen content increased rapidly after enteric galactose feeding and was higher than after glucose feeding at 60, 120, and 180 min. Significant glycogen synthesis after oral glucose was delayed and occurred at 240 min. Carbon radioactivity in glycogen was higher in galactose fed pups between 15 and 360 min of the study. Serial determination of hepatic metabolites revealed an increase of galactose-1-phosphate levels after oral galactose at 240 and 300 min and a transient decline of ATP at 15 min. Other hepatic metabolites did not demonstrate significant differences between the two groups. These data suggest that hepatic glycogen synthesis is more rapid and occurs sooner after galactose than after glucose alimentation in previously fasted newborn rats. Galactose may enter a more direct pathway for neonatal hepatic glycogen synthesis. The relatively delayed entry of glucose label into hepatic glycogen and the delay of net glycogen synthesis after oral glucose suggest that glucose entry is not direct and may require further metabolism before incorporation into glycogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

The current physical therapy regimens of 108 consecutive patients attending a regional cystic fibrosis unit.

Comprehensive assessment of patients attending the Regional Cystic Fibrosis Unit includes a detailed evaluation of their physical therapy habits and management. The following were analysed during the assessment by the physiotherapist: the frequency of patient contact with a physiotherapist, the techniques used for chest clearance, the exercise habits, the postural drainage equipment used, if any, and the frequency of respiratory cultures. The results were divided into three groups: group 1, 72 patients (66%), were first-referral patients (FR) to our cystic fibrosis unit; group 2, 26 (24%), received all their care at our unit (CFU); group 3, 10 (9%), were attending a local hospital but had had a previous assessment at our unit (PA). For all factors examined the CFU and PA patients had a more effective management than the FR patients cared for by local hospitals, with the conclusion drawn that regular contact with a physiotherapist at a cystic fibrosis unit improves the understanding, compliance, and effectiveness of the patient's treatment programme.

Ambulatory Care Facilities↗
PubMed1987

The metabolic response of the canine neonate to twenty-four hours of fasting.

The metabolic effects of 24 hours of neonatal fasting in unanesthetized dogs were compared to fasting for three hours during the first day of life. Blood glucose, lactate, and ketones were unaltered while FFA (0.94 +/- 0.07 v 0.70 +/- 0.04 mmol/L, P less than .01), glycerol (0.21 +/- 0.01 v 0.12 +/- 0.01 mmol/L, P less than .01), and triglycerides (0.41 +/- 0.03 v 0.23 +/- 0.03 mmol/L, P less than .01) were lower at 24 hours. Glucose production and lactate and alanine turnover were unaffected while palmitate turnover declined (8.8 +/- 0.7 v 5.1 +/- 0.5 mumol/kg/min, P less than .01). Oxygen consumption decreased (6.9 +/- 0.4 v 6.0 +/- 0.3 mL/kg/min, P less than .02) while RQ increased (0.79 +/- 0.02 v 0.86 +/- 0.03, P less than 0.05) at 24 hours. Hepatic glycogen content declined (575 +/- 37 to 266 +/- 32 mumol/g, P less than .001) and could account for a GP of 12 mumol/kg/min between 3 and 24 hours of age. Both gluconeogenesis from lactate and alanine increased, together accounting for 7% and 21% of glucose production at 3 and 24 hours. The increment in gluconeogenesis may be facilitated by augmented hepatic cytosolic phosphoenolpyruvate carboxykinase at 24 hours (1.8 +/- 0.2 v 14.1 +/- 0.8 nmol/min mg protein, P less than .01). Despite the decline in VO2, hepatic ATP and energy charge were unaltered by 24 hours of fasting. These data suggest that FFA availability diminishes during a prolonged neonatal canine fast resulting in lower VO2. Furthermore, as FFA availability declines, glucose utilization becomes the predominant precursor for energy production.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗