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Biomedical subjects

M Herbert

Publications and source records attributed to M Herbert.

At least 19 recordsLinked to original sources

The monosodium glutamate symptom complex: assessment in a double-blind, placebo-controlled, randomized study.

BACKGROUND: Considerable debate swirls about the validity of symptoms described by many people after ingestion of monosodium glutamate (MSG), and the question has remained unresolved largely because of a paucity of well-designed challenge studies. METHODS: We conducted oral challenge studies in self-identified MSG-sensitive subjects to determine whether they had a statistically significant difference in the incidence of their specific symptoms after ingestion of MSG compared with placebo. First, 5 gm MSG or placebo was administered in random sequence in a double-blind fashion. Subjects who reacted only to a single test agent then underwent rechallenge in random sequence in a double-blind fashion with placebo and 1.25, 2.5, and 5 gm MSG. A positive response to challenge was defined as the reproduction of > of 2 of the specific symptoms in a subject ascertained on prechallenge interview. RESULTS: Sixty-one subjects entered the study. On initial challenge, 18 (29.5%) responded to neither MSG nor placebo, 6 (9.8%) to both, 15 (24.6%) to placebo, and 22 (36.1%) to MSG (p = 0.324). Total and average severity of symptoms after ingestion of MSG (374 and 80) were greater than respective values after placebo ingestion (232 and 56; p = 0.026 and 0.018, respectively). Rechallenge revealed an apparent threshold dose for reactivity of 2.5 gm MSG. Headache (p < 0.023), muscle tightness (p < 0.004), numbness/tingling (p < 0.007), general weakness (p < 0.040), and flushing (p < 0.016) occurred more frequently after MSG than placebo ingestion. CONCLUSIONS: Oral challenge with MSG reproduced symptoms in alleged sensitive persons. The mechanism of the reaction remains unknown, but symptom characteristics do not support an IgE-mediated mechanism. According to Food and Drug Administration recommendations, the symptoms, originally called the Chinese restaurant syndrome, are better referred to as the MSG symptom complex.

Administration, Oral

Neurotoxicity after spinal anaesthesia induced by serial intrathecal injections of magnesium sulphate. An experimental study in a rat model.

We have previously demonstrated in a rat model that the lumbar intrathecal injection of 0.02 ml 6.3% magnesium sulphate, a concentration iso-osmolar with rat plasma, produces a state of spinal anaesthesia and general sedation which reversed completely after 6 h, without evidence of neurotoxicity, immediately or during the week thereafter. Using the same model and five groups of six animals in each, we administered the same volume and concentration of magnesium sulphate and compared its clinical effects with those of 0.02 ml 12.6% magnesium sulphate, 0.02 ml 2% lignocaine and 0.02 ml 0.9% sodium chloride solution, given as a series of 15 injections on alternate days for a period of 1 month. The animals were then killed and their spinal cords and meninges examined histologically. No significant differences were noted in the times of onset, durations of sensory and motor blockade and the times to full recovery throughout the entire period of 1 month's observation in the animals receiving intrathecal 6.3% magnesium sulphate. In the group receiving 12.6% magnesium sulphate, the time of onset of sensory and motor blockade was shorter and the duration of both parameters was significantly longer than in the former group. Full clinical recovery and resumption of normal eating and drinking took place in both groups throughout the entire series of 15 successive intrathecal injections. Identical, mild, uniform histopathological changes in the spinal cord were seen in all the five groups, including the group in which only the intrathecal catheter was implanted. The complete recovery and benign consequences of repeated intrathecal injections of iso-osmolar magnesium sulphate in a rat model indicate a lack of neurotoxicity and provide an impetus for further trials in larger animal species, before initial clinical trials of this substance, given intrathecally, in humans.

Anesthesia, Spinal

A comparison of 20 or 40 mg per day of carbimazole in the initial treatment of hyperthyroidism.

OBJECTIVE: The optimal dosage regimen for carbimazole (CBZ) in the treatment of hyperthyroidism remains uncertain, despite clinical use of the drug for approximately fifty years. We have compared the early clinical and biochemical responses to 20 or 40 mg/day of CBZ given as initial treatment for hyperthyroidism. DESIGN: Prospective open multicentre trial. PATIENTS: Sixty-three patients presenting with hyperthyroidism. MEASUREMENTS: Serum total and free thyroid hormones, serum TSH and SHBG were measured at baseline and at 4 and 10 weeks after start of therapy. Weight, pulse and a symptom questionnaire were also monitored at 6 and 12 weeks. RESULTS: Patients randomized to a starting dose of 40 mg/day CBZ had lower total (98 +/- 10 vs 158 +/- 11 nmol/l, P < 0.001) and free T4 (19.4 +/- 2.6 vs 35.2 +/- 3.7 pmol/l, P < 0.001) and total (2.6 +/- 0.3 vs 4.3 +/- 0.4 nmol/l, P < 0.001) and free T3 (8.3 +/- 1.0 vs 13.7 +/- 1.2 pmol/l, P < 0.01) at 4 weeks than those receiving 20 mg/day. Clinical responses at 6 and 12 weeks (weight, pulse, symptom score) and SHBG concentrations were similar. Drug-related hypothyroidism was less likely to occur at 4 and 10 weeks in those patient who initially received 20 mg CBZ/day, but this dose was less effective at controlling hyperthyroidism in those with more severe hyperthyroidism with baseline TT4 > 260 nmol/l. CONCLUSIONS: In treating hyperthyroidism, 20 mg/day carbimazole is effective, convenient and has a lower risk than 40 mg/day of iatrogenic hypothyroidism in patients with mild or moderate hyperthyroidism. Higher doses are required for those with severe hyperthyroidism.

Adolescent

Superoxide dismutase activity in Helicobacter pylori-positive antral gastritis in children.

Reactive oxygen metabolites have been implicated in gastric mucosal injuries. Superoxide dismutase, a scavenger of superoxide radical, is a key enzyme in gastric mucosal protection against several damaging factors. This study was aimed at investigating the relationship of superoxide dismutase activity to Helicobacter pylori-induced antral gastritis in children. Two groups of 11 children each, one positive and the other negative for Helicobacter pylori, were studied. Biopsies from the antrum and corpus were obtained for evaluation of Helicobacter pylori by CLOtest and histology as well as for superoxide dismutase activity (cytochrome c method). Erythrocytic and serum superoxide dismutase levels were determined as well. Superoxide dismutase activity was significantly higher only in the antrum of children with Helicobacter pylori-induced antral gastritis. There was no significant difference in superoxide dismutase activity in the corpus, erythrocytes, or serum of both groups. These findings may suggest a pathogenic relationship between the presence of Helicobacter pylori and oxygen radicals in inducing antral mucosal injury.

Adolescent

A prospective study of the psychological effects of rhinoplasty.

Fifty-three consecutive patients referred for rhinoplasty within the National Health Service by their General Practitioner were evaluated prospectively to determine the psychological impact of this procedure. The patients were independently assessed before surgery, and then 1 week and 4 months after the surgery using the Derogatis Stress Profile, a Self-Esteem Inventory, an Introspectiveness Inventory and a range of questions relating to their expectations of the surgery. Photographs were taken at their initial visit and at 4 months after surgery. These were rated at random order by 28 independent lay people. Pre-operatively, the surgeon also documented his objectives and later assessed how well he had achieved them. Surgical intervention had strong effects in improving self-esteem ratings. These effects became more marked from the first post-operative assessment to those at four months making it likely that this is a real effect of surgery.

Adolescent

Fatal insomnia in a case of familial Creutzfeldt-Jakob disease with the codon 200(Lys) mutation.

Fatal familial insomnia (FFI) has been exclusively associated with a pathogenic mutation at codon 178 in the PRNP gene coupled with methionine (Met) at codon 129. We now describe a subject with familial Creutzfeldt-Jakob disease, heterozygous for the pathogenic lysine (Lys) mutation at codon 200 and homozygous for Met at codon 129 of the PRNP gene, who was affected by severe insomnia. At autopsy the patient had significant involvement of the thalamus, as previously described in subjects affected by FFI with the codon 178 mutation. This case demonstrates the wide variability of the clinical expressions in patients with the codon 200 mutation, that may include insomnia and thalamic pathology.

Amyloid

The advocacy role in hospital social work.

Hospital social workers were asked to describe their roles and functions, with particular emphasis on the amount of time spent doing traditional advocacy on behalf of patients. The results indicated that workers spent the least amount of time on advocacy as compared with other traditional social work roles. A case is made for emphasizing the advocacy role as a strategy to counteract the potentially negative effects on social work of organizational changes in Canadian hospitals. The implications of the findings for schools of social work, professional associations and employers of social workers are discussed.

Adult

Therapy for paraneoplastic neurologic syndromes in six patients with protein A column immunoadsorption.

BACKGROUND: Paraneoplastic neurologic syndromes, although rare, cause significant morbidity and mortality. They are thought to be immunologically mediated, but to date those involving the central nervous system (CNS) have not been particularly responsive to immunologic therapy. The use of the novel immunomodulator, protein A immunoadsorption, was explored to address this question. METHODS: Six patients with neurologic paraneoplastic syndromes were treated with this technique, using the "off line" method. Two hundred fifty ml of plasma was perfused through a column containing protein A covalently attached to a silica matrix. The plasma was then returned to the patient. RESULTS: Five of the patients responded to the therapy, with complete and durable responses in three patients with opsoclonus-myoclonus, objective, though transient, improvement in one patient with paraneoplastic brainstem encephalitis associated with a Merkel cell tumor, and stabilization and partial improvement in one patient with paraneoplastic limbic encephalitis. The patient without response developed a cutaneous vasculitis after the second treatment, and therapy was discontinued. CONCLUSIONS: This therapy appears beneficial for a number of paraneoplastic syndromes, most dramatically in the opsoclonus/myoclonus syndrome.

Adult

Effect of amlodipine, atenolol and their combination on myocardial ischemia during treadmill exercise and ambulatory monitoring. Canadian Amlodipine/Atenolol in Silent Ischemia Study (CASIS) Investigators.

OBJECTIVES: This study compared the effects of amlodipine, atenolol and their combination on ischemia during treadmill testing and 48-h ambulatory monitoring. BACKGROUND: It is not known whether anti-ischemic drugs exert similar effects on ischemia during ambulatory monitoring and exercise treadmill testing. METHODS: Patients with stable coronary artery disease and ischemia during treadmill testing and ambulatory monitoring were randomized to receive amlodipine (n = 51) or atenolol (n = 49). Each group underwent a counterbalanced, crossover evaluation of single drug and placebo, followed by evaluation of the combination. RESULTS: Amlodipine and the combination prolonged exercise time to 0.1-mV ST segment depression by 29% and 34%, respectively (p < 0.001) versus 3% for atenolol (p = NS). During ambulatory monitoring, the frequency of ischemic episodes decreased by 28% with amlodipine (p = 0.083 [NS]), by 57% with atenolol (p < 0.001) and by 72% with the combination (p < 0.05 vs. both single drugs; p < 0.001 vs. placebo). Suppression of ischemia during exercise testing and ambulatory monitoring was similar in patients with and without exercise-induced angina. Exercise time to angina improved by 29% with amlodipine (p < 0.01), by 16% with atenolol (p < 0.05) and by 39% with the combination (p < 0.005 vs. placebo, atenolol and amlodipine). In patients with angina, total exercise time improved by 16% with amlodipine (p < 0.001), by 4% with atenolol (p = NS) and by 19% with the combination (p < 0.05 vs. placebo and either single drug). In those patients without angina, no therapy significantly improved total exercise time. CONCLUSIONS: Ischemia during treadmill testing was more effectively suppressed by amlodipine, whereas ischemia during ambulatory monitoring was more effectively suppressed by atenolol. The combination was more effective than either single drug in both settings.

Amlodipine

Intradiscal pressure measurements above an instrumented fusion. A cadaveric study.

STUDY DESIGN: An in vitro study to determine the intradiscal pressure changes during flexion in levels above a simulated fusion was performed. OBJECTIVES: To determine if intradiscal pressure increases more during flexion in discs above an instrumented spinal segment compared to an uninstrumented segment. SUMMARY OF BACKGROUND DATA: The progressive degeneration of intervertebral discs adjacent to a fused or fixed segment is a phenomenon that is noted but poorly understood. Intuitively, the degeneration appears to be a function of altered biomechanics of the motion segments in the spine. METHODS: Two intervertebral disc levels were evaluated, L3-L4 and L4-L5 from each of six fresh frozen cadaver spines. Pressure measurements were taken with the spine uninstrumented, with bilateral pedicle screw-rod instrumentation from L5 to S1, and with bilateral pedicle screw-rod instrumentation from L4 to S1. Pressure measurements were accomplished with Millar Mikro-Tip pressure transducers. The transducers were placed within the nucleus pulposus of L3-L4 and L4-L5 intervertebral discs. Pressure data were recorded by computer data acquisition. The pressure data were compared by intervertebral level and by the effects of added instrumentation. RESULTS: In general, the addition of instrumentation significantly affected the intradiscal pressure in the levels above a simulated fusion. The intradiscal pressure increased as the amount of levels involved in the simulated fusion increased. The intradiscal pressure increased as flexion motion increased. A greater increase was seen at the L4-L5 level than the L3-L4 level. When L5-S1 fixation was added, the intradiscal pressure increased. When L4-S1 fixation was added, the intradiscal pressure further increased. CONCLUSION: This study demonstrated increasing intradiscal pressures during flexion.

Aged

The fate of long-standing intraperitoneal gallstone in the rat.

Gallstones are occasionally spilled into the peritoneal cavity during open and laparoscopic cholecystectomy. Using the rat model, we investigated the long term effect of such retained intraperitoneal gallstones. During a follow-up period of one year, no systemic deleterious outcome could be attributed to the presence of the implanted gallstones except for mild local effects. Based on the rat model we conclude that reasonable effort should be made in order to retrieve an escaped gallstone, but there is no justification whatsoever for a conversion of the laparoscopic procedure to an open laparotomy only for the purpose of retrieving a lost stone.

Animals

Differential work assignments of social work practitioners in hospitals.

This article reports the results of a survey concerning the differential assignment of tasks to social workers with bachelor of social work (BSW) and master of social work (MSW) degrees by social work directors in Canadian hospitals. It also provides data relative to the variation in amount of supervision provided to workers in those settings where both BSW-level and MSW-level workers perform the same tasks. It is intended that this study will yield useful information to assist the profession in defining the appropriate assignment of tasks to hospital social workers.

Adult

The thiol reagent, thimerosal induces intracellular calcium oscillations in mature human oocytes.

The aim of this study was to investigate the effects of thimerosal on intracellular calcium in human oocytes related to the stage of nuclear maturity. A total of 20 oocytes from superovulated women undergoing gamete intra-Fallopian transfer (GIFT) were studied. The calcium-sensitive fluorescent dye Fura-2 was used to monitor intracellular calcium. Regular oscillations in the concentration of cytosolic calcium were observed in 13 out of 20 oocytes following exposure to thimerosal; five oocytes did not respond to thimerosal treatment, and spontaneous oscillations of cytosolic free calcium were recorded in two oocytes. Thimerosal induced oscillations of intracellular calcium in a significantly higher proportion of metaphase II oocytes (10/11) compared with metaphase I oocytes (3/8; P < 0.2). These findings demonstrate that thimerosal is a potentially useful agent for the study of the calcium signalling processes in human eggs and suggest that the underlying cellular mechanisms develop at a relatively late stage of oocyte maturation.

Calcium

A collaborative model of training for parents of children with disruptive behaviour disorders.

The purpose of this paper is to highlight the heavy costs to individuals, families and the community of the disruptive behaviour disorders of childhood and adolescence. The financial costs of these potentially long-term behavioural problems bear down heavily on the health, social and education services. The human suffering they cause is immeasurable. However, not all is gloom. Psychological therapies, based broadly on social learning theory, have been shown to be effective in mitigating such problems for a significant number of children and their families. These methods, imbedded in a collaborative approach to training parents of children with conduct disorders, are illustrated in terms of their theoretical context and practical applications.

Child

Mitotic activity during preimplantation development of human embryos.

The rate of cell division of human embryos in vitro was estimated throughout the preimplantation period. Seventy-five human embryos were assessed by performing nuclei counts on whole mount preparations at 24 h intervals between day 2 and day 6 of development. The results indicate that the cell doubling time increases after the first two division cycles. The mean (+/- SEM) doubling time between day 2 and day 6 was 31 +/- 2.51 h. At the end of the designated culture periods, embryos were exposed to a microtubule disrupting agent, which caused the nuclei to arrest in metaphase. Thus, a profile of the mitotic activity at given stages of development was obtained. The numbers of actively dividing cells were frequently lower than anticipated, indicating that nuclei counts cannot be directly correlated with continuing mitotic activity.

Blastocyst

Psychomotor skills of surgical trainees compared with those of different medical specialists.

Forty-eight trainees in surgery, psychiatry, anaesthetics and medicine underwent objective testing of manual dexterity (Mandex test), hand-eye coordination (Gibson spiral maze test) and visuospatial ability (embedded figures task). Surgical trainees performed significantly more quickly on the spiral maze test than psychiatrists (P = 0.03) but made more errors (P = 0.02). Combining male and female subjects across all groups, women were significantly more accurate than men. When men only were compared no psychomotor differences between specialty groups could be demonstrated. There were no differences in visuospatial ability by either sex or specialty. Self-selection on the basis of such skill is therefore unlikely.

Adult