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Biomedical subjects

D L Davidson

Publications and source records attributed to D L Davidson.

At least 37 records · Page 2Linked to original sources

Western blotting analysis in patients with MS using human brain vessels as antigen.

Serum samples from patients suffering from multiple sclerosis, other neurological diseases and normal controls were screened by "western blotting" for antibody directed against proteins of human brain vessels purified from a post mortem brain. A small number of sera contained autoantibodies against some of the proteins of the brain vessels, particularly in patients suffering from MS, epilepsy and migraine. The significance of these results is discussed.

Antibody Specificity↗

Parathyroid hyperplasia associated with thymoma.

The case of a 65 year old female with myasthenia gravis and hypercalcaemia is presented. Failure of medical control of the myasthenia necessitated thymectomy at which time parathyroid exploration was also carried out. This revealed parathyroid hyperplasia and a thymoma. This association has not been previously documented in the literature.

Aged↗

Adoptive immunotherapy of human cancer using low-dose recombinant interleukin 2 and lymphokine-activated killer cells.

The adoptive transfer of recombinant-methionyl human interleukin 2 (rIL-2)-activated autologous peripheral blood mononuclear lymphokine-activated killer (LAK) cells to cancer patients is being evaluated as an alternative to conventional cancer therapy. We have independently developed an alternative regimen to previously reported adoptive immunotherapy protocols using rIL-2 and LAK cells which features the prolonged administration of low-dose rIL-2 (30,000 units/kg) and an automated, entirely enclosed system of peripheral blood cell procurement, culture, harvest, and reinfusion of activated cells. The cell culture system was tested with a murine tumor model in which LAK cells generated in plastic culture bags were reinfused into tumor-bearing mice. Tumor regression was as effective with cells activated in the bags as in conventional culture flasks. Twenty-eight cancer patients were treated for 5 consecutive days with low-dose rIL-2, followed by leukapheresis, infusion of LAK cells, and prolonged IL-2 administration. At least 50% tumor regression was observed in 46% of all patients treated. These data imply that human peripheral blood mononuclear cells retain fully their capacity for rIL-2-induced activation and effector cell function under this alternative approach, and further, that a low-dose rIL-2 regimen with markedly reduced toxicities can be as effective as high-dose rIL-2 regimens if low-dose rIL-2 is given for a prolonged period of time following LAK cell infusion.

Adult↗

The effective evaluation of thyroid status in patients on phenytoin, carbamazepine or sodium valproate attending an epilepsy clinic.

To assess the most efficient means of monitoring thyroid status in an epilepsy clinic, total thyroxine (T4), free thyroxine stimulating hormone (TSH) were measured in 71 adult patients treated long-term with either phenytoin (DPH), carbamazepine (CBZ) or sodium valproate (VAL). Twenty-seven patients with one or more abnormal thyroid hormone results were further investigated by a thyrotrophin releasing hormone (TRH) test and clinical assessment. T4 was found to be normal in 85% on VAL, 40% on CBZ and 39% on DPH. FT4 was normal in more patients, namely 95% on VAL, 70% on CBZ and 65% on DPH. The TRH tests indicated that FT4 was the most efficient screening test for hypothyroidism in this epileptic population. We estimate that the use of FT4 alone as a screening test would have reduced by 60% the number of TRH tests required.

Adult↗

The effects of age on carbamazepine pharmacokinetics and adverse effects.

The pharmacokinetics and effect of single oral doses of carbamazepine (400 mg) were compared in a group of six young volunteers aged between 20 and 25 years, and a second group of five elderly volunteers aged between 66 and 84 years. No age related changes in salivary or plasma pharmacokinetics or in psychomotor function were detected.

Adult↗

Lipid peroxidation products and antioxidant proteins in plasma and cerebrospinal fluid from multiple sclerosis patients.

Lipid peroxidation (LPx) products were measured as thiobarbituric acid-reactive substances (TS) and lipid-soluble fluorescent pigments (FP) in both plasma and CSF from MS patients and controls. Although no significant changes were found in MS plasma, we report here for the first time increases in both TS and FP in MS CSF (p less than 0.05 and p less than 0.01, respectively, compared with patients with other neurological diseases), indicating that increased LPx in CNS may be a feature of MS. Levels of transferrin were normal but caeruloplasmin (CP), a major antioxidant plasma protein, was significantly raised in MS patients (p less than 0.01) and this may represent an adaptive response to increased oxidative challenge. Neither of these proteins was detectable in CSF using radial immunodiffusion. There was no significant correlation between the severity or duration of the disease nor the period since the last relapse and either LPx products or CP suggesting that the changes observed in this work are not simply the direct result of demyelination and tissue damage.

Antioxidants↗

Erythrocyte antioxidant enzymes in multiple sclerosis and the effect of hyperbaric oxygen.

The activities of catalase, glutathione peroxidase, and glutathione reductase, were not significantly different from normal whereas that of superoxide dismutase was decreased (P less than 0.05) in erythrocytes from patients with multiple sclerosis. Assay of the lipid peroxidation product, malondialdehyde, after incubation of erythrocytes with 10 mM H2O2 under carefully controlled conditions (peroxide stress test) demonstrated that MS erythrocytes are significantly (P less than 0.001) less susceptible to H2O2-induced lipid peroxidation in vitro. This finding suggests that the level of an endogenous antioxidant, possibly vitamin E, may be elevated in MS red cells. After treatment with hyperbaric O2, the activity of MS erythrocyte catalase is significantly (P less than 0.01) elevated by 2-6-fold.

Adult↗

Erythrocyte membrane glycerophospholipid organization is normal in multiple sclerosis.

The phospholipid composition of erythrocyte membranes from patients with multiple sclerosis (MS) was found to be normal, in agreement with previous reports. The transbilayer asymmetry of the glycerophospholipids in MS red cells was probed using bee venom phospholipase A2 and was also found not to be significantly different from normal. Abnormal membrane glycerophospholipid organisation is therefore not involved in the increased red cell size, osmotic fragility, and electrophoretic mobility associated with MS.

Erythrocyte Membrane↗

Brain biopsy in the diagnosis of cerebral mycosis fungoides.

A case of cerebral mycosis fungoides co-existing with progressive multifocal leucoencephalopathy presented with dementia. Brain biopsy established the diagnosis of mycosis fungoides after cerebrospinal fluid examinations and computerised tomographic scanning of the brain produced non-specific abnormalities.

Biopsy↗

Serum prolactin and cortisol concentrations after grand mal seizures.

Serial serum prolactin and cortisol levels were measured in five patients after a grand mal seizure and in four volunteers with simulated seizures. Single levels were measured after a witnessed seizure in 26 patients and in a matched control group. Significant increase in both prolactin and cortisol levels occurred after seizures. The change in cortisol level may reflect a non-specific stress response, but the increase in prolactin levels could not be accounted for on this basis, and probably indicates an alteration in hypothalamic neurotransmitter activity during the seizure. These findings may have clinical value in the diagnosis of epilepsy.

Adult↗

Ouabain induced stereotyped behavior in rats.

Stereotyped behavior was induced in rats with ouabain administered intraventricularly in doses of 2, 3 and 4 microgram in 50 microliter saline. Haloperiodol reduced the stereotyped behaviour. Monoamine turnover studies showed a reduction in concentration of norepinephrine in hippocampus and midbrain, an increase in norepinephrine turnover in the medulla oblongata and a reduction in dopamine turnover in the striatum. The interpretation of these finds is discussed. It is suggested that this model could be significant clinically as it demonstrates that impairment of Na+-K+-ATP'ase may result in behavioral abnormalities characterised by stereotypy.

Animals↗