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Biomedical subjects

J Mertin

Publications and source records attributed to J Mertin.

At least 37 records · Page 2Linked to original sources
PubMed1982

Double-blind controlled trial of immunosuppression in the treatment of multiple sclerosis: final report.

In a double-blind controlled trial 43 patients with relapsing-remitting multiple sclerosis were treated either with anti-lymphocyte globulin, prednisolone, and azathioprine, or with placebo preparations. Treatment began with a combination of the three medicaments but after 1 month was continued for another 14 months with azathioprine (3 mg/kg dialy) only. There was a marginally beneficial effect of immunosuppression on the overall relapse rate and clinical progression. However, there were significant effects on in-vitro lymphocyte function and in the visual evoked potentials in favour of the group receiving suppressive treatment. Placebo-treated patients of the HLA A3 tissue type had significantly more relapses than placebo-treated patients who were not of type HLA A3. Nevertheless, HLA-A3-positive patients treated with immunosuppression had significantly fewer relapses than A3-positive placebo-treated patients.

Adolescent↗
PubMed1982

Intensive immunosuppression versus prednisolone in the treatment of connective tissue diseases.

Intensive immunosuppression (IIS) was compared with prednisolone alone over a 2-year period in the treatment of severe connective tissue diseases. IIS consisted of 15 daily infusions of 750 mg antilymphocyte globulin (ALG), azathioprine 2.5 mg/kg/day, and prednisolone reducing from 150 mg, followed by maintenance azathioprine and prednisolone. The initial dose for prednisolone by itself was 60 mg and patients not responding to this regimen over a minimum of one month were then given IIS. Forty-one patients with life-threatening or severely disabling polyarteritis nodosa (PAN), dermatomyositis/polymyositis (DM), or systemic lupus erythematosus received one or other treatment. All 11 patients who received IIS for PAN remitted. Ten of these had renal impairment which was reversed or halted with IIS, and in 6 of these renal function had been deteriorating with prednisolone alone. One patient died of pneumonia in renal failure 9 months later but with PAN in remission. Two further patients, neither having renal involvement, achieved remission with prednisolone alone. Early cytotoxic treatment would seem to be indicated in PAN when there is renal involvement. Two patients with DM entered remission or prednisolone alone. The remaining 12, of whom 5 had failed steroid therapy, received IIS. Improvement or halting of deterioration was achieved in all 12 with best results in those without marked muscle wasting consequent to disease of long duration. The results suggest that IIS may be a useful adjunct in those patients failing to respond to prednisolone. IIS seemed no more effective than prednisolone alone in the treatment of the 14 patients with SLE and in particular lupus nephritis. Flares in disease activity were common in both groups and appeared to be related to prednisolone dosage. IIS was generally well tolerated, though infection occurred in 2 patients. Vertebral collapse or osteonecrosis of the femoral head occurred in 3 patients following IIS, all of whom had been previously receiving prednisolone for long periods.

Adolescent↗
PubMed1981

Cell number requirements for lymphocyte stimulation in vitro: changes during the course of multiple sclerosis and the effects of immunosuppression.

Peripheral blood lymphocytes from 20 patients with clinically definite, relapsing and remitting multiple sclerosis (MS) were studied during their participation in a double-blind trial of immunosuppressive treatment. Proliferative responses occurring with different numbers of cells in culture and on different days of culture in the presence of phytohaemagglutinin (PHA) or with allogeneic cells from lymphoid cell lines (MLC) were assessed. Cells taken from patients before treatment showed similar responses to cells from laboratory personnel. However, when cells were taken from patients in relapse or from untreated patients as the disease progressed, there was an alteration in the pattern of response; higher number of cells were required in culture to produce responses. A change in the responsiveness to PHA or in MLC may therefore accompany the progression of the disease in MS (reflecting clinical relapses and possibly subclinical activity of the disease), perhaps resulting from a simple reduction in the proportion of cells able to respond. After intense immunosuppression followed by long-term maintenance on azathioprine, cells from patients gave similar responses to those found before treatment. Thus long-term immunosuppression prevented the progressive alteration in lymphocyte function. Shifts in the total cell number and time in culture required to allow proliferation with mitogens of cells from untreated MS patients could explain both the 'low' of PHA responses reported and the changes of in vitro 'suppressor' function of these cells.

Adult↗
PubMed1981

A new neurological rat mutant "mutilated foot".

A new autosomal recessive mutant rat (mutilated foot) with a neurological disorder is described. Affected animals become ataxic and the feet, generally of the hind limbs, are mutilated. Quantitative studies show a severe reduction in numbers of sensory ganglion cells and fibres, including unmyelinated fibres. The numbers of ventral root fibres, particularly those of small diameter, are also reduced. Markedly decreased numbers of spindles are found in the limb muscles. These quantitative abnormalities are present in animals of all ages and appear to be congenital. No nerve fibre degeneration is found in the spinal cord of young animals, but progressive degeneration of ascending tracts is seen with increasing age. Mossy fibre degeneration in the cerebellum confirms that the spinocerebellar tract is affected. The neurological disease in this mutant shows many similarities to that found in human hereditary sensory neuropathy.

Animals↗
PubMed1980

Double-blind, controlled trial of immunosuppression in treatment of multiple sclerosis.

30 multiple sclerosis patients in a double-blind, controlled trial were given immunosuppressive treatment consisting of antilymphocyte globulin, prednisolone, and azathioprine, or placebo. After 15 months of treatment the immunosuppressed group had a reduction in the number of relapses and some retardation of the clinical course of the disease (p < 0.06). The beneficial effect was seen only in females.

Antilymphocyte Serum↗
PubMed1980

[Immunosuppressive treatment im multiple sclerosis].

The results of various uncontrolled trials of immunosuppression in the treatment of multiple sclerosis have indicated an amelioration in the clinical course of the disease in about half of the treated patients. These observations have recently been confirmed by the findings in a double blind controlled study. The aim of future clinical trials has to lay in increasing the efficacy of conventional immunosuppressive agents in the treatment of multiple sclerosis. Further progress in immunological research and a better understanding of the etiology of multiple sclerosis may allow one day a more specific immunotherapy with the help of immunoregulatory substances.

Adrenocorticotropic Hormone↗
PubMed1980

Linoleic acid therapy in severe experimental allergic encephalomyelitis in the guinea-pig: suppression by continuous treatment.

The effect of oral linoleic acid (LA) treatment on experimental allergic encephalomyelitis (EAE) in guinea-pigs in three trials of differing disease intensity has been investigated. The efficacy of LA treatment was linked to the severity of the disease being suppressed. The trial with the greatest disease severity showed no beneficial effect. The other two trials with less severe disease showed a marked therapeutic response to LA, but only when treatment was started before immunization and given continuously. This was apparent in both clinical and histopathological responses. These results support an immunoregulatory mechanism for LA treatment in EAE and by analogy in multiple sclerosis.

Animals↗
PubMed1979

An influence of diet on transplantation immunity.

It was discovered by chance that mice raised under otherwise entirely conventional conditions of husbandry but fed upon autoclaved diet (diet A) had stronger cell-mediated immune reactions than those of mice raised under the same conditions but with an unmodified diet (diet B) : skin allografts were rejected more quickly, transplantation tolerance was more difficult to procure and fibrosarcomas induced by the injection of methylcholanthrene (MCA) arose more slowly and less often. Analysis showed that these findings could be explained at least in part by the discovery of Mertin & Hunt (1976, p. 928) that a partial deprivation of polyinsaturated fatty acids led to an intensification of cell-mediated immunity; on the other hand, experiments with dietary mixtures made it seem unlikely that this was the whole explanation and pointed towards some positive immunopotentiation by an ingredient of autoclaved diet. This, it was proposed, might be a compound of unknown composition resulting from the interaction of vitamin A with other dietary constituents. This interpretation was not supported by direct evidence but by confirming that retinol derivatives, especially retinyl acetate, could exercise an immunopotentiation of the kind and degree under investigation: retinyl acetate could counteract the immunosuppressive action of linoleic acid, though retinyl methyl ether was ineffective. Although retinyl derivatives may protect against MCA tumours by impeding its metabolic conversion to an oncogenic form, the effects of an autoclaved diet upon skin allograft survival, the induction of tolerance and the formation of tumours is probably mediated through an immunological mechanism.

Animals↗
PubMed1979

Effects of the obese (ob/ob) genotype on spleen cell immune function.

Spleen cells from mice homozygous for the obese (ob) mutation killed DBA/2 mastocytoma target cells less well than spleen cells from lean littermates or unrelated age-and sex-matched controls of the same strain. Killing was impaired only when the attacker cells were primed in vivo, not following in vitro priming. Hence the effect of the ob/ob genotype is not to produce an irreversible functional change in the lymphocyte, but rather to produce an environment in which lymphocytes are less able to react to priming antigen. Not only were the spleen cells of in vivo primed obese mice less active than those of lean controls, but also their number per spleen was significantly decreased. Such a quantitive difference was no longer found in adrenalectomised animals, but the qualitative difference in spleen cell cytotoxic activity still occurred. This suggests that adrenocortical hyperfunction may affect immune function in obese mice, without necessarily being the only factor in the in vivo environment of obese mouse spleen cells capable of depressing cellular immune reactivity.

Adrenalectomy↗
PubMed1979

The spleen is required for the suppression of experimental allergic encephalomyelitis by prostaglandin precursors.

In this paper we report a study of the effects of splenectomy on the immunosuppressive action of essential fatty acids (EFA) which is thought to be mediated through prostaglandins (PG) produced in the spleen. Experimental allergic encephalomyelitis (EAE) was induced in normal, splenectomized and sham splenectomized Lewis rats. EFA were administered orally, the animals in the control groups being treated with liquid paraffin. Treatment with EFA significantly suppressed clinical disease in those animals in which EAE was induced by the inoculation of central nervous system material of guinea-pigs or by passive transfer by Con A-stimulated spleen cells. Splenectomy abrogated the suppressive effect of EFA. This observation, together with previous results showing the abrogation of EFA immunosuppression by an inhibitor of the biosynthesis of PG from EFA, led us to postulate a close relationship between EFA, PG and a splenic factor suppressing immunopathological mechanisms in EAE.

Animals↗
PubMed1978

[EEG changes following spirolactone treatment (author's transl)].

EEG studies were done on patients with CNS disease who were treated with d-aldosterone and spirolactone. The baseline EEGs of these patients were found to be slightly abnormal. During infusion of the spirolactone derivative potassium canrenoate a transient deterioration of preexisting EEG disturbances was observed; in addition, bursts of increased muscle activity and transient relative bradycardia were seen. These findings indicate that potassium canrenoate or its lipophilic metabolite canrenone may affect the nervous system directly, possibly via a disturbance in the electrolyte balance. These results are compatible with recent findings in animal studies.

Aldosterone↗
PubMed1978

Reduction by linoleic acid of the severity of experimental allergic encephalomyelitis in the guinea pig.

This paper reports the effects of supplementation of the diet with linoleic acid on the severity of experimental allergic encephalomyelitis (EAE) in guinea pigs. Clinical signs of disease (e.g. paresis, paraplegia, urinary incontinence), weight loss, frequency of perivascular lesions in the central nervous system and ability of isolated lymph node cells to respond to myelin basic protein in vitro were all reduced by linoleic acid supplementation. Linoleic acid was effective when fed at a dose of 0.5 ml/day from 7 to 21 days after sensitization of the animals with basic protein, i.e., before and during the time in which clinical signs normally appeared. The same daily dose fed from 7 days before to 7 days after sensitization, i.e., ceasing about 7 days before the normal time of appearance of clinical signs, produced no significant effect. Feeding linoleic acid to normal guinea pigs significantly altered the fatty acid composition of their serum and lymph nodes, but not of their brain. Of several possible explantations for the protective effect of lineolic acid in EAE, we considered action by this essential fatty acid on the immune system most likely.

Animals↗
PubMed1978

Suppression by essential fatty acids of experimental allergic encephalomyelitis is abolished by indomethacin.

Experimental allergic encephalomyelitis in Lewis rats was suppressed by treatment with essential fatty acids (EFA) given perorally. This treatment effect could be abolished by administration of a drug (Indomethacin) known to inhibit biosynthesis of certain prostaglandins from EFA. This observation suggests that the suppressive effect of EFA on cell-mediated immune reactions is brought about by EFA-derived prostaglandins.

Animals↗