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Biomedical subjects

G Nesher

Publications and source records attributed to G Nesher.

At least 19 recordsLinked to original sources

Antiperinuclear factor in juvenile rheumatoid arthritis.

The serological diagnosis of juvenile rheumatoid arthritis (JRA) is difficult, with only 7-10% of patients 19S IgM rheumatoid factor positive. About 60-70% of patients are positive for hidden 19S IgM rheumatoid factor, but this test requires serum separation and is not available in most laboratories. Antiperinuclear factor has been described in both seropositive and seronegative adult patients with rheumatoid arthritis, but has not been thoroughly evaluated in children with JRA. This study determined the diagnostic sensitivity and specificity of antiperinuclear factor in patients with JRA. Serum samples from 64 children with JRA, 24 with systemic lupus erythematosus (SLE), and 24 control subjects were tested for the presence of antiperinuclear factor. A total of 10 (83%) of seropositive, polyarticular onset and six (37%) of seronegative, polyarticular onset patients with JRA were positive for antiperinuclear factor. The occurrence of antiperinuclear factor in five (19%) with pauciarticular onset and one (10%) with systemic onset (JRA) as well as in four (17%) with SLE was not increased compared with the control subjects (1/24 (4%)). These data show an overall diagnostic sensitivity and specificity of 34 and 90% respectively in this group of patients. Although less sensitive than the hidden rheumatoid factor assay, the antiperinuclear factor assay is easier to perform and may contribute to the serological diagnosis of JRA.

Antibodies, Antinuclear

Production of IgM rheumatoid factor by normal lymphocytes after stimulation with preparations containing IgM rheumatoid factor from patients with juvenile arthritis.

Preparations containing IgM rheumatoid factor (RF) and hidden IgM RF were isolated from the serum samples of nine patients with juvenile rheumatoid arthritis. Six of these preparations stimulated lymphocytes from normal donors to produce IgG and IgM, of which up to 11% had IgM RF activity. In contrast, the polyclonal activator pokeweed mitogen also stimulated IgM production, but only 1% had IgM RF activity. A relation between the activator and IgM RF or hidden IgM RF is suggested. This is based on the positive correlation between IgM RF concentration in these preparations and their ability to stimulate lymphocytes to produce IgG, IgM, and IgM RF. These data indicate that preparations from patients with juvenile rheumatoid arthritis containing IgM RF and hidden IgM RF are potent stimulants of lymphocytes from normal donors, with specific production of IgM RF.

Adolescent

In vitro effects of methotrexate on peripheral blood monocytes: modulation by folinic acid and S-adenosylmethionine.

The mechanism of action of low dose methotrexate in rheumatoid arthritis has not been established. It has been shown to have an anti-inflammatory effect and to inhibit neutrophil chemotaxis, but the effect on monocytes has not been widely studied. Normal donor peripheral blood monocytes were incubated with methotrexate in vitro and their superoxide production, chemotaxis, and phagocytosis subsequently assessed. Additionally, the influence of different culture media, and of folinic acid, and the methyl donor S-adenosylmethionine, and spermidine on the methotrexate mediated effects were evaluated. It was found that methotrexate in low concentrations inhibited in vitro monocyte chemotaxis and superoxide production but only after prolonged incubation. This inhibition was augmented by incubation in medium containing a low methionine concentration and was abolished by folinic acid and S-adenosylmethionine, suggesting that methotrexate may interfere with specific methylation reactions.

Cell Movement

The in vitro effects of methotrexate on peripheral blood mononuclear cells. Modulation by methyl donors and spermidine.

The mode of action of low-dose methotrexate (MTX) in rheumatoid arthritis (RA) is unclear. The effects of MTX are mediated primarily through inhibition of dihydrofolate reductase, resulting in a dose-dependent inhibition of purine and pyrimidine synthesis. Other folate-dependent metabolic pathways might be secondarily affected. One such pathway is the regeneration of methionine from homocysteine, with subsequent formation of the methyl donor S-adenosylmethionine (SAM) and polyamines, which are important in cell-mediated immune reactions. To assess whether MTX inhibits SAM and polyamine synthesis in lymphocytes, pokeweed mitogen-stimulated mononuclear cells from healthy donors were incubated with MTX. This resulted in decreased proliferation and IgG, IgM, and IgM rheumatoid factor synthesis. However, addition of folinic acid, methionine, SAM, or spermidine resulted in reversal of the MTX-mediated inhibition. These data suggest that MTX inhibits the folate-dependent pathway of methionine regeneration, thereby inhibiting SAM and polyamine synthesis. Since RA lymphocytes have increased concentrations of polyamines, the beneficial effects of MTX in RA may be related to its potential ability to reduce polyamine synthesis.

Antibody-Producing Cells

[Masked depression].

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Antidepressive Agents

Steroid-responsive hearing loss in temporal arteritis.

An unusual case of temporal arteritis presenting with sensorineural hearing loss is presented. Deafness was improved dramatically by corticosteroid treatment. The diagnosis of temporal arteritis should be considered in elderly patients presenting with sensorineural hearing loss.

Aged

Recurrent ventricular tachycardia in hypothyroidism--report of a case and review of the literature.

A 47-year-old woman suffered from recurrent attacks of ventricular tachycardia. Her electrocardiogram showed low voltage, right bundle branch block and prolonged QT interval. Hormonal studies disclosed primary hypothyroidism. The arrhythmia responded to treatment with procainamide and did not recur following thyroid replacement therapy. The QT interval returned to normal. Five similar cases reported in the literature are reviewed, emphasizing the importance of QT prolongation, in the context of hypothyroidism, as a risk factor for the occurrence of ventricular tachycardia.

Electrocardiography

Reduced incidence of hyperkalemia and azotemia in patients receiving sulindac compared with indomethacin.

The incidence and severity of hyperkalemia and azotemia was investigated in a prospective randomized study involving 74 patients receiving either sulindac 200 mg p.o. b.i.d. or indomethacin 25 mg p.o. t.i.d. and 100 mg p.r. The mean +/- SE posttreatment increment in serum potassium was 0.8 +/- 0.1 mmol/l in patients treated by indomethacin compared to 0.5 +/- 0.1 in those receiving sulindac (p less than 0.025). The mean +/- SE posttreatment increment in blood urea nitrogen (BUN) was 3.1 +/- 0.4 mmol/l in patients on indomethacin compared to only 0.9 +/- 0.3 in patients on sulindac (p less than 0.001). In 5 patients who developed hyperkalemia while on indomethacin, changing to sulindac resulted in a sharp reduction of serum potassium in 3, and normalization of BUN in all patients. These data support the claim of a reduced risk of impaired renal function associated with the use of sulindac.

Aged

Involvement of the peripheral nervous system in temporal arteritis-polymyalgia rheumatica. Report of 3 cases and review of the literature.

Involvement of the peripheral nervous system is very uncommon in the temporal arteritis-polymyalgia rheumatica syndrome. Three different presentations of the involvement can be recognized: mononeuropathy, polyneuropathy and brachial neuropathy--C-5 radiculopathy. We report 3 patients in whom peripheral nerve symptomatology dominated the clinical picture of the disease, and review 20 previously published cases.

Aged

Pulmonary manifestations of temporal arteritis.

Temporal arteritis is a well-recognized multi-systemic disease. Pulmonary manifestations, however, are extremely rare. In two patients with biopsy-proven temporal arteritis, lung involvement was observed. One patient presented with multinodular pulmonary lesions, while the second had a diffuse interstitial pattern. Both patients responded well to corticosteroid treatment. In a review of the literature, only four additional cases associating lung involvement with temporal arteritis were found. The possibility of primary pulmonary vasculitis should be considered in elderly patients with temporal arteritis.

Adrenal Cortex Hormones

Masked depression. Help for the hidden misery.

Depression that is hidden by somatic or other symptoms is called masked depression. Although one of the more common illnesses in medical practice, masked depression is often misdiagnosed or ignored and usually inappropriately treated. Treatment consists of many of the same measures used in any other major depression--a combination of antidepressant medication and psychotherapy.

Adult

Medical problems in Ethiopian refugees airlifted to Israel: experience in 131 patients admitted to a general hospital.

Within a 2 month period 131 Ethiopian immigrants were admitted for treatment at a general hospital in Jerusalem. There were 52 patients with malaria, 13 with typhoid fever, 24 with pneumonia, seven with tuberculosis, nine with shigella and 11 with campylobacter. Over three-quarters of these patients were anaemic. In the majority of cases anaemia was normocytic and was most probably secondary to malaria and other intercurrent infections. The prevalence of diffuse non-toxic goitre was 7% in children and 19% in adults with a male to female ratio of 4:13. A positive rapid plasma reagin (RPR) test was found in 4% of sera tested and a positive HBsAg in 13%. IgG antibodies to HBc antigen were found in 75% of subjects. All patients with infectious diseases responded to therapy and, despite their poor condition at arrival, there were no fatalities and no late sequelae. The high HBsAg carrier state calls attention to the risk of vertical transmission by infected mothers and underlines the need for active immunization of infants at risk. The high prevalence of untreated tuberculosis and malaria poses a potential public health hazard, but with the current systematic screening of this population leading to identification and effective treatment of affected subjects, chances for the practical eradication of malaria and tuberculosis are excellent. Finally, the large scale transfer of a population from rural Africa to a modern and largely urban society presents a unique opportunity for a prospective study of the impact of environment on the emergence of diseases which plague modern society such as diabetes, atherosclerotic cardiovascular disease, hypertension and cancer.

Adolescent

Hyperkalemia associated with sulindac therapy.

Hyperkalemia has recently been recognized as a complication of nonsteroidal antiinflammatory agents (NSAID) such as indomethacin. Several recent studies have stressed the renal sparing features of sulindac, owing to its lack of interference with renal prostacyclin synthesis. We describe 4 patients in whom hyperkalemia ranging from 6.1 to 6.9 mEq/l developed within 3 to 8 days of sulindac administration. In all of them normal serum potassium levels reached within 2 to 4 days of stopping sulindac. As no other medications known to effect serum potassium had been given concomitantly, this course of events is suggestive of a cause-and-effect relationship between sulindac and hyperkalemia. These observations indicate that initial hopes that sulindac may not be associated with the adverse renal effects of other NSAID are probably not justified.

Adult