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Biomedical subjects

R Seth

Publications and source records attributed to R Seth.

53 records · Page 3Linked to original sources

Antidepressant therapy in the chronic fatigue syndrome.

The chronic fatigue syndrome is a condition receiving increasing recognition. Symptoms of depression are not infrequent and may be persistent and severe enough to warrant treatment. The controversy over the use of antidepressant therapy in this condition may present a dilemma for the general practitioner considering possible treatments. This paper draws on the literature and on the authors' own observations of patients with the chronic fatigue syndrome to suggest guidelines for the use of antidepressant therapy.

Antidepressive Agents↗

Biological activity of calcitonin and its assessment.

Radioimmunoassay has been the method of choice for the routine determination of calcitonin (CT) in biological fluids, mainly due to its precision, sensitivity, and ability to handle large numbers of samples. However, spuriously high results are often obtained due to undefined cross-reactivities of polyclonal antisera to precursors, polymers, metabolites, or fragments of CT, or to other physiological and pathological variants of the hormone. In routine practice, radioimmunoassays of CT are being replaced by immunometric two-site 'sandwich' assays utilizing monoclonal antibodies against defined antigenic epitopes. Hormone activity is, however, accurately quantifiable by biological assays based on the exquisite hormonal sensitivity of isolated osteoclasts. The assays are highly specific and remarkably sensitive. Their use in routine laboratories is nevertheless limited only to specific situations.

Antibodies, Monoclonal↗

Development and performance of a highly sensitive and specific two-site immunometric assay of calcitonin gene-related peptide.

Calcitonin gene-related peptide (CGRP), a potent endogenous circulating vasodilator, is produced by the alternative splicing of the calcitonin/CGRP gene and is expressed mainly in neural and cardiovascular tissues. We recently reported a highly sensitive radioimmunoassay of CGRP, based on an antiserum recognizing the C-terminus of the molecule. We have also found that circulating immunoreactive CGRP is heterogeneous; thus we are unable to measure selectively the intact molecule with our one-site competitive approach. We therefore attempted to construct a two-site immunometric assay involving two antibodies, one that detects the C-terminus and another that recognizes the midregion of the molecule. To enhance assay sensitivity, we applied a colorimetric amplification system to this assay. This rapid, robust, and reproducible assay provides more nearly accurate estimates of circulating CGRP and offers a sensitive and more specific alternative to the radioimmunoassay, with advantages in speed, simplicity, and convenience.

Amino Acid Sequence↗

Acute and sustained release of atrial natriuretic factor with acute myocardial infarction.

The present investigation was designed to determine if acute ischemic cardiac injury causes the release of atrial natriuretic factor (ANF). Seventeen patients with acute myocardial infarction but without clinical evidence of congestive heart failure had their circulating concentration of ANF and creatine phosphokinase monitored daily for 14 days. All 17 patients had an elevated plasma ANF concentration at time of presentation. Maximal increase in ANF was on day 2 and 3 post-infarction. This maximal increase correlated with the size of infarction estimated by the maximal creatine phosphokinase concentration (r = 0.475; p less than 0.05), but did not correlate with the amount of left ventricular dysfunction. ANF began to decrease by day 4 post-infarction and was normal at 10 days post-infarction in 14 of the 17 (82%) patients. At 12 days post-infarction, all 17 patients had normal ANF levels. Another three patients with acute myocardial infarction were treated with tissue plasminogen activator (tPA). The measured ANF levels in these patients were within our normal range and were significantly lower (p less than 0.001) than those seen in patients with acute myocardial infarction not given thrombolytic therapy. Six patients with unstable angina likewise had normal circulating ANF concentrations during prolonged episodes of chest pain. These levels were also significantly lower (p less than 0.001) than the 17 patients with acute infarcts not given tPA. The distinct pattern of release of ANF may be useful as an adjunct to serum cardiac enzymes in determining if a myocardial infarction has occurred.

Adult↗

The development of a two-site enzyme immunometric assay (EIA) for calcitonin and its application in the measurement of the hormone in normal subjects, MTC-patients and post-menopausal women.

We have developed a sensitive, two-site enzyme immunometric assay (EIA) using high affinity monoclonal antibodies for the measurement of immunoreactive human calcitonin (i-hCT) and compared the performance of the assay with that of the conventional radioimmunoassay (RIA). The sensitivity of an overnight EIA (2 pmol/l) was comparable with the long incubation (7 days) RIA. Both, the EIA and the RIA have been applied for the measurement of i-hCT in three groups: normal volunteers (n = 53), post-menopausal women (n = 25) and patients with MTC (n = 20). The results showed that in all three groups, the level of i-hCT was somewhat lower than that measured by RIA due to its greater specificity. The EIA can provide an attractive alternative to the conventional RIA for both routine diagnostic work and physiological studies.

Antibodies, Monoclonal↗

A highly specific and sensitive enzyme-immunometric assay for calcitonin gene-related peptide based on enzyme amplification.

Calcitonin gene-related peptide (CGRP) is an important member of the peptide family encoded by the calcitonin gene. It has been found to be a potent vasodilator in man and a major circulating gene product (Girgis et al., 1985). The present study reports the development of a sensitive and rapid two-site immunoassay for CGRP based on enzyme amplification (Self, 1985). The assay has been easy to construct, taking advantage of available antisera raised for other purposes. Nevertheless it has been found to be clearly superior to our previous radioimmunoassay in terms of sensitivity, specificity, speed and convenience.

Animals↗

Calcitonin determination by a fast and highly sensitive enzyme amplified immunoassay.

A colorimetric enzyme amplification system was used to develop an immunoassay for human calcitonin (hCT) with a sensitivity of 6 pmol/l, and intra- and inter-assay CVs of 12% and 11.8% respectively for the low pool, and 10% and 11.2% for the high pool. The mean recovery of added synthetic hCT (58.5 pmol) from the plasma of 10 patients was 110% (64.4 pmol). The correlation coefficient between radioimmunoassay (RIA) and amplified enzymo-immunoassay was found to be 0.96 (p 0.001). The assay was successfully applied to the measurement of elevated calcitonin levels in plasma from patients with medullary carcinoma of the thyroid (MCT). AEIA offered a reliable and sensitive alternative to RIA for calcitonin determination with the added advantage of convenience as the label employed was much more stable.

Calcitonin↗

A sensitive and specific two-site enzyme-immunoassay for human calcitonin using monoclonal antibodies.

A highly sensitive, specific and rapid two-site enzyme-immunometric assay (EIA) for the measurement of immunoreactive (ir) human calcitonin (hCT) in human plasma was developed using high-affinity monoclonal antibodies. The assay was validated in terms of sensitivity, specificity and reproducibility and its performance compared with that of a radioimmunoassay (RIA) employing a polyclonal antiserum. The sensitivity of the overnight EIA (2 pmol/l) was comparable with the long-incubation (7 days) RIA. The overnight RIA had a sensitivity of 10 pmol/l. The inter- and intra-assay variations of the EIA were less than 12%. Some related and non-related peptides were compared with synthetic hCT for cross-reactivity in the assay and were found to be negative. The mean recovery of added synthetic hCT from plasma of normal volunteers was 96%. Both RIA and EIA have been applied to the measurement of ir-hCT in normal volunteers and in patients with medullary carcinoma of the thyroid. In both groups, the level of ir-hCT measured by EIA was found to be lower than that measured by RIA, presumably due to the ability of the more specific EIA to detect only the 'mature' form of the hormone. EIA offers an attractive alternative to the more cumbersome and lengthy RIA in current usage, with the added advantage of employing a non-isotopic label.

Alkaline Phosphatase↗

Minoxidil-induced systemic lupus erythematosus.

A patient treated for two months with the antihypertensive agent minoxidil developed pleural and pericardial effusions in association with a positive antinuclear antibody titer. No evidence of central nervous system or renal involvement was present, and results of specific tests for idiopathic systemic lupus erythematosus, including anti-double-stranded DNA and anti-Smith antibodies, were negative. Complement levels were normal. The patient's clinical picture improved and titers of antinuclear antibody decreased after discontinuation of minoxidil therapy, suggesting that minoxidil induced a lupus-like syndrome in this patient.

Aged↗

Increasing the inotropic effect and toxic dose of digitalis by the administration of antikaliuretic drugs--further evidence for a cardiac effect of diuretic agents.

In prior studies, we have shown that the antikaliuretic drugs, triamterene and amiloride, through a direct cardiac effect reduce the loss of cardiac potassium induced by the administration of digitalis. Since loss of myocardial potassium is thought to underlie digitalis arrhythmias, this study was performed to determine whether triamterene and amiloride also extend the toxic dose and thus the therapeutic effect of digitalis. In twelve dogs, acetylstrophanthidin was infused (100 ug per minute) serially at 2.5-hour intervals. Trimterene (400 mg. in divided doses) was infused before the third acetylstrophanthidin infusion. This extended the dose required to produce a toxic arrhythmia by 110 per cent. In fourteen additional studies, nine dogs received 400 mg. of triamterene prior to the third acetylstrophanthidin infusion and five animals received 100 mg. of amiloride during the same period. In these fourteen studies, not only was the toxic dose of digitalis extended, but its inotropic effect (see article) (common peak developed isovolumic ventricular pressure) was also increased. These studies have demonstrated that through a cardiac effect, by reducing the digitalis-induced loss of cardiac potassium, the potassium-sparing drugs, triameterene and amiloride, extend the toxic dose of digitalis and thus permit txtension of its inotropic activity.

Amiloride↗