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Biomedical subjects

L Shenkman

Publications and source records attributed to L Shenkman.

At least 19 recordsLinked to original sources
PubMed1992

Identification and preliminary characterization of two human digitalis-like substances that are structurally related to digoxin and ouabain.

In order to characterize the structure of endogenous digitalis-like immunoreactive factor (DLIF), we utilized peritoneal dialysis fluid from patients with chronic renal failure as a source of endogenous digitalis-like immunoreactive factor (DLIF), and subjected it to one-step ion exchange chromatography, followed by one step reverse HPLC. Crude dialysis fluid contained 0.09 ng/ml of DLIF, and using Amberlite XAD-2 chromatography we extracted 110 ng of DLIF from 800 ml of dialysis fluid. By applying this partially purified DLIF to our HPLC system, we discerned three peaks of DLIF activity, with retention times of 34, 58 and 63 minutes. The first peak overlapped the elution profile of ouabain, and the third peak co-eluted precisely with digoxin. The second DLIF peak was not in proximity to any of the digitalis-like markers employed. Thus, our results indicate that DLIF isolated from peritoneal dialysis fluid exists in three distinct forms, one of which resembles ouabain, and one which is identical to digoxin.

Digoxin↗
PubMed1992

Endogenous digoxin-like immunoreactive factor is elevated in advanced chronic respiratory failure.

Digoxin-like immunoreactive factor (DLIF) is an endogenous substance with natriuretic and diuretic activity. Elevated plasma levels of DLIF are found in various clinical states characterized by water and sodium retention. Chronic respiratory failure, particularly of an advanced stage, also is frequently associated with water and sodium retention. In order to determine whether elevated plasma levels of DLIF are present in chronic respiratory failure, we measured plasma DLIF levels in seven patients (four with COPD [two of whom had associated sleep apnea disturbance] and three with kyphoscoliosis) suffering from advanced chronic respiratory failure with severe hypoxemia and hypercapnia. We found that in these patients plasma levels of DLIF were significantly higher than in healthy control subjects. We conclude that patients with advanced chronic respiratory failure respond with increased levels of DLIF. This may represent an attempt at homeostasis of water and sodium metabolism which is frequently deranged in this clinical condition.

Blood Proteins↗
PubMed1992

Fatal methemoglobinemia caused by inadvertent contamination of a laxative solution with sodium nitrite.

We describe two cases of fatal methemoglobinemia resulting from ingestion of laxative solution inadvertently contaminated with sodium nitrite. Postmortem toxicological examination revealed methemoglobin levels in excess of 75% in both patients--a level that is uniformly fatal. The laxative solution was found to contain sodium nitrite instead of sodium sulphate at a concentration of 15 g/l. The pathophysiology of methemoglobinemia and a review of other reported cases of toxic methemoglobinemia are presented. Marked cyanosis in the face of intact cardiorespiratory function should alert the physician to the possibility of toxic methemoglobinemia.

Aged↗
PubMed1991

Variable hormonogenesis in Cushing's syndrome.

Four patients with Cushing's syndrome and variable cyclic hormonogenesis are reported and 40 other cases from the literature are reviewed. These cases were divided into four categories depending on regular or irregular cyclic adrenal hypersecretion and presence or absence of concomitant fluctuations in the clinical course. The manifestations of cyclic adrenal hypersecretion in these patients varied from daily to yearly intervals. Cyclic activity persisted for as long as 25 years, with cycle lengths varying from 12 hours to 85 days. Some patients demonstrated complex biochemical cyclic patterns. Clinical presentations varied from a single outstanding symptom, such as recurring oedema, to a complex clinical syndrome. The aetiology in these patients varied: 12 appeared to be pituitary dependent, 11 had corticotropin-producing tumours and another eight were described as showing 'adrenal hyperplasia'. A hypothalamic disorder was found in four, a benign adrenal adenoma in two, and an adrenal 'mass' and adrenocortical nodular dysplasia in single patients. Evaluation during the intercyclic phase may reveal normal pituitary function. Inconsistent responsiveness to administration of dexamethasone in different phases of cyclic activities may suggest the presence of cyclic Cushing's syndrome.

Adrenocorticotropic Hormone↗
PubMed1991

Prevalence of overt diabetic nephropathy in patients with noninsulin-dependent diabetes mellitus.

We performed a retrospective study on 1,019 patients with noninsulin-dependent diabetes who were followed for the past 20 years in our Diabetic Unit in order to determine the prevalence of overt diabetic nephropathy in relation to the other known complications of diabetes. In comparison with neuropathy, retinopathy and peripheral vascular disease, whose prevalence was 23.4%, 28.0%, and 27.4% respectively, the prevalence of macroproteinuria was significantly lower (7.0%). The prevalence of complications was correlated directly with patient age and duration of diabetes, and inversely with the degree of metabolic control. The reasons for the low prevalence of overt diabetic nephropathy in our population of noninsulin-dependent diabetics may be related to genetic factors, diet, other unknown environmental factors, or higher mortality rates in patients with renal disease.

Adult↗
PubMed1990

Contamination of blood cultures during venepuncture: fact or myth?

Contamination of blood cultures is believed to occur mainly during the venepuncture procedure. Consequently, meticulous preparation of the venepuncture site is widely recommended. To determine whether the contamination rate is indeed affected by the quality of the antiseptic procedure at the venepuncture site, 181 paired cultures were collected from 176 patients during a 6-month period after either strict antiseptic cleansing of skin with alcohol followed by povidone-iodine, or after brief disinfection with alcohol alone. The contamination rate was not influenced by the antiseptic procedure, and corresponded to the accepted percentage reported in most other studies. Eight false positive cultures (4.4%) were obtained after strict antisepsis of the skin and 6 (3.3%) after short simple cleansing with alcohol (P = 0.39). Our results suggest that contamination of blood cultures may not be related to the venepuncture procedure--regardless of the antiseptic technique used--but may be due to later stages of laboratory handling and processing of the specimens. Review of the literature has provided further indirect evidence to support this conclusion.

Antisepsis↗
PubMed1990

Atrial natriuretic peptide-induced increase of glomerular filtration rate, but not of natriuresis, is mediated by prostaglandins in the rat.

This study addressed the question of whether some renal effects of atrial natriuretic peptide (ANP) are mediated by prostaglandins (PGs). Inhibition of PG synthesis (aspirin, 10 mg/kg) abolished the increase in inulin clearance (CIN) induced by ANP in rats. In contrast, diuresis and natriuresis remained significantly elevated after aspirin administration. ANP, either infused in vivo immediately before sacrifice or added to the incubation tubes, stimulated the synthesis of PGE2 and 6-keto-PGE1 alpha by isolated rat glomeruli but not by medullary or papillary slices. We conclude that the effect of ANP on the glomerular filtration rate is PG dependent, whereas that on diuresis and natriuresis is direct.

Animals↗
PubMed1990

Nonazotemic hyperkalemia with renal and extrarenal defects in potassium transport: association with high levels of digoxin-like immunoreactive factor.

We report a hypertensive patient with nonazotemic hyperkalemia caused by a combined disturbance in both the internal and external balance of potassium. During a follow-up of 30 months, exacerbations of hyperkalemia were observed, interposed with a return to the previous baseline. Two brief normokalemic periods were recorded. Blood pressure tended to be higher during hyperkalemic peaks. The following findings were detected: (1) hyperchloremic hyperkalemic acidosis with normal glomerular filtration rate, adequately elevated plasma aldosterone levels, and normovolemia; (2) a tubular defect in potassium excretion, refractory to intravenous sodium sulfate (nonreabsorbable anion) and mineralocorticoids; (3) impaired tissue uptake of potassium under insulin administration; (4) exaggerated hyperkalemia following beta-adrenergic blockade and blunted hypokalemic response to a beta-agonist; and (5) a defect in Na/K transport in erythrocytes detected in vitro, coexistent with an elevated level of free digoxin-like immunoreactive factor in serum. These results suggest that our patient had a generalized abnormality in potassium transport.

Acid-Base Equilibrium↗
PubMed1989

Endogenous digoxin-like factor raises blood pressure and protects against digitalis toxicity.

Digoxin-like immunoreactive factor (DLIF) is an endogenous natriuretic material which causes diuresis and natriuresis after salt or fluid loading and which may play a pathogenetic role in various hypertensive states. In order to study the cardiovascular effects of DLIF, we administered partially purified material (500 ng/kg) iv to normal rats. DLIF administration caused a significant rise in blood pressure, induced a brisk diuresis, and slowed the heart rate. In addition, DLIF protected against digitalis toxicity. While iv digoxin, 1 mg/kg, uniformly produced lethal arrhythmias, administration of DLIF 15 min prior to digoxin infusion consistently protected against arrhythmias. These findings support the theory that DLIF may play a role in hypertension. In addition, DLIF may compete with digoxin for cardiac receptors.

Animals↗
PubMed1989

Endogenous digoxin-like factor in neonates: effect of age and relation to serum bilirubin levels.

Endogenous digoxin-like immunoreactive factor(s) (DLIF) have been found in serum and urine of newborn infants, including those born prematurely. We assessed the effect of age on serum levels of DLIF in 73 samples obtained from 66 healthy full term newborn infants at birth and during the first two months of life. DLIF concentrations were highest at birth and fell progressively with age. In cord blood, DLIF levels were 0.73 +/- 0.35 ng/ml (mean +/- SD). DLIF concentrations were 0.45 +/- 0.11 ng/ml on day 1, 0.26 +/- 0.08 ng/ml on day 3, 0.19 +/- 0.07 ng/ml on day 5, 0.17 +/- 0.09 ng/ml on day 11, 0.11 +/- 0.02 ng/ml on days 15-30, and not detectable after 45 days of life. We also studied the relation between serum levels of DLIF and bilirubin in 23 jaundiced newborns between 3-5 days of life. We found a highly significant positive correlation between serum bilirubin concentrations and DLIF. These findings support the assumption that DLIF plays a role in impeding bilirubin excretion in the neonatal period, perhaps by inhibiting the activity of (Na-K)ATPase.

Age Factors↗
PubMed1989

Neutrophil chemotaxis, random migration, and adherence in patients with hyperthyroidism.

We have examined neutrophil adherence, chemotactic activity, and random migration in 35 hyperthyroid patients with Graves' disease and 106 normal volunteers. No statistically significant differences were found between granulocyte adherence of 17 hyperthyroid subjects (67 +/- 15.6%) and 81 healthy volunteers (63.1 +/- 17%). In 3 thyrotoxic patients, impaired neutrophil adherence was found, which resolved when thyroid function returned to normal. The neutrophil chemotactic activity of 32 normal controls was 107.5 +/- 21.4 cells, and the random migration 36 +/- 15.5 cells. No statistically significant difference was demonstrated in 13 hyperthyroid patients who had a neutrophil chemotactic activity of 102 +/- 14.6 cells and a random migration of 31.2 +/- 13.2 cells. Defective chemotactic activity and random migration was found in 2 patients. Neutrophil functions returned to normal in one of the two subjects who were re-evaluated when thyroid function recovered. In summary, 14% of hyperthyroid patients had impaired leukocyte functions. However, severe pyogenic infections are quite rare in hyperthyroid patients, indicating that the observed alterations in function of phagocytic cells are not clinically important.

Cell Migration Inhibition↗
PubMed1989

Abnormal thyroid function in hyperemesis gravidarum.

Thyroid function was evaluated in 41 consecutive women with hyperemesis gravidarum (HG). In 11, increased free thyroxin concentrations (FT4) were measured. After one week of conservative therapy, 4 patients with persistent emesis were treated with antithyroid agents. Three of these 4 displayed other signs of hyperthyroidism. Emesis resolved in the other 7 patients within a week of conservative therapy. FT4 levels also returned to normal in these 7 patients within several weeks. Thyrotropin-releasing hormone (TRH) was administered to 10 of the 11 patients. Abnormal TSH responses, suggesting varying degrees of autonomous thyroid function were noted in all 4 patients treated with antithyroid drugs and in 3 of the untreated patients. Underlying clinical signs and symptoms of hyperthyroidism should be sought in patients with HG. In the presence of persistent emesis, despite conservative therapy of at least one week's duration and the presence of abnormal thyroid function studies, the use of antithyroid agents should be considered.

Adult↗
PubMed1989

Plasma levels of atrial natriuretic peptide and digoxin-like immunoreactive substances in intermittent peritoneal dialysis.

Plasma atrial natriuretic peptide (ANP) and digoxin-like immunoreactive substances (DLIS) levels were assayed in 10 patients on intermittent peritoneal dialysis (IPD) before and after a 12 hour dialysis session. Ultrafiltration volumes and blood pressures, pre and post dialysis were recorded. Left atrial diameter (LAD), as determined by M-mode echocardiography was measured prior to and at the end of each dialysis session. Ten age matched patients on hemodialysis (HD) served as controls. Predialysis plasma ANP was significantly higher in HD as compared to IPD patients and dialysis resulted in a significant decrease of plasma ANP in IPD and HD patients (37.9 +/- 28.0 to 23.1 +/- 28.5 and 201.9 +/- 110.7 to 117.0 +/- 75.6 pg/ml, respectively, p less than 0.05). Ultrafiltration volumes in IPD averaged 1840 +/- 645 ml/dialysis. The corresponding decrease in body weight in HD was 2000 +/- 220 g. Total DLIS levels in IPD and HD did not change with dialysis. LAD decrease significantly post dialysis (41.3 +/- 5.0 to 38.6 +/- 5.7 cm, p less than 0.001). Calculated ANP clearance during IPD was 5.6 +/- 3.9 ml/min. Plasma ANP correlated significantly with ultrafiltration volumes and LAD. It thus appears that ANP is sensitive to volume status in dialysed patients. Its dialysance, in IPD, approaches that of other middle molecules. Under the conditions tested ANP does not influence DLIS levels.

Aged↗
PubMed1988

Atrial natriuretic peptide administration to normal and salt depleted rats--effects on digoxin-like immunoreactive factor, aldosterone, ACTH, and renal function.

In view of the known interrelationships between renin, aldosterone, and atrial natriuretic peptide (ANP), we sought to examine whether there also exists an interaction between ANP and digoxin-like immunoreactive factor (DLIF). We therefore studied the effects of ANP administration on normal and salt-depleted rats, and measured the effects on blood pressure, urine output, glomerular filtration rate, sodium excretion, aldosterone, ACTH, and DLIF levels. ANP administration resulted in a significant elevation of sodium excretion and glomerular filtration rate and a fall in blood pressure. DLIF concentrations in plasma rose significantly, as did urinary DLIF excretion. ANP administration resulted in a fall in aldosterone as well as ACTH. These observations suggest that ANP has a direct inhibitory effect on ACTH secretion. Our findings support the concept of an interrelationship between ANP and DLIF.

Adrenocorticotropic Hormone↗
PubMed1988

Predicting outcome of inhospital cardiopulmonary resuscitation.

We conducted a prospective study of CPR in our hospital in order to learn more of the factors influencing outcome. In a 7-month period, 71 patients underwent CPR. Twenty-nine (41%) were successfully resuscitated; of these, 13 (18% of the total group) survived to be discharged from the hospital. Factors associated with a successful outcome included occurrence of cardiopulmonary arrest within 24 h of hospitalization, short duration of CPR, and the absence of cardiogenic shock, sepsis, acute renal failure, cancer, and pneumonia. Factors which did not influence outcome included the patients' age, sex, location in hospital during the arrest (general ward vs. intensive cardiac care unit), time of day of the arrest, or the participation of senior physicians or anesthesiologists in the resuscitation.

Adult↗