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Biomedical subjects

D Modai

Publications and source records attributed to D Modai.

At least 19 recordsLinked to original sources

Effect of exercise training on glomerular filtration rate of mice with various degrees of renal mass reduction.

We studied the effect of repeated heavy physical activity on glomerular filtration rate (GFR) in healthy, uninephrectomized and experimentally uremic mice. Exercise consisted of running uphill in the inner surface of a rotating cylinder in ideal environmental temperature. In the control groups, no extra physical activity was imposed. In sham-operated and nephrectomized mice, GFR rose significantly following training. By contrast, GFR did not change significantly in the exercised mice with experimental renal failure 24 h following the last exercise session. During the same period, no significant change was observed in GFR of any of the control groups. Following training in each experimental group, mean aortic blood pressure as well as fractional kidney weight (kidney weight/body weight) were not different from the respective controls. Our results indicate that the capacity to augment GFR by physical training is dependent upon the amount of remaining functional renal tissue.

Animals

Postnephrectomy mesangial cells secrete a factor(s) that stimulate(s) tubular cell growth in vitro.

Rat kidney mesangial cells were procured from 5 sham-operated and 10 previously uninephrectomized rats. They were grown in cell culture medium supplemented with 20% fetal calf serum. Cell free conditioned medium was collected on the 10th day. Tubular cell cultures were then prepared from 18 normal unoperated 3-week-old rats. Tubular cells from each separate kidney sample were grown in pooled-mesangium conditioned medium from sham-operated or from nephrectomized rats, supplied with 20% pooled serum from either sham-operated or nephrectomized animals. 3H-thymidine incorporation of normal tubular cell cultures grown in nephrectomy mesangium conditioned medium supplemented with sera from nephrectomized animals proved to be significantly greater than that of any of the other three experimental variations. No statistically significant difference was evident when either preconditioned medium of postnephrectomy mesangial cells or postnephrectomy serum were used alone.

Animals

Pulse oximetry in the evaluation of the painful hand after arteriovenous fistula creation.

Five patients with a side-to-side arteriovenous fistula complaining of pain, numbness, and cold sensation were evaluated by pulse oximetry. Low SaO2 was noticed in all five. Closure of a major proximal venous collateral vessel eliminated the steal and resulted in SaO2 correction and was followed by clinical amelioration. Pulse oximetry proved to be a helpful adjunct in the evaluation of the painful hand after creation of an arteriovenous fistula. By applying the pulse oximeter to the patient's affected limb, we were able to determine whether the pain was a result of ischemia and if the correction of the steal improved oxygenation.

Arteriovenous Shunt, Surgical

Effect of diuretics on captopril-induced urinary zinc excretion.

The urinary zinc/creatinine ratio has been measured in five groups of patients with essential hypertension and in a group of healthy controls. The first four groups of patients consisted of subjects being treated for at least three months with captopril alone, hydrochlorothiazide alone, captopril plus hydrochlorothiazide, or captopril and furosemide. The fifth group comprised hypertensive patients not on any medication. The first four patient groups exhibited significantly increased urinary zinc/creatinine ratios when compared to the control and untreated hypertensive groups, but in the two combination regimens there was little zincuria. It is suggested that both diuretics inactivate the zincuric effect of captopril by binding to its sulphydryl group within the tubular lumen.

Adult

Zinc metabolism in patients treated with captopril versus enalapril.

Several zinc parameters were assessed in 13 patients with essential hypertension who were chronically taking only captopril (six subjects) or enalapril (seven subjects), as well as in six untreated hypertensives, and nine healthy controls. Serum zinc levels were comparable in all groups. Twenty-four-hour urinary zinc excretion was significantly increased in the captopril-treated patients compared with the other three groups. The zinc:creatinine ratio in 24-hour urine was significantly increased in both captopril and enalapril groups, but was significantly greater in the former. Although plasma zinc concentrations were comparable in all groups, red blood cell (RBC) zinc values were significantly decreased in the captopril group compared with the other three groups. We conclude that (1) although both captopril and enalapril produce renal zinc loss, this loss is far greater in patients receiving captopril; and (2) captopril administration over 3 months or more generates RBC zinc depletion.

Captopril

Interleukin-2 receptor is similarly expressed by activated lymphocytes from patients on chronic hemodialysis and healthy subjects.

We studied peripheral blood mononuclear cells (PBMC) from 10 patients on chronic hemodialysis vs 10 healthy controls. T cells were counted by E rosette formation. Interleukin (IL)-2 receptor (IL-2R) carrier cells were identified by Dako-IL-2R, which was chosen as a monoclonal antibody that binds to the alpha chain of IL-2R without interrupting the cell machinery of mitogen-induced IL production. Fluorescein-tagged goat anti-rabbit IgG1* was used for subsequent cell staining, and cells were counted by FACS. Net numbers of PHA-activated IL-2R carrier cells were derived by subtracting appropriate background controls. The average number of these cells relative to numbers of total T cell population in uremic PBMC was statistically not different from healthy controls. Several defects in cellular activation associated with IL-2 mechanisms could be envisaged to account for the impaired proliferative response to PHA, manifested by uremic T cells.

Adult

Aeromonas in adult diarrhea: an enteropathogen or an innocent bystander?

This is a study from a district hospital in Israel serving a population of 250,000. During 1986-1987, 1,005 stool specimens were cultured from 932 adult inpatients with acute diarrhea. Seventeen yielded Aeromonas species. Of the 12 strains phenotyped, 10 qualified as enteropathogenic. Five hundred stool specimens from asymptomatic control subjects, inhabitants of the same region, were negative for Aeromonas. The finding of Aeromonas as the apparently sole pathogen in acute adult diarrhea in a geographical area with a negligible asymptomatic carriage rate lends support to the possibility that Aeromonas is an enteropathogen in adults.

Adolescent

Induction of suppressor cell activity by cyclosporin A and/or uremic serum in normal versus uremic peripheral blood mononuclear cells.

We investigated induction of suppressor cell activity in peripheral blood mononuclear cells (PBMC) from normal or uremic subjects. The cells were primed with cyclosporin A (CS-A), uremic serum, or both and subsequently cocultured with fresh phytohemagglutinin-stimulated normal allogeneic responders. CS-A-primed normal as well as uremic PBMC significantly suppressed responder cell thymidine incorporation. Uremic serum primed normal, but not the uremic, PBMC exerted a significant suppression on responder cell proliferation. No significant additive suppressive effect was detected following coculture of responders with PBMC primed by CS-A and uremic serum together. Exclusion of a distinct suppressor cell subset by panning, using anti-Leu-2b monoclonal antibody, did not result in blunting suppressive activity of the CS-A or uremic serum pretreated cells. On the other hand, adherent cell depletion of primed PBMC completely abolished their subsequent suppressive effect on responder cell proliferation.

Adult

Induction of suppressor cell activity in normal peripheral blood mononuclear cells by sera from predialytic uremic patients.

Normal peripheral blood mononuclear cells (PBMC) were primed with sera from 22 predialytic uremic patients, normal sera, concanavalin A, or both. Their suppressive activity was subsequently tested on fresh phytohemagglutinin-stimulated allogeneic responders (i.e., genetically unrelated to either primed cell or sera donors). Uremic serum induced suppressor cell activity in the normal PBMC. No correlation was found between serum urea/creatinine levels and their effects on suppressor cell activity. The induced activity, expressed as percent suppression, was similar to that induced by concanavalin A. In PBMC primed with both concanavalin A and uremic serum, an additive suppressive effect was evident. The suppressor subset(s) induced by uremic serum proved to belong to adherent cell population. Addition of indomethacin or catalase to responder systems did not abolish the suppressive effects, thus suggesting a mechanism of action other than prostaglandin or hydrogen peroxide release.

Adult

Dual challenge for glomerular damage in mice: uninephrectomy and repetitive pregnancies.

We examined the effects of unilateral nephrectomy (UNx) and repetitive pregnancies (RP) on glomerular damage and blood pressure in mice. Four groups of 10 female mice, 7 weeks old, underwent sham nephrectomy (SV) alone, sham nephrectomy and six pregnancies (SP), right nephrectomy alone (NV) and right nephrectomy followed by six repetitive pregnancies (NP). UNx resulted in a significant elevation of serum creatinine up to 11 weeks. In all animals pregnancy was associated with a temporary decrease in serum creatinine except at termination of the 6th pregnancy in group NP. UNx and RP did not result in an increase in protein excretion. UNx in both virgin and pregnant mice resulted in blood pressure elevation without any renal histological abnormalities by the end of the 6th pregnancy. We conclude that at least up to the end of the 3rd pregnancy, gestation was associated with augmentation in function of a single kidney. This effect was lost by the end of the 6th pregnancy. Multiple repetitive pregnancies in uninephrectomized animals entailed renal functional deterioration and a rise in blood pressure without renal histological abnormalities on light microscopy.

Animals

Increased concanavalin A-induced suppressor cell activity in humans with occupational lead exposure.

E-rosette-forming cells (E-RFC), mitogen-induced blast transformation, OKT4+, OKT8+ cells, and their ratio were found to be normal in 10 subjects chronically exposed to lead with blood levels of 40-51 micrograms%. However, concanavalin A (Con A)-induced suppressor cell activity (SCA) in these subjects was significantly greater than in normal matched controls. The clinical relevance of this observation is not clear, but it may have some bearing on the various immunologic defects described in lead exposure.

Adult

Uninephrectomy and repetitive pregnancies in mice: a combined stimulus for renal hypertrophy.

Three hundred 7-week-old Beit Dagan female mice underwent right nephrectomy or sham operation, and either remained virgin or were exposed to six repetitive pregnancies. Fractional kidney weight, dry weight and protein content were determined at ages 9, 10, 11, 17 and 26 weeks corresponding to the ends of the first, second and third trimester of the first pregnancy and completion of the third and sixth pregnancies respectively. In addition histological sections were evaluated morphologically and morphometrically. Renal dry weight and protein content per kidney increased abruptly to maximal values a week after nephrectomy and remained stable thereafter. Repetitive pregnancies were associated with progressive increments in both parameters. The effects of unilateral nephrectomy and repetitive pregnancy were additive. Following unilateral nephrectomy or pregnancy the number of glomeruli per field, as well as fractional glomerular area, increased more rapidly than in sham-operated virgin controls. However, the maximal glomerular number or fractional area attained did not differ from control values. We conclude that (a) in 8-week-old mice pregnancy is associated with renal cell hypertrophy; (b) repetitive pregnancies in these animals produce progressive augmentation in both renal dry weight and protein content; (c) the effects of repetitive pregnancy and unilateral nephrectomy on renal cell hypertrophy are additive; (d) this would indicate that neither manoeuvre exhausts maximal renal capacity for cell hypertrophy, and would suggest some possibilities for the underlying mechanisms.

Animals

Cimetidine-related cardiac conduction disturbances and confusion.

A 70-year-old woman free of renal or hepatic dysfunction developed reversible mental confusion, sinus bradycardia, and extreme QT interval prolongation following initiation of intravenous cimetidine 1200 mg daily. The association of mental confusion with cardiac conduction impairment in a single patient in the context of cimetidine toxicity is highly unusual. We review this and other reports on potentially fatal cimetidine-related cardiac conduction disturbances to suggest that in patients at risk, in addition to reducing cimetidine dosage, electrocardiogram (ECG) follow-up is indicated to identify dangerous bradycardia and QT interval prolongation.

Aged

Acute resin phenol-formaldehyde intoxication. A life threatening occupational hazard.

1. A 38-year-old previously healthy worker accidentally spilled phenol-formaldehyde resin over a large area of his skin. 2. Several days later he was hospitalized with extensive necrotic skin lesions, fever, hypertension, adult respiratory distress syndrome (ARDS), proteinuria and renal functional impairment. 3. All symptoms improved progressively and eventually disappeared. 4. We propose that toxic materials originating from the necrotic skin lesions and the continued facilitated absorption of the resin and/or its components via the skin lesions were the main factors responsible for this alarming multisystem involvement. 5. Workers handling this material should be instructed to take appropriate precautions and physicians should be alerted to the potential pathophysiological consequences.

Adult

Rhabdomyolysis and acute renal failure induced by paraphenylenediamine.

1. We present a 40-year-old healthy man who developed a typical clinical picture of rhabdomyolysis following the administration of paraphenylenediamine by a witchdoctor as a pain killer. 2. Two groups of 15 mice were given paraphenylenediamine 70 mg/kg and 35 mg/kg respectively. Biochemical and histological findings of rhabdomyolysis developed in both groups, without kidney damage. 3. Paraphenylenediamine may cause rhabdomyolysis resulting in acute renal failure in humans. In mice, however, it produces rhabdomyolysis, but the kidneys are not affected.

Acute Kidney Injury