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Biomedical subjects

S M Shasha

Publications and source records attributed to S M Shasha.

At least 37 records · Page 2Linked to original sources

Histochemical studies of progressive p53 mutations during colonic carcinogenesis in Sprague-Dawley rats induced by N-methyl-N-nitro-nitrosoguanidine or azoxymethane.

We studied the increasing expression of the p53 tumor suppressor gene in Sprague-Dawley rats, chemically induced to develop colon cancer. p53 expression was evaluated histochemically at various stages of tumor progression (during a period of 40 weeks) that can be followed by colonic hyperproliferation labeled by 3H-thymidine incorporation. We found that high level nuclear expression of p53 protein correlates with progression of malignancy in carcinogen-induced animals, whereas cytoplasmic staining is related to the onset and early development of malignancy.

Adenocarcinoma↗

Tubal anastomosis in the rat using the tissue adhesive cyanoacrylate (Histoacryl).

n-Butyl-2-cyanoacrylate (Histoacryl) is said to be as effective as microsurgery for tubal anastomosis. In a prospective controlled study at the regional teaching hospital research laboratories, 40 female laboratory rats underwent laparotomy, with ligation of the uterine horns, and reanastomosis by microsurgery or cyanoacrylate tissue adhesive. Main outcome measures were patency of uterine horns following anastomosis, histologic examination of anastomotic sites and pregnancy rate following anastomosis by each of the two methods. Patency rates were 100% with both methods of anastomosis, although foreign-body granulomas were more prominent in horns anastomosed by microsurgery. When cyanoacrylate was used on one horn and the contralateral horn ligated, a 90% pregnancy rate was achieved; when microsurgery was used, the pregnancy rate was 80%. In microsurgically anastomosed tubes there was a longer narrow segment, resulting in a lower number of embryos per rat. Cyanoacrylate tissue adhesive is successful in tubal reanastomosis and has certain advantages over classical microsurgical techniques: fewer foreign-body granulomas occur; there is less narrowing of the uterine horn; less skill is required in its use.

Anastomosis, Surgical↗

Red cell filterability in cigarette smokers and its relations to cardiac hypertrophy.

The relationship among daily cigarette consumption, washed and non-washed RBC filterability time (FT) as an indicator of erythrocyte deformability and echocardiographic left ventricular mass (LVM) were examined in 25 clinically healthy smokers and in 25 non-smoking controls matched for sex and age. FT of non-washed RBC was significantly higher in smokers than in non-smokers (25.2 +/- 3.6 vs. 16.8 +/- 2.2 min, P < 0.001). A highly significant linear correlation between number of cigarette consumption and FT was found. These differences were not observed when RBC were washed three times with isotonic saline. LVM was significantly greater in smokers (85.5 +/- 13.4 g/m2) than in controls (61.8 +/- 6.7 g/m2, P < 0.001). A linear correlation between daily cigarette consumption and LVM was observed. A positive relationship between LVM and FT of non-washed RBC was also found. These results demonstrated that LVM is significantly elevated in smokers and is linearly correlated with both cigarette consumption and RBC filtratibility. The increased deformability found in smokers may be a determinant to the cardiac hypertrophy. The association of both elevated LVM and rheological impairment may indicate unfavourable prognosis.

Adult↗

Effect of oxygen tension on activity of antioxidant enzymes and on renal function of the postischemic reperfused rat kidney.

The aim of the present study was to examine the effect of exposing animals to 100% oxygen instead of room air on renal function and endogenous antioxidant enzymes of the postischemic reperfused rat kidney. Superoxide dismutase (SOD), catalase and glutathione peroxidase (GPX) were determined in the homogenate of the left kidney after 45 min of ischemia, caused by clamping the left renal artery, 10 and 90 min after reperfusion while the animals breathed room air or 100% O2. The right kidney served as a control. The possible influence of trapped blood in the clamped kidney was also investigated by the use of a correction factor based on the Hb concentration in the homogenate. The results indicate that such correction is necessary as the blood adds significant antioxidant activity. The activities of all 3 enzymes after 45 min of ischemia decreased significantly in the left (ischemic) compared to the right (control) kidney, to 64% of the control levels for catalase, 58% for SOD and 49% for GPX. After 10 min of reflow, a further decrease in the activities of catalase (to 49%) and of GPX (to 29%) was found. SOD activity, however, increased to 64%. After 90 min of reperfusion, restoration toward normal levels was noticed (SOD activity increased to 70%, catalase to 76% and GPX to 58%). Breathing 100% O2 resulted in a significant decrease in all enzyme activities (to 38.6% for catalase, 45% for SOD and to 27.4% for GPX). This inactivation can be explained by increased reactive oxygen species (ROS) activity during hyperoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Assessment of combined 24,25(OH)2D3 and 1 alpha (OH)D3 therapy for bone disease in dialysis patients.

An increasing body of experimental data suggests a role for 24,25(OH)2D3 in bone metabolism. The present study was carried out to assess a possible therapeutic role of this vitamin D metabolite in renal osteodystrophy. Twenty-two chronic dialysis patients, most of whom were previously maintained on 1 alpha (OH)D3 therapy, received additional treatment with 10 micrograms/day 24,25(OH)2D3 and were compared to 19 patients receiving 1 alpha (OH)D3 alone. Analysis of transiliac bone biopsies obtained at study entry and following 10-16 months of treatment revealed that the combined therapy produced a decrease in bone turnover. Specifically, the addition of 24,25(OH)2D3 inhibited an increase in trabecular bone volume (BV/TV) and suppressed osteoclastic parameters. Thus BV/TV increased from 26.2 +/- 8.6 to 32.1 +/- 7.5% (p < 0.01) in the 1 alpha (OH)D3 group, but it remained unchanged in the combined therapy group. In contrast, the eroded surface (ES/BS), the osteoclast surface (Oc.S/BS), and the osteoclast numbers were significantly suppressed in patients receiving both 24,25(OH)2D3 and 1 alpha (OH)D3, as compared with those receiving 1 alpha (OH)D3 alone (p < 0.01, p < 0.01, and p < 0.001, respectively). These improvements were independent of changes in 1 alpha (OH)D3 dosage. The extent of bone aluminium deposits was unrelated to the administration of 24,25(OH)2D3 or to its effect. 24,25(OH)2D3 therapy was not associated with any adverse effects.

24,25-Dihydroxyvitamin D 3↗

Proliferative response of T lymphocytes to mitogenic lectins in essential hypertension.

Several studies in human and experimental models indicate the existence of a partial relationship between essential hypertension (EH) and the immune system. In this study, cellular immune functions were investigated in 13 patients with untreated and uncomplicated essential hypertension (EHP) and in 10 of their offspring (EHO) and compared to 13 age- and sex-matched normotensive controls (NC) and 10 of their offspring (NCO). The total number of T cells and T cell subsets were similar in all groups examined. In the EHP, basal lymphocyte transformation without lectins was significantly lower (1,126 +/- 261 cpm of [3H]-thymidine uptake) than in the NC (3,223 +/- 736, p less than 0.01); the response to both phytohemagglutinin (PHA) and concanavalin A (ConA) revealed reduced [3H]-thymidine uptake as compared with NC (21,890 +/- 5,432 compared to 64,574 +/- 9,723 for PHA and 10,488 +/- 2,621 compared to 37,334 +/- 8,148 for ConA, respectively, p less than 0.01). However, the ability to proliferate as a response to lectins was normal. This was leading to a normal stimulation index in both groups. In the EHO, non-significant decrease in basal transformation and reduced uptake with PHA (49,537 +/- 7,478) versus NCO (69,911 +/- 7,254) and NC (64,574 +/- 9,723) were found. These findings suggest that the proliferative response of T lymphocytes is partially suppressed in EH.

Adult↗

Effect of converting enzyme inhibitor captopril on T cell functions in essential hypertension.

T cell function tests were performed in 6 patients with uncomplicated essential hypertension (EH) before and after treatment with captopril, an angiotensin-converting enzyme inhibitor. Total T and T cell subsets were within normal range and were not affected by the drug. The response of PBL to lectin stimulation was significantly impaired. While the stimulation index (SI) was almost normal when washed PBL were used (32.2 +/- 6.90 with PHA and 20.17 +/- 4.1 with Con A) or after their incubation with serum taken from normal subjects (40.42 +/- 10.9 and 15.53 +/- 3.4, respectively), autologous serum significantly reduced the SI (15.04 +/- 5.9 with PHA, p less than 0.05 and 6.68 +/- 1.45 with Con A, p less than 0.005). While captopril seemed to suppress the SI of washed PBL after 1 week of treatment, it enhanced the SI from 32.21 +/- 6.91 to 55.32 +/- 10.76 for PHA and from 20.17 +/- 4.13 to 30.63 +/- 5.41 for Con A (p less than 0.001). This effect was more obvious when the stimulations were performed with normal serum (from 40.42 +/- 10.9 to 96.47 +/- 17.51 for PTH and from 15.53 +/- 3.43 to 40.02 +/- 8.0 for Con A, (p less than 0.001). These results confirm previous reports indicating that the cellular immune response is impaired in EH. It seems that an inhibitory factor found in the serum of these patients is responsible for this impairment. Our findings may suggest that this factor may be angiotensin II.

Aged↗

Effect of a calcium-enriched diet on the colonic epithelial hyperproliferation induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats on a low calcium and fat diet.

We examined whether hyperproliferation of colonic crypt epithelium during cancer induction by N-methyl-N-nitro-N-nitrosoguanidine (MNNG), in rats on a low fat and calcium diet could be reduced by added calcium p.o. From the age of 4 weeks, 104 male Sprague-Dawley rats received a low fat (3.5%), low calcium (0.05% calcium ion), and low vitamin D (0.4 IU/g) diet. Sixty-four also had calcium salts, derived from either calcium lactate or solubilized calcium carbonate, added to their drinking water; therefore their total calcium intake was about 1% of daily diet. At age 12 weeks the rats were divided into 4 treatment groups: 8 rats, not receiving added calcium, had rectal saline instillations weekly (saline control group) and were sacrificed after a further 28 weeks; 3 groups of 32 rats each received intrarectal MNNG (1.5 mg) weekly. One group, not receiving added calcium, was the MNNG control group; while the second group also received added calcium lactate, and the third group received calcium carbonate. Groups of 24 were sacrificed periodically until 28 weeks of treatment. Rats were sacrificed and epithelial proliferation was estimated, 1 week after the last intrarectal instillation, by in vivo labeling with tritiated thymidine and measuring the ratio of labeled to total colonic crypt epithelial cells. The mean labeling index of the MNNG treated and added calcium groups were significantly higher (8.7-9.5%) than that of the saline controls (2.8%) only at week 28; however, it was then still significantly less than that of the MNNG controls not having added calcium (17.9%). Hyperproliferation, during induction of colonic cancer by MNNG in rats on a low calcium diet, can be reduced by a calcium enriched diet even in the presence of a low fat intake.

Animals↗

Cardiac arrhythmia in chronic renal failure: Holter monitoring during hemodialysis and intermittent peritoneal dialysis.

Twenty patients undergoing intermittent peritoneal dialysis (IPD) and 20 patients on hemodialysis (HD) for end-stage kidney disease underwent Holter ECG monitoring for a continuous 24-h period, starting prior to the onset of dialysis and continuing until several hours after it. Clinically significant ventricular arrhythmias were found in only 2 of 20 patients in the HD group; no such ventricular arrhythmias were observed in the IPD group. Supraventricular arrhythmias were equally prevalent in both groups. Thus, the differences between IPD and HD are not great and it seems that HD is, at most, a mild arrhythmogenic procedure. However, in patients with proven heart disease or signs of left ventricular hypertrophy, peritoneal dialysis (intermittent or continuous ambulatory) appears to be preferable to HD.

Adult↗

Effect of parathyroidectomy on T cell functions in patients with primary hyperparathyroidism.

The notion that parathyroid hormone (PTH) can serve as an immunomodulator was examined. T cell function tests were performed in 3 patients with primary hyperparathyroidism before and 1 month after parathyroidectomy (PTX). Three normal volunteers, age and sex matched, were used as controls. One patient with lipoma of the neck was also examined before and after surgical removal of the lesion. In the primary hyperparathyroidism patients the total T cells were lower, the suppressors were higher and the helper to suppressor ratio was significantly lower than in control subjects. The lectin-stimulated lymphocyte transformation was significantly inhibited. All these abnormalities were restored to normal after PTX. Depressed lymphocyte activity was found also in the patient with lipoma. However, no change occurred after surgery. These results support the assumption that excess blood levels of PTH may have an immunosuppressive effect.

Adjuvants, Immunologic↗

Estimation of quantitative proteinuria by using the protein-creatinine ratio in random urine samples.

The protein-creatinine ratio was measured in urine samples obtained at three different times of the day and compared to the 24-hour protein excretion in 51 patients with a wide spectrum of renal function and proteinuria. A linear correlation, which was highly significant, was found between the two variables. The higher correlation was found in urine samples obtained at 08.00 and at 12.00 h and the lowest in samples obtained at 16.00 h. This correlation did not depend on the degree of proteinuria or on the sex of the patients, but was slightly dependent on the glomerular filtration rate. The protein-creatinine ratio was essentially identical with the 24-hour protein excretion. Thus, the normal range of proteinuria was represented by a ratio of less than 0.2, while nephrotic patients had a ratio above 3.5. We suggest that the protein-creatinine ratio in random urine samples could replace the timed collection methods at least for follow-up and screening.

Adolescent↗

In vitro effect of PTH on normal T cell functions.

Uremia is associated with impairment of various cell-mediated immunity functions. The effect of parathyroid hormone (PTH) - known to be elevated in uremia - on several T cell functions has been studied. Normal peripheral blood lymphocytes incubated with increasing amounts of human PTH (HPTH) or bovine PTH (BPTH) showed a considerable decrease (up to 40%) in lectin-induced lymphocytes transformation, significant decrease in helpers to suppressors ratio, and marked inhibition of E rosette formation and T11-positive cells. PTH alone showed no cytotoxic effect on lymphocytes when incubated with or without mitogens. Glucagon, in concentrations up to 10-fold those found on uremia, had no effect on T cell function. Thus the effect of PTH was specific to the hormone action. The direct effect of PTH on normal T lymphocytes and some of their immunological responses is not clear. However, the results of this study support the hypothesis that excess blood levels of PTH may play a role in the pathogenesis of the impairment of the immune response in uremia.

Concanavalin A↗

Tracking of blood pressure in children: results of 7 years' follow-up. The Nahariya Study.

Four hundred and seventy-five school children initially aged 7, 8 and 9 years were examined for blood pressure and risk factors at intervals over a period of 7 years (1978, 1980 and 1985). A significant correlation between successive blood pressure measurements was found after 2 years of follow-up for systolic blood pressure, with tracking coefficients of 0.16 for boys and 0.22 for girls. A similar correlation was found after 7 years, with correlations of 0.16 and 0.26, respectively. For diastolic blood pressure the correlations were 0.15 and 0.18 after 7 years. Children greater than 7 years old were more likely to be above the 90th percentile, with increasing percentiles found in the initial examination. A significant correlation was found between the initial weight, as recorded in the first examination, and the blood pressure percentiles in all three measurements. The correlation coefficient values increased progressively in the successive examinations--0.11, 0.23 and 0.25, respectively, for systolic pressure, and 0.10, 0.14 and 0.19, respectively, for diastolic pressure. There was significant correlation between the initial body mass index and the blood pressure levels in the last examination. Thus, both initial blood pressure levels and body mass appear to be valid predictors of future blood pressure levels.

Adolescent↗

Glucose, insulin and glucagon response to intravenous glucose load in patients on chronic hemodialysis.

We examined the theory that patients with chronic renal failure exhibit glucose intolerance that is not completely corrected by dialysis. I.v. glucose tolerance tests (IVGTT) were performed in 11 uremic patients who were on chronic intermittent hemodialysis therapy for a mean of 33 months, before and 24 h after dialysis. The glucose disappearance constants (K-glucose) were normal in all subjects and were not affected by dialysis. Insulin response was within normal limits, with minimal changes by dialysis. Serum glucagon was higher than normal. The early, middle and late insulin levels were the same as in the normal population. These results indicate that chronic hemodialysis therapy, together with continuous effective control of biochemical impairment, can achieve normal glucose tolerance in uremic patients.

Adolescent↗

Blood pressure of children aged 3 to 5 years--the Nahariya Study.

A total of 974 preschool children aged 3 to 5 years in the city of Nahariya, Israel had their blood pressure measured during the 1983-84 school year. Charts of selected percentiles of blood pressure were developed, and distribution curves were drawn. Mean systolic pressure increased with age--though not significantly--in both sexes, and it tended to be higher in boys than in girls. The mean diastolic pressures increased slightly with age in both sexes, but no differences were found between boys and girls. The mean diastolic pressures in this survey were significantly lower than those reported in other studies, presumably because we used the fifth Korotkoff sound for determination of diastolic pressure instead of the fourth, as was done in most other studies. The percentiles of blood pressure in our study indicated for both sexes that systolic blood pressure above 108 mm Hg at age 3, 110 mm Hg at age 4 and 112 mm Hg at age 5 and diastolic pressures above 62, 64 and 68 mm Hg, respectively, must be considered abnormal.

Blood Pressure↗

Blood pressure measurement in children aged 6 to 15 years--the Nahariya Study.

A total of 5,323 school students aged 6 to 15 years in the city of Nahariya, Israel, had their blood pressure measured during the 1981-82 school year. Height, weight, sex, region of birth and parent's region of birth were also recorded. Charts containing selected percentiles of blood pressure were developed, and distribution curves were drawn. Mean systolic blood pressure increased with age in both sexes. The diastolic pressure, however, remained unchanged. The mean systolic pressures were slightly higher than those found in Bogalusa and than the pooled means published in the recent report of the Task Force on Blood Pressure Control in Children, but lower than those of most other studies. The diastolic pressures were higher than those of the Bogalusa study; they were slightly higher than the pooled means reported by the Task Force for children aged 6 to 9, and for above these ages they were lower by 3 to 7 mm Hg. The selected percentiles of both systolic and diastolic blood pressure in both sexes were lower than those in the charts published initially by the Task Force in 1977 but were very close to those published in their second report in 1987. The mean blood pressure levels were not associated with the parents' region of birth. A highly significant correlation between systolic blood pressure and body mass (as expressed by weight or Quetelet's index) was found.

Adolescent↗

Management of uremic pericarditis.

Five uremic patients with hemodynamically significant pericardial effusion, which did not respond to conservative treatment (intractable effusion) or tamponade, were treated with instillation into the pericardial sac of a nonabsorbable steroid, triamcinolone hexacetonide, and with intermittent drainage. This was done by insertion of a drainage catheter into the pericardial space under direct vision by subxiphoid pericardiotomy performed under local anesthesia. All patients responded well to the procedure, and immediate relief of the symptoms was achieved. No complications of the procedure were observed, and the drainage catheters were removed 48 to 72 h thereafter. Two patients died of unrelated causes--1 month and 3 years after the events. Two other patients are still alive and on a hemodialysis program, and one has a functioning kidney graft. During the 3 to 8 years of follow-up, no recurrent pericarditis was observed, and no constrictive pericarditis developed in any patient.

Administration, Topical↗