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Biomedical subjects

D Silverberg

Publications and source records attributed to D Silverberg.

17 recordsLinked to original sources

Methylene blue, a nitric oxide inhibitor, prevents haemodialysis hypotension.

BACKGROUND: Plasma nitric oxide (NO) levels have been found to be high in haemodialysis (HD) patients, especially in those prone to hypotension in dialysis. The aim of the study was to prevent dialysis hypotension episodes by i.v. administration of methylene blue (MB), an inhibitor of NO activity and/or production. METHODS: MB was given i.v. in 18 stable HD patients with hypotensive episodes during almost every dialysis, in 18 HD patients without hypotension during dialyses, and in five healthy controls. MB was given as a bolus of 1 mg/kg bodyweight followed by a constant infusion of 0.1 mg/kg bodyweight lasting 210 min until the end of the dialysis session and only as a bolus on a non-dialysis day. Systolic and diastolic blood pressures (BP) were measured at 10-min intervals during HD sessions with or without MB and on a non-dialysis day with MB. RESULTS: In hypotension-prone patients, MB completely prevented the hypotension during dialysis and increased both systolic and diastolic BP on non-dialysis days. In normotensive patients, MB increased BP during the first hour of dialysis and for 90 min on the non-dialysis day. The BP in the healthy controls remained unchanged. Plasma and platelet NO(2)+NO(3) (stable metabolites of NO) levels were determined. The NO(2)+NO(3) generation rate in the first post-dialysis day was calculated. The plasma and platelet NO(2)+NO(3) were higher in the hypotensive group than in the normotensive dialysis group. The generation rate of nitrates was higher (P<0.01) in the hypotensive group (1.21+/-0.13 micromol/min and 0.74+/-0.16 after MB) than in the normotensive patients (0.61+/-0.11 micromol/ min and 0.27+/-0.14 after MB). No side-effects were recorded. CONCLUSIONS: MB is an efficient therapy in the prevention of dialysis hypotension.

Adult↗

[Acute colonic pseudo-obstruction].

Colonic Pseudo-obstruction is a poorly understood syndrome. It was first described by Ogilvie in 1948 and is characterized by signs of large bowel obstruction with a non-mechanical etiology. The suggested cause of this pathophysiology is an imbalance in the autonomic nerve supply to the colon. The syndrome affects mainly old, bedridden patients, usually hospitalised for non-colonic causes. The actual incidence of this syndrome is unknown, mainly due to the fact that spontaneous recovery may occur. When massive abdominal distention is apparent, diagnosis and treatment are usually problematic and other causes of obstruction must be ruled out. It is usually managed by water soluble contrast administered orally or rectally, or by colonic decompression. In extreme cases surgical treatment is required with significant morbidity and mortality. Pharmacologic management with parasympathomimetic drugs has been suggested recently. We describe the successful treatment of a patient with neostigmine and review the current literature.

Acute Disease↗

Treatment of acute colonic pseudo-obstruction with neostigmine.

BACKGROUND: Colonic pseudo-obstruction is a poorly understood syndrome, described by Ogilvie, and characterized by signs of large-bowel obstruction, without a mechanical cause. An imbalance in the autonomic nerve supply to the colon has been suggested as the pathophysiology. Recently, promising results with pharmacologic manipulation with neostigmine have been described. STUDY DESIGN: A prospective study was undertaken with 11 consecutive patients with clinical and radiologic signs of colonic pseudo-obstruction, in one general hospital, over a 1-year period. Patients were treated primarily with 2.5 mg of neostigmine in 100 mL of saline for 1 hour, under cardiac monitoring. Results were assessed by the clinical and radiologic responses. RESULTS: Rapid and effective spontaneous decompression of the colon was achieved in 8 patients after a single dose of neostigmine, within a mean of 90 minutes from the beginning of treatment. In another two patients decompression occurred only after a second dose was administered 3 hours after the first dose. In one patient, no changes were observed and colonoscopic decompression was performed. No significant bradycardia was observed in any of the patients. CONCLUSIONS: Neostigmine is a simple, safe, and effective therapy for treatment of colonic pseudo-obstruction.

Acute Disease↗

Pregnancy decreases immunoreactive parathyroid hormone level in rats with chronic renal failure.

Normal pregnancy is associated with an increase in serum parathyroid hormone and 1,25-dihydroxyvitamin D3 (calcitriol). The effect of pregnancy on these hormones in chronic renal failure (CRF) is unknown. The present work was undertaken to study the changes of serum immunoreactive parathyroid hormone (iPTH) and calcitriol in pregnant rats with CRF. The following experimental groups were studied: CRF1 (5/6 nephrectomized virgin female rats), CRF2 (5/6 nephrectomized pregnant rats at day 20-21 of pregnancy), CRF3 (5/6 nephrectomized rats 2 weeks after delivery) and their respective sham-operated control groups: N1, N2 and N3. The 5/6 nephrectomy (CRF1) resulted in renal failure with very high serum iPTH (100+/-18 pg/ml) and low calcitriol levels (10.6+/-4.3 pg/ml) compared with normal rats [N1: 14+/-2.5 pg/ml (P<0.001) and 18.2+/-4.2 pg/ml (P<0.01) respectively]. The pregnancy in CRF rats (CRF2) resulted in normalization of serum iPTH levels (18.2+/-5.41 pg/ml), which was associated with a parallel increase in serum calcitriol (29.4+/-8.0 pg/ml) similar to that in pregnancy of normal rats (N2). Two weeks after delivery the CRF rats (CRF3) once again had high serum iPTH (87+/-17 pg/ml) and low calcitriol levels (9.3+/-1.2 pg/ml), similar to those observed in non-pregnant uraemic rats (CRF1). It is concluded that pregnancy decreases serum iPTH in 5/6 nephrectomized CRF rats most probably by the increased level of calcitriol synthesized by the feto-placental unit.

Analysis of Variance↗

Low nitric oxide production in patients with chronic renal failure.

BACKGROUND: Rats with chronic renal failure have a low nitric oxide (NO) production and a diminished NO excretion. The supplementation of L-arginine has an inhibitory effect on the progression of renal insufficiency. METHODS: The present study was designed to determine whether chronic renal failure patients have a low NO production. Plasma and urine nitrate (NO3) and nitrite (NO2), stable metabolites of NO, were measured in 83 consecutive patients with chronic renal failure. The 83 chronic renal failure patients were divided into three groups: group 1, mild renal failure (creatinine clearance >60 ml/min/1.73 m2); group 2, moderate renal failure (creatinine clearance >30 <60 ml/min/1.73 m2), and group 3, severe renal failure (creatinine clearance <30 ml/min/1.73 m2). Thirty-three healthy volunteers served as controls. RESULTS: The daily urinary NO excretion was significantly lower in patients with moderate and severe renal failure as compared with those with mild renal failure and normal controls. The lowest values were found in the severe renal failure group. When the 24-hour urinary NO excretion or NO per milligram creatinine and the NO clearance were correlated with the renal function in all patients as a group, these parameters were directly correlated with the creatinine clearance and inversely correlated with the serum creatinine level. The plasma NO concentration was not different between the three chronic renal failure groups, but higher than in the controls. Plasma NO in renal failure patients was not correlated with the creatinine clearance or serum creatinine levels. CONCLUSIONS: Chronic renal failure is a state of NO deficiency. Treatment strategies to increase NO production (L-arginine supplementation or other NO compounds) may prove to be useful in maintaining the renal function and slow the progression of renal disease.

Aged↗

Randomised crossover trial of naltrexone in uraemic pruritus.

BACKGROUND: Most dialysis patients develop pruritus, for which current treatment is unsatisfactory. Endogenous opioids may be involved in this pruritus. We studied the effect of the opioid antagonist naltrexone on the pruritus of haemodialysis patients. METHODS: Naltrexone 50 mg per day by mouth was given to 15 haemodialysis patients with severe resistant pruritus in a randomised, double-blind, placebo-controlled crossover trial. The naltrexone or placebo periods lasted 7 days each with a 7-day washout between the two periods. Pruritus was assessed by the patients on a visual analogue scale from 0 (no pruritus) to 10 (maximum), and mean daily scores were calculated. Plasma histamine and beta-endorphin levels were measured, and spontaneous and stimulated basophil histamine-release were determined. FINDINGS: The median pruritus scores at the end of the naltrexone treatment were 2.1 (interquartile range 1.5-2.15) for the naltrexone-placebo sequence and 1.0 (0.4-1.15) for the placebo-naltrexone sequence. The respective values before naltrexone was given were 9.9 (9.85-9.95) and 9.9 (9.3-10.0). Plasma beta-endorphin levels were normal and remained unchanged during the study. Plasma histamine levels were high (mean 2.32 [SD 0.11] ng/mL, normal < 1.0) and decreased after naltrexone (to 1.8 [0.09], p < 0.01). Basophils from haemodialysis patients stimulated by interleukin-3 plus IgE antibodies released high amounts of histamine. The increase was 78.3 (19.3)% compared with 26.6 (16.3)% for five normal controls (p < 0.01). Incubation of the basophils with naloxone, another opioid antagonist, prevented this effect. INTERPRETATION: Our data suggest short-term efficacy with few side-effects for the amelioration of uraemic pruritus with naltrexone.

Cross-Over Studies↗

Nitric oxide in ischaemic acute renal failure of streptozotocin diabetic rats.

Changes in nitric oxide (NO) levels were determined in ischaemic acute renal failure in streptozotocin-induced diabetes mellitus rats. Two weeks after streptozotocin administration and immediately after right nephrectomy, the left renal artery was occluded for 60 min. Similar procedures were carried out in non-diabetic rats. The nitrite (NO2) + nitrate (NO3) levels were measured in plasma and urine. The effects of chronic oral supplementation with L-arginine and an NO synthase inhibitor (N-omega-nitro-L-arginine) were also studied in both diabetic and non-diabetic rats before and after renal artery clamping. The rats with diabetic acute renal failure had a much lower creatinine clearance (90 +/- 22 microliters.min-1. 100g body weight-1, p < 0.005), and higher fractional excretion of sodium (FENa)% (10.90 +/- 4.2, p < 0.001) and protein excretion (2078 +/- 69 micrograms/ml creatinine clearance, p < 0.001) compared with the respective values in the non-diabetic groups (163 +/- 30; 1.46 +/- 86; 453.3 +/- 31). The plasma and urine NO2 + NO3 levels were significantly higher in the untreated diabetic rats compared with the untreated normal rats before ischaemia (p < 0.001). The ischaemic acute renal failure in non-diabetic rats increased the plasma and urinary NO2 + NO3 excretion after ischaemia. The urinary excretion of these metabolites decreased significantly and their plasma levels remained unchanged in the ischaemic diabetic rats. The L-arginine administration resulted in a small but significantly higher creatinine clearance after clamping in the non-diabetic rats. The NO synthase inhibitor caused deterioration in renal function in all ischaemic and non-ischaemic groups. In summary, the greater vulnerability to ischaemia of the diabetic kidney seems to be associated with both impaired response to and impaired production of NO.

Acute Kidney Injury↗

Oral administration of L-arginine and captopril in rats prevents chronic renal failure by nitric oxide production.

The effect of oral supplementation of L-arginine, the substrate of nitric oxide, (1.25 g/liter water) and captopril (15 mg/liter water) was studied in 5/6 nephrectomized rats for a period of three months. N-omega-nitro L-arginine, a nitric oxide synthase inhibitor, was given orally (70 mg/liter water) with or without L-arginine or captopril. The urinary excretion of nitrite (NO2) + nitrate (NO3), the known metabolites of nitric oxide, was taken as an index of nitric oxide production. Chronic renal failure rats were characterized by a low creatinine clearance, high FENa%, proteinuria, hypertension and a low urinary excretion of NO2 + NO3; 0.152 +/- 0.06 (P < 0.001) nmol/micrograms creatinine compared with 0.481 +/- 0.004 (P < 0.001) in normal rats and 0.479 +/- 0.11 (P < 0.001) in untreated sham-operated rats. Both L-arginine and captopril were effective in the normalization of all these parameters. The combination of L-arginine and captopril had no additive effects. The nitric oxide synthase inhibitor significantly diminished the captopril beneficial effect. It is concluded that chronic renal failure in rats is a low nitric oxide production state. The supplementation of L-arginine is shown to overcome this condition. It is suggested that the beneficial effect of captopril on chronic renal failure is through a specific L-arginine--nitric oxide synthase--nitric oxide pathway.

Administration, Oral↗

Head injuries after serious bicycle accidents.

Between 1987 and 1988 there were 47 serious or fatal injuries among bicycle riders in the city of Tel Aviv-Yafo (Serious injury was defined as being hospitalized for at least 24 hours). Collisions with vehicles, mostly cars, were responsible for about 80% of these cases. Two-thirds of the accidents occurred in adults aged 20 and over. We were able to trace the records of 24 of the 47 who were injured. Head trauma was the most common form of severe injury, occurring in 11 of the 24 cases. Two of the 11 died instantly and one died after 14 days of hospitalization, all from severe brain damage. Eight suffered severe head trauma, 7 of which had brain injury and 2 of the 7 were left with severe residual brain damage. In view of the efficacy of bicycle helmets in preventing head trauma there is a great need to expand their use among bicyclists in Israel.

Accidents, Traffic↗

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↗

Cultured mouse marrow cell lines: interactions between fibroblastoid cells and monocytes.

Continuous cell lines were derived from primary cultures of adherent bone marrow cells from SJL/J, BALB/c, C3H/eb, RF, and nude-ICR mice. All these lines readily assumed a pure fibroblastoid appearance with the exception of the BALB/c line (MBA-14), which retained both fibroblastoid and monocytoid cells. This particular line could promote the proliferation of myeloid progenitors (CFU-C) in short-term bone-marrow cultures. The two cell types that composed the MBA-14 cell line were successfully isolated and grown separately; the monocytes as the 14M and 14M1 cell lines and the fibroblastoid cells as the 14F clones. The latter were found to be preadipocytes and accumulated fat in the absence of added hydrocortisone, in medium supplemented with fetal calf serum. Growth of the monocyte lines (14M and 14M1) was dependent upon the mononuclear phagocyte stimulator CSF-1. In the parent MBA-14 cell line the growth of monocytes seemed to depend upon stimulating factor(s) produced by the fibroblastoid cells. The 14M1 monocytes were able to process and degrade antigen as efficiently as primary macrophages. Furthermore, processed antigen produced by 14M1 cells evoked proliferative response by antigen-primed lymph-node cells. In addition to these immunological functions the 14M1 cells were capable of modulating the colony-stimulating activity and degree of adipogenesis exhibited by the fibroblastoid cells. These interactions between monocytes and fibroblastoid cells may constitute part of the mechanism controlling the activity of the hematopoietic microenvironment.

Adipose Tissue↗

The effect of articular malposition after total shoulder arthroplasty on glenohumeral translations, range of motion, and subacromial impingement.

The articular surface of the normal humeral head has a variable posterior and medial offset with respect to the central axis of the humeral shaft. Recreation of the normal humeral head shaft offset is postulated to be an important consideration during shoulder arthroplasty. However, the effect of humeral head malposition is unknown. The purpose of this study was to determine the effect of articular malposition after total shoulder arthroplasty on glenohumeral translation, range of motion, and subacromial impingement. Twenty-one human cadavers were dissected and tested with the use of an active or passive shoulder model. Range of motion and translation were recorded by means of an electromagnetic tracking device. The experiment was performed in 2 phases. For kinematics study, 11 cadaver shoulders were positioned both passively and actively from maximum internal rotation to maximum external rotation at 90 degrees of total elevation in the scapular plane. Three rotator cuff and 3 deltoid muscle lines of action were simulated for active joint positioning. Passive joint positioning was accomplished with the use of a torque wrench and a nominal centering force. The testing protocol was used for the natural joint as well as for 9 prosthetic head locations: centered and 2- and 4-mm offsets in the anterior, posterior, inferior, and superior directions. Repeated-measures analysis of variance was used to test for significant differences in the range of motion and translation between active and passive positioning of the natural joint as well as all prosthetic head positions. (2) For impingement study, 10 cadaver shoulders were used in a passive model, loading the tendons of the rotator cuff with a 30-N centering force. The humerus was passively rotated from maximum internal rotation (1500 Nmm) to maximum external rotation (1500 Nmm) by means of a continuous-recording digital torque wrench. Trials were performed with the use of centered, 4-, 6-, and 8-mm offset heads in the anterior, posterior, superior, and inferior positions before and after removal of the acromion and coracoacromial ligament. The relation between change in mean peak torque (with and without acromion), passive range of motion, and humeral head offset was analyzed by means of repeated-measures analysis of variance. In the kinematics study, total range of motion and all humeral translations were greater with passive joint positioning than with active positioning (P =.01) except for total superior-inferior translation and superior-inferior translation in external rotation. Anterior to posterior humeral head offset was associated with statistically significant changes in total range of motion (P =.02), range of internal rotation (P =.02), range of external rotation (P =.0001), and total anterior-posterior translation (P =.01). Superior to inferior humeral head offset resulted in statistically significant changes in total range of motion (P =.02), range of internal rotation (P =.0001), anterior-posterior translation during external rotation (P =.01), and total superior-inferior translation (P =.03). In the impingement study, there was a significant increase in torque from centered to 4-mm inferior offset (P =.006), 6-mm inferior offset (P <.001), and 8-mm inferior offset (P <.001). There was no significant increase in torque with superior, anterior, and posterior offsets. Glenohumeral motion significantly decreased from 129 degrees for centered head to 119 degrees for 8-mm superior (P =.002), 119 degrees for 8-mm anterior (P =.014), 118 degrees for 8-mm inferior (P <.001), and 114 degrees for 8-mm posterior (P =.001). Humeral articular malposition of 4 mm or less during prosthetic arthroplasty of the glenohumeral joint may lead to small alterations in humeral translations and range of motion. Inferior malposition of greater than 4 mm can lead to increased subacromial contact; offset of 8 mm in any direction results in significant decreases in passive range of motion. Therefore if subacromial contact is to be minimized and glenohumeral motion maximized after shoulder replacement, anatomic reconstruction of the humeral head-humeral shaft offset to within 4 mm is desirable.

Adult↗

Obstructive sleep apnea and hypertension: from correlative to causative relationship.

Sleep-disordered breathing, manifested by repetitive episodes of partial or complete cessation of breathing during sleep associated with brief arousal and autonomic activation, is estimated to affect as many as 4% of adult men and 2% of adult women. Studies conducted during the 1980s revealed a strong association between sleep-disordered breathing and hypertension. The results of these early studies, which relied on relatively small samples of patients, have been confirmed in recent years by large-scale epidemiologic studies that are controlled for all possible confounding factors. This paper reviews the evidence suggesting a causative relationship between hypertension and disordered breathing in sleep. The authors discuss the possible underlying mechanisms of the two entities and address the clinical implications of this relationship. They conclude by recommending a proactive approach to the diagnosis of breathing disorders in sleep, in order to prevent the cardiovascular sequelae of this syndrome.

Confounding Factors, Epidemiologic↗