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Biomedical subjects

H Silverman

Publications and source records attributed to H Silverman.

At least 37 records · Page 2Linked to original sources
PubMed1992

Exercise-induced cellular alterations in the diaphragm.

Limited data exist concerning the effects of exercise training on cellular oxidative capacity in the diaphragm of senescent animals. In this study we examined the changes in cellular oxidative capacity, muscle cell cross-sectional area (CSA), and capillarity within the costal diaphragm of senescent animals after a 10-wk endurance-training program. Twelve 24-mo-old female Fischer 344 rats were divided into either a sedentary control group (n = 6) or exercise training group (n = 6). The trained animals exercised on a motor-driven treadmill (60 min/day, 5 days/wk) at a work rate equal to approximately 55-65% VO2max. Capillaries were identified histologically and fiber types determined using adenosinetriphosphatase (ATPase) histochemistry. Succinate dehydrogenase (SDH) activity and CSA in individual fibers were measured using a computerized image analysis system. Exercise training did not increase (P > 0.05) the capillary-to-fiber ratio for any fiber type. However, training significantly decreased CSA (P < 0.05) and increased capillary density (capillary number/CSA) (P < 0.05) in type I, type IIa, and type IIb fibers. Furthermore, exercise training resulted in small but significant increase in SDH activity (P < 0.05) in type I and IIa fibers, whereas training did not alter SDH activity (P > 0.05) in type IIb fibers. These data demonstrate that endurance training in senescent animals results in small relative improvements in both oxidative capacity and capillary density in costal diaphragmatic type I and IIa muscle fibers. The increase in both capillary density and fiber SDH activity was largely due to a reduction in fiber CSA.

Aging↗
PubMed1992

Adult respiratory distress syndrome. Sequence and importance of development of multiple organ failure. The Prostaglandin E1 Study Group.

STUDY OBJECTIVE: To determine the epidemiology of multiple organ failure (MOF) in patients with the adult respiratory distress syndrome. PATIENTS: We followed up 50 patients with serial determinations of respiratory and nonrespiratory organ function for seven days after diagnosis. DESIGN: Data were stratified between patients who died and those who survived (defined as hospital discharge). MEASUREMENTS AND RESULTS: Values that did not differ at any time between the two groups of patients included oxygen availability, oxygen consumption, oxygen extraction, PaCO2, respiratory rate, heart rate, systolic blood pressure, cardiac output, stroke index, systemic vascular resistance, and temperature. Patients who died had greater defects in oxygenation (from day 1 through day 7). They also exhibited decreased arterial oxygen content (from day 1 to day 4), decreased mixed venous oxygen content (day 1), increased peak inspiratory pressure (present on day 2, persisted to day 5, reappeared on day 7), decreased diastolic blood pressure (seen on days 1 through 3, reappeared on day 7), and increased mean pulmonary artery pressure (seen on days 2 and 3). Nonsurvivors also exhibited greater degrees of thrombocytopenia (from day 1 to day 4). Decreases in pH (seen on day 1, reappeared from days 4 to 7), abnormalities in liver function (seen only on day 1), and increases in serum creatinine levels (appeared on day 7) were also observed. CONCLUSIONS: Multiorgan dysfunction (MOD) was frequently observed in both groups of patients. Alterations in organ function and the pattern of abnormalities were often subtle and would not be characterized as significant organ dysfunction by most available organ scoring systems. Adult respiratory distress syndrome is a manifestation of systemic disease produced by widespread increases in endothelial permeability; lung dysfunction dominates the early clinical course. When respiratory function is supported, it becomes evident that alterations occur in other organs. Multiorgan failure is really a misnomer; the term emphasizes end-stage changes. Multiorgan dysfunction is common and often resolves without progressing to MOF. Alternatively, MOD can progress to MOF.

Blood Pressure↗
PubMed1992

The effects of prostaglandin E1 on non-pulmonary organ function during clinical acute respiratory failure. The Prostaglandin E1 Study Group.

The effects of prostaglandin E1 (PGE1) on non-pulmonary vital organs in critically ill patients are not well defined. This study evaluated the role of exogenous PGE1 in systemic homeostasis during the adult respiratory distress syndrome (ARDS). Indicators of end-organ function were analyzed retrospectively in 146 septic or post-trauma patients with ARDS who received PGE1 (30/ng/kg/min) or placebo IV for up to 7 days in a randomized, double-blind clinical trial. Hemodynamic variables and serum levels of creatinine, bilirubin, and SGOT, platelet count, and changes in the white blood cell count were measured daily. Our results indicate that mean arterial pressure, pulmonary artery pressure, and systemic and pulmonary vascular resistance indices were significantly lower in the PGE1 group versus the placebo-treated group. Cardiac index, stroke index, and oxygen delivery index were significantly increased in the PGE1 group. Serum bilirubin and SGOT were decreased significantly among PGE1-treated patients compared with placebo-treated patients, while the white blood cell count increased more significantly from baseline values with PGE1 treatment. Intergroup differences in platelet count and serum creatinine levels were not statistically significant. The results indicate that PGE1 improves cardiovascular performance, hepatic function, and leukocyte availability during clinical ARDS. Prostaglandin E1 did not affect platelet counts and renal function in this study.

Acute Disease↗
PubMed1992

Treatment of common eye emergencies.

Some ocular conditions represent serious emergencies requiring immediate treatment. Chemical exposure requires prompt irrigation with saline. Major trauma with possible globe perforation requires eye shielding and referral for surgical evaluation. Sudden loss of vision may represent vascular occlusion and should be evaluated promptly by an ophthalmologist. Angle closure glaucoma is rare; drug treatment may be instituted in consultation with an ophthalmologist. Patients with orbital cellulitis should be hospitalized for intravenous antibiotic therapy. Less urgent eye conditions can be treated within 24 hours of onset. Minor trauma with hyphema requires cycloplegic medications, eye shielding and ophthalmologic consultation. Visual floaters, light flashes or "curtains" may represent vitreous or retinal detachment and should be evaluated by an ophthalmologist. Foreign bodies can usually be removed by irrigation or careful instrumentation.

Emergencies↗
PubMed1991

Age-related changes in enzyme activity in the rat diaphragm.

Limited data exist concerning the effect of growth and aging on the metabolic properties of the diaphragm. Therefore, we investigated age-related changes in protein concentration and glycolytic and Krebs cycle enzyme activity in the diaphragm as well as the plantaris muscle of female Sprague-Dawley rats ranging in age from 1 to 12 months. Samples from the costal and crural diaphragm and the plantaris muscle were obtained from 38 animals in the following age groups: (1) 1 month old (N = 7); (2) 4 month old (N = 6) (3) 6 month old (N = 13); and (4) 12-month-old (N = 12). Body weight and diaphragm weight increased rapidly by a factor of 6 and in parallel during 1-4 months postpartum before reaching a plateau at 6 months of age. No significant difference (P greater than 0.05) existed in the ratio of diaphragm weight to body weight among age groups. Protein concentration was significantly higher (P less than 0.05) in the costal diaphragm and plantaris at 4 and 6 months when compared to 1 and 12 months of age. In the crural diaphragm, protein concentration was significantly lower (P less than 0.05) at 1 month postpartum when compared to all other age groups. Succinate dehydrogenase (SDH) activity was significantly higher (P less than 0.05) at 1 month of age in the plantaris, the costal diaphragm and the crural diaphragm when compared to older animals. In contrast, the activity of lactate dehydrogenase (LDH) in the plantaris, the costal diaphragm and the crural diaphragm was significantly lower (P less than 0.05) in the 1-month-old animals when compared to all other ages.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1991

Glyconeogenic and glycogenic enzymes in chronically active and normal skeletal muscle.

The chronically active (pseudomyotonic) gastrocnemius muscle in the C57B16J dy2J/dy2J mouse contains both elevated lactate and glycogen as well as fibers that have high amounts of glycogen and enhanced glyconeogenic activity. In the present study we analyze the activities of some key glyconeogenic enzymes to assess the causes of elevated muscle glycogen and to determine the pathway for glycogen synthesis from lactate. Glycogen synthase, malate dehydrogenase, phosphoenolpyruvate carboxykinase, and malic enzyme were all elevated in homogenates of the chronically active muscle. Activities of glycogen phosphorylase and fructose 1,6-bisphosphatase were decreased in whole muscle homogenates. Histochemistry demonstrated that the high-glycogen fibers were typically fast-twitch glycolytic fibers that had high glycogen synthase, glycogen phosphorylase, and malic enzyme activities. Malate dehydrogenase activity followed succinate dehydrogenase activity and did not correlate to high-glycogen fibers. Thus the high-glycogen fibers have an elevated enzymatic capacity for glycogen synthesis from lactate, and the pathway may involve use of the pyruvate kinase bypass enzymes.

Animals↗
PubMed1991

Blockade of the ATP-sensitive potassium channel modulates reactive hyperemia in the canine coronary circulation.

The mechanism of reactive hyperemia remains unknown. We hypothesized that reactive hyperemia was related to the opening of ATP-sensitive potassium channels during coronary occlusion. The resulting hyperpolarization of the smooth muscle cell plasma membrane might reduce calcium influx through voltage-dependent calcium channels and result in relaxation of smooth muscle tone and vasodilation. In eight open-chest, anesthetized dogs, 30-second coronary occlusions resulted in an average flow debt repayment of 200 +/- 41%. After low-dose (0.8 mumol/min) and high-dose (3.7 mumol/min) infusion of intracoronary glibenclamide, flow debt repayment fell to 76 +/- 14% and 50 +/- 8%, respectively (p less than 0.05 compared with control for both). The decline in flow debt repayment was due to a significant reduction both in maximum coronary conductance during reactive hyperemia and in its duration. In addition, there was a significant decline in the sensitivity of the coronary circulation to adenosine-induced vasodilation after glibenclamide. While more variable, there was no overall change in the sensitivity of the coronary vasculature to acetylcholine-induced vasodilation after glibenclamide. We conclude that reactive hyperemia is determined in a large part by the ATP-sensitive potassium channel, probably through its effect on membrane potential and voltage-sensitive calcium channels. Because reactive hyperemia was never fully abolished at the highest doses of glibenclamide tested, it is possible that additional mechanisms are involved in the genesis of this complex phenomenon.

Acetylcholine↗
PubMed1990

Endurance-training-induced cellular adaptations in respiratory muscles.

Controversy exists concerning the adaptability of mammalian respiratory muscles in response to endurance training. We examined the effects of 8 wk of progressive treadmill exercise (45 min/day 5 days/wk) on the biochemical adaptations of rat diaphragm and intercostal muscles. Female Sprague-Dawley rats were randomly assigned to a sedentary control (n = 10) or an exercise-training group (n = 10). Endurance training resulted in an enhanced oxidative capacity in the anterior costal diaphragm as evidenced by a 29% increase (P less than 0.05) in the activity of succinate dehydrogenase (SDH) in trained animals compared with controls (4.15 +/- 0.13 vs. 3.21 +/- 0.17 mumol.g-1.min-1). Similarly, SDH activity in the intercostal muscles was 32% greater (P less than 0.05) in the trained animals than in the untrained animals (1.72 +/- 0.11 vs. 1.30 +/- 0.06 mumol.g-1.min-1). In contrast, the crural region of the diaphragm showed no significant increase (P greater than 0.05) in oxidative capacity as a result of the training program (3.28 +/- 0.12 vs. 3.13 +/- 0.18). Furthermore, training did not alter (P less than 0.05) lactate dehydrogenase activity in the intercostals or in the crural or the costal diaphragm. These data demonstrate that the oxidative capacity of the costal diaphragm and the intercostal muscles can be enhanced by increasing respiratory loads via regular endurance exercise. We speculate that the lack of metabolic adaptation in the crural region of the diaphragm was not due to limited plasticity of the fibers in this area but to failure to the exercise-training program to provide the appropriate stimulus for cellular adaptation.

Adaptation, Physiological↗
PubMed1990

Regional metabolic differences in the rat diaphragm.

This study characterized the biochemical properties of the rat diaphragm by measuring the activities of selected citric acid cycle and glycolytic enzymes. The diaphragm was removed from 10 female Sprague-Dawley rats (180 days old) and dissected into five discrete anatomic regions: crural (region 1), left posterior costal (region 2), left anterior costal (region 3), right anterior costal (region 4), and right posterior costal (region 5). Sections were assayed for total protein concentration and the activities of succinate dehydrogenase (SDH) and lactate dehydrogenase (LDH). The SDH activity in the crural region was approximately 18% lower (P less than 0.05) than that in any costal region. Furthermore, protein concentration was significantly lower (P less than 0.05) in the crural region compared with all costal regions. In contrast, costal regions 2-5 did not significantly differ from each other in protein concentration or SDH activity. LDH activity did not differ significantly (P greater than 0.05) between regions. Finally, the LDH-to-SDH activity ratio was significantly higher (P less than 0.05) in the crural diaphragm compared with all costal regions. We conclude that the crural region of the rat diaphragm is significantly lower in oxidative capacity than all the costal regions. Investigators who use a rodent model to study diaphragmatic function and plasticity should consider the oxidative heterogeneity of the diaphragm when designing experiments.

Animals↗
PubMed1989

Glycogen synthesis from lactate in a chronically active muscle.

In response to neural overactivity (pseudomyotonia), gastrocnemius muscle fibers from C57Bl/6Jdy2J/dy2J mice have different metabolic profiles compared with normal mice. A population of fibers in the fast-twitch superficial region of the dy2J gastrocnemius stores unusually high amounts of glycogen, leading to an increased glycogen storage in the whole muscle. The dy2J muscle also contains twice as much lactate as normal muscle. A [14C]lactate intraperitoneal injection leads to preferential 14C incorporation into glycogen in the dy2J muscle compared with normal muscle. To determine whether skeletal muscles were incorporating lactate into glycogen without body organ (liver, kidney) input, gastrocnemius muscles were bathed in 10 mM [14C]lactate with intact neural and arterial supply but with impeded venous return. The contralateral gastrocnemius serves as a control for body organ input. By using this in situ procedure, we demonstrate that under conditions of high lactate both normal and dy2J muscle can directly synthesize glycogen from lactate. In this case, normal whole muscle incorporates [14C] lactate into glycogen at a higher rate than dy2J whole muscle. Autoradiography, however, suggests that the high-glycogen-containing muscle fibers in the dy2J muscle incorporate lactate into glycogen at nearly four times the rate of normal or surrounding muscle fibers.

Adenosine Triphosphatases↗
PubMed1989

Randomized double-blind, multicenter study of prostaglandin E1 in patients with the adult respiratory distress syndrome. Prostaglandin E1 Study Group.

Prostaglandin E1 (PGE1) was compared to placebo in a 100-patient (50 PGE1, 50 placebo) randomized, double-blind, clinical trial to determine whether PGE1 therapy enhances survival of patients with adult respiratory distress syndrome (ARDS) when infused through a central line at 30 ng/kg/min continuously for seven days. At 30 days postinfusion, 30 PGE1 and 24 placebo patients had died. Total deaths judged to be related to the syndrome were 32 and 28 in the PGE1 and placebo groups respectively at six months. We conclude that PGE1 did not enhance survival in patients with established ARDS. PGE1 augmented the hyperdynamic circulation of these patients by reducing systemic and pulmonary vascular resistance, which resulted in a reduction of blood pressures and increased stroke volume, cardiac output, and heart rate. An improvement in oxygen availability and oxygen consumption was observed with PGE1 therapy. PGE1 was associated with an increased incidence of diarrhea (six patients in the PGE1 group vs one in the placebo group, p less than 0.05). Other adverse effects included hypotension (ten patients in the PGE1 group vs seven in the placebo group), fever (six patients in the PGE1 group vs three in the placebo group), and non-fatal dysrhythmias (ten in the PGE1 group vs five in the placebo group).

Alprostadil↗
PubMed1989

An early test of survival in patients with the adult respiratory distress syndrome. The PaO2/FIo2 ratio and its differential response to conventional therapy. Prostaglandin E1 Study Group.

Patients with established adult respiratory distress syndrome (ARDS) have a mortality rate that exceeds 50 percent. We analyzed the magnitude of hypoxemia as manifest by the PaO2/FIO2 ratio and its early response to conventional therapy including positive end-expiratory pressure (PEEP) in the placebo group of a large multicenter study. The PaO2/FIO2 ratio was not different at the time of diagnosis of ARDS in those patients who lived compared to those who subsequently died. After one day of conventional therapy including PEEP, those patients who survived increased their PaO2/FIO2 ratio. The nonsurvivors did not improve over a seven-day course. The difference in the PaO2/FIO2 ratio was significant throughout the seven-day observation period. We conclude that the early response to conventional therapy picks a patient population with a good prognosis and can be used as a test of likely survival from ARDS.

Alprostadil↗
PubMed1988

Fecal incontinence in elderly patients.

Fecal incontinence is a common and important problem in the care of the elderly. An understanding of the defecation mechanism, appropriate differential diagnosis, and the best choice of treatment method are necessary to control this problem. Establishing a regular bowel program takes time and energy, but when the final result is continence, it is time and energy well spent.

Aged↗
PubMed1986

Age-related changes in oxidative capacity of the gastrocnemius muscle in normal and dystrophic (dy2J/dy2J) mice.

The hind limb muscles of dy2J/dy2J mice appear more oxidative than normal hind limb muscles when assayed histochemically. In some cases, biochemical assay of oxidative capacity does not match histochemical data, and in some dy2J mice, particularly old animals, there appears to be a decline in biochemically assayed oxidative enzymes. The current study cyto-biochemically assayed succinic dehydrogenase activity of the gastrocnemius muscle in dy2J and normal mice. The assays were conducted over a maturation time course of 1 to 6 months of age. Additionally, the gastrocnemius muscle was divided into two distinct regions, a superficial region, containing largely glycolytic fast-twitch fibers (SGM), and a deeper region of mixed, largely oxidative fibers (DGM) in normal animals. Assay of the whole muscle and the two regions of each individual muscle showed that the dy2J muscle increased in SDH activity with maturation and was significantly greater than the change observed in normal muscle during the same period. The increase in the whole muscle SDH activity was accounted for increases noted in the SGM. The dy2J DGM, which showed marked morphologic degeneration, had neither an increase nor a decrease in measured SDH activity. Michaelis-Menton analysis of the enzymatic assay indicated that the Vmax, and not the Km, of the dystrophic muscle enzyme system was higher than normal, suggesting a change in quantity of enzyme present, and not altered function of the system. The observed increases occurred for 4 months of maturation and then began a decline, which was noted at 6 months. Coupled with the time course of gastrocnemius muscle degeneration (the glycolytic region was slow--very little by 4 months; the mixed was fast--highly degenerated by 1 to 2 months), the results of this study suggest that oxidative capacity in the dy2J gastrocnemius muscle increased with maturation until it became obscured by inherant muscle wasting in a particular dy2J muscle region. By comparison, analysis of the large glycolytic triceps muscle, a forelimb muscle which does not receive pseudomyotonia, indicated that this muscle did not increase in SDH activity in dystrophic animals, which showed the abnormal increase in the activity of the hind limb gastrocnemius. Thus the relationship of pseudomyotonia to increasing oxidative activity in the hind limb muscles of dystrophic animals was evident.

Animals↗
PubMed1985

Clear cell ameloblastoma--an odontogenic carcinoma.

Two cases of aggressive intraosseous epithelial tumor of the jaws are presented. Both tumors demonstrated an unusual biphasic pattern with areas of acceptable follicular ameloblastoma together with a conspicuous clear-cell component. The clinical course indicates these lesions should be considered as low grade odontogenic carcinomas. Further subclassification according to the World Health Organization classification and the recently proposed modification by Elzay is discussed.

Aged↗
PubMed1985

Efficacy and safety of naloxone in septic shock.

We evaluated the effectiveness and safety of iv naloxone in 12 septic patients who remained hypotensive despite volume replacement, appropriate antibiotics, and vasopressor therapy. Only four patients responded positively to naloxone, by increases in mean arterial pressure of between 10 to 15 mm Hg that lasted for 15 to 60 min. These patients could not be distinguished from the others on the basis of underlying illness, laboratory or physical findings, length of preceding hypotension, or glucocorticoid therapy. Four patients had adverse reactions: one developed pulmonary edema, one patient had a grand-mal seizure, and two patients became severely hypotensive. We conclude that in patients with well-established septic shock, naloxone does not reliably improve mean arterial pressure or other physiologic variables, and may cause severe adverse reactions.

Aged↗
PubMed1984

Chronic phenytoin administration alters the metabolic profile of superficial gastrocnemius muscle fibers in dystrophic mice.

Phenytoin is known to reduce neural overactivity (pseudomyotonia) affecting the hind limb musculature in C57B1/6J dystrophic (dy2J/dy2J) mice. This study reports a change in the metabolic profile of superficial gastrocnemius muscle fibers from dy2J/dy2J animals after chronic phenytoin treatment. The superficial gastrocnemius muscle region from normal mice is composed of 98% fast-twitch glycolytic muscle fibers. In dystrophic mice these fibers (FG) show increased oxidative capacity without evidence of morphologic degeneration during the first few months ex utero. Many of these fibers also store abnormally large amounts of glycogen as determined by periodic acid-Schiff histochemistry. After 104 days of phenytoin treatment, the dy2J/dy2J FG muscle fibers showed a reduction in abnormally high oxidative capacity as monitored by succinic dehydrogenase activity; there was also a reduction of glycogen storage in a number of dy2J/dy2J fibers. One hypothesis suggests that the increase in oxidative capacity of the dy2J/dy2J superficial gastrocnemius muscle fibers is the expected result of overstimulation by the pseudomyotonia. Our experiments indicated that the abnormal metabolic profile observed in those fibers can be altered simply by a reduction in pseudomyotonia. These results mimic those seen after short-term denervation of the same dy2J/dy2J muscle. After phenytoin treatment the mean dy2J/dy2J superficial gastrocnemius muscle fiber cross-sectional area was significantly increased compared with untreated animals. Cursory examination of the degenerated deep region of this same muscle suggested that similar changes did not occur after drug treatment. This suggests that the pseudomyotonia was partially different from the factor(s) causing early degeneration of the oxidative muscle fibers in the dy2J/dy2J animals.

Animals↗