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Biomedical subjects

B Levy

Publications and source records attributed to B Levy.

At least 73 records · Page 4Linked to original sources

Prospective trial of daily and extended wear disposable contact lenses.

PURPOSE: The current study prospectively evaluates the response to daily and extended wear of disposable lenses with each patient acting as his/her own control. This paradigm allowed for elimination of individual variation as a confounding factor, as well as determining whether an intrinsic factor, other than lens wear, predisposed patients to complications. METHODS: One hundred thirty-four patients were randomly assigned to contralateral daily wear (DW) or extended wear (EW) with Acuvue lenses for 1 year. All lenses were disposed of on a weekly basis. Bilateral bacteriology of lids, conjunctivae, lenses, and fingers was carried out on those patients presenting with complications. RESULTS: The results after 1 year indicate a higher incidence of complications in the EW eye (peripheral infiltrative keratopathy, 12%; corneal striae, 3%). No significant clinical complications occurred in the DW eye. Microbiological cultures did not reveal any significant difference between those eyes with keratopathy and those of controls. The most common pathogen was Staphyloccocus epidermidis. No gram-negative organisms grew from any of the culture sites. CONCLUSIONS: The results of this study indicate that extended wearing schedules, and not the lens entity, predispose the patient to a higher risk of keratopathy with disposable contact lenses. No microbiological association with the adverse events could be determined, and no intrinsic patient factor could be demonstrated that would predict the likelihood of complications.

Adult↗

Effect of 14 days' subcutaneous administration of the human amylin analogue, pramlintide (AC137), on an intravenous insulin challenge and response to a standard liquid meal in patients with IDDM.

Individuals with insulin-dependent diabetes mellitus (IDDM or type 1 diabetes) are deficient in both insulin and amylin, peptides secreted by the beta cell. We have investigated the effects of amylin replacement therapy employing the human amylin analogue, pramlintide (25, 28, 29-pro-human amylin, previously referred to as AC137), upon the responses to a standardized insulin infusion (40 mU. kg-1. h-1) for 100 min and a liquid Sustacal meal (360 kcal) in 84 healthy IDDM patients. Following baseline evaluations, patients were randomly assigned to receive subcutaneous injections of placebo, 30, 100 or 300 micrograms pramlintide 30 min before meals for 14 days. There was no meaningful difference between adverse events reported by the 30-micrograms pramlintide and the placebo groups, but ten subjects withdrew due to nausea, eight of these in the 300-micrograms dose group. Peak plasma pramlintide concentrations for the 30-micrograms group were 21 +/- 3 and 29 +/- 5 pmol/l on Days 1 and 14, respectively. These values are similar to postprandial plasma amylin concentrations in normal volunteers. The plasma glucose, free insulin, glucagon, epinephrine and norepinephrine concentrations during the insulin infusion test before and after therapy were identical in each of the group. Prior to pramlintide therapy, Sustacal ingestion produced a 4.0-4.8 mmol/l rise in plasma glucose concentrations in each of the groups. Pramlintide therapy reduced postprandial hyperglycaemia as reflected by the 3-h incremental AUCglucose (AUCglucose above or below fasting glucose concentration) Day 1 vs Day 14: 30 micrograms, 322 +/- 92 vs -38 +/- 161 mmol/l.min, p = 0.010; 100 micrograms, 317 +/- 92 vs -39 +/- 76 mmol/l.min, p = 0.001; and 300 micrograms, 268 +/- 96 vs -245 +/- 189 mmol/l.min, p = 0.077. Thus, pramlintide therapy with these regimens did not appear to impair either in vivo insulin action or the counter-regulatory response to hypoglycaemia but did show a clear effect of blunting postprandial hyperglycaemia following a standardized meal.

Adolescent↗

Neuropathology of murine mucopolysaccharidosis type VII.

We describe the neuropathology in mucopolysaccharidosis type VII (MPS VII) mice with a recessively inherited deficiency of the lysosomal enzyme beta-glucuronidase. Affected animals have a shortened life span, are dysmorphic, dwarfed and have clinical evidence of behavioral and memory deficiencies. Widespread lysosomal distention with glycosaminoglycan accumulation affects most viscera. In the central nervous system there is progressive accumulation of lysosomal storage in neurons, glia and mesenchymal tissue. The morphological character and the amount of lysosomal storage varies among neuronal groups. In the hippocampus, regional variation in the abundance of lysosomal storage in the MPS VII mice correlates with regional variation in the amount of beta-glucuronidase activity in normal mice. The MPS VII mouse provides a well-defined genetic system for the analysis of the neuropathology of MPS VII and is an attractive model on which to test the effects of potential therapies for lysosomal storage disease on the central nervous system.

Animals↗

Improving memory in old age through implicit self-stereotyping.

This research demonstrates that subliminally activated stereotypes can alter judgments about oneself and can change cognitive performance. In the first study, an intervention that activated positive stereotypes of aging without the participants' awareness tended to improve memory performance, memory self-efficacy, and views of aging in old individuals; in contrast, an intervention that activated negative stereotypes of aging tended to worsen memory performance, memory self-efficacy, and views of aging in old participants. A second study demonstrated that for the strong effects to emerge from the shifting stereotypes, the stereotypes must be important to one's self-image: Young individuals randomly assigned to the same conditions as the old participants in the first study did not exhibit any of the significant interactions that emerged among the old participants. This research highlights the potential for memory improvement in old individuals when the negative stereotypes of aging that dominate the American culture are shifted to more positive stereotypes.

Adolescent↗

Chronic infusion of low-dose angiotensin II potentiates the adrenergic response in vivo.

OBJECTIVE: The aim of this study was to investigate the role of angiotensin II-induced potentiation of the alpha 1-adrenergic contractile response in the aetiology of low-dose angiotensin II-induced hypertension. METHODS: Wistar rats (250g) received angiotensin II (120 ng/kg per min) from subcutaneous minipumps for 21 days. The responses of vaso-active properties of second-order mesenteric arteries (200 micron) to potassium, phenylephrine, angiotensin II and acetylcholine were assessed. The acute amplification effects of angiotensin II on the response to phenylephrine were examined. RESULTS: Angiotensin II induced a progressive hypertension, which reached a plateau after approximately 5 days. The responses to potassium, angiotensin II and acetylcholine were not significantly modified in rats treated chronically with angiotensin II. The major finding of this study is that the response to phenylephrine (1-3 mumol/l) was potentiated (sevenfold at 1.75 mumol/l) after chronic treatment with angiotensin II. In control vessels acute addition of angiotensin II (10(-10) mol/l) produced no contraction but induced potentiation of the phenylephrine response (1-3 mumol/l). No further potentiation of the phenylephrine response was observed in the rats treated chronically with angiotensin II. CONCLUSIONS: Thus, although the direct contractile responses to potassium and angiotensin II remain unaffected following chronic angiotensin II treatment, the alpha 1-adrenergic contractile response to phenylephrine is significantly potentiated by angiotensin II in this model of hypertension. We suggest that this potentiation contributes to the hypertension observed in response to infusion of low-dose angiotensin II.

Acetylcholine↗

Safety, toleration, and pharmacokinetics of intravenous azithromycin.

To date, the clinical pharmacology of large intravenous doses of azithromycin has not been described. In the present study, single 2-h intravenous infusions of 1, 2, and 4 g of azithromycin were administered to three parallel groups (in each group, six received active drug and two received placebo) of healthy male subjects. Toleration (assessed by scores of subject-administered visual analog scale tests spanning 0 [good] to 10 [poor]), safety, pharmacokinetics, and serum motilin levels were monitored for up to 240 h after the start of each intravenous infusion. Mean nausea scores of 0.0, 0.0, 1.0, and 0.5 and abdominal cramping scores of 0.0, 0.0, 0.4, and 0.4 for 12-h periods after doses of 0, 1, 2, and 4 g of azithromycin, respectively, suggested that azithromycin was well tolerated. Because of the standardized 1-mg/ml infusates, all subjects in the 4-g dosing group complained of an urgent need to urinate. There were no consistent trends in endogenous motilin levels throughout the study. The maximum concentration of azithromycin in serum (10 micrograms/ml after a 4-g dose) and the area under the concentration-time curve (82 micrograms.h/ml after a 4-g dose) were dose related. The mean pharmacokinetic parameters were an elimination half-life of 69 h, total systemic clearance of 10 ml/min/kg, and a volume of distribution at steady state of 33.3 liters/kg. The pharmacokinetic results suggest that the long half-life of azithromycin is due to extensive uptake and slow release of the drug from tissues rather than an inability to clear the drug. Single intravenous doses of up to 4 g of azithromycin in healthy subjects are generally well tolerated, and quantifiable concentrations may persist in serum for 10 days or more.

Adolescent↗

Enzyme replacement with recombinant beta-glucuronidase in murine mucopolysaccharidosis type VII: impact of therapy during the first six weeks of life on subsequent lysosomal storage, growth, and survival.

Treatment of mucopolysaccharidosis type VII (MPS VII) mice with recombinant mouse beta-glucuronidase injections has been shown to deliver enzyme to most tissues and to reduce lysosomal storage during the first 6 wk of life. Here we determine the effect of enzyme therapy limited to the first 6 wk of life on survival and growth and follow the subsequent accumulation of lysosomal storage after beta-glucuronidase treatment is discontinued. MPS VII mice received 28,000 U of beta-glucuronidase i.v. at weekly intervals from birth to 6 wk of life and were killed at intervals up to 1 y after the last injection. By 29 d after the last enzyme injection, lysosomal storage in bone was no different in amount than that seen in untreated MPS VII mice. By 85 d, the fixed tissue macrophage system, meninges, and brain glia had also accumulated storage comparable to that seen in untreated controls. One year after treatment, lysosomal storage was similar to that of untreated MPS VII mice in all sites except cortical neurons, where there was still a slight reduction. All treated mice that were not killed earlier, lived longer, were larger, and had milder facial and skeletal deformities than untreated MPS VII mice. These data show that enzyme replacement therapy in MPS VII mice during the first 6 wk of life improve survival and growth. After treatment is discontinued, storage accumulates slowly in the brain and more rapidly in the fixed tissue macrophage system. Whether therapy continued later in life can further improve survival and growth remains to be established.

Animals↗

Therapeutic optimization including inhaled nitric oxide in adult respiratory distress syndrome in a polyvalent intensive care unit.

OBJECTIVE: To investigate the effects of inhaled nitric oxide (NO) in adult respiratory distress syndrome (ARDS) associated with a therapeutic optimization strategy on oxygen parameters, barotrauma, and evolution in a medical and surgical intensive care unit. DESIGN: Prospective study. MATERIALS AND METHODS: Twenty consecutive patients with ARDS were studied (Murray score 3.6 +/- 0.2). Eleven were surgical patients and nine were medical patients. All fulfilled the extracorporeal membrane oxygenation entry criteria. The APACHE II score predicted mortality was 39%. All were ventilated with FiO2 1 with positive end-expiratory pressure (PEEP) of 11 +/- 1 cm H2O. Therapeutic optimization included permissive hypercapnia, tracheal gas insufflation, prone position, continuous hemofiltration, treatment of infection, and pleural drainage. We used NO continuously inhaled at a concentration ranging from 5 to 10 ppm. MEASUREMENTS AND MAIN RESULTS: After 1 hour, inhaled NO improved PaO2 in all patients except one (78 +/- 11 to 130 +/- 25 mm Hg) (p < 0.05), allowing a reduction of FiO2 and PEEP. After 24 hours, mean pulmonary arterial pressure decreased from 31 +/- 3 to 25 +/- 2 mm Hg (p < 0.05). Systemic hemodynamics were unaffected. Oxygen delivery increased from 531 +/- 135 to 603 +/- 125 mL/minute/m-2 (p < 0.05). Barotraumatic lesions were present in only one patient. Reversal of ARDS was obtained in 16 patients, of whom 14 (70%) were discharged. CONCLUSIONS: This study was shorter to demonstrate an improvement in the survival rate. Nevertheless, these preliminary results are encouraging. Because of its safety, effectiveness, and easy use, inhaled NO should be used as a part of a therapeutic optimization protocol before considering more invasive and expensive procedures, such as extracorporeal respiratory support or intravascular oxygenation.

APACHE↗

Intracranial hypertension and adult respiratory distress syndrome: usefulness of tracheal gas insufflation.

The management of increased intracranial pressure (ICP) in patients with an associated acute lung injury is difficult. High levels of PaCO2 as tolerated for permissive hypercapnia are deleterious for cerebral circulation. In such circumstances, tracheal gas insufflation (TGI), which was recently proposed to reduce PaCO2, may be of benefit. We report the cases of two patients with severe adult respiratory distress syndrome and head trauma complicated with elevated ICP. The introduction of TGI decreased PaCO2 by 17 and 26%, decreased ICP, and increased calculated cerebral perfusion pressure. We conclude that TGI could be added to a pressure-targeted strategy of ventilatory management when severe adult respiratory distress syndrome was associated to an intracranial hypertension.

Adult↗

Structural changes and in situ aortic pressure-diameter relationship in long-term chemical-sympathectomized rats.

This study determined the effects of long-term chemical sympathectomy with guanethidine (GN) on the mechanical properties and composition of the distal abdominal aorta in Wistar rats. GN was daily administered for 3 mo (3M-GN, from 1 to 12 wk), 5 wk (5W-GN, from 7 to 12 wk), and 8 days (8D-GN, from 11 to 12 wk). All experiments were performed at 12 wk of age to avoid age differences at examination. We used a high-resolution echo-tracking system to determine in situ, in the systolic-diastolic range, the aortic diameter-, compliance-, and distensibility-pressure curves in anesthetized rats. We observed an equivalent significant fall in the tyramine pressor response in all conscious GN-treated rats. Blood pressure was not affected by sympathectomy after 8 days and 5 wk of treatment but was significantly reduced in 3M-GN rats. Chronic sympathetic denervation increased aortic diameter and compliance in 8D-GN rats, compared with those obtained at the same distending pressure in control rats, suggesting vascular smooth muscle relaxation. In contrast, in 5W-GN and 3M-GN rats, the distensibility pressure-curves were significantly shifted toward lower levels of distensibility and pressure, indicating a decreased aortic distensibility at the same level of arterial pressure. Sympathectomy produced a significant reduction in the content of elastin, one of the most distensible components of the arterial wall in 5W-GN and 3M-GN rats. These results suggest that intact sympathetic nerves are necessary to maintain normal functional and structural properties of large arteries in rat. The reduction in aortic distensibility, in long-term sympathectomized rats, could have resulted from complex interactions between local aortic denervation, change in the set point of distending pressure, and changes in aortic smooth muscle tone and/or wall composition.

Animals↗

Hemodynamic and metabolic effects of rapid correction of hypophosphatemia in patients with septic shock.

STUDY OBJECTIVE: To examine the hemodynamic and metabolic short-term effects of hypophosphatemia correction in patients with septic shock receiving catecholamine therapy. DESIGN: Prospective, single cohort study. SETTING: ICU, university hospital. PATIENTS: Ten patients with septic shock and hypophosphatemia below 2 mg/dL. INTERVENTIONS: Infusion of glucose-1-phosphate solution (20 mmol of elemental phosphorus) for 60 min. MEASUREMENTS AND RESULTS: Hemodynamic, oxygen-derived, acid-base, and electrolyte parameters before and immediately after phosphate infusion. Left ventricular stroke work index increased significantly (22%) from a mean low value of 24 +/- 10 g/m2 without changes in filling pressures. Systolic arterial pressure improved by 12%. Arterial pH improved slightly but significantly. Ionized calcium level slightly decreased within the normal range values. Other parameters remained unchanged. CONCLUSIONS: Severe hypophosphatemia may be considered as a superimposed cause of myocardial depression, inadequate peripheral vasodilatation, and acidosis in septic shock. A rapid correction of hypophosphatemia is well tolerated and may have both myocardial and vascular beneficial effects. The magnitude of the response, however, is variable and unpredictable on the basis of serum phosphorus levels.

Adult↗

Effect of diclofenac sodium (Voltaren) on hypoxia-induced corneal edema in humans.

We evaluated the effect of diclofenac sodium (Voltaren) drops on patients with hypoxia-induced corneal edema. Thirty age- and sex-matched subjects were randomly assigned to one of three groups. Members of each group received masked solutions of either Voltaren, Voltaren vehicle, or a non-preserved lubricant (Cellufresh) every 6 hours for 24 hours and then hourly for 2 hours immediately prior to inducing corneal edema in the experimental eye. Bilateral ultrasonic pachymetry was performed prior to applying a thick contact lens and light patch on the experimental eye of all subjects for 3 hours. The fellow eye served as the control. Following lens removal, bilateral corneal thickness was measured every 30 minutes. The percentage change in corneal swelling for each subject and group was calculated. The findings were also normalized to the control eye to minimize diurnal and individual variability. The results were plotted both as percentage change from hour 0 and percentage change normalized to the control eye. Corneal swelling ranged from 9-11% in all 3 groups, with recovery at 2-3 hours. No significant difference was found among the three groups (P > 0.05, ANOVA). There was a slight trend toward reduced thickness in the Cellufresh group, but this was not statistically significant. Voltaren does not appear to have an effect on the hypoxia-induced corneal edema associated with the production of arachidonic acid pathway metabolites.

Adult↗

Topical and subcutaneous alpha-interferon fails to suppress corneal neovascularization.

Corneal neovascularization is a potentially blinding complication of a variety of corneal disorders. alpha-Interferon has been shown to inhibit endothelial cell migration and proliferation. It has been used successfully in the treatment of pediatric pulmonary hemangioma and hairy cell leukemia. This study was undertaken to evaluate the effect of topical and subcutaneous (s.c.) alpha-interferon on corneal neovascularization. Corneal neovascularization was induced in 40 male New Zealand white rabbits by placing silk sutures (7.0) bilaterally in each rabbit eye at the 3 and 9 o'clock positions of the cornea, 3 mm from the limbus. Animals were randomized into two main treatment groups for topical (group 1) and s.c. (group 2) administration of interferon. Group 1 (n = 24) was then randomized into four subgroups and treated daily with topical doses of (a) rabbit specific alpha-interferon; (b) alpha-interferon plus 1% prednisolone acetate; (c) 1% prednisolone acetate; and (d) buffered phosphate control. Group 2 (n = 16) was randomized into two subgroups that received s.c. injections every other day of (a) alpha-interferon and (b) phosphate buffer. Rate of corneal neovascularization was documented photographically, with the end-point being the arrival of vessels at the suture for each group. The results of this study indicated that at the concentration and dosing regimens we used, neither topical nor s.c. alpha-interferon inhibits the rate of corneal vascular growth significantly when compared with our phosphate buffered solution control group (p = 0.88 and p = 0.84, respectively). Prednisolone acetate appeared to be the most effective in inhibiting corneal neovascularization (p = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

[Clinico-pathological study on giant cell fibroma of oral mucosa].

The biopsy specimens of the Department of Oral Pathology, Dental School, UMBC, between 1985-1988 were reviewed in 1990 and. 124 cases of giant cell fibroma (GCF) of oral mucosa were found. GCF may develop at any age, but the highest incidence is middle adult life. GCF is slightly common in female than in male (1: 0.85). GCF occurs frequently in gingiva, tongue and cheek and is mistaken commonly for irritation fibroma, neurofibroma, papilloma and pyogenic granuloma, because there are no specific clinic features of it. The fusiform cells, star cells and multinucleated giant cells in the lesion are common histologic features of GCF. Local removal is usually successful.

Adolescent↗