Search PubMed⌕ Search

Biomedical subjects

L Levine

Publications and source records attributed to L Levine.

At least 163 records · Page 9Linked to original sources
PubMed1982

Clinical implications of reported timolol-induced side effects.

Since its approval by the Food and Drug Administration (FDA), timolol has been widely used for the treatment of open-angle glaucoma. Contrary to the clinical trials before FDA approval, many reports of possible ocular and systemic side effects have now appeared. Cardiovascular, respiratory, and gastrointestinal systemic effects occur relatively often and are attributable to beta-adrenergic antagonism, but central nervous system (CNS) effects are not so explainable. The most frequent ocular side effects are instillation pain and blurred vision, often requiring discontinuation of timolol. Superficial punctate keratitis and associated reduced corneal sensitivity have been reported and pose a risk for affected contact lens wearers. The incidence of side effects in two prospective studies was about 20%, with some 40% of those having to discontinue timolol. Of optometric interest are reports that timolol increases the electro-oculogram (EOG) ratio (Arden Index), and that it may be used to lower intraocular pressure in acute angle closure when pilocarpine alone is unsuccessful.

Adrenergic beta-Antagonists↗
PubMed1982

Mydriatic effectiveness of dilute combinations of phenylephrine and tropicamide.

The effects of two solutions, each consisting of a combination of tropicamide and phenylephrine at lower than conventional concentrations, were studied in 79 students at Pacific University College of Optometry. Clinically effective diameters (CED's), measured when the eye was illuminated for direct ophthalmoscopy, were followed for 90 min after mydriatic instillation. Intraocular pressure (IOP), systolic arterial blood pressure (sBP), and the systolic BP/IOP ratio were also monitored for 90 min. Both combination A (0.25% tropicamide + 1.25% phenylephrine) and combination B (0.125% tropicamide + 2.0% phenylephrine) produced CED's as large as produced by 0.5% tropicamide in the opposite eye. By combining a low concentration of a sympathomimetic with a parasympatholytic agent, it is possible to achieve mydriasis superior to that produced by 0.5% tropicamide or 2.5% phenylephrine while reducing the risk of systemic or ocular side effects.

Adult↗
PubMed1982

A possible role of arachidonate metabolism in allergic air pouch inflammation in rats. Anti-inflammatory effect of indomethacin and dexamethasone and the level of prostaglandin E2 in the exudate.

The effect of indomethacin and dexamethasone on an allergic inflammation in rats, a novel model of allergic inflammation of an air pouch type, was examined. Indomethacin and dexamethasone exerted a dose-dependent inhibition of both the accumulation of inflammatory exudate and the migration of leukocytes into the exudate. And although prostaglandin E2 levels in the exudate were lowered to the same extent by treatment with indomethacin and dexamethasone, inhibition of both exudate accumulation and and leukocyte migration was more pronounced after treatment with dexamethasone. The difference in the effectiveness of indomethacin and dexamethasone in terms of inhibition of arachidonate metabolism in the allergic air pouch inflammation are discussed.

Animals↗
PubMed1982

Thromboxane mediation of cardiopulmonary effects of embolism.

Humoral factors released from platelets during pulmonary embolism may be the cause of several attendant cardiopulmonary abnormalities. This study examines the role of thromboxanes (Tx) after experimental embolism induced with 0.5 g/kg autologous clot in four groups of five dogs: (a) untreated embolized controls; (b) pretreatment with the Tx synthetase inhibitor, imidazole 25 mg/kg . h i.v., starting 30 min before embolization; (c) pretreatment with the cyclooxygenase inhibitor indomethacin, 5 mg/kg, 12 h per os and 1 mg/kg, 1 h i.v. before the experiment; (d) treatment with prostacyclin (PGI(2)) 100 etag/kg . min i.v. for 1 h, 1 h after embolization. Within 30 min, embolization led to increases of 6-keto-PGF(1alpha), the stable hydrolysis product of PGI(2), from 0.11+/-0.08 etag/ml (mean+/-SD) to 0.33+/-0.10 etag/ml (P < 0.005) and TxB(2), the stable product of TxA(2), from 0.10+/-0.04 etag/ml to 0.38+/-0.06 etag/ml (P < 0.001). Increases were observed in total dead space (V(D)/V(T)) from 0.46+/-0.03 to 0.61+/-0.08 (P < 0.025, physiologic shunting (Q(S)/Q(T)) from 16+/-4% to 38+/-9% (P < 0.01), pulmonary vascular resistance (PVR) from 2.27+/-0.59 mm Hg.min/liter to 9.21+/-1.90 mm Hg.min/liter (P < 0.005) and mean pulmonary arterial pressure from 14+/-6 mm Hg to 34+/-1 mm Hg (P < 0.001). Cardiac index (CI) fell from 139+/-11 ml/kg.min to 95+/-17 ml/kg.min in 4 h (P < 0.025). Imidazole pretreatment prevented a rise of TxB(2), but not 6-keto-PGF(1alpha); indomethacin blocked both. Both agents maintained V(D)/V(T) at base line and limited increases in Q(S)/Q(T) and PVR. CI was higher after imidazole pretreatment compared with controls (P < 0.025). Indomethacin led to intermediate levels of CI. PGI(2) lowered TxB(2) (P < 0.025), V(D)/V(T) (P < 0.025), Q(S)/Q(T) (P < 0.025) and PVR (P < 0.05) within 30 min. During PGI(2) infusion, CI was higher than controls. Concentrations of TxB(2) correlated with V(D)/V(T), r = 0.79 and Q(S)/Q(T), r = 0.69 (P < 0.001). Treatment of three dogs with the imidazole derivative ketoconazole, 10 mg/kg IV, 30 min after 0.75 g/kg autologous clot resulted in a lowering of physiologic dead space, but no other improvement of cardiopulmonary function. These results show that a number of cardiopulmonary abnormalities induced by pulmonary embolism are related directly or indirectly to platelet secretions and that V(D)/V(T) is closely allied to TxA(2) levels.

Animals↗
PubMed1982

Platelet-derived growth factor stimulates bone resorption via a prostaglandin-mediated mechanism.

Platelet-derived growth factor (PDGF) stimulated up to 15-fold the production of prostaglandin E2 (PGE2) and bone resorption in neonatal mouse calvaria in organ culture. The action of PDGF on bone resorption occurred at low concentrations of the protein (ED50 = 10 ng/ml). All concentrations of PDGF which stimulated resorption also enhanced the production of PGE2 by bone; concentrations of PDGF which did not stimulate resorption did not enhance PGE2 production. PDGF-induced formation of PGE2 and bone resorption were inhibited completely by indomethacin (100 ng/ml) and hydrocortisone (1 microgram/ml). Indomethacin did not inhibit the bone resorption-stimulating activity of exogenous PGE2. In the continued presence of a maximum concentration of PDGF (100 ng/ml), an increase in bone resorption, as measured by an increase in medium calcium, was detected at 16 h (P less than 0.01), but not at 12 h; however, an increase in PGE2 production occurred within the first 2 h of treatment. A similar lag period for the onset of bone resorption was seen after the addition of exogenous PGE2 to the culture medium. On the other hand, exposure of bones to PDGF (50 ng/ml) for as brief a period as 5-15 min, followed by washout of PDGF, triggered bone resorption over the subsequent 48 h. PDGF increased cAMP production by bone within 30 min, and this effect of PDGF was blocked completely by indomethacin while the action of exogenous PGE2 on the production of cAMP was not blocked by indomethacin. The action of a low concentration of PDGF (1 ng/ml), which did not stimulate bone resorption alone, was potentiated by the phosphodiesterase inhibitor isobutylmethylxanthine (4 microM). We conclude that low concentrations of PDGF stimulate bone resorption via the enhanced local production of PGE2.

1-Methyl-3-isobutylxanthine↗
PubMed1982

Dexamethasone suppressible hyperaldosteronism in a child with nephrosclerosis.

A 9 year old Mexican boy presented with severe hypertension, hypokalaemia and features suggesting acute glomerulonephritis. Nephrosclerosis was present on renal biopsy. Aldosterone levels were unresponsive to variations in dietary salt intake and plasma renin activity was suppressed. Following oral dexamethasone therapy (2 mg/day), plasma aldosterone decreased to undetectable levels, serum potassium normalized and plasma renin activity gradually increased. Dexamethasone also restored the normal responsiveness of the renin-aldosterone system to postural stimuli. The patient exhibited a marked response to a single dose of ACTH with a rise in plasma aldosterone. Long-term blood pressure control and normal potassium levels have been achieved with oral prednisone therapy (5 mg/day) for a period of one year. This case of dexamethasone suppressible hyperaldosteronism (DSH) illustrates that the degree of hypertension in this syndrome may produce severe renal microvascular lesions. DSH should be considered in all children who present with low renin hypertension.

Adrenocorticotropic Hormone↗
PubMed1982

Circulating negative inotropic agent(s) following pulmonary embolism.

Pulmonary emboli may impair myocardial performance, causing declines in cardiac index (CI) and right and left ventricular stroke work (LVSW) because of mechanical events. We postulate that embolism also leads to the generation of a humoral factor(s) that may reduce cardiac contractility. Eleven mongrel dogs were infused with 0.5 gm/kg clot. Decreases in CI and LVSW were observed 1 hour after embolization. The stable metabolites of prostacyclin and thromboxane (Tx) A2--6-keto-PGF1 alpha and TxB2, respectively--increased within 30 minutes (P less than 0.005, P les than 0.001) and then decreased. These changes did not correlate with the declines in CI or LVSW. Plasma from embolized animals used to bathe an isolated rat papillary muscle reduced developed tension (Tpd) (P less than 0.001) and decreased calcium ATPase (Ca++-ATPase) activity of a myofibril preparation (P less than 0.001) obtained from rat cardiac muscle. The correlation between the reduction of TPd and myofibril Ca++-ATPase activity was 0.72 (P less than 0.001). The decline in Ca++-ATPase was also related to the decreases in CI (r = 0.59, P less than 0.001) and LVSW (r = 0.57, P less than 0.001). Five animals pretreated with indomethacin prior to embolization had no decrease in LVSW as compared with controls (P less than 0.001). Postembolism plasma did not depress papillary muscle Tpd and did not lower Ca++-ATPase activity of myofibrils. Anesthesia itself did not alter cardiopulmonary function. These results suggest that pulmonary emboli cause the release of a negative inotropic agent(s) into plasma that affects energy availability in the heart and reduces contractility. The production of this agent(s) is inhibited by indomethacin pretreatment.

6-Ketoprostaglandin F1 alpha↗
PubMed1982

Coexisting childhood pemphigus foliaceus and Graves' disease.

We report herein the concurrent appearance of childhood pemphigus foliaceus and Graves' disease in a 14-year-old girl who was initially seen with crusted and hyperpigmented plaques on her chest, back, abdomen, and legs. The diagnosis of pemphigus foliaceus was confirmed by biopsy and immunofluorescent microscopic studies while the diagnosis of Graves' disease was based on clinical and laboratory findings. The coexistence of these two immune-mediated diseases in a single patient suggest that some persons may bear a unique predisposition to the development of two or more autoimmune-type disorders that may affect diverse organ systems.

Adolescent↗
PubMed1981

Glycyrrhizin inhibits prostaglandin E2 production by activated peritoneal macrophages from rats.

Glycyrrhizin was found to inhibit prostaglandin E2 production by activated rat peritoneal macrophages. Preincubation of the cells with glycyrrhizin increases its inhibitory effectiveness. Glycyrrhetinic acid, the aglycone of glycyrrhizin, at a dose of 100 microgram per ml also inhibited prostaglandin E2 production, but the inhibition was considered to be attributable to a toxic effect on the cells since more than 30% of the cells were detached from the dish during the 8 hr incubation period. In contrast, glycyrrhizin did not detach the cells from the dish at doses up to 3 mg per ml. Release of [3H]arachidonic acid from prelabeled cells was also inhibited by glycyrrhizin. It is likely that anti-inflammatory activity of glycyrrhizin depends at least in part on its inhibitory effect of the production of prostaglandin E2.

Animals↗
PubMed1981

The effect of phenothiazines and their metabolites on prostaglandin production by rat basophilic leukemia cells in culture.

Seven clinically important phenothiazine drugs (chlorpromazine, promazine, triflupromazine, thioridazine, fluphenazine, trifluoperazine and perphenazine) stimulated synthesis of PGE2 and PGF2alpha in RBL-1 cells in culture. Structural differences in the side chain at N10 had little effect on their activities. Some of the metabolites also were active, in keeping with the clinical observation that phenothiazines may have antipsychotic effects long after the parent compound has been eliminated from the circulation. Among the chlorpromazine metabolites, methoxy substituents on the phenothiazine nucleus did not strikingly affect stimulating activity. Monohydroxy derivatives were slightly more effective than the parent compound; there was little difference between hydroxy substitution at 7 or 8 position. The 7,8 dioxo, the N-oxido, the sulfoxide, and the 7-OH glucuronide derivatives were inactive.

Animals↗