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Biomedical subjects

L J Kaplan

Publications and source records attributed to L J Kaplan.

At least 37 records · Page 2Linked to original sources
PubMed1994

Infected biatrial myxoma: transesophageal echocardiography-guided surgical resection.

We identified a biatrial myxoma using transesophageal echocardiography whose right atrial component was missed with conventional transthoracic techniques. Identifying the biatrial component directs a safer approach to right heart catheterization. Infected biatrial myxomas are both rare and successfully managed using prolonged intravenous antibiotic therapy followed by resection. Atrial septal defects created during the resection of an infected myxoma may be safely repaired using a prosthetic patch.

Anti-Bacterial Agents↗
PubMed1994

Studies on the ocular hypotensive effects of prostaglandin F2 alpha ester prodrugs and receptor selective prostaglandin analogs.

The use of natural prostaglandins (PG), such as PGD2, PGE2, PGF2 alpha, and PGI2, for treating glaucoma is limited by their ocular side effects. One approach to achieve the required separation of ocular hypotensive activity from side effects is to employ ester prodrugs. From a novel series of 11- and 15-mono and 11,15-diacyl esters of PGF2 alpha we identified prodrugs where PGF2 alpha formation rates in the iris-ciliary body exceeded those in the conjunctiva, sclera, and corneal endothelium. Compared to PGF2 alpha-1-isopropyl ester the ocular tissue hydrolysis rates of the 11-monopivaloyl, the 11,15-dipivaloyl ester and the 1,11-lactone were up to 1000 fold less. Despite this large disparity in hydrolysis rates, the pivaloyl esters and the 1,11-lactone were potent ocular hypotensives in our animal models. In studying prostaglandin analogs, we found that a diverse variety of prostanoid receptor selective agonists lowered intraocular pressure in dogs and/or monkeys. These included DP-, EP1-, EP2-, EP3-, and FP-receptor selective compounds. These findings were surprising and prompted us to re-examine the receptor selectivity of these agonists by radioligand binding studies. Using radiolabelled PGE2, 17-phenyl PGF2 alpha, and sulprostone we were able to confirm the selectivity of the agonists currently used for receptor characterization directly by radioligand binding competition studies. It appears that multiple prostanoid receptor subtypes may be involved in regulating intraocular pressure.

3T3 Cells↗
PubMed1994

Studies on a novel series of acyl ester prodrugs of prostaglandin F2 alpha.

A novel series of prostaglandin F2 alpha (PGF2 alpha) prodrugs, with acyl ester groups at the 9, 11, and 15 positions, was prepared in order to design clinically acceptable prostaglandins for treating glaucoma. Studies involving isolated esterases and ocular tissue homogenates indicated that 9-acyl esters cannot provide a prodrug since PGF2 alpha would not be formed as a product. In contrast, 11-mono, 15-mono, and 11, 15-diesters were converted to PGF2 alpha in ocular tissues and could, therefore, be considered as prodrugs of PGF2 alpha. Carboxylesterase (CE) appeared critically important for the hydrolytic conversion of those PGF2 alpha prodrugs where the 11 or 15-OH group was esterified and such prodrugs were not substrates for acetylcholinesterase (ACHE) or butyrylcholinesterase (BuCHE). The enzymatic hydrolysis of PGF2 alpha-1-isopropyl ester was also investigated for comparative purposes. This PGF2 alpha prodrug was a good substrate for CE, but was also hydrolysed by BuCHE, albeit at a much slower rate. The most striking feature of the enzymatic hydrolysis of PGF2 alpha-1-isopropyl ester in ocular tissue homogenates was that it was much faster than for prodrugs esterified at the 11 and/or 15 positions. In terms of ocular hypotensive activity, all prodrugs which showed detectable conversion to nascent PGF2 alpha were potent ocular hypotensives. Although no separation of ocular hypotensive and ocular surface hyperaemic effects was apparent for PGF2 alpha-1-isopropyl ester, a temporal separation of these effects was apparent for the novel PGF2 alpha ester series. This difference may reflect an unfavourably rapid conversion of PGF2 alpha-1-isopropyl ester in ocular surface tissues compared with anterior segment tissues.

3T3 Cells↗
PubMed1993

Protecting myocardial creatine kinase activity during reperfusion improves bioenergetics and contractile function.

The exact mechanisms underlying reperfusion (RP) injury are unclear but are thought to involve toxic oxygen metabolites such as H2O2. The purpose of our study was to determine whether increasing endogenous catalase (CAT) stores would protect creatine kinase (CK) activity and improve bioenergetics and mechanical function during RP. Rats (n = 6/group) were pretreated with myristic acid (MA) or nothing 6 to 12 hr prior to cardiectomy. Hearts were Langendorff perfused and developed pressure (DP) was monitored during 25 min of 37 degrees C ischemia and 10 or 40 min of RP. CK activity was determined at baseline, end ischemia, and 40 min RP. CAT activity and H2O2 production was assayed at baseline, end ischemia, and 10 min RP. 31P NMR spectra were continuously acquired to determine ATP and phosphocreatine (PCr) concentrations. MA-pretreated hearts demonstrated elevated CAT stores (121 +/- 4%, P < 0.05). No H2O2 was produced during ischemia, and both groups generated significant but equal amounts of H2O2 at RP 10 (P < 0.001 vs preischemia (PI), P = NS between groups). By RP 40, MA-pretreated hearts recovered more DP than did control hearts (75 +/- 5% of PI vs 35 +/- 4% of PI, P < 0.001) and retained more CK activity as well (66 +/- 4% vs 52 +/- 2%, P < .05). PCr/ATP ratios of control hearts were abnormally elevated above baseline and that of MA hearts during RP (2.4 +/- 0.1 vs 1.85 +/- 0.08, P < 0.05 at RP 40).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1993

Role of noradrenergic innervation of brown adipose tissue in thermoregulatory deficits following prenatal alcohol exposure.

The development of thermoregulation in newborns is delayed by prenatal alcohol exposure in an animal model of moderate maternal drinking. Newborn mammals generate heat primarily via nonshivering thermogenesis in brown adipose tissue (BAT), which is activated by the sympathetic nervous system. In this study, the effects of prenatal alcohol exposure on the development of the sympathetic innervation of BAT was investigated by assessing the concentration of norepinephrine (NE) in interscapular BAT. Pregnant dams were given either a liquid diet with 35% of the calories derived from alcohol, a liquid diet without alcohol to control for any effects of the liquid diet administration, or ad libitum food and water. Interscapular brown adipose tissue was excised from 5-, 10-, and 20-day-old male and female offspring. At 5 days of age, alcohol-exposed pups had significantly lower NE concentrations than did pups in either control group. However, 20-day-old alcohol-exposed pups had significantly higher NE concentrations than either control group. These results suggest a delay in the development of the sympathetic activation of BAT thermogenesis, followed by a compensatory overactivation. These findings may have important implications for understanding the mechanisms underlying thermoregulatory deficits seen after prenatal alcohol exposure. In addition, these results suggest that maternal alcohol consumption may increase the risk of sudden infant death syndrome, which has been linked to inappropriate BAT thermogenesis.

Adipose Tissue, Brown↗
PubMed1992

Severe measles in immunocompromised patients.

OBJECTIVE: To describe the severity of measles in immunocompromised hosts and to assess preventive and therapeutic modalities. DATA SOURCES: Patients admitted to two academic medical centers between September 1989 and December 1990 and English language references obtained by MEDLINE from 1963 to 1991. Bibliographies were used to identify reports prior to 1963. STUDY SELECTION: We identified nine immunocompromised patients with measles. Further analysis was based on 35 patients from two cohort studies of measles in oncology patients and 24 reported cases of measles in human immunodeficiency virus (HIV)-infected patients. DATA EXTRACTION: Clinical data are presented from the nine patients we treated. Information concerning measles complications, presence of rash, use of prophylactic immunoglobulin, and therapeutic measures was extracted from the literature. DATA SYNTHESIS: Of our nine patients, eight developed severe complications and two died. Two patients had no rash. In combining our patients with those from the literature, severe complications occurred in about 80%. The case fatality rate for severe measles was about 70% for oncology patients and about 40% for HIV-infected patients. Rash was absent in about 30%. The efficacy of prophylactic or therapeutic measures could not be assessed due to the small number of patients. However, we observed a rapid defervescence following administration of ribavirin. Vaccinated, HIV-infected patients had a lower mortality rate than those not previously vaccinated (P = .06). CONCLUSIONS: Measles is a severe illness in immunocompromised patients, and the absence of rash is frequent. While treatment is supportive, ribavirin requires further study. Measles vaccine may be efficacious in HIV-infected patients. Vaccination of oncology patients should be reassessed.

Adolescent↗
PubMed1992

Safe intraaortic balloon pump placement through the ascending aorta using transesophageal ultrasound.

Intraaortic balloon pumping salvages a substantial number of patients who fail to be weaned from cardiopulmonary bypass after an open heart operation. Patients with severe peripheral vascular disease may require ascending aortic balloon pump insertion. We describe a simple method of direct aortic puncture for intraaortic balloon pump placement using transesophageal ultrasound as a means of avoiding complications during insertion and documenting correct balloon position.

Aorta↗
PubMed1991

Synthesis of chiral and achiral pyranenamine derivatives. Potent agents with topical ocular antiallergic activity.

The SS, RR and meso stereoisomers of pyranenamine SK&F 84210 were synthesized stereospecifically starting from commercially available (R)-(-)- or (S)-(+)-2,2-dimethyl-1,3-dioxolane-4-methanol. In addition, two achiral pyranenamines 19 and 26 were also synthesized. When evaluated by intravenous and topical routes in the rat passive ocular anaphylaxis (POA) assay, (SS)- and meso-2 as well as achiral compounds 19 and 26 were found to be more potent antiallergic agents than (RR)-2.

Anaphylaxis↗
PubMed1985

Ptosis and cataract surgery. A multivariant computer analysis of a prospective study.

A prospective study investigated the effect of local anesthesia, eyelid edema and superior rectus muscle injury on postoperative ptosis. Patients were randomized into four groups to study these effects. Group A received a Van Lint eyelid block and a superior rectus bridle suture. Group B received a Van Lint block and an episcleral retraction suture. Group C received a Nadbath retroauricular facial nerve block and a superior rectus bridle suture. Group D received a Nadbath block and an episcleral retraction suture. Results of the study indicate that postoperative ptosis can be significantly reduced by varying our operative techniques. Postoperative ptosis was significantly increased in group A and reduced in group D. It appears that trauma to the superior rectus muscle complex is the most critical factor in postoperative ptosis. Fifty five and one-half percent of the population entered the study with preoperative ptosis. Preoperative ptosis had no effect on postoperative ptosis. Lid crease, superior sulcus fullness and lash rotation are poor anatomical landmarks of levator insertion in the elderly population, both preoperatively and postoperatively.

Adolescent↗
PubMed1984

The structure of chromatin reconstituted with phosphorylated H1. Circular dichroism and thermal denaturation studies.

The effect of binding enzymatically phosphorylated H1 histone on the structure of reconstituted chromatin was determined by circular dichroism and thermal denaturation studies at low ionic strength. Procedures were developed for the selective removal of the lysine-rich histones H1 and H5 from chicken erythrocyte chromatin (stripped chromatin) and for the specific reconstitution of chromatin, without nucleosome sliding. Reconstitution was carried out with either rat thymus H1, phosphorylated rat thymus H1 (containing an average of 5.3 phosphates/molecule, or chicken erythrocyte H5. The maximum ellipticity in 1.0 mM phosphate buffer, pH 7.4, of stripped chromatin [( theta]282.5 = 4800 degree cm2/dmol) was effectively reduced to the value for native chromatin [( theta]282.5 = 3900 degree cm2/dmol) through reconstitution with approximately one molecule of either H1 [( theta]282.5 = 4050 degree cm2/dmol) or phosphorylated H1 [( theta]282.5 = 4100 degree cm2/dmol) per 200 base pairs of DNA. As the circular dichroic spectra for chromatin reconstituted with H1 and phosphorylated H1 are similar, it appears that phosphorylation per se does not induce a major structural alteration of chromatin structure. Thermal denaturation studies at low ionic strength of chromatin reconstituted with either H1 or phosphorylated H1 revealed a transition that occurs at a slightly lower temperature than the high temperature transition of native chromatin. This transition was shifted approximately 1 degree C to lower temperature when the chromatin was reconstituted with phosphorylated H1 as compared to H1. Thus, phosphorylation of H1 caused a significant destabilization of the chromatin structure at low ionic strength. When thermal denaturation was carried out on chromatin reconstituted with H5, native-like profiles were obtained.

Animals↗
PubMed1984

Amiodarone-induced corneal deposits.

Amiodarone, 2-N-butyl-3-(4'diethylaminoethoxy-3',5-diiodobenzoyl)benzofuran, also known as Cordarone, is presently under clinical investigation in the United States. It is an alpha and beta antagonist and is extremely effective in treating otherwise uncontrollable ventricular arrhythmias. To date, 27 patients participating in our ongoing study since 1977 have had corneal deposits. The deposits are in the corneal epithelium basal cell layer, and occur in stages (mild, moderate, and severe), which seem to correlate with dosage and duration of treatment. Vision is rarely diminished by these deposits, and if it is, discontinuation of the drug therapy will cause regression of the deposits with eventual return to normal beginning within two to four weeks but possibly taking as long as 1 1/2 years. The deposits look similar to those seen in chloroquine toxicity and Fabry's glycolipidosis. Other adverse effects reported in the European literature include thyroidopathy, cutaneous pigmentation, and neuromyopathy.

Amiodarone↗