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Biomedical subjects

L S Rosenberg

Publications and source records attributed to L S Rosenberg.

13 recordsLinked to original sources
PubMed1992

Meniscal injury in the anterior cruciate-deficient knee. A rationale for clinical decision-making.

Meniscal injury is common in acute or chronic anterior cruciate ligament insufficiency. The patterns of meniscal lesions are predictable in the acute and chronically unstable knee. The early incidence of meniscal injury is high and increases with time. Meniscal repair has become increasingly successful. Techniques for anterior cruciate ligament reconstruction have also improved, and with more progressive rehabilitation programmes, this has become a more tolerable procedure for both patients of highly athletic lifestyles and more moderate recreational athletes. The decision-making process for the sports medicine physician requires an overall assessment of many variables. A delicate balance of factors such as age, sex, joint laxity, activity level, individual motivation, social circumstances, associated meniscal, collateral ligament and/or chondral damage may sway the surgeon towards a nonoperative or operative decision. At the present time, a 'cook book' answer to each case presented is not available. As in all of medicine, each patient is an entity that requires an individual evaluation and a specific course of treatment. This review aims to help in this decision-making process. Future prospective studies investigating the many variables mentioned will hopefully objectively delineate guidelines for the choice of the most effective therapeutic regimen.

Adolescent↗
PubMed1988

An accurate prediction of the pH change due to degradation: correction for a "produced" secondary buffering system.

Esmolol hydrochloride degrades in aqueous solutions by the hydrolysis of a labile aliphatic carboxyester group. The products are methanol and ASL-8123. The resulting aliphatic carboxylic acid moiety (ASL-8123) has a pK of 4.80, which is within 1 pH unit of the pH of the formulation. ASL-8123 therefore acts as a "secondary buffer" and minimizes the change in pH due to degradation. Equations are presented to calculate the change in the pH when the primary degradation product acts as a secondary buffer. This information can be used in the development of a parenteral product to predict, a priori, the concentration of buffer necessary for optimal pH maintenance. This knowledge can reduce the number of formulation screens required to determine the necessary buffer capacity for optimal drug stability.

Buffers↗
PubMed1986

The antitumor agent mitoxantrone binds cooperatively to DNA: evidence for heterogeneity in DNA conformation.

The equilibrium binding of the antitumor compound DHAQ, or mitoxantrone [1,4-dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]-9,10- anthracenedione], to various DNAs has been examined by optical titration and equilibrium dialysis methods. At low r (bound drug/DNA base pair) values, r less than 0.03, DHAQ binds, in a highly cooperative manner, to calf thymus and Micrococcus lysodeikticus DNAs. The binding isotherms for the interaction of DHAQ with Clostridium perfringens DNA and poly(dA-dT).poly(dA-dT) exhibit a small positive slope at low r values, suggestive of cooperative binding. In contrast, the binding of DHAQ to poly(dG-dC).poly(dG-dC) shows no evidence of cooperative binding even at very low r values. At higher r values (r greater than 0.05), the binding of DHAQ to all the DNAs studied is characterized by a neighbor-exclusion process. A model is proposed to account for the two modes of binding exhibited in the cooperative binding isotherms. The main feature of the proposed model is that local sequence and structural heterogeneity of the DNA give rise to sets of binding sites to which DHAQ binds in a highly cooperative manner, while the majority of the DNA sites bind DHAQ via a neighbor-exclusion process. This two-site model reproduces the observed binding isotherms and leads to the conclusion that DHAQ binds in clusters to selected regions of DNA. It is suggested that clustering may play a role in the physiological activity of drugs.

Animals↗
PubMed1984

Microcalorimetric investigation of the binding of some chemotherapeutic agents and related molecules to calf thymus DNA.

Batch microcalorimetry was used to estimate directly the standard enthalpies of the binding of small molecules to DNA. These values were compared with those obtained from spectrophotometric binding constants and van't Hoff plots. The close agreement between the independently obtained enthalpies indicates that the appropriate (best) binding model has four phosphates per binding site. Thermodynamic binding constants were obtained from apparent binding constants measured at different ionic strengths. From these and the measured standard enthalpies, standard free energies and standard entropies of binding were calculated. The weak, presumably external, binding alleged to occur at high formal molar concentration ratios of ligand to DNA bases could not be detected by a measurable heat of binding.

Aminacrine↗
PubMed1982

On the cooperative and noncooperative binding of ethidium to DNA.

The equilibrium binding of ethidium bromide to native DNAs and to poly(dG-dC) X poly(dG-dC) has been studied by both phase partition and direct spectrophotometric techniques. The binding isotherms obtained from both experimental techniques show that ethidium binds in a cooperative manner to E. coli DNA. On the other hand, no evidence of cooperative binding was observed in the binding isotherms obtained with calf thymus, C. perfringens, M. lysodeikticus, or poly(dG-dC) X (dG-dC) under the experimental conditions used (0.1 M NaCl).

Animals↗
PubMed1979

Primary pulmonary hypertension presenting as portal hypertension.

A two and a half-year old child is described who presented with signs of portal hypertension (hematemesis, hepatosplenomegaly, ascites). Her subsequent work-up revealed that the "pressure-head" originated within the pulmonary arterial bed. Indeed, severe changes of primary pulmonary hypertension were found at autopsy. What is unique about this case is the absence of cardiopulmonary symptoms prior to the development of suprahepatic portal hypertension. In addition, the pulmonary disease developed in the absence of underlying chronic hepatic disease or extrahepatic portal vein thrombosis which, reportedly, can lead to pulmonary hypertension.

Autopsy↗
PubMed1979

Radioimmunoassay for phencyclidine.

A sensitive and specific radioimmunoassay has been developed for the drug phencyclidine (PCP). Levels as low as 50 pg (200 femto-moles) of PCP can be detected. The specificity of the antisera has been investigated by inhibiting the [3H]PCP-anti PCP reaction with the parent drug, metabolites, and other related compounds. Three urinary metabolites, 4-phenyl-4-piperidinocyclohexanol, 1-(1-phenylcyclohexyl)-4-hydroxypiperidine and 1-phenylcyclohexylamine inhibit 2,5, and 0.002% as effectively as PCP respectively. Plasma samples supplemented with PCP (1.2 to 10,000 ng/ml) can be analyzed directly by this procedure.

Animals↗
PubMed1978

Spectroscopic approach to estimation of microequilibrium constants of prototropic reactions of aminobenzoic acids.

The microequilibrium constants of protolytic dissociation of diprotic acids, dihydric bases, or ampholytes such as the aminobenzoic acids, with dissimilar ionizing groups, can be estimated by spectrophotometric titration and measurement of the molar absorptivity at the long wavelength absorption maximum of simple alkylated derivatives. The method is applicable when the long wavelength absorption spectral bands of the tautomeric species are well resolved. Compared to the traditional method of estimating microequilibrium constants using the dissociation constants of alkylated derivatives, the proposed method is simpler, faster, and more accurate.

Aminobenzoates↗
PubMed1978

Tautomerism of singly protonated chloroquine and quinacrine.

Differential absorptiometric pH titrations of the antimalarials chloroquine and quinacrine, employing the respective uncharged species at pH 12.5 in the reference cell, show that protolytic dissociation from the heterocyclic ring nitrogen atoms occurs over pH 6--12. This finding indicates that the singly charged cations of the drugs exist measurably in two tautomeric forms. The tautomeric equilibrium constants were calculated from the titration data. The existence of these tautomeric equilibria may have significance in the pharmacodynamics of chloroquine and quinacrine.

Chloroquine↗