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Biomedical subjects

S M Klein

Publications and source records attributed to S M Klein.

At least 37 records · Page 2Linked to original sources
PubMed1998

A comparison of 0.5% bupivacaine, 0.5% ropivacaine, and 0.75% ropivacaine for interscalene brachial plexus block.

UNLABELLED: The onset time and duration of action of ropivacaine during an interscalene block are not known. The potentially improved safety profile of ropivacaine may allow the use of higher concentrations to try and speed onset time. We compared bupivacaine and ropivacaine to determine the optimal long-acting local anesthetic and concentration for interscalene brachial plexus block. Seventy-five adult patients scheduled for outpatient shoulder surgery under interscalene block were entered into this double-blind, randomized study. Patients were assigned (n = 25 per group) to receive an interscalene block using 30 mL of 0.5% bupivacaine, 0.5% ropivacaine, or 0.75% ropivacaine. All solutions contained fresh epinephrine in a 1:400,000 concentration. At 1-min intervals after local anesthetic injection, patients were assessed to determine loss of shoulder abduction and loss of pinprick in the C5-6 dermatomes. Before discharge, patients were asked to document the time of first oral narcotic use, when incisional discomfort began, and when full sensation returned to the shoulder. The mean onset time of both motor and sensory blockade was <6 min in all groups. Duration of sensory blockade was similar in all groups as defined by the three recovery measures. We conclude that there is no clinically important difference in times to onset and recovery of interscalene block for bupivacaine 0.5%, ropivacaine 0.5%, and ropivacaine 0.75% when injected in equal volumes. IMPLICATIONS: In this study, we demonstrated a similar efficacy between equal concentrations of ropivacaine and bupivacaine. In addition, increasing the concentration of ropivacaine from 0.5% to 0.75% fails to improve the onset or duration of interscalene brachial plexus block.

Adult↗
PubMed1994

Human liver carbamazepine metabolism. Role of CYP3A4 and CYP2C8 in 10,11-epoxide formation.

A number of drugs inhibit the metabolism of carbamazepine catalyzed by cytochrome P450, sometimes resulting in carbamazepine intoxication. However, there is little information available concerning the identity of the specific isoforms of P450 responsible for the metabolism of this drug. This study addressed the role of CYP3A4 in the formation of carbamazepine-10,11-epoxide, the major metabolite of carbamazepine. Results of the study showed that: (1) purified CYP3A4 catalyzed 10,11-epoxidation; (2) cDNA-expressed CYP3A4 catalyzed 10,11-epoxidation (Vmax = 1730 pmol/min/nmol P450, Km = 442 microM); (3) the rate of 10,11-epoxidation correlated with CYP3A4 content in microsomes from sixteen human livers (r2 = 0.57, P < 0.001); (4) triacetyloleandomycin and anti-CYP3A4 IgG reduced 10,11-epoxidation to 31 +/- 6% (sixteen livers) and 43 +/- 2% (four livers) of control rates, respectively; and (5) microsomal 10,11-epoxidation but not phenol formation was activated 2- to 3-fold by alpha-naphthoflavone and progesterone and by carbamazepine itself (substrate activation). These findings indicate that CYP3A4 is the principal catalyst of 10,11-epoxide formation in human liver. Experiments utilizing a panel of P450 isoform selective inhibitors also suggested a minor involvement of CYP2C8 in liver microsomal 10,11-epoxidation. Epoxidation by CYP2C8 was confirmed in incubations of carbamazepine with cDNA-expressed CYP2C8. The role of CYP3A4 in the major pathway of carbamazepine elimination is consistent with the number of inhibitory drug interactions associated with its clinical use, interactions that result from a perturbation of CYP3A4 catalytic activity.

Adolescent↗
PubMed1993

Recovery and elimination of the biotherapeutic agent, Saccharomyces boulardii, in healthy human volunteers.

Saccharomyces boulardii (Sb) is a nonpathogenic yeast used to treat intestinal illnesses such as pseudomembranous colitis and antibiotic associated diarrhea. The behavior of this biotherapeutic agent in humans was determined (1) in investigating the effect of dose on the steady-state level and recovery and (2) in quantitating the effect of ampicillin on the recovery and elimination profile. As the Sb dose increased, the mean steady-state concentration of Sb increased significantly. The percentage recovery was dose independent. When a single Sb dose was administered 24 hr after beginning a course of ampicillin, there was a significant increase (P < 0.01) in both the area under the concentration versus time curve and the maximum fecal concentration compared to values obtained without ampicillin. Ampicillin increased steady-state recovery of the drug about twofold (P < 0.05) and steady-state levels about 2.4 times (P < 0.01). These studies have shown that there is a relationship between the dose and the amount of Sb recovered and that perturbation of the GI flora by ampicillin increases steady-state levels of Sb.

Adult↗
PubMed1983

Increased microsomal oxidation of hydroxyl radical scavenging agents and ethanol after chronic consumption of ethanol.

The oxidation of ethanol by rat liver microsomes is increased after chronic ethanol consumption. Previous experiments indicated that hydroxyl radicals play a role in the mechanism whereby microsomes oxidize ethanol. Experiments were therefore carried out to evaluate the role of these radicals in ethanol oxidation by microsomes from ethanol-fed rats, and to determine whether the increase in ethanol oxidation by these induced microsomes correlates with an increase in the generation of hydroxyl radicals. Rat liver microsomes from ethanol-fed rats catalyzed the oxidation of two typical hydroxyl radical scavenging agents, dimethylsulfoxide and 2-keto-4-thiomethylbutyric acid, at rates which were two- to threefold greater than rates found with control microsomes. This increased rate of oxidation of hydroxyl radical scavengers was similar to the increased rate of microsomal oxidation of ethanol. Azide, which inhibits contaminating catalase in microsomes, increased the oxidation of dimethyl sulfoxide and 2-keto-4-thiomethylbutyric acid by both microsomal preparations. This suggests that H2O2 may serve as the microsomal precursor of the hydroxyl radical. Cross competition for oxidation between ethanol and the hydroxyl radical scavenging agents was observed. Moreover, the oxidation of ethanol, dimethyl sulfoxide, or 2-keto-4-thiomethylbutyric acid was inhibited by other compounds which interact with hydroxyl radicals, e.g., benzoate, and the free-radical, spin-trapping agent, 5,5-dimethyl-1-pyrroline-N-oxide. These results suggest that the increase in the rate of ethanol oxidation found with microsomes from ethanol-fed rats may be due, at least in part, to an increase in the rate of production of hydroxyl radicals by these induced microsomes. Increased production of oxyradicals may possibly result in oxidative damage to the liver cell as a result of ethanol consumption.

Alcoholism↗
PubMed1983

Hepatitis, toxic epidermal necrolysis and pancreatitis in association with sulindac therapy.

We report 2 patients who had serious adverse effects after taking sulindac. One of these patients developed toxic hepatitis and Stevens-Johnson/toxic epidermal necrolysis syndrome which resulted in death. Such fatal reaction to sulindac therapy has not been reported previously. There was temporal relation of ingestion of sulindac to 2 episodes of acute pancreatitis in the 2nd patient, strongly suggesting drug induction. Recent reports of similar side effects with other nonsteroidal antiinflammatory drugs suggest that these drugs may have potentially more serious toxicity than has been recognized.

Acute Disease↗
PubMed1977

Composition of a photosystem I chlorophyll protein complex from Anabaena flos-aquae.

The use of Triton X-100 to solubilize membrane fragments from Anabaena flos-aquae in conjunction with DEAE cellulose chromatography allows the separation of three green fractions. Fraction 1 is detergent-solubilized chlorophyll, and Fraction 2 contains one polypeptide in the 15 kdalton area. Fraction 3, which contains most of the chlorophyll and shows P-700 and photosystem I activity, shows by SDS gel electrophoresis varying polypeptide profiles which reflect the presence of four fundamental bands as well as varying amounts of other polypeptides which appear to be aggregates containing the 15 kdalton polypeptide. The four fundamental bands are designated Band I at 120, Band II at 52, Band III at 46, and Band IV at 15 kdaltons. Band I obtained using 0.1% SDS contains chlorophyll and P-700 associated with it. When this band is cut out and rerun, the 120 kdalton band is lost, but significant increases occur in the intensities of Bands II, III, and IV as well as other polypeptides in the 20-30 kdalton range. The use of 1% Triton X-100 coupled with sucrose density gradient centrifugation allows the separation of three green bands at 10, 25 and 40% sucrose. The 10% layer contains a major polypeptide which appears to be Band IV. The 25 and 40% layers show essentially similar polypeptide profiles, resembling Fraction 3 in this regard, except that the 40% layer shows a marked decrease in Band III. Treatment of the material layering at the 40% sucrose level with a higher (4%) concentration of Triton X-100 causes a loss (disaggregation) of the polypeptides occurring in the 60-80 kdalton region and in increase in the lower molecular weight polypeptides. Thus, aggregation of the lower molecular weight polypeptides accounts for the variability seen in the electrophoresis patterns. Possible relations of the principal polypeptides to the known photochemical functions in the original membrane are discussed.

Cell Membrane↗
PubMed1975

Photophosphorylation and related properties of reaggregated vesicles from spinach photosystem I particles.

The small Photosystem I particles prepared from spinach chloroplasts by the action of Triton X-100 (TSF 1 particles) reaggregate into membrane structures when they are incubated with soybean phospholipids and cholate and then subjected to a slow dialysis. The membranes so formed are vesicular in nature and show the capability of catalyzing phenazine methosulfate-mediated cyclic photophosphorylation at rates which are usually about 20% of those observed with chloroplasts, but higher rates have been obtained. When coupling factor is removed from the chloroplasts by treatment with EDTA, a requirement for coupling factor can be shown for the subsequent ATP formation. The uncouplers carbonylcyanide 3-chlorophenyl-hydrazone, valinomycin, Triton X-100 and NH+4 are effective with the reformed vesicles, which do not show the typical light-induced pH gradient observed with chloroplasts. Incubation of the TSF 1 particles with phospholipids alone allows for the formation of membrane vesicles, but such vesicles are only slightly active in ATP formation. In most properties investigated, the reformed membrane vesicles resemble the original chloroplast membrane so far as phenazine methosulfate-mediated cyclic photophosphorylation is concerned, which indicates a high degree of selectivity in the reaggregation process. The major difference between chloroplasts and the reformed vesicles is the failure of the latter to show a light-induced pH gradient.

Cell Membrane↗
PubMed1974

Polypeptide Composition of Photosynthetic Membranes from Chlamydomonas reinhardi and Anabaena variabilis.

Anabaena variabilis, a blue-green alga lacking chlorophyll b, shows an absence of the major 22 and 24 kilodalton polypeptides which are present in the photosynthetic membranes of Chlamydomonas reinhardi and higher plants. These data are consistent with other investigations which have shown that these polypeptides are associated with chlorophyll b in the chloroplasts of higher plants, and indicate the presence of a light harvesting chlorophyll-protein complex in higher plants which contains the chlorophyll b of the photosynthetic membrane.

Journal Article↗