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Biomedical subjects

L M Newman

Publications and source records attributed to L M Newman.

At least 37 records · Page 2Linked to original sources
PubMed1991

Inhibition of arachidonic acid incorporation into erythrocyte phospholipids by peracetic acid and other peroxides. Role of arachidonoyl-CoA: 1-palmitoyl-sn-glycero-3-phosphocholine acyl transferase.

To explore possible mechanisms of the arachidonic acid deficiency of the red blood cell membrane in alcoholics, we compared the effect of ethanol and its oxidized products, acetaldehyde and peracetic acid, with other peroxides on the accumulation of [14C]arachidonate into RBC membrane lipids in vitro. Incubation of erythrocytes with 50 mM ethanol or 3 mM acetaldehyde had no effect on arachidonate incorporation. Pretreatment of erythrocytes with 10 mM hydrogen peroxide, 0.1 mM cumene hydroperoxide or 0.1 mM t-butyl hydroperoxide had little effect on [14C]arachidonate incorporation in the absence of azide. However, pretreatment of cells with N-ethylmaleimide, 0.1 mM peracetic acid or performic acid, with or without azide, inhibited arachidonate incorporation into phospholipids but not neutral lipids. In chase experiments, peracetate also inhibited transfer of arachidonate from neutral lipids to phospholipids. To investigate a possible site of this inhibition of arachidonate transfer into phospholipids by percarboxylic acids, we assayed a repair enzyme, arachidonoyl CoA: 1-palmitoyl-sn-glycero-3-phosphocholine acyl transferase (EC 2.3.1.23). As in intact cells, phospholipid biosynthesis was inhibited more by N-ethylmalemide and peracetic acid than by hydrogen peroxide, cumene hydroperoxide, and t-butyl hydroperoxide. Peracetic acid was the only active inhibitor among ethanol and its oxidized products studied and may deserve further examination in ethanol toxicity.

1-Acylglycerophosphocholine O-Acyltransferase↗
PubMed1991

Fate of 2,2,2-trichloroacetaldehyde (chloral hydrate) produced during trichloroethylene oxidation by methanotrophs.

Four different methanotrophs expressing soluble methane monooxygenase produced 2,2,2-trichloroacetaldehyde, or chloral hydrate, a controlled substance, during the oxidation of trichloroethylene. Chloral hydrate concentrations decreased in these cultures between 1 h and 24 h of incubation. Chloral hydrate was shown to be biologically transformed to trichloroethanol and trichloroacetic acid by Methylosinus trichosporium OB3b. At elevated pH and temperature, chloral hydrate readily decomposed and chloroform and formic acid were detected as products.

Chloral Hydrate↗
PubMed1991

Efficacy of ephedrine in the prevention of postoperative nausea and vomiting.

Although reported in the aerospace literature and anecdotally by anesthesiologists, the putative antiemetic effect of ephedrine remains unquantitated. We therefore prospectively studied ephedrine as an antiemetic agent in the perioperative setting in 97 patients undergoing general anesthesia for outpatient gynecologic laparoscopy. Patients were assigned in a double-blind randomized fashion to receive a standardized general anesthetic followed by an intramuscular dose of either ephedrine (0.5 mg/kg), droperidol (0.04 mg/kg), or saline before the conclusion of surgery. Nausea, retching, or vomiting, as well as the degree of sedation and discharge times, were assessed in the recovery room and for 24 h postoperatively. Ephedrine was found to have a significantly antiemetic effect (P less than 0.05) when compared with placebo and an antiemetic effect similar to that of droperidol. Sedation scores were also significantly less in the ephedrine group than in both placebo and droperidol groups. Finally, variations in mean arterial blood pressure among the three groups were not statistically significant. We conclude that ephedrine is an effective antiemetic agent with minimal sedative side effects in patients undergoing outpatient laparoscopy.

Adult↗
PubMed1990

The in vitro activation of cyclophosphamide in the Hydra Developmental Toxicology Assay.

The proteratogen cyclophosphamide (CP) was tested in the Hydra Assay in the presence and absence of an in vitro metabolic activation package (MAP) consisting of rat hepatic microsomes (0.06 nmol P450/ml), 500 microM NADPH, and 25 microM MgCl. This metabolic system was developed through a series of interrelated biochemical and biological assays to provide maximum cytochrome P450 mixed-function monooxygenase (MFO) metabolic capacity while controlling the inherent toxicity of the hepatic preparation and the attendant cofactors. Bioactivation of CP was confirmed under standard hydra assay conditions of pH 7.0 and 20 degrees C and compared with activation at 37 degrees C. Estimation of total metabolic capacity and verification of activation were made through the appearance of alkylating metabolites both in the absence and in the presence of hydra. Chemical exposure was maintained throughout the 92 +/- 2 hr assay with periodic renewal of media (and additives) at 4, 20, 28, 42, and 66 hr of incubation. Inclusion of bioactivation increased the toxicity of CP by two orders of magnitude. The minimal affective concentration in the adult and developmental portions of the assay was decreased from 4000 to 20 micrograms CP/ml and from 1000 to 4 micrograms CP/ml, respectively. By limiting the inherent toxicity of the MFO package, it was possible to avoid pulse-type exposures and ensure that all ontogenic stages were exposed to active metabolites. The addition of metabolic activation capacity to an in vitro assay, while not essential, markedly enhances its utility and breadth of application in developmental toxicity safety evaluations.

Animals↗
PubMed1990

Prediction of the developmental toxicity hazard potential of halogenated drinking water disinfection by-products tested by the in vitro hydra assay.

A series of seven randomly selected potential halogenated water disinfection by-products were evaluated in vitro by the hydra assay to determine their developmental toxicity hazard potential. For six of the chemicals tested by this assay (dibromoacetonitrile; trichloroacetonitrile; 2-chlorophenol; 2,4,6-trichlorophenol; trichloroacetic acid; dichloroacetone) it was predicted that they would be generally equally toxic to both adult and embryonic mammals when studied by means of standard developmental toxicity "teratology" tests. However, the potential water disinfection by-product chloroacetic acid (CA) was determined to be over eight times more toxic to the "embryonic" developmental portion of the assay than it was to the adults. Because of this potential selectivity, CA is a high-priority item for developmental toxicity tests in pregnant mammals to confirm or refute its apparent unique developmental hazard potential and/or to establish a NOAEL by the route of most likely human exposure.

Animals↗
PubMed1990

Hepatic tumors: signal enhancement at Doppler US after intravenous injection of a contrast agent.

Experiments were carried out to detect and establish the origin of Doppler and echo signal enhancement in small vessels of the systemic circulation and of tumors after intravenous injection of a contrast agent. Eight woodchucks (Marmota monax) were studied; each woodchuck had naturally occurring hepatocellular carcinoma. Injections of 0.1-4.0 mL of air-filled human serum albumin microspheres were administered into a hind limb or jugular vein. Ultrasound (US) examination included transabdominal duplex scanning, color Doppler imaging, placement of a Doppler transducer on the exposed tumor, and surgical implantation of pulsed Doppler cuffs. Doppler signals were assessed by recording color Doppler images and results of spectral analysis. While subjective echo level was unaffected within the tumors, dramatic Doppler signal enhancement was recorded in both normal and tumor vessels. At optimum dose levels, a signal gain of approximately 10 dB was recorded from the tumor. Analysis showed that the echo enhancement was due to the presence of the contrast agent in branches of the hepatic artery. These results suggest that tumor detection may be enhanced by intravenous administration of a US contrast agent.

Animals↗
PubMed1988

Postnatal effects of prenatal insult.

Exogenous agents may perturb development during the embryonic period and adversely affect the formation of organs. However, adverse effects on development are not limited to the embryonic period nor are the manifestations restricted solely to outright gross structural malformation, but may instead be expressed as a decrement or abberration of postnatal function. Susceptibility to altered development may extend well into the postnatal period. Studies of functional parameters in several organ systems have demonstrated the broad-based susceptibility, subtlety of expression and potential of long-lasting effects of altered development assessed by physiologic assays. Adverse effects on functional development, whether in the CNS, reproductive, gastrointestinal, genitourinary, respiratory, or immune systems, etc., merit continuing investigation. From the viewpoint of risk estimation and hazard detection, evaluations of postnatal functional parameters may be relevant for several reasons. First, such parameters may serve as low-dose triggers. Second, they may be useful as a focal point for epidemiological studies. Finally, a more thorough understanding of the degree and magnitude of such postnatal functional deficits is needed since an adverse maternal effect may be transient, considered acceptable, or unperceived, but the effect on the conceptus may be permanent and severe. The immune and respiratory systems are discussed as two examples of how subtle and protean adverse effects on functional development may be.

Animals↗
PubMed1988

Barbiturate anesthesia and alcohol tolerance in a rat model.

Anesthetic responses to a variety of barbiturates were examined in adult male rats rendered alcohol-tolerant by administration of an ethanol-containing balanced liquid diet for 3 weeks. Within 9 hours of withdrawing the diets, groups of 10-15 ethanol-fed rats and pair-fed controls were injected intraperitoneally with one of the following drug/dose combinations: thiamylal 20, 40, or 60 mg/kg; methohexital 10, 20, or 40 mg/kg; secobarbital 20, 30, or 40 mg/kg; pentobarbital 10, 20, or 40 mg/kg; or phenobarbital 80, 120, or 160 mg/kg. Each animal was monitored for time to loss of righting reflex (onset of anesthesia), absence of response to a painful stimulus (analgesia), and sleeping time (duration of anesthesia). None of these three anesthetic responses differed significantly in ethanol-fed and control rats with any dose of thiamylal, methohexital, or secobarbital. In contrast, all three responses were significantly less in rats given the middle dose of pentobarbital (20 mg/kg) than they were in control rats. Onset and duration of anesthesia were also shorter with the middle dose of phenobarbital (120 mg/kg), but analgesia was not. The results of this study, in combination with others, suggest that 1) cross-tolerance to anesthetic effects of barbiturates in ethanol-tolerant rats is not uniform with all barbiturates: and 2) because shorter-acting barbiturates show negligible cross-tolerance with alcohol, higher doses of these agents may not be required for satisfactory anesthesia in chronically alcoholic humans.

Animals↗
PubMed1986

Effects of chronic alcohol intake on anesthetic responses to diazepam and thiopental in rats.

The effect of chronic alcohol intake on anesthetic responses to alcohol, thiopental, or diazepam was examined in adult male Sprague-Dawley rats. Alcohol-fed animals were maintained solely on a complete balanced liquid diet containing 6.54% ethanol (w/w) for 21 days; pair-fed control animals received equal amounts of the same diet with alcohol isocalorically replaced by sucrose or dextrin. Nine hours after diets were withdrawn on the twenty-second day, the following drug/dose combinations were administered intraperitoneally to separate groups of alcohol-fed and control rats (10-15 animals in each group): ethanol 2.4, 3.2, and 4.0 g/kg; thiopental 20, 40, and 80 mg/kg; and diazepam 10, 20, and 40 mg/kg. Three different responses were assessed in every animal: 1) loss of righting reflex (induction of anesthesia); 2) response to a painful stimulus (analgesia); and 3) sleeping time (duration of anesthesia). Alcohol-fed rats compared with controls were significantly less tolerant of pain at an acute alcohol dose of 2.4 g/kg, and loss of righting reflex and sleeping time were reduced at 4.0 g/kg. All three anesthetic responses were also attenuated in alcohol-fed rats at a diazepam dose of 20 mg/kg. In contrast, none of the three responses was reduced in alcohol-fed rats at any of the three thiopental doses. Thus, chronic alcohol intake sufficient to produce tolerance to anesthetic doses of alcohol in rats also produced cross-tolerance to diazepam but not to thiopental in equianesthetic doses. These results suggest that blanket recommendations for adjusting intravenous anesthetic dosages in alcoholic humans may be inadequate as guides to anesthetic management.

Alcoholism↗
PubMed1986

The sit-up position for breast reconstruction.

For breast reconstruction, we have found that breast symmetry can be created optimally when the patient is brought to a totally upright position with the trunk vertical and perpendicular to the floor. The size of the opposite breast can better be appreciated. Nipple and areola position can be determined accurately even with the patient asleep if she is brought to the upright position. The safety of the upright positioning is documented in our series but depends on planning with the anesthesiologist preoperatively and allowing time to move the patient cautiously. An anesthesia technique for intraoperative vertical positioning is reported.

Adult↗
PubMed1985

Regional blood flow and cerebral metabolic changes during alcohol withdrawal and following midazolam therapy.

Regional blood flows and cerebral oxygen consumption (CMRO2) were measured following alcohol withdrawal in alcohol-dependent rats. In addition, the authors tested the ability of midazolam (0.057, 0.575, or 5.75 mg X kg-1) to modify alcohol-induced changes. Rats received a 3-week treatment of daily ad libitum access to a liquid diet containing 6.54% ethanol or a sham treatment with the same caloric intake but with white dextrin substituted for alcohol. Regional blood flow was measured 12 h after alcohol withdrawal with radioactive microspheres. Nitrous oxide (70% in oxygen) was used as the control anesthetic. Rats withdrawn from alcohol treatment had significantly increased heart rate, cortical cerebral blood flow (CBF) (39 +/- 8%, mean +/- SE), and CMRO2 (41 +/- 9%) compared with sham-treated rats (P less than 0.05). Subcortical CBF (49 +/- 8%), myocardial (52 +/- 18%), and hepatic arterial blood flow (298 +/- 47%) also were increased in alcohol-withdrawn rats. Renal blood flow decreased 47 +/- 5%, while skeletal muscle and small intestinal blood flow were not significantly different between the two groups. Midazolam infusion decreased CBF, CMRO2, and hepatic arterial blood flow in alcohol-withdrawn rats to similar levels as sham-treated rats and increased renal blood flow in both groups. Skeletal muscle and intestinal tissues showed no change in blood flow in response to midazolam. The authors conclude that midazolam may be effective in lowering blood pressure and brain metabolism and reversing regional blood flow changes produced by alcohol withdrawal in the rat.

Anesthesia, Inhalation↗
PubMed1985

Temporomandibular malformations in the bonnet monkey (Macaca radiata) fetus following maternal ingestion of thalidomide.

Structural abnormalities of the temporomandibular region were seen and described in the fetal bonnet monkey (Macaca radiata) after maternal ingestion of thalidomide. A single oral dose of 10 mg/kg of thalidomide was given on day 24, 25, 26, 27, 28 or 29 or 30 mg/kg on day 25 or 28 of gestation to 25 pregnant monkeys (day of mating = 0). The skeletons, processed and stained with alizarin red S, were examined for gross changes in configuration of craniofacial bones. Temporomandibular defects, in varying severity, were seen in four 70-day-old and seven 100-day-old fetuses associated with a single treatment between day 24 and day 28. The highest risk appeared to occur following treatment on day 25 (4/5) and the lowest on day 28 (2/8). Characteristic expression of the defects included 1) temporo-zygomatic hyperplasia involving the articular tubercle and postglenoid process and 2) mandibular hypoplasia, primarily of the condyles and the angular and coronoid processes. Micrognathia, apertognathia, and partial extraarticular ankylosis were seen. Although the sensitivity periods of the temporomandibular and ear regions seem to overlap and the embryonic origins are similar, the defects of each region appeared to be independent. Although the ear demonstrated a definite temporal relationship characterized by a decrease in severity in the expression of the ear malformations with respect to increased gestational age at the time of thalidomide insult, the temporomandibular region failed to exhibit a specific pattern. Although the temporo-zygomatic hyperplasia was dissimilar to any reported human condition, the mandibular changes were similar.

Abnormalities, Drug-Induced↗
PubMed1984

Lung volume and compliance in neonatal rats.

Lung volumes and static lung compliance were measured in decapitated three day-old neonatal Long Evans' rat pups. Compliance was measured in situ (open chest method) using a water manometer and syringe system. Mean total lung capacity at 20 cm H2O pressure (TLC20) was 0.678 ml. Minimum lung volume after experimental inflation was 0.197 +/- 0.048 ml, and vital capacity was 0.56 ml (Vmax20). The mean lung compliance value for the approximate tidal loop (between 3 and 12 cm H2O) equalled 26.2 microliters air/cm H2O for the inflation limb and 23.1 microliters/cm H2O for the deflation limb.

Animals↗