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Biomedical subjects

G D Anderson

Publications and source records attributed to G D Anderson.

At least 127 records · Page 7Linked to original sources

Placental transfer of 14C-hexoprenaline.

The placental transfer of a single intravenous injection of 14C-hexoprenaline was studied in eight pregnant New Zealand white rabbits. Maternal and fetal blood was sampled intermittently for 60 minutes after the injection. An initial rapid decrease in the levels of 14C-hexoprenaline in maternal blood was followed by a second slower phase, whereas fetal levels remained insignificant. The conclusion, therefore, is that the rapid improvement in fetal heart rate after the administration of a single maternal intravenous injection of hexoprenaline in the treatment of fetal distress is due to the action on the uterus and/or on maternal cardiovascular function, and not to direct stimulation of the fetus.

Animals↗

Lidocaine clinical pharmacokinetics.

A review of the clinical pharmacokinetics of lidocaine is presented. Available evidence suggests that antiarrhythmic effects are reasonably well correlated wih plasma concentration. Adverse effects also covary with plasma concentration, but available evidence suggests that the correlation is not strong. A simple, multiple-bolus loading schedule appears to be superior to techniques using loading infusions; most of the multiple-bolus protocols mandate that only enough drug be given to attain the desired pharmacologic effect. In contrast, the loading infusion protocols almost invariably require the administration of a fixed dose, regardless of what fraction of the dose has been given when arrhythmia suppression is achieved. Since multiple-bolus and constant-rate infusion techniques have been shown to reduce substantially the incidence of primary ventricular fibrillation, they should be considered appropriate prophylactic and treatment regimens for acute myocardial infarction patients.

Humans↗

Eclampsia: treatment and referral.

Although the recognition and treatment of preeclampsia theoretically should eliminate eclampsia, it has not disappeared and remains a substantial threat to maternal and fetal well-being. The therapy of choice for treatment and prevention of convulsions is magnesium sulfate (MgSO4 . 7H2O USP) and that for severe hypertension is intravenous hydralazine. Delivery of the fetus and placenta is recommended after the mother is stabilized from the effects of the convulsion(s). If the mother is to be transported before delivery, it is important that she receive an adequate dose of MgSO4.

Adolescent↗

Eclampsia II. Clinical significance of laboratory findings.

Sixty-seven cases of eclampsia were managed between August 1977 and July 1980. Routinely acquired laboratory tests of these cases have been analyzed. In addition, the group of patients with eclampsia was compared with a group of 24 healthy pregnant women. There was no significant difference in platelet count, serum fibrinogen, and bilirubin values. The activated partial thromboplastin time was abnormal in 42% of patients with eclampsia. There was no clinical evidence of disseminated intravascular coagulation in any patient. Patients with eclampsia had abnormalities of lactic dehydrogenase, alkaline phosphatase, SGOT, uric acid, BUN, and creatinine. However, in any individual patients there was no single test of great clinical usefulness and no test predictive of maternal or fetal outcome. At present the authors recommend complete blood count (including blood smear and platelet count), clot observation, and serum creatinine tests. Liver function tests are reserved for the patient with upper abdominal pain. Additional tests are recommended if the diagnosis of eclampsia is questionable or if an additional disease process is suspected.

Alkaline Phosphatase↗

Plasma volume determination in pregnancies complicated by chronic hypertension and intrauterine fetal demise.

Plasma volume determinations for 9 women with severe chronic hypertension who delivered live-born infants with birth weights appropriate for gestational age (AGA) were compared with those for 7 women with chronic hypertension whose pregnancies ended in intrauterine fetal demise. Plasma volume determinations using Evans blue dye dilution technique were performed at 20 to 25 weeks' gestation (12 patients) and at 26 to 29 weeks' gestation (16 patients). In addition, plasma volume measurements were performed at 8 weeks post partum in 5 patients who had intrauterine fetal demise. Analysis of the clinical course, laboratory findings, and pregnancy outcome revealed that the degree of plasma volume expansion was the factor most significantly differing between the 2 groups of patients. The plasma volumes of 9 women who delivered AGA infants were comparable with those values previously reported for normal singleton pregnancy. In contrast, each patient with intrauterine fetal demise demonstrated failure in plasma volume expansion at 20 to 25 weeks' gestation when compared with her own postpartum value. In each of the 6 patients who had a second plasma volume determination at 26 to 29 weeks' gestation, there was a decrease (mean decrease, 13.5%) from the value at 20 to 25 weeks. Plasma volume determinations may be very helpful in making clinical decisions regarding women with severe hypertension. Plasma volume determination may be most helpful in identifying a subgroup of women who are at particular risk for having infants with intrauterine growth retardation and intrauterine fetal demise.

Adult↗

Meperidine metabolism in the parturient.

A study of meperidine metabolism was undertaken in 21 normal parturients at term. Meperidine, 50 mg intravenously, was the sole analgesic agent used during the intrapartum period. Maternal and cord blood assessment for meperidine and normeperidine was done by gas chromatography-mass spectrophotometry. Most maternal sera showed a typical meperidine elimination curve. A secondary rise in maternal meperidine 30 to 180 minutes after injection was found in 4 patients. One patient showed a significant alteration in normeperidine appearance. These data add further validity to the hypothesis that the pregnant woman can metabolize meperidine by several pathways.

Adolescent↗

Effects of hexoprenaline on the lecithin/sphingomyelin ratio and pressure-volume relationships in fetal rabbits.

A placebo-controlled, double-blind trial was carried out on 74 New Zealand White rabbit fetuses from 15 does to assess the effect of a fetal injection of hexoprenaline on surfactant release. After the uterus was exposed, half the fetuses received 0.1 ml (0.25 microgram) of hexoprenaline injected intraperitoneally through the intact uterine wall; the other half received an equivalent volume of placebo. After 3 hours, the abdomen was reopened, and the fetuses were surgically delivered and killed before breathing. The lecithin/sphingomyelin (L/S) ratios, obtained from lung washings, revealed a mean of 1.59:1 for the placebo group and 1.92:1 for the hexoprenaline group (p less than 0.001). Pressure/volume curves were generated from the lungs of 24 fetuses from 10 does, and the volume of air in the lungs for each pressure was analyzed in four ways: total volume, volume per gram of fetal body weight, volume per gram of dry lung weight, and as a percentage of total lung capacity at a pressure of 40 cm H2O. A first and second inflation-deflation curve was obtained for each experiment. The lungs from the hexoprenaline-treated group retained significantly more air than those from the placebo group. The most significant comparison was obtained when lung volume was expressed per gram of dry lung weight. The possibility of administering a beta 2-sympathomimetic drug to the mother in advanced preterm labor, specifically to release surfactant in the fetal lung, is suggested.

Amniotic Fluid↗

Evaluation of Corometrics 315 telemetry system for fetal monitoring.

The Corometrics 315 telemetry system is a commercially available unit which can transmit both fetal heart rate (FHR) and intrauterine or external pressure data to a standard fetal monitor. This system was evaluated in 40 patients, ten of whom were monitored simultaneously by telemetry and direct-wire fetal monitoring. Because of some differences in electronic engineering between the telemetry and direct fetal monitoring systems, the following differences were found: Comparison of the simultaneously obtained FHR recordings revealed that the telemetry system rejected most of the motion artifacts while maintaining true variability. There were no differences as regards readability, FHR, and beat-to-beat variability. The intrauterine pressure values were the same, although the telemetry system gave a smoother waveform with less motion artifact. The main advantages of the telemetry system were found to be: (1) The patient was free to move about and ambulate during labor. (2) It was possible to obtain uninterrupted monitoring while the patient was moved from the labor room to the delivery room and throughout the second stage of labor.

Evaluation Studies as Topic↗

Effect of maternal dietary restriction on fetal growth and placental transfer of alpha-amino isobutyric acid in rats.

Maternal net weight gain, plasma clearance, and placental and fetal accumulation of I.V. administered 14C-alpha amino isobutyric acid (AIB) on day 20 of gestation were measured in pregnant rats: 1) fed ad libitum throughout gestation (Control), 2) fed 50% of the normal daily food intake during the last week of gestation (catabolic phase), and 3) fed 50% of the normal daily food intake throughout gestation. Dietary restriction during the catabolic phase only resulted in a loss of 54% of the net maternal weight gained during the first two weeks of gestation, while dietary restriction throughout gestation resulted in a net loss of 5.4% of the dams prepregnant weight. Both dietary regimens caused significant growth retardation of the fetus. Maternal plasma clearance of AIB was rapid and occurred at the same rate in all three groups. Placental accumulation and transfer of AIB to the fetus was reduced relative to the controls only in dams fed the restricted diet throughout gestation. Fetal to placental AIB concentration ratios were similar for each group indicting no difference in ability of placentas to release amino acid into the fetal circulation. The results indicate that mechanisms other than reduced nutrient transfer may be responsible for fetal growth retardation induced by maternal malnutrition during the catabolic phase of pregnancy only.

Aminoisobutyric Acids↗

Alkali treatment of cereal grains. II. Digestion, ruminal measurements and feedlot performance.

Two trials were conducted to determine the effects of feeding alkali-treated corn on various metabolic and performance characteristics of cattle. In the first trial, four ruminally-fistulated cows were fed high moisture corn (HMC) in the following forms: whole, rolled, sodium hydroxide (NaOH)-treated and ammonium hydroxide-treated. The corn was fed as 75% of the diet (dry matter basis) in four 15-day feeding periods in a 4 x 4 Latin square design. NaOH-treated HMC produced the highest dry matter digestibility (P less than .05), the highest rumen pH (P less than .05), the highest ruminal fiber digestion (P less than .05) and the highest fecal pH (P less than .05). Rolled HMC produced the lowest rumen pH (P less than .05) and lowest fiber digestion (P less than .05). Ammonium hydroxide-treated HMC produced no response in comparison to whole HMC and had the lowest rate of passage (P less than .05). Fecal starch, fecal water content, rumen fill and rumen ammonia were unaffected by treatments. In the second trial, 90 yearling steers were randomly allotted to five groups of 18 (six steers per pen). Steers were fed ad libitum a diet of 20% corn silage, 5% supplement and 75% corn as dry shelled corn, whole HMC, rolled HMC, NaOH-treated dry shelled corn or NaOH-treated HMC. There were no treatment effects on daily dry matter intake. Cattle fed either of the NaOH-treated corns had lower (P less than .05) average daily gains and poorer (P less than .05) feed efficiencies. No treatment effect was apparent for any carcass characteristic measured except yield grade, which was lower (P less than .05) for steers fed NaOH-treated HMC. Whole HMC produced the highest (P less than .05) fecal pH values while both NaOH treatments produced lower (P less than .05) fecal pH values than the other treatments.

Animal Feed↗

Clinical and laboratory evaluation of cefoperazone.

Cefoperazone, a third-generation cephalosporin derivative, has been reported to have excellent antibacterial activity against a wide range of gram-positive and gram-negative pathogens, including Pseudomonas aeruginosa. We treated 54 patients with a variety of clinical infections with cefoperazone and determined the susceptibilities of their 90 bacterial isolates. An additional 25 aerobic isolates obtained from patients treated with cefamandole in a comparison study were also tested for susceptibility to cefoperazone. Thus a total of 115 isolates were studied in vitro. One hundred nine (95%) of 115 bacterial isolates, including gram-positive and gram-negative aerobes and anaerobes, were susceptible to less than or equal to 32 microgram/ml. Only four isolates (three Escherichia coli and one Serratia marcescens) were highly resistant (minimal inhibitory concentration greater than or equal to 128 microgram/ml). We were able to assess clinical outcome of cefoperazone therapy in 53 patients; favorable responses (cure of improvement) were found in 48 (91%). P. aeruginosa was a major pathogen in three patients treated with cefoperazone; all three showed a favorable response. Side effects of cefoperazone therapy were noted in seven (13%) patients, and laboratory abnormalities were observed in 11 (20%) patients; all of these were mild and readily reversible. Cefoperazone thus appears to be safe, well tolerated, and suitable for use in a variety of human infections.

Bacterial Infections↗

Diurnal and short-term variation of blood pressure: comparison of preeclamptic, chronic hypertensive, and normotensive patients.

It has been suggested that the decrease in blood pressure during sleep is greater in patients with chronic hypertension than in preeclamptic patients. The DINAMAP (device for indirect noninvasive automatic mean arterial pressure) monitor was used to determine the mean arterial, systolic, and diastolic blood pressure, at 15-minute intervals, and 24 hours. Three groups of 15 patients each were studied: mildly preeclamptic, chronically hypertensive, and normotensive patients in the third trimester. In addition, 2 patients with severe preeclampsia were studied. The automatic readings were compared with auscultated blood pressures. There was short-term variation in the systolic and diastolic blood pressure of 20 to 40 and 15 to 30 mmHg, respectively, with consecutive 15-minute recordings. A decrease in blood pressure during sleep was seen in all groups, except in the 2 patients with severe preeclampsia. This fall varied between 5 and 20 mmHg systolic and 5 and 18 mmHg diastolic. The auscultated blood pressure differed from the automatic blood pressure by 5 to 40 mmHg systolic and 5 to 35 mmHg diastolic. In the clinical management of patients, these findings are significant, as they demonstrate short-term variation in blood pressure and differences in the auscultated versus automatic blood pressure readings. Also, changes in blood pressure occur during sleep; this may be important with regard to the timing and dose of medication given to pregnant patients with chronic hypertension or preeclampsia.

Blood Pressure↗

Eclampsia. I. Observations from 67 recent cases.

Sixty-seven cases of eclampsia were managed from 1977 to 1980, for an incidence of 1 in 310 deliveries. Eighty-four percent of patients were nulliparous and 82% had received some prenatal care. Prior to convulsion, 14 patients (21%) had a diastolic blood pressure below 90 mmHg, 39% had no edema, and 21% had no proteinuria. Thirty-seven patients (55%) had their first convulsion in the hospital. Eight patients had convulsions while receiving magnesium sulfate therapy. Convulsions occurred post partum in 25 patients (37%). In 11 patients the onset of eclampsia occurrred 3 to 11 days after delivery. The total perinatal mortality was 8.6% for all cases of eclampsia. Excluding postpartum cases, perinatal mortality was 13.3%, but was only 5% for those fetuses alive on admission to the perinatal center. Abruptio placentae was present in 9 cases and accounted for 4 of the 6 perinatal deaths. The high incidence of eclampsia at the authors' center has not decreased over the past 20 years, but maternal mortality has been reduced from 2.1 to 0%. It was disturbing to find that management error played some role in the development of eclampsia in 50% of the cases. Significant errors--including ineffective magnesium sulfate therapy, failure to treat adequately prior to transport, and lack of communication with a perinatal center--are discussed.

Abruptio Placentae↗

Hexoprenaline pharmacokinetics in pregnant and nonpregnant sheep.

Hexoprenaline, a beta 2-sympathomimetic agent, is used to suppress uterine contractions in the treatment of premature labor. However, little is known regarding the potential of this drug to undergo placental transfer or whether the pregnant state alters any of the pharmacokinetic parameters. Using sheep as a model, intravenous doses of 14C-hexoprenaline were administered to pregnant and non-pregnant animals. Measurable levels of radioactivity did not appear in fetal blood samples. After intravenous bolus administration, blood concentrations in the ewe could be fitted by a triexponential curve characteristic of a three-compartment pharmacokinetic model. Following intravenous infusion, a biexponential curve described the decline in blood concentrations. Mean terminal half lives for total radioactivity ranged from 2.5 to 4.2 hours. The pregnant animals tended to exhibit smaller apparent volumes of distribution and lower values for total body clearance, normalized to body weight, compared to non-pregnant sheep.

Animals↗

Reassessment of intravenous MgSO4 therapy in preeclampsia-eclampsia.

The occurrence of seizures in preeclamptic and eclamptic women is considered very unlikely during treatment with the standard dose of continuous intravenous magnesium sulfate. During a 21-month period, the authors encountered 13 patients who developed seizure activity while receiving intravenous MgSO4. Serum magnesium (Mg) levels at the time of seizure were below the therapeutic range in 11 of the 13 patients, thus prompting a study of serum Mg levels in preeclamptic patients treated with MgSO4. Random serum Mg samples were obtained from 120 patients treated with intravenous MgSO4 for preeclampsia-eclampsia. The samples were collected 2 to 48 hours after the loading dose and while the patients were taking a maintenance dose of either 1, 2, or 3 g/hr. When a maintenance dose of 1 or 2 g/hr was used, 98 and 50% of the respective serum magnesium values were below levels considered therapeutic by several authors. Therapeutic levels were achieved in ll patients receiving a maintenance dose of 3 g/hr. The recommended maintenance dose of MgSO4 of 1 g/hr was found insufficient to prevent the occurrence of eclamptic seizures in some preeclamptic patients.

Eclampsia↗