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Biomedical subjects

A A Mitchell

Publications and source records attributed to A A Mitchell.

At least 73 records · Page 4Linked to original sources

Serological characterisation of a mouse monoclonal anti-P-like antibody.

An IgM mouse monoclonal antibody, LM 147/328, raised against an Escherichia coli immunogen, was found to possess anti-P-like specificity. It is proposed that this antibody recognises an epitope on a Gal beta 1-3GalNAc disaccharide structure (GalNAc = N-acetyl-D-galactosamine). The haemagglutinating activity of this antibody was consistently strong with adult erythrocytes, but gave significantly weak reactions with about 7% of cord erythrocyte samples.

Animals↗

Ipecac-induced emesis and reduction of plasma concentrations of drugs following accidental overdose in children.

Syrup of ipecac is widely used following accidental drug overdosage in children. Proof of its efficacy, however, in reducing the risk of poisoning is limited. We prospectively studied the effect of early v late induction of emesis by ipecac in 50 children younger than 5 years of age with accidental acetaminophen poisoning. The mean estimated ingested dose was 165 mg/kg, and all patients vomited within 15 to 255 (mean 78) minutes postingestion. Although the predicted four-hour plasma acetaminophen concentration was 97 +/- 4 micrograms/mL (mean +/- SEM, calculated on the basis of the estimated ingested dose), the measured four-hour plasma acetaminophen concentration was 34 +/- 5 micrograms/mL (P less than .01). To assess the efficacy of early v late ipecac-induced emesis, we used the ratio of measured to predicted four-hour acetaminophen plasma concentration. The ratio of the measured to predicted four-hour level increased as the delay in time to vomiting increased (r = .60, P less than .001). Ipecac syrup was administered more promptly when available in the home than when obtained from a pharmacy or a medical facility (26 +/- 8 v 83 +/- 13 minutes postingestion, respectively; P less than .001) and vomiting occurred earlier (49 +/- 9 v 103 +/- 12 minutes postingestion; P less than .01). Although the mean estimated doses ingested were greater in patients who received ipecac syrup at home, their four-hour plasma acetaminophen concentrations were lower. These data suggest that prompt administration of ipecac syrup results in a greater reduction in plasma acetaminophen concentrations in potentially toxic overdosages in children.(ABSTRACT TRUNCATED AT 250 WORDS)

Accidents, Home↗

Heparin use as a risk factor for intraventricular hemorrhage in low-birth-weight infants.

In a systematic review of data on drug use and adverse clinical events in infants with birth weights under 2000 g, we observed an association between germinal matrix-intraventricular hemorrhage and the use of heparin to maintain the patency of vascular catheters. Sixty-six infants with germinal-matrix (periventricular) or intraventricular hemorrhage or both (cases) were matched with 254 infants with other conditions (controls), and analysis, taking the matching factors into account, yielded an odds ratio of 14.0 (95 percent confidence interval, 5.4 to 34). When potential confounding factors were taken into account, the odds ratio was 3.9 (1.4 to 11). The association did not appear to vary according to the severity of hemorrhage or to the method of administration or dose of heparin. The data suggest that the routine use of heparin in neonatal intensive care units is associated with a four-fold increase in the risk of germinal matrix-intraventricular hemorrhage. Because of the possibility that confounding may have been incompletely controlled for, the true risk cannot be determined from these data, and a controlled clinical trial of heparin use in low-birth-weight infants is recommended.

Catheterization↗

Effect of questionnaire design on recall of drug exposure in pregnancy.

Case-control studies of antenatal drug exposure and birth defects often rely on maternal recall of drug use in pregnancy. Differential recall among mothers of cases and controls can lead to information bias ("maternal recall bias"), and the opportunity for such bias increases as ascertainment of drug exposure diminishes. The effect of questionnaire design on the ascertainment of drug use in pregnancy was examined in two studies. In a pilot interview study of 532 women in obstetric/gynecologic practices, information on drug use in the past year was obtained by means of three questions asked in sequence: The first question was open-ended, the second asked about drug use for selected indications, and the third asked about use of specifically named drugs. Among obstetric patients who reported use of any of five drugs, less than 50% did so in response to the open-ended question, and approximately 20-40% reported use only when the specific drug name was asked. In a case-control Birth Defects Study of 5,435 mothers of malformed children, information on drug use in pregnancy was obtained by asking questions in sequence about indications and specifically named drugs. Among the women who reported use of any of 11 drugs, 6-40% did so only when asked about the specific drug by name. These findings suggest that completeness of ascertainment of antenatal drug exposure varies according to how the mother is questioned and is directly related to the specificity of the questions asked.

Abnormalities, Drug-Induced↗

Risk factors for neonatal hyperglycemia associated with 10% dextrose infusion.

As part of an intensive drug surveillance program, we identified rates and associated risk factors for hyperglycemia related to intravenous 10% dextrose solution in a population of 1,157 newborns in two neonatal intensive care units. Hyperglycemia related to 10% dextrose solution was observed in 64 exposed infants (5.5%), a rate similar to that observed for hypoglycemia (6.7%) in this population. There was a highly significant trend toward an increasing risk of hyperglycemia with decreasing body weight, such that the risk of hyperglycemia among infants weighing less than 1,000 g was 18 times greater than the risk among infants weighing more than 2,000 g. The risk of hyperglycemia also increased with increasing dextrose dose. The effects of weight and dose were independent. Certain measures of disease severity also were associated with increased risks of hyperglycemia. Because increases in blood glucose levels may affect renal function or possibly lead to intraventricular hemorrhage, it is important that glucose levels in neonates receiving 10% dextrose solution be carefully monitored, and the total dextrose dose be adjusted accordingly.

Birth Weight↗

A study of adverse reaction algorithms in a drug surveillance program.

To improve agreement among observers, several investigators have recently proposed methods (algorithms) to standardize assessments of causality for presumed adverse drug reactions. We evaluated one such method in the context of an intensive pediatric drug surveillance program. Four observers rated 50 randomly selected case reports drawn from the program, first using only general guidelines and then, several months later, using the strict criteria of the algorithm. Agreement among observers was poor in both study phases. The presence of selected characteristics of adverse events (e.g., major severity) did not improve agreement in either phase of the study. We conclude that routine use of such algorithms in drug surveillance programs is not likely to be of benefit.

Child↗

Birth defects in relation to Bendectin use in pregnancy. II. Pyloric stenosis.

To test the hypothesis that the use of Bendectin in pregnancy increases the risk of pyloric stenosis, we determined rates of antenatal Bendectin exposure among 325 infants with pyloric stenosis and among two control groups comprising infants with other defects; one consisted of 3,153 infants with other conditions, and the other, a subset of that group, consisted of 724 infants with defects that may have had their origins at any time in pregnancy. Comparisons between the cases and the two control series yielded estimated relative risks of 0.9 (95% confidence interval, 0.6 to 1.2) and 1.0 (0.7 to 1.4), respectively. The findings from this large case-control study suggest that Bendectin does not increase the risk of pyloric stenosis.

Abnormalities, Drug-Induced↗

Lack of relation of oral clefts to diazepam use during pregnancy.

The hypothesis that in utero exposure to diazepam increases the risk of oral-cleft anomalies was evaluated in a case-control study, in which 445 infants with cleft lip with or without cleft palate and 166 with cleft palate without cleft lip (cleft palate alone) were compared with 2498 control infants having other birth defects. For exposure to diazepam during lunar months 1 through 4 relative to no exposure during pregnancy, the estimated relative risks were 1.0 for cleft lip with or without cleft palate (95 per cent confidence interval, 0.5 to 2.1) and 0.8 for cleft palate alone (0.3 to 2.7). After control for all identified potential confounding factors, the corresponding estimates were 0.8 (0.4 to 1.7) and 0.8 (0.2 to 2.5), respectively. The findings were unchanged when maternal suspicion that diazepam might be a teratogen was taken into account. The data suggest that first-trimester exposure to diazepam does not materially affect the risk of cleft lip with or without cleft palate or of cleft palate alone.

Cleft Lip↗

Birth defects and vaginal spermicides.

In a cohort study of 50, 282 pregnancies recruited between 1958 and 1965, there were 462 gravidae who used nonmercurial spermicides (mostly nonoxynol-9 (95% confidence limits, 0.6 to 1.6). There were also 889 women who used phenylmercuric acetate (no longer available as a spermicide); the corresponding rate ratio was 0.9 (0.6 to 1.3). Limb reduction deformities, neoplasms, Down's syndrome, and hypospadias did not occur in excess in children exposed to spermicides.

Abnormalities, Drug-Induced↗

Risks to children from computed tomographic scan premedication.

We observed serious adverse reactions after premedication for computed tomographic (CT) head scans and therefore determined rates and risk factors for such reactions among 106 hospitalized children monitored by an intensive drug surveillance program. Reactions occurred in 13 patients (13%), including four cases of life-threatening cardiorespiratory depression or arrest after narcotic premedication. Other reactions included CNS depression, behavior changes, voiding problems, and vomiting. The risk of reaction was elevated in subjects who received high doses of a premedication drug (relative risk, 5.2) and in those who received four or more premedication (relative risk, 3.7). All life-threatening reactions occurred among infants younger than 3 months, and two of these followed medication with only morphine sulfate, in the recommended dose. Risks of adverse reactions from premedication should be considered by physicians who order CT scans for hospitalized children.

Adolescent↗

Acetaminophen and aspirin. Prescription, use, and accidental ingestion among children.

Among 3,587 hospitalized children monitored by the Pediatric Drug Surveillance Program between 1974 and 1979, acetaminophen was prescribed for 32% and aspirin for 3%. In the three months before admission, 23% reported use of either drug. In both inpatient and preadmission settings, acetaminophen use increased between 1975 and 1977 and decreased subsequently. Aspirin prescriptions were consistent over the entire study period among inpatients, but preadmission use decreased substantially. The Massachusetts Poison Information Center observed a 36% increase in calls concerning aspirin from 1976 to 1977 and 1977 to 1978, similar to the increase in all calls, but acetaminophen calls increased by 87%. Long-standing concerns about the toxic effects of aspirin, coupled with recent concerns about hepatotoxic effects of acetaminophen in overdose, may be leading physicians and parents to decrease the use of both drugs for the treatment of fever.

Acetaminophen↗

Patterns of preadmission medication use among hospitalized children.

To determine patterns of medication use prior to hospital admission, we reviewed records of 3,487 infants and children monitored by the Pediatric Drug Surveillance Program. Subjects were admitted to selected monitored wards at the Children's Hospital Medical Center and Brigham and Women's Hospital between 1974 and 1979. The median number of drugs taken in the three months prior to admission was 3.5; 220 children (6%) reported taking no preadmission drugs, and 351 (10%) reported taking ten or more drugs. Preadmission drug use was highest in patients with cancer and children with chronic diseases (such as cystic fibrosis), and use was also high among infants transferred to a referral neonatal ICU. The most common preadmission medications for selected discharge diagnoses and indications are presented. In addition, review of the data revealed changes in the use of specific drugs (chloramphenicol, ampicillin, amoxicillin, Dimetapp, and cimetidine) over the study period. These data suggest that there is substantial use of medications by pediatric patients prior to hospital admission and that the nature of such drug use changes over time.

Adolescent↗