Clinical use and toxicity of intravenous lidocaine. A report from the Boston Collaborative Drug Surveillance Program

To determine the natural history of Meckel's diverticulum, 202 case records of proved disease of Meckel's diverticulum were retrieved, covering a fifteen year period, from all the hospitals of King County, Washington (population, 1,143,800). Using the figure of 2 per cent incidence of Meckel's diverticulum, we calculated that a Meckel's diverticulum has a 4.2 per cent likelihood of causing disease during a lifetime, decreasing to zero with old age. Using previously published mortality and morbidity figures, we calculated that to save one patient's life from the complications of Meckel's diverticulum, it would be necessary to remove approximately 800 asymptomatic Meckel's diverticula. This would be likely to incur a significant amount of postoperative morbidity from postoperative intestinal obstruction and infection. We suggest that the prophylactic removal of Meckel's diverticulum is rarely, if ever, justified.     

The physical state of alkali ions in a Halobacterium: some NMR results

The 46th case of known pregnancy-induced pancytopenia is reported. Pregnancy may play an etiologic role in this rare condition, but the specific mechanism is unknown. Maternal mortality is 63%, and fetal and neonatal wastage is 46%. The patient reported is a 24-year-old Oriental woman who delivered a healthy female infant. Her survival is attributed to conservative management with carefully timed packed cell and platelet transfusions.     

Enteric hyperoxaluria: dependence on small intestinal resection, colectomy, and steatorrhoea in chronic inflammatory bowel disease

The importance of intestinal resection, exclusion of the colon, and steatorrhoea for secondary hyperoxaluria was studied in 81 patients with Crohn's disease and 12 patients with ileostomy after colectomy for ulcerative colitis during a metabolic regime including a fixed oral supply of fat, calcium, and oxalate. Hyperoxaluria (greater than 48 mg (greater than 0.5 mmol) per 24 h) was present in 21 patients with Crohn's disease. All but one half or more of the colon preserved. Renal oxalate excretion was related to the amount of ileum resected. 14C-oxalate absorption was significantly higher in patients with ileal resection and the whole colon preserved than in patients with ileal resection plus hemicolectomy, despite the fact that the latter group had the most extensive ileal resections. Faecal fat and oxalate excretion agreed well in patients without ileostomy (r = 0.76, p less than 0.001), and renal oxalate excretion was significantly higher in patients with steatorrhea and the colon preserved than in patients without steatorrhoea. In all 93 patients 14C-oxalate absorption and renal oxalate excretion was positively correlated with a coefficient of correlation of 0.76 (p less than 0.001). No correlation was present between 47Ca- and 14C-oxalate absorption. The study confirm that a preserved colon is necessary for secondary hyperoxaluria and stresses the importance of ileal resection and steatorrhoea.     

Strain differences in histopathologic, hematologic, and blood chemistry changes induced in mice by a technical and a purified preparation of 2,4,5-trichlorphenoxyacetic acid

Including controls, 978 mice were studied. On days corresponding to days 6 through 14 of pregnancy, groups of pregnant and nonpregnant CD-1 mice and male and nonpregnant female dihybrid cross F2 mice received by gavage 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) ranging in dosage from 30 to 140 mg/kg. Some groups received a technical preparation containing 97.9 +/- 0.4% 2,4,5-T and some a purified preparation containing 99 +/- 0.3% 2,4,5-T. Mice were sacrificed when they became moribund and at 1, 2, 4, 6, 8, and 11 days after beginning treatment. Sick or moribund mice sacrificed after 2-9 doses of 2,4,5-T often showed severe myocardial lesions, hypocellularlity of the bone marrow, and depletion of lymphocytes in the thymus, spleen or lymph nodes. They also showed marked hematologic and blood chemistry changes. Treated mice remaining healthy showed few or no lesions or blood chemistry changes, but often developed a mild anemia attributable to a hemolytic effect of 2,4,5-T. The incidence of animals becoming moribund was less than 1% in the CD-1 mice, including those given 140 mg/kg, and 53-82% in groups of male and female F2 mice receiving 120 mg/kg 2,4,5-T. The incidence of moribund mice tended to be higher in male than in female F2 mice and in those given the purified compound. These findings indicate that impairment of maternal health by severe lesions early in gestation is not the primary cause of an increase in incidence of fetal abnormalities observed in mice given 2,4,5-t. they also indicate that the lesions are due primarily to 2,4,5-T, rather than contaminants in the technical preparation, and illustrate the importance of using more than one strain of mouse in a toxicologic or teratologic study.     

The development of creatine kinase in rat skeletal muscle. Changes in isoenzyme ratio, protein, RNA and DNA during development

The activity of cytosolic creatine kinase in rat skeletal muscle rises stepwise during development. The increases occur simultnaeously with transient increases in DNA content. The second increase is accompanied by a rise in total protein, soluble sarcoplasmic protein and RNA/DNA ratio. Such changes are not observed at 20 days after birth, when creatine kinase finally accumulates to the adult level. Transient higher amounts of the MB and BB isoenzymes are observed after the first and second stepwise increase. The increase in creatine kinase activity observed after birth is predominantly due to an activation of the M gene. The BB isoenzyme is still present in adult skeletal muscle, but contributes little to the total activity.     

The enantiomers of phenprocoumon: pharmacodynamic and pharmacokinetic studies

The pharmacodynamics and pharmacokinetics of the optical enantiomers of phenprocoumon were studied in 5 normal subjects and compared to the racemic mixture. Each subject received a single oral dose of 0.6 mg/kg of racemic, S(-), and R(+) phenprocoumon. S(-) phenprocoumon was 1.6 to 2.6 times as a potent as R(+) phenprocoumon when the area under the effect/time curve was used to quantify the total anticoagulant effect per dose. Comparing the plasma concentrations that elicited the same anticoagulant effect, S(-) phenprocoumon was 1.5 to 2.5 times as potent as R(+) phenprocoumon. The anticoagulant activity of the racemic mixture was between that of the enantiomers. There was no distinct difference in the rate of elimination between the enantiomers. The apparent volume of distribution and the plasma clearance for S(-) phenprocoumon were less than those for R(+) phenprocoumon. When the binding of the enantiomers to human serum albumin was compared, S(-) phenprocoumon was more highly bound than R(+) phenprocoumon. The protein binding of racemic phenprocoumon was between that of the enantiomers. The results show that S(-) phenprocoumon is more potent anticoagulant than R(+) phenprocoumon and that the pharmacokinetic differences between the enantiomers are due mainly to differences in their distribution.