Pulmonary pathologic changes in rats exposed to marihuana smoke for 1 year.

Exposure of rats to marihuana or placebo smoke for periods up to 365 days was performed with an automatic inhalator. Δ⁹-Tetrahydrocannabinol (Δ⁹-THC) concentrations in the marihuana smoke were similar to those inhaled by man and were presented to the rats in a 50-ml puff volume of 2-sec duration and a 30-sec exposure interval followed by a 30-sec period of fresh air each minute (1 puff/min). By varying the number of puffs from three simultaneously smoked marihuana cigarettes (0.9 to 1.2% Δ⁹-THC), 8 to 10 Fischer rats simultaneously received a single daily Δ⁹-THC dose of 0.4, 0.8 or 1.5 mg/kg, 6–7 days per week for 365 days. All treatment groups contained 30 males and 30 females except for the high-dose group which had 50 males and 50 females. At each of the lower doses $\text{2}\text{60}$ (3%) of the animals died while at the higher dose $\text{18}\text{108}$ (17%) died. Twenty-five percent ($\text{15}\text{60}$) of the placebo-smoked rats died primarily from carbon monoxide poisoning. No sham-smoked rats died. In deceased marihuana-smoked rats, organ congestion and focal petechial hemorrhages in the brain suggested circulatory failure. In contrast with an earlier 87-day inhalation study, pulmonary irritation progressed beyond a dose-related focal alveolitis or pneumonitis with the accumulation of yellow-brown alveolar macrophages admixed with a few neutrophils and mononuclear cells, to a spectrum of more pronounced inflammatory and focal proliferative changes. The development of focal granulomatous inflammation in the lung with giant cell forms of macrophages and cholesterol-like clefts were striking new developments in the marihuana-smoked rats, especially since these effects were dose related and nonreversible after a 30-day recovery period.     

Cerebral metabolism in the newborn lamb with polycythemia

Infants with polycythemia and hyperviscosity are known to have a reduced cerebral blood flow. Eight newborn lambs were studied to determine what effect the reduction in cerebral blood flow might have on the cerebral delivery and uptake of oxygen, glucose, lactate, pyruvate, beta-hydroxybutyrate, and acetoacetate. Measurements of cerebral blood flow, hematocrit, blood viscosity as well as delivery and uptake of the forementioned substrates were made during a control period and at 60, 180, and 300 min after an exchange transfusion with packed newborn red blood cells was performed to increase the hematocrit. Sixty min after the exchange transfusion, cerebral blood flow fell while cerebral oxygen delivery and uptake were stable. Although arterial glucose concentration remained unchanged, there was a significant fall in cerebral glucose delivery. At 180 min after the exchange transfusion, the arterial glucose concentration fell from 90 to 70 mg/100 ml causing the cerebral glucose delivery to further decrease. This resulted in a significant fall in the cerebral glucose uptake and glucose:oxygen quotient. At 300 min arterial glucose concentration remained low but a rise in cerebral blood flow resulted in a small increase in the cerebral glucose delivery and consequently the cerebral glucose uptake and glucose:oxygen quotient returned to normal. We conclude that polycythemia results in a decrease in cerebral glucose delivery and uptake during normoglycemia.     

Pulmonary hemorrhage in neonates of early and late gestation

Our objectives in this study of pulmonary hemorrhage (PH) were to define common characteristics of infants who develop PH, identify factors associated with PH and report the outcome. Neonates (42/2980 admissions) with PH and matched controls were identified. Early gestation (< or = 35 weeks) infants with PH [EGPH] (n = 34; 12 survived) had occurrence of PH at 3.6 +/- 1.1 (mean +/- sem) days and were significantly associated with multiple births (p = 0.03), RDS (p < 0.01) and use of Survanta (p < 0.02). Among EGPH, small for gestational age (SGA) infants (n = 7) had a 100% mortality rate. Late gestation (> or = 36 weeks) infants with PH [LGPH] (n = 8; 6 survived) had occurrence of PH at 0.7 +/- 0.3 days and were significantly associated with low 1 minute (p = 0.04) and 5 minutes (p = 0.01) Apgar scores. All infants were managed with increases in mean airway pressure (MAP) and/or use of cocaine/epinephrine through the endotracheal tube. We have identified 2 groups of neonates with distinct factors associated with PH; use of 1:10,000 epinephrine (0.1 ml/kg) and/or 4% cocaine (4 mg/kg) may be useful adjuncts to increases in MAP for management of PH.     

Preclinical toxicologic evaluation of chromomycin A3 (NSC-58 514) in mice, dogs and monkeys

The toxicity of chromomycin A3, a potent antitumor antibiotic derived from Streptomyces griseus, was assessed in mice, dogs and monkeys. In mice, the LD50 after 5 daily iv doses was 603 μg/kg. In dogs and monkeys, the single-dose iv minimal lethal dose was 200 and 330 μg/kg, respectively, while this value after 5 daily iv doses was 100 μg/kg for both species. The principal clinicopathologic findings in dogs and monkeys that became moribund or died included emesis, hemorrhagic diarrhea, fever, dehydration, and necrosis of intestinal and lymphoid tissues with occasional necrosis in other organs. Laboratory findings were consistent with clinical signs. Dogs and monkeys that survived treatment exhibited mild, reversible toxic alterations.     

Intussusception in the 1970s: Indications for operation

Eighty-one patients with proven intussusception were treated at the Cincinnati Children's Hospital from 1970–1974. One died. Seven of these had ileo-ileal intussusception, all treated surgically. Seventy-four had colonic components of their intussusceptions. In 58 of these patients (78%), reduction was attempted at barium enema, successfully in 32. Hydrostatic reduction was abandoned and the patient operated upon when the intussusception was not pushed out of the colon, when barium failed to reflux into several loops of ileum, or when there was a large persistent filling defect in the cecum or terminal ileum. Primary operation without barium enema was done in 16 patients. The appearance of intestinal obstruction by abdominal x-ray seemed to give the best warning about the complicated, incarcerated, or gangrenous intussusception. Primary operation is, therefore, advised for the patient with intussusception if there is x-ray evidence of intestinal obstruction. The age of the patient and the duration of his symptoms do not seem important in this regard, except as they correlate with peritonitis or obstruction. For the patient without peritonitis or intestinal obstruction, attempted reduction of the intussusception at barium enema seems safe and effective, regardless of the patient's age or duration of his symptoms.     

Gastroesophageal reflux in infants < 32 weeks gestational age at birth: lack of relationship to chronic lung disease

The objective of this study was to determine the incidence of gastroesophageal reflux (GER) as documented by extended esophageal pH monitoring in symptomatic premature infants and to identify its relationship with chronic lung disease (CLD). This was a retrospective study of 629 infants born < 32 weeks gestational age and admitted to the neonatal intensive care unit during the study period. Univariate analyses were done on the 137 infants undergoing the test for the association of the following risk factors with acid reflux: birth weight, gestational age, race, sex, length of stay, bronchopulmonary dysplasia (BPD; O2 requirement at 28 days), and severe CLD (O2 requirement at 36 weeks postmenstrual age). Eighty-seven of 137 infants were positive for GER. There was no association of GER with the risk factors studied, nor were there correlations with BPD or severe CLD. GER is common (63%) in premature infants < 32 weeks gestational age but clinical symptoms and CLD are poorly correlated with this diagnosis.