Robert C Boerth

Prednisolone Plus Albuterol Versus Albuterol Alone in Mild to Moderate Bronchiolitis

To evaluate combination therapy of mild to moderate bronchiolitis with bronchiodilators and corticosteroids, we treated 51 young children with first-time wheezing and symptoms of respiratory tract infection with albuterol plus either prednisolone or placebo for 5 days. Disease severity was scored on days 0, 2, 3, and 6. On day 2, prednisolone resulted in significantly lower scores (2.7 ±1.4 vs. 4.0 ±1.5 in all patients evaluated, p<0.05) than placebo, whereas there was no detectable difference on day 6, suggesting that addition of prednisolone to albuterol transiently accelerates recovery from bronchiolitis. The clinical significance of this effect needs to be evaluated in further studies.

Hypertension associated with naloxone treatment for clonidine poisoning

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Myocardial Dysfunction in Group B Streptococcal Shock

ABSTRACT: A rabbit model of group B Streptococcal (GBS) shock was used to determine if myocardial dysfunction contributes to GBS shock and, if so, to ascertain if prostaglandins modulate this dysfunction. The infusion of heat-killed GBS (group I) produced a dramatic decrease in the first derivative of left ventricular pressure with respect to time (LVdP/dt) from baseline values (p < 0.05). LVdP/dt remained stable in rabbits pretreated with indomethacin (group II) and in saline-infused control rabbits (group III), and was significantly different at 30 min from LVdP/dt in group I (p < 0.05). Values for group I mean arterial pressure, cardiac output, pulmonary vascular resistance, and heart rate and for pH and pO2 after GBS infusion were all significantly different from baseline values and from postinfusion values for groups II and III (p < 0.05). Systemic vascular resistance and left ventricular end diastolic pressure did not change significantly in any group at any time interval. These results indicate a primary role for myocardial dysfunction in the pathogenesis of GBS shock, and suggest strongly that prostaglandins modulate GBS-induced myocardial dysfunction.

Prostaglandin Synthetase Inhibition in Group B Streptococcal Shock: Hematologic and Hemodynamic Effects

ABSTRACT. A rabbit model of group B Streptococcal (GBS) shock was used to study the effects of prostaglandin synthetase inhibition on the hemodynamic and hematologic response to GBS shock. The infusion of heat-killed GBS in groups I and II produced significant decreases in mean arterial pressure, neutrophil counts, and platelet counts (p < 0.05), and significant rises in concentrations of thromboxane B2 and 6-KetoPGFla, the stable metabolites of thromboxane A2 and prostacyclin (p < 0.05). Administration of indomethacin (4 mg/kg) after GBS infusion (group II) was associated with a significant rise in mean arterial pressure and a significant decline in thromboxane B2 and 6-Keto-PGFla concentrations (p < 0.05) but had no effect on GBS-induced hematologic alterations. Indomethacin administration before GBS infusion (group III) prevented alterations in mean arterial pressure and was associated with a decrease in thromboxane B2 and 6-Keto-PGFla concentrations. Indomethacin in group III did not prevent neutropenia and thrombocytopenia and may have exacerbated neutropenia. Alteration of experimental GBS shock with prostaglandin synthetase inhibition produces disparate hemodynamic and hematologic response.

Acute effects of iron on contractile function in isolated rabbit myocardium.

Changes in contractile function following exposure to iron (Fe) salts were evaluated in isolated isometrically contracting rabbit left atrial strips and right ventricular papillary muscles. Fe acutely depressed myocardial contractility as evidenced by dose-related declines in developed force and maximal rate of force development. There were no significant changes in duration of contraction or resting force. The tissue Fe content was increased nearly 3-fold after a 60 min exposure to Fe and subsequently was not decreased by repeated washing or by treatment with deferoxamine. Isoproterenol, but not deferoxamine, reversed the Fe-mediated impairment of myocardial contractility. These findings suggest that in cases of severe acute iron poisoning, depression of cardiac contractility might occur which may be improved by treatment with isoproterenol.

Hepatic function as assessed by lidocaine metabolism in sickle cell disease

OBJECTIVE To evaluate hepatic drug metabolism, as determined by the formation of monoethylglycinexylidide (MEGX) after lidocaine injection and indocyanine green (ICG) clearance, in patients with sickle cell disease. STUDY DESIGN A case-control study including 19 patients with homozygous hemoglobin S, and 13 age- and sex-matched black control subjects. Serum MEGX concentration was measured after intravenous injection of 1 mg/kg (maximum 50 mg) lidocaine. ICG (0.5 mg/kg) was injected concomitantly and absorbance (805 nm) of serum was measured over time to determine its volume of distribution, serum half-life, and hepatic blood flow. RESULTS MEGX formation at 15 minutes was decreased in patients with sickle cell disease compared with formation in the control subjects (39.9 +/- 18.0 vs 65.6 +/- 50.0 micrograms/L, respectively, p < 0.02). The volume of distribution of ICG was increased in patients with sickle cell disease compared with that in the control subjects (0.21 +/- 0.09 vs 0.11 +/- 0.03 L/kg, p < 0.01). This partly accounts for the decreased MEGX formation. The ICG half-life was similar in both groups (3.8 +/- 1.5 vs 3.1 +/- 1.0 min). Hepatic blood flow, derived from ICG clearance, was increased in sickle cell patients compared with that of the control subjects (12.2 +/- 4.5 vs 8.1 +/- 2.1 ml/kg/min, p < 0.01). CONCLUSION Hepatic drug metabolism, as assessed by MEGX formation after lidocaine injection, is impaired in patients with sickle cell disease. This impairment may have clinical implications when using hepatically metabolized medications in patients with sickle cell disease.

17 ORAL CONTRACEPTIVES IN ADOLESCENTS: LONGITUDINAL EVALUATION OF SERUM LIPIDS AND BLOOD PRESSURE

Oral contraceptive (OC) use has been associated with multiple metabolic effects in adult women. Similar data for adolescents are incomplete, however, even though OC use is increasing among teenagers. We examined serum cholesterol (CH, mg/dl), serum triglyceride (TG, mg/dl), and blood pressure (BP) in 131 adolescents, ages 12 to 22 yrs. (mean 17.8). Initial studies were done before beginning OCs with follow-up evaluations after 6-30 months (mean 13.5) of OC use. Mean results before (BOC) and during (DOC) OC use are tabulated below.During OC use, CH increased significantly in whites, and diastolic BP increased in all groups. Systolic BP increased significantly (p<0.01) only in pts. using OCs for greater than 20 months. No significant changes in TG were found. Age, weight, smoking, OC strength, and family history were unrelated to the observed changes. The increases in CH and BP found in this study are small but statistically significant. The long term effect of these changes on the subsequent health of adolescents on OCs must be determined.

Assessment of hepatic function in cystic fibrosis by lidocaine metabolism.

Background To determine hepatic drug metabolism in patients with cystic fibrosis, as measured by monoethylglycinexylidide formation after lidocaine injection and indocyanine green (ICG) clearance. Methods The following study is a case–control study, which included 19 patients with cystic fibrosis and 13 control subjects. Serum monoethylglycinexylidide concentration was measured after intravenous injection of 1 mg/kg (maximum, 50 mg) lidocaine. Indocyanine green (0.5 mg/kg) was injected concomitantly, and absorbance (805 nm) of serum was measured over time to determine its volume of distribution, serum half-life, and hepatic blood flow. Results Monoethylglycinexylidide formation was decreased in patients with cystic fibrosis compared with controls (39.4 ± 16.9 &mgr;g/L versus 70.3 ± 45.7 &mgr;g/L, mean ± SD , respectively, P < 0.02). Indocyanine green half-life (4.6 ± 2.7 min versus 3.0 ± 1.0 min), volume of distribution (8.6 ± 5.5 L versus 8.3 ± 3.4 L), and hepatic blood flow (10.9 ± 5.9 ml · kg−1 · min−1 versus 7.4 ± 2.0 ml · kg−1 · min−1) were similar in both groups. Conclusion Monoethylglycinexylidide formation after lidocaine injection is impaired in patients with cystic fibrosis. This impairment may have clinical implications when using hepatically metabolized medications in patients with cystic fibrosis.

The Comparison of Myocardial Dysfunction in Three Forms of Experimental Septic Shock

ABSTRACT. A rabbit model of septic shock was used to determine if 1) myocardial dysfunction is a common component of shock due to diverse neonatal pathogens, and 2) prostaglandins modulate septic myocardial dysfunction. The infusion of heat-killed Escherichia coli (group I), Haemophilus influenzae (group II), or Staphylococcus epidermidis (group III) produced significant decreases in the first derivative of left ventricular pressure with respect to time (p<0.05). Each organism also produced significant changes in mean arterial pressure, cardiac output, and heart rate, while pulmonary artery pressure was altered in groups I and III. Saline-infused control animals (group IV) exhibited no significant changes in any hemodynamic variable. Blood gas variables were not significantly changed in any group. These cardiovascular changes appeared dependent on arachidonic acid metabolism since indomethacin pretreatment prevented the cardiovascular changes induced by bacterial infusion. These results suggest that septic myocardial dysfunction is a common component of gram-negative and gram-positive septic shock, and that myocardial dysfunction is modulated by prostaglandin products.

310 DEPRESSION OF MYOCARDIAL CONTRACTILE FUNCTION (MCF) IN ACUTE JRON POISONING

Shock produced by acute iron (Fe) poisoning is thought to be due to venous dilation with decreased ventricular filling. This study examined the effects of acute Fe++ on MCF. Heart rate(HR), mean blood pressure(BP), mean right atrial pressure(RAP), cardiac output(CO), strain gauge measurement of right ventricular force (RVF; % of time 0), and arterial pH were measured in open-chest rabbits. Animals were divided into 3 groups (N=7 in each group): 1)Control (no Fe); 2) Fe(200mg/kg administered into the duodenum); and 3)Fe(200mg/kg)plus NaHCO3 (9 meq/hr, IV). Variables did not differ among the groups at time 0. Results (mean ± SEM) 30 minutes after Fe administration are shown below.Within 30 minutes, Fe produced a significant reduction in MCF as evidenced by decreased CO and RVF, with no reduction in filling pressure (RAP). Fe produced myocardial depression independent of acidosis. The direct depressant effect of Fe on MCF could be responsible, in part, for the shock seen in acute Fe ingestion. These findings may provide the basis for new approaches to the treatment of shock in Fe poisoning.