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Biomedical subjects

J Wolfsdorf

Publications and source records attributed to J Wolfsdorf.

At least 19 recordsLinked to original sources

Effect of extracorporeal membrane oxygenation on tobramycin pharmacokinetics in sheep.

BACKGROUND AND METHODS: Critically ill infants undergoing extracorporeal membrane oxygenation (ECMO) therapy often receive multiple pharmacologic agents. Although the disposition of many drugs has been assessed in patients undergoing cardiopulmonary bypass and in patients receiving mechanical ventilation, only limited data exist for selected medications in patients undergoing ECMO. To evaluate the potential influence of ECMO on aminoglycoside pharmacokinetics, we studied the disposition of tobramycin in ten sheep before and during ECMO therapy. Each sheep received a single iv dose of tobramycin during a control period before ECMO and on a study day during ECMO. Identically timed serial blood samples over 4 hrs were obtained after each tobramycin dose. Paired serum tobramycin concentrations were obtained pre- and postmembrane oxygenator during ECMO in six sheep. RESULTS: Alterations in specific pharmacokinetic variables for tobramycin were observed as a result of ECMO. Estimates of elimination half-life and volume of distribution for tobramycin were significantly increased during ECMO as compared with control (pre-ECMO) values (1.8 +/- 0.3 vs. 2.7 +/- 0.8 [SD] hrs [p < .01] and 0.3 +/- 0.1 vs. 0.5 +/- 0.2 L/kg [p < .005], respectively). Tobramycin body clearance was unaffected by the procedure (1.8 +/- 0.8 vs. 1.7 +/- 0.4 mL/min/kg). Paired serum tobramycin concentrations obtained pre- and postmembrane oxygenator demonstrated no drug removal. CONCLUSIONS: These data suggest that ECMO circuitry does not sequester tobramycin and that the prolonged elimination half-life observed during ECMO therapy is not due to a change in drug clearance but is due to an ECMO-induced increase in tobramycin volume of distribution. To achieve and maintain preselected target tobramycin serum concentrations during ECMO, the usual dosage interval should remain unchanged, but the dose should be increased to compensate for the alteration in the drug's volume of distribution. The clinical applicability of these findings needs to be confirmed in carefully controlled clinical studies involving infants receiving ECMO therapy.

Animals

Familial nesidioblastosis: severe neonatal hypoglycemia in two families.

Severe neonatal hypoglycemia with pathologic findings of diffuse nesidoblastosis of the pancreas is described in five children of both sexes from two families with unaffected parents. This appears to represent an autosomal recessive disorder of pancreatic development. Despite extensive testing, the diagnosis of hyperinsulinism was difficult in the index case of each family and delayed definitive treatment. Medical therapy with steroids and diazoxide was unsuccessful; pancreatectomy was required to treat persistent hypoglycemia. An abnormality of circulating glucagon found in one child with this disorder suggested that hyperinsulinism may not be the sole hormonal imbalance present, but rather that this disease is one of generalized disturbance of islet cell function. The history of severe, persistent neonatal hypoglycemia in an older sibling should lead the physician to investigate subsequent children for the presence of asymptomatic hypoglycemia.

Chromosome Aberrations

An animal model simulating acute infective upper airway obstruction of childhood and its use in the investigation of croup therapy.

Twelve heartworm-free mongrel dogs (10 males, 2 females) mean weight 22.2 kg (range 17.7--28.2 kg) were sedated and placed in a supine position with the neck extended. A double tracheotomy was performed under sterile conditions. The first tracheotomy tube was inserted 2 cm above the sternum in the direction of the carina using a shortened Silastic American tracheotomy tube (id 10 mm); the second was inserted two cartilage rings proximal to the first and approximately 5 cm distal to the larynx. All animals were kept deeply anesthesized by repeated iv injections of 3--6 mg/kg pentobarbitone sodium so that all reflexes (in particular laryngeal and palatal) were abolished. After control translaryngeal pressure measurements were obtained, the vocal cords were visualized, and steam was introduced onto the through the cords for a mean of 10 sec from above. For 2 hr after this, repeat pressure measurements, as described above, were made. After an overnight stabilizing period, two to three of five randomly chosen air environments were passed over the larynx at 10 liters/min via the proximal tracheotomy, and four half-hourly pressure measurements taken with control periods of at least 2 hr, as described above, separating each experiment. Environments utilized were as follows: i) "cold dry" air, i.e., air at a mean temperature of 9 degrees, obtained by passing compressed air through a coil placed in a solution of alcohol/Dry Ice; ii) "cold moist" air, i.e., air as above, subsequently passed over cold water at a mean temperature of 11 degrees; iii) "warm dry" air, i.e., air at a mean temperature of 36.5 degrees, obtained by passing compressed air through a copper coil, immersed in hot water; iv) "warm moist" air at a mean temperature of 36 degrees, obtained by passing compressed air through a heated Puritan humidifier; v) "ultrasonically produced mist" at room temperature (24 degrees), produced by a De Vilbiss ultrasonic nebulizer 900, set at maximum output. Six 2-hr experimental periods were utilized for each regimen of treatment (i--v). The mean of the combined experimental resistance calculations for each environment were compared statistically with those of its similarly acquired control data, expressed as a positive or negative percentage change, and displayed as a histogram. In addition, the data from each experimental environment were compared with the others, and mean percentage changes from control against time were calculated. Results indicate no statistically significant change in resistance from control for ultrasonic mist or warm moist treatment regimens. Warm dry, cold dry, and cold moist treatments, however, all produced significant reductions in translaryngeal resistance (74%, 60%, and 54%, respectively), there being no difference between cold dry and cold moist and warm dry and cold dry. Significant differences between warm dry and cold moist treatments were obtained, the former decreasing translaryngeal resistance the greatest amount...

Acute Disease

Hepatic enzymes, their induction and usefulness in predicting maximal serum bilirubin levels in premature newborn infants.

Sixty-seven babies were utilized to (a) document the serum bilirubin lowering effect and safety of a phenobarbitone and nikethamide combination in neonatal hyperbilirubinaemia of non-hemolytic origin; (b) determine whether birthweight and/or SGOT, SGPT or SGGT activity on day one of life correlated with the maximum serum bilirubin level achieved; and (c) investigate the pattern of hepatic enzyme levels in serum under normal conditions anf following drug induction. Results indicate a significantly lower serum bilirubin level in the treated group of babies. Birthweight and day one SGGT levels, and SGGT/birthweight ratio correlated well with the maximum serum bilirubin reached, the latter ratio being particularly useful in predicting the degree of hyperbilirubinaemia.

Alanine Transaminase

Kerosene absorption in primates.

Kerosene, labeled with 3H-toluene or 14C-hexadecane, was given to baboons by nasogastric tube after a tracheostomy had been performed. Six hours later the animals were killed and samples of tissues taken for analysis. The radioactive label was recovered from all the tissues analyzed. 3H-toluene appeared to be absorbed and taken up by most tissues to a greater extent than was 14C-hexadecane. No abnormal neurologic signs or behavior was noted in the baboons which were conscious during the study period. It appears that primates absorb kerosene from the gastrointestinal tract, but the volumes are very small and do not cause gross neurologic signs.

Adrenal Glands

Congenital adrenal hyperplasia in Blacks.

Two patients with salt-losing adrenal hyperplasia are reported. The occurrence of this condition among Blacks in Southern Africa has not yet been recorded. Both patients presented in the first month of life with dehydration, although they did not have diarrhoea. One was a boy, and the other a girl who had signs of virilisation. The typical biochemical changes of this condition were demonstrated. Congenital adrenal hyperplasia appears to be less common in Blacks than in Whites.

Adrenal Hyperplasia, Congenital

Complications of nasojejunal tube feeding.

The frequency and duration of complications were compared in premature babies fed by nasojejunal and nasogastric tubes. Some factors may have weighted the results against the nasojejunal tube-fed group, but this study failed to demonstrate differences in the rate and duration of complications.

Diarrhea, Infantile

Kerosene intoxication: an experimental approach to the etiology of the CNS manifestations in primates.

Baboons were utilized to investigate the clinicopathologic effects of kerosene, given via various routes, on the primate brain. The animals were divided into five groups: Group 1 - normal controls; Group II - kerosene administered intratracheally; Group III - kersoene injected into the left cardiac ventricle; Group IV - kerosene injected into right carotid artery; Group V - kerosene injected into portal vein. Results indicate that the primate brain is resistent to the direct toxic effects of kerosene. Even when the dose is very large, the microcirculation of the liver and lung filter out sufficient amounts of kerosene to protect the brain from damage. It is assumed that the CNS manifestations following ingestion of kerosene are due to hypoxia secondary to aspiration pneumonia.

Animals

Growth and nutrition of uremic piglets.

Piglets aged 6 days were rendered uremic by subtotal nephrectomy and their growth and dietary intakes studied over the next 21 days. Eleven control piglets fed a voluntary intake of a sow's milk substitute (group A), 11 nephrectomized piglets fed a voluntary intake of the same feed (group B), 6 nephrectomized piglets tube fed the same milk (group C), and 11 nephrectomized piglets fed a voluntary intake of a low protein, isocaloric food (group D) were studied. After nephrectomy the piglets had an initial rapid rise in blood urea concentration which had fallen by day 7 and then leveled out around 13 mmol/liter in group B and 8 mmol/liter in group D. After operation control piglets (group A) ate more from day 4 and were larger from day 7 than the nephrectomized piglets (group B). Those piglets tube fed (group C) were of a similar size to the controls but all died between day 7 and day 11 with associated high blood urea concentrations. Piglets fed the low protein, isocaloric feed (group D) were smaller than both the controls and group B. They also ate less food than the controls and those nephrectomized piglets in group B which were on a voluntary intake of the normal feed.

Animals

Bicarbonate excretion in kwashiorkor.

Children with kwashiorkor have an impairment of bicarbonate excretion which may result in the inappropriate production of acid urine in the presence of systemic alkalosis. This defect has resolved after 2 weeks of treatment.

Bicarbonates

Early discharge of infants of low birth weight: a prospective study.

A total of 495 African infants of low birth weight were discharged from Harari Maternity Hospital, Salisbury, between October 1972 and September 1973. Criteria used for discharge were (a) no clinical evidence of disease, (b) satisfactory feeding by mouth (breast or bottle or both), and (c) stable temperature control under normal room conditions. Of the 495 babies 264 fulfilled these criteria when they weighed 1801-1900 g (group 1), 99 when they weighed 1901-2000 g (group 2), and 132 (group 3) when they weighed 2001-2500 g. The overall follow-up rate of those infants living in greater Salisbury was 85-5%, the health visitor playing an important contributory role in their progress, especially those in group 1. More than two clinic visits in the first four to five weeks after discharge were essential for continuing weight gain in groups 1 and 2 but not in group 3. The mean daily weight gain for all babies at the end of four to five weeks was 26 g. Readmission rates for babies in groups 1,2, and 3 were 9-5%, 1%, and 0-8%, respectively, the largest single cause for readmission being bronchopneumonia associated with hypothermia. Altogether 60% of the readmissions occurred during the two winter months (June and July). Hypothermia, associated with low environmental temperatures played a significant part in morbidity and mortality, and twins, particularly in group 1, had a mortality rate three times greater than singletons in the same group. In general, even in underdeveloped communities singleton babies born outside the winter months with reasonable clinic or home visiting facilities can be discharged at a weight of 1800 g or more.

Birth Weight

The influence of body position on pulmonary function in low birthweight babies.

The influence of the prone and supine body positions on the respiratory rate, arterial pH, pO2, pCO2 and serum bicarbonate level; on alveolar pO2 and pCO2; and on alveolar/arterial gradients for carbon dioxide and oxygen, were compared in 10 low birthweight infants. THE ALveolar pCO2 was higher in the prone, while pO2 was higher in the supine position, possibly as a result of ventilation/perfusion imbalance with increased physiological dead space in the supine position. There were no significant differences between the other parameters studied. Since aspiration of feed by the low birthweight infant is a major cause of morbidity and mortality, evidence is presented in favour of the prone nursing position.

Bicarbonates