Into Africa: the telemedicine links between Canada, Kenya and Uganda.
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Biomedical subjects
Publications and source records attributed to S MacLeod.
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We report the frequency of parasitic infections 1971-84 in a major New York City Medical Center whose catchment area includes many immigrants from Dominican Republic. Infection with 7,803 parasites was documented in 41,958 laboratory specimens. Trends were toward fewer total specimens being sent and fewer still being positive, although a rise in G. lamblia, E. histolytica, and Cryptosporidium is apparent in recent years. Parasitology laboratories should provide similar data to alert clinicians to the parasites prevalent locally.
Renal tubular secretion of digoxin appears to be one of the main ports of elimination of the glycoside from the body. Because of its narrow therapeutic window and severe toxicity, the mechanisms of tubular handling of digoxin are important. Moreover, several drugs which are commonly administered with digoxin, including quinidine, spironolactone, verapamil and amiodarone have been shown to decrease renal clearance of digoxin without affecting GFR. We studied the handling of digoxin using in vitro and in vivo approaches. The handling of the glycoside by the brush border suggests passive reabsorption which is not enhanced by commonly coadministered drugs. Digoxin binding to the antiluminal (basal) membrane suggests that the secretion of the glycoside may not involve the pharmacologic receptor, the Na+, K+, ATPase. Using the multiple indicator dilution technique, we could directly show the two steps of secretion of digoxin: Its sequestration from the postglomerular circulation, and its appearance in the urine after transtubular transport. Digoxin transport is not inhibited by a cationic or anionic molecule (PAH and tolazoline). It is possible that digoxin is secreted by a yet unidentified transport mechanism.
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Within 15 minutes of terminating general anaesthesia, progressive recovery of consciousness, spontaneous ventilation and cough, and limb movements were assessed in 60 young children (age range 0-5 years, mean +/- SEM; 2.83 +/- 0.34; weight 13.86 +/- 0.41 kg). All patients were ASA physical status class I-III, received a standard intravenous induction (atropine 0.02 mg X kg-1, thiopental sodium 5 mg X kg-1, diazepam 0.2 mg X kg-1), were intubated with an orotracheal tube following the administration of metocurine, 0.4 mg X kg-1, and were maintained under general anaesthesia with nitrous oxide and oxygen in a 70:30 mixture administered by a T-piece circuit. They were ventilated mechanically to maintain normal blood-oxygen tension and normocarbia. The patients were assessed in three equal groups according to the anaesthetic supplement they received. Group I received intravenous infusions of morphine sulfate (loading dose 60 micrograms X kg-1 administered over 5 minutes followed by a continuous intravenous infusion of 2 micrograms X kg-1 X min-1. Patients in Groups II and III had 0.5 per cent halothane and 1.0 per cent isoflurane respectively added to the nitrous oxide/oxygen fresh gas mixture rather than morphine sulphate infusions. By the end of the study period, there was no significant difference in the degree of recovery between the morphine and the isoflurane groups but the patients in the halothane group had recovered to a lesser degree. Generally, the patients in the morphine group were awake but not crying, while those in the other two groups were less sedated.
Digoxin serum concentrations were measured by a routine radioimmunoassay in 30 neonates not receiving digoxin; nonetheless, digoxin levels were between 0.17 nM and 1.64nM (means = 0.64nM +/- 0.27 nM). There was a negative correlation between gestational age and concentration of an endogenous digoxin-like substance (EDLS). Neonates less than or equal to 32 wk gestational age had higher levels of EDLS than neonates greater than 32 wk old. EDLS concentrations were compared in 22 mothers and their 24 offspring and were higher in all newborn infants (0.34nM +/- 0.09nM and 0.15nM +/- 0.08nM). EDLS was shown to inhibit Na+-K+-adenosinetriphosphatase activity by measurement of 86Rb uptake in erythrocytes exposed to sera samples from 30 infants in the study. EDLS levels greater than 0.6 ng/ml were associated with lesser 86Rb uptake. Simulation kinetics suggest that the presence of 0.6nM EDLS would lengthen the digoxin t1/2 by 64%, reduce the volume of distribution by 23%, and lower clearance by 53% if the peak "true" digoxin level were 2 ng/ml. EDLS concentrations of 1.5 ng/ml would increase the t1/2 by 207% while reducing the volume of distribution by 43% and clearance by 81%. These considerations cast serious doubts on the validity of currently accepted digoxin kinetics and dosing in preterm infants.
The nephrotoxicity of gentamicin and amikacin was compared during presumed sepsis in 107 premature neonates. To examine the possibility that nephrotoxicity was directly associated with the clinical conditions of "sepsis," a control group of 26 chloramphenicol-treated newborns was also studied. Two markers of proximal renal tubular injury, N-acetyl-beta-glucosaminidase (NAG) and beta 2-microglobulin, were measured in 6-hr aliquots of urine. Because urine creatinine excretion increased with postconception age, markers were expressed in terms of excretion rate rather than per milligram of creatinine. The NAG excretion rate was significantly higher in gentamicin-treated patients (138 +/- 10 U/min, mean +/- SE) than in amikacin-treated patients (85 +/- 7 U/min) but did not differ between patients treated with amikacin and those treated with chloramphenicol (81 +/- 11 U/min). Excretion of beta 2-microglobulin did not differ among the three patient groups. We conclude that amikacin may be less nephrotoxic than gentamicin in the premature newborn.
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We studied pharmacokinetics of chloramphenicol in 9 neonates having a mean gestational age of 31.2 +/- 1.9 weeks (mean +/- SEM). The studied dose was the final dose of treatment in 8 of these and the first dose in 2 of these. 1 neonate was studied twice. Concentrations of chloramphenicol and its 3-monosuccinate and 1-monosuccinate esters were measured in serum by high performance liquid chromatography. Apparent total body clearance of chloramphenicol correlated with postnatal age (r = 0.81, p less than 0.01). Mean apparent clearance was 1.1 ml X min-1 X kg-1. Serum concentrations of succinate esters were below assay sensitivity after 6 h postdose. Factors leading to excessive chloramphenicol concentrations (greater than 25.0 mg/l) were evaluated in another 44 newborns. Instability of the patient's clinical condition was an important cause of excessive serum concentrations during ongoing therapy.
The disposition of intravenously and orally administered theophylline was compared in 10 patients with cystic fibrosis (CF) and 10 healthy volunteers. The mean total body clearance of the patients with CF was twice that of the control subjects (p less than 0.001). The volume of distribution of theophylline was also greater in the patients with CF (p less than 0.05). These observations indicate that if theophylline is used in patients with CF, doses larger than those commonly given to asthmatics may be required to maintain therapeutic serum concentrations.
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To evaluate the ability of a loading dose of chloramphenicol succinate to rapidly, achieve adequate serum concentrations of chloramphenicol, we compared two intravenously administered dosages of chloramphenicol succinate given to initiate treatment. Thirteen premature neonates received an initial dose of 12.5 mg/kg; 26 received a loading dose of 20 mg/kg. Capillary blood samples were obtained at two, four, and 12 hours after the first dose. After the dose of 12.5 mg/kg, 45% of the neonates did not achieve serum concentrations greater than 10 mg/L. After the loading dose of 20 mg/kg, all neonates achieved concentrations greater than 10 mg/L. The peak chloramphenicol concentrations after the 12.5 mg/kg dose was 8.8 +/- 11.2 mg/L (+/- SEM) and after the 20 mg/kg loading dose, 15.9 +/- 0.7 mg/L. The disposition of chloramphenicol was age dependent. Chloramphenicol concentration peaked at four hours in neonates less than or equal to 2 days postnatal age and at two hours in neonates 3 to 55 days postnatal age. Chloramphenicol succinate concentrations were greater in younger than in older neonates at both two and four hours after the dose. We conclude that a loading dose is appropriate when using chloramphenicol succinate in neonates.
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