How much zidovudine is safe for children with advanced HIV?
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Biomedical subjects
Publications and source records attributed to R McKinney.
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Zidovudine pharmacokinetics were determined in 16 children with human immunodeficiency virus infection who were being treated intravenously and orally on an intermittent schedule (every 6 hours). The intravenous doses studied were 80 (n = 3), 120 (n = 4), and 160 (n = 5) mg/m2/dose, infused over 1 hour. Fourteen patients were monitored after an oral dose of zidovudine at 120 (n = 2), 180 (n = 7), or 240 (n = 5) mg/m2/dose. Zidovudine was assayed with a reverse-phase high-pressure liquid chromatography method. Zidovudine disappearance after intravenous administration was rapid and biexponential, with half-lives of 14 and 90 minutes and a total clearance of 641 +/- 161 ml/min/m2. The volume of distribution at steady state was 45 +/- 28 L/m2. These pharmacokinetics parameters are very similar to those reported in adults. When administered orally, zidovudine was rapidly absorbed. The fraction of the oral dose that was bioavailable was 0.68 +/- 0.25, so that a 50% increment in the dose, in the conversion from intravenous to oral administration, resulted in plasma zidovudine concentrations after oral dosing that were nearly identical to those achieved with the 1-hour intravenous infusion. However, a dose of 180 mg/m2 given orally every 6 hours maintained plasma zidovudine concentrations in the target range of 1 mumol/L for less than half of the dosing interval. Other schedules, routes of administration, or oral drug formulations may have to be considered if sustained continuous exposure to micromolar zidovudine concentrations is desired.
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Sensitivity to nonmodified poliovirus infection is an autosomal dominant trait, specific to primates. The gene for poliovirus sensitivity (PVS) is encoded on human chromosome 19. In order to sublocalize the PVS gene, we infected rodent-human hybrid cell lines that divide human chromosome 19 into four regions with poliovirus 1 and/or 3. When infected, these hybrid cell lines showed the typical cytopathic effect of poliovirus infection only if they contained 19q12----q13.2 as the smallest region of overlap. Appropriate negative and positive controls were used. PVS may be of relevance to myotonic dystrophy (DM) and the inherited motor neuron diseases: to DM because it localizes to the same region of chromosome 19 and to the inherited motor neuron diseases because it encodes a cell-surface receptor expressed on motor neurons.
Magnetic forces exerted on surgical clips and the magnetic resonance imaging distortion they create in phantoms and rabbits at magnetic field strengths of 1.5 Tesla were investigated. Results are reported for both ligation and aneurysm clips manufactured from three types of stainless steel as well as titanium, tantalum and niobium metals. Paramagnetism and eddy currents were measured in a customized moving Gouy balance. Direct measurements of other magnetic forces were carried out in a 1.5T MRI system. The titanium and tantalum clips showed the least interaction with the magnetic field, both in terms of forces exerted and the observed image distortion with the larger clips generating the larger interactions. The strongest field distortions and attractive forces occurred with 17-7PH stainless steel clips. These interactions were ferromagnetic in origin and of sufficient strength to present significant risk to patients having this type of clip present during an MRI scan.
In late April 1984, an outbreak of Pontiac fever was investigated in an office building in lower Manhattan (New York City). The outbreak was characterized by a high attack rate (78 per cent overall); the predominant symptoms were myalgias, chills, fatigue, fever, and headache. There was a clustering of cases in an office that was air cooled by a dedicated cooling tower separate from the remainder of the building. A high concentration of live L. Pneumophila cells in the cooling tower was quantified. Airborne spread via settle plates placed along the air intake system and within the office was demonstrated. Legionella pneumophila serogroup 1 antigen was found in the urine of two cases, and identical monoclonal antibody reactivity patterns of isolates from all sources was observed. Difficulty was experienced in eliminating the organism from the tower.
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Adolescents who have grand mal epilepsy and their parents were interviewed, and the adolescents were evaluated neurologically. Better seizure control and less neurologic disability were unexpectedly associated with less open communication between the adolescents and their families and friends, and with a poorer self-image and poorer expectations for the future. These findings were unrelated to IQ or school performance. This outcome is consistent with other studies of invisible defects and stigmatization, and suggests that youngsters who have relatively mild defects involving social disability may be more troubled than those with more apparent defects, for which denial may be operative. An incidental finding in the study was that a question more predictive of overall family, social, and academic function than the neurologic findings was simply whether or not the youngster was attending the appropriate grade in school for his or her age.
We have described methods of labeling antibody preparations with FITC, TMRI, and RBI. The degree of labeling with FITC can be precisely controlled by using well-defined conjugation procedures and FITC of a known degree of purity. Our experience shows that relatively high F/P ratios of the order of 20 to 25 mug/mg are desirable for antibacterial conjugates. Many commercial preparations of rhodamine isothiocyanate are of very poor quality and are unsatisfactory for use in conjugate preparation. Therefore, one should analyze the rhodamine isothiocyanate product before preparing immune conjugates. Our experience indicates that very satisfactory conjugates of immune IgG or pure antibody can be prepared with TMRI of about 60% purity by using a dye-protein ratio of 20 mug/mg. The optimal dye-IgG ratio for labeling with RBI appears to be about two times that for labeling with TMRI because of the lower specific absorbance and fluorescence emission of RBI. Rhodamine conjugates may be preferred to FITC conjugates in certain situations where tissue autofluorescence interferes with the observation of the yellow-green emission of FITC. Furthermore, mixed rhodamine and FITC conjugates of different specificity can be used to great advantage in double-staining techniques that allow simultaneous screening for two antigenically different organisms on a single microscope slide.
Surgical clips in postoperative patients create streak artifact on computed tomographic (CT) studies which often significantly degrade image quality. We have evaluated three types of surgical clips: tantalum, stainless steel, and titanium in a phantom and animal model to assess their relative CT artifact. Tantalum clips showed the greatest artifact, stainless steel intermediate, and titanium the least artifact. Artifact could be reduced with the use of faster scan times. The type of clip used may enter into surgical decision making depending upon the need for high resolution scanning to detect small pathological processes in the area of surgical clips.
Iodoacetate at 10(-3) M and 10(-4) M concentrations was found to strongly inhibit incorporation of both 14C-choline and 3H-inositol into phospholipids of calvaria from newborn rats; it had somewhat less effect on ethanolamine incorporation and almost no effect on serine incorporation. Similar though less dramatic results were observed with cyanide or dinitrophenol at similar concentrations.