Maternal drug therapy for fetal disorders.
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Arrhythmias, Cardiac↗
Biomedical subjects
R M Ward
Publications and source records attributed to R M Ward.
Factors modifying the use of anaesthetic drugs in the elderly.
The elderly are forming an ever greater proportion of our hospital population. The process of ageing produces a gradual erosion of all the body's margins of safety coupled with a decreasing ability to adapt. This has significant effects on the physiological responses to the surgical and pharmacological trespass encountered during anaesthesia. In addition elderly people often suffer from multiple pathology and polypharmacy, both of which play important roles in the selection of the optimal anaesthetic regimen.
Aged↗
Evidence for positional coding in hyperacuity.
Observers performed simple pattern discriminations [tests of orientation (vernier) acuity and spatial-interval acuity] with targets consisting of spatially separated squares. We investigated the effects on acuity of supernumerary squares placed at various mean positions between the two squares constituting the target configuration. The exact position of the supernumerary squares relative to the target squares changed randomly from trial to trial, so that their spatial relationship to the targets could not serve as a cue. Observers attempted to ignore these supernumerary squares and to base their judgments on the outer target squares alone. The supernumerary squares raised thresholds if they were sufficiently close (4.4-arcmin separation) to the target squares but not if they were at a greater distance (21.0 arcmin). The results therefore show that the observers could ignore the supernumerary squares, even when they fell into the space between the target squares. This finding suggests that observers can select a class of length- and orientation-tuned filter that is suited exactly to the requirements of a particular psychophysical task. We argue that filter models of hyperacuity are insufficient unless they address this critical issue of filter selection and that a complete model requires an explicit spatial representation of target feature position.
Humans↗
Serial renal function in an ovine model of unilateral fetal urinary tract obstruction.
Renal tubular and glomerular function following ovine fetal urinary tract obstruction has been studied predominantly in anesthetized, exteriorized fetuses immediately after relief of obstruction. Since surgery and anesthesia may alter fetal cardiovascular and renal physiology, we developed a chronically catheterized, ovine model of unilateral fetal urinary tract obstruction to compare function of the unobstructed and obstructed kidneys repeatedly after relief of obstruction. Split renal function of the previously obstructed kidneys and unobstructed kidneys was measured serially in 7 fetal sheep after obstruction at 55 to 85 days per 147 days of gestation for 30 to 49 days. Seventy-five split clearances were determined on days 1, 2, 3 to 4 and 5 to 6 postoperatively. Not every fetus was studied each day. By 2-way ANOVA, renal function was stable on day 1 after surgery and did not change with time. Previously obstructed kidneys had lower creatinine clearance (0.16 versus 0.71 ml. per minute, p equals 0.0001), higher fractional sodium excretion (33.04 versus 6.02 per cent, p equals 0.0001) and higher urine sodium/creatinine ratio (4.80 versus 0.90 mEq. per mg., p equals 0.0001). Urine flow in the unobstructed kidneys did not differ significantly from that of the obstructed kidneys (0.122 versus 0.083 ml. per minute, p equals 0.35). Obstruction reduced kidney weight (4.7 versus 9.7 gm., p equals 0.0006), cortical thickness (-39 per cent) and nephrogenic zone (-59 per cent), and it increased collecting duct dilatation and medullary fibrosis. No cysts or dysplasia was noted. Fetal urinary tract obstruction for 39.7 days alters renal histology, glomerular function and tubular function. Renal function is stable by 1 day after catheterization and does not change from days 1 to 6 following relief of obstruction.
Animals↗
Maternal-placental-fetal unit: unique problems of pharmacologic study.
Fetal exposure to different drugs has increased, but few prospective, controlled, blinded trials have been conducted of adverse fetal effects following fetal drug exposure. The quantitative exposure of the fetus to drugs varies during pregnancy with changes in the MPFU. Prospective, controlled, blinded studies of adverse fetal effects of drugs are very difficult; investigators therefore have used alternative study designs that make the conclusions more tentative. Such studies may be limited by accuracy of recall of drug intake and its timing, oversimplification of complex drug exposure, separating the effects of drugs from that of the underlying disease, and a lack of correlation between human and animal effects of fetal drug exposure. Intentional drug treatment of the fetus has begun but should proceed from thorough laboratory study to clinical applications, not the reverse.
Epidemiologic Methods↗
Spatial properties of mechanisms for detection of moving dot targets in dynamic visual noise.
The maximum displacement threshold for direction discrimination (dmax) was determined for single or paired dot targets moving discretely against a background of dynamic visual noise. dmax rose as the spatial density of noise was reduced, or when the interframe interval was decreased. dmax was greater for dot pairs than for single dots, and rose progressively as the distance between the dots was reduced. dmax was also greater if the orientation of the target dot pairs differed from the orientation of paired dots in the background noise. Dichoptic presentation of the target and background noise allowed the target to be detected with an accuracy that did not depend on displacement.
Female↗
Continuous arteriovenous hemofiltration in experimental iron intoxication.
This study evaluated continuous arteriovenous hemofiltration (CAVH) as a method for removing the iron-deferoxamine complex in experimental iron intoxication. Five anesthetized dogs were instrumented for hemodynamic monitoring and then given 600 mg/kg of elemental iron as ferrous sulfate. After a 3-h absorption period, CAVH was begun from the femoral artery to femoral vein. Deferoxamine was infused into the arterial lines of the CAVH cartridge at increasing doses. We found a dose-dependent increase in the ultrafiltrate excretion of iron. However, most of the deferoxamine was excreted unbound. The efficiency of complex formation was greater at lower BP and ultrafiltrate formation rate, suggesting that inadequate mixing of deferoxamine with blood may occur when arterial administration is used. Iron excretion in the urine over the same time period was not significantly greater than that removed by CAVH. We conclude that CAVH can remove iron using deferoxamine as a chelating agent.
Animals↗
Management of posthemorrhagic hydrocephalus in the low-birth-weight preterm neonate.
Over a period of 34 months from 1987 to 1990 we inserted ventricular catheter reservoirs (VCR) into 20 premature low-birth-weight infants who had developed progressive, symptomatic posthemorrhagic hydrocephalus following grade III or IV intraventricular hemorrhages. The mean estimated gestational age was 27.7 +/- 5.3 weeks and mean birth weight was 1,041 +/- 699 g. The ventricular catheter reservoirs were placed on day of life 30.7 +/- 29.7 and tapped for a total of 3-34 days at varying frequencies and for varying volumes. Of the 20 patients, 4 died on days of life 25, 76, 88, and 187. There were two reservoir infections, both occurring in infants who eventually died. The 16 survivors have been followed from 2 to 24 months (adjusted age). Four (25%) remain shunt-free and 3 have undergone VCR removal. There have been two shunt infections in the 12 shunted patients; ten shunt revisions have been performed overall. At the time of last follow-up, 14 patients were old enough to undergo neurodevelopmental evaluation. Five patients (36%) were 'normal' on gross neurological screening examination, 5 (36%) had 'mild developmental delay' and 4 (28%) had 'significant developmental delay'. We feel these data support the continued use of ventricular catheter reservoirs in the management of posthemorrhagic hydrocephalus and offer hope that some of these patients might remain shunt-free and most will have a normal or mildly delayed neurodevelopmental outcome.
Brain Damage, Chronic↗
Neonatal lupus syndrome: optimism justified?
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Adult↗
Developmental pharmacology and toxicology: principles of study design and problems of methodology.
Pharmacologic investigations in the fetus, neonate and child are difficult for the various reasons outlined above, ranging from ethical constraints to difficulties with microanalytic techniques. Attempts to circumvent these difficulties through animal studies, retrospective analyses, and prospective surveys have provided only partial answers. These studies have often helped to guide subsequent similar studies in humans. Results of developmental pharmacologic studies applied to the human must be conducted in humans. The alternatives to randomized, controlled trials presented above may help with these studies, but these innovative study designs must be applied carefully to avoid biasing the results. Although difficult, definitive studies in developmental pharmacology are possible with investigators willing to work within the ethical constraints outlined above, to sensitively consider the needs of perinatal and pediatric patients, and to adhere to the strictest standards of study design.
Animals↗
The detection of deviation from straightness in lines.
A wide range of differently shaped perturbations were introduced into long thin straight lines, and threshold amplitude for their detection was measured. This amplitude threshold varies over a 20-fold range, depending on the shape of the cue, but can be economically expressed as just one numerical value, irrespective of the cue shape. This quantity is the area of the largest bump in the target around a least squares regression line axis, and its value is 0.3 arc min2. This value can be related to a fundamental spatial error of 3 arc sec (standard deviation) which is the limiting constraint on shape sensitivity.
Discrimination, Psychological↗
Quantitative determination of tolazoline in human serum by high performance liquid chromatography.
A micro high performance liquid chromatography assay is reported for the measurement of tolazoline in newborn infants. Pharmacokinetic data are presented for a single infant receiving tolazoline therapy. Tolazoline and the internal standard, clonidine, are extracted from alkaline serum into butylchloride/isopropanol (95/5). The organic layer is then back extracted with 50 mM phosphoric acid. A portion of the phosphoric acid layer is injected onto a 15-cm CN-bonded phase column. A mobile phase consisting of acetonitrile and phosphate buffer (pH 3) is used to elute tolazoline and the internal standard in less than 5 min. The effluent is monitored with a fixed wavelength detector at 214 nm. Using 50 microliters of serum, concentrations as low as 0.25 mg/L can be routinely determined with a coefficient of variation (CV) of 7.2%. However, when a 100-microliters sample is used, and the injection volume increased, a concentration of 0.05 mg/L can be routinely monitored with a CV of 1.2%. Interference from other drugs that are often used concurrently with tolazoline therapy was not observed.
Chromatography, High Pressure Liquid↗
Antibodies to P. acnes and P. acnes exocellular enzymes in the normal population at various ages and in patients with acne vulgaris.
Total serum IgM and IgG agglutinins to P. acnes and neutralizing antibodies to P. acnes lipase, hyaluronate lyase and acid phosphatase were measured in normal individuals of different age groups. Agglutinins to P. acnes were detected in infants at 4 months of age and were present at a high level throughout life. A switch from predominantly IgM agglutinins in children, to IgG agglutinins in adults, occurred during adolescence. Anti-P. acnes lipase antibodies were present in 20% of teenagers and 17-42% of adults. Anti-P. acnes hyaluronate lyase antibodies were found in adults only (4-17%). Antibodies to acid phosphatase were not detected. Agglutinins to P. acnes were measured in individuals with mild, moderate and severe acne, and in normal controls. Only patients with severe acne had significantly higher titres than the controls. IgM and IgG agglutinins were determined in 13-14-year-olds with mild, moderate and severe acne, and in normal controls. Thirty-three per cent, 60% and 100% of the acne patients, respectively, but none of the normal controls, had predominantly IgG agglutinins. No difference in the prevalence or titre of antibodies to P. acnes exocellular enzymes was observed when patients with severe acne were compared with normal controls. There was no evidence to suggest a role for antibodies to P. acnes exocellular enzymes in the initiation of inflammatory acne.
Acne Vulgaris↗
Comment: ambulatory kinetic monitoring.
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Ambulatory Care↗
Cystosarcoma phyllodes. A clinicopathologic study of 26 cases.
Twenty-six cases of cystosarcoma phyllodes diagnosed at M. D. Anderson Hospital were reviewed. The following criteria were evaluated for possible correlation with local recurrence, uncontrolled local recurrence, metastasis, and tumor death: tumor size, stromal overgrowth, tumor necrosis, mitotic rate, stromal cellularity, nuclear size and pleomorphism, the presence of specialized stroma, and initial therapy. Of the 26 tumors, seven caused death. Five patients developed metastatic spread, and all of them died of tumor. Five patients had local recurrence, which was uncontrolled in three (two patients died with uncontrolled recurrence alone, and one with uncontrolled recurrence and metastasis). Stromal overgrowth was present in eight cases. Six of the seven patients who died of tumor had stromal overgrowth, including all five with metastasis. Correlation of stromal overgrowth with metastatic spread and tumor death was significant at P levels of 0.0014 and 0.02, respectively. It is concluded that stromal overgrowth is a significant histologic indicator of malignant behavior in cystosarcoma phyllodes.
Adult↗
Renal function in the fetal lamb: a chronic model to study physiological effects of ureteral ligation and deligation.
Between 53 and 98 days of gestation 11 fetal lambs were subjected to unilateral ureteral ligation. In 8 fetuses re-exploration was performed 35 to 41 days after ligation. Chronic catheterization of the obstructed kidney, bladder and fetal vascular system was used for analysis of physiological data. Average creatinine clearance was 1.35 +/- 0.067 ml. per minute in the control kidney and 0.226 +/- 0.057 ml. per minute in the obstructed kidney after diversion. Free water clearance, osmolar clearance and fractional sodium excretions were not statistically significantly different in control and obstructed kidneys.
Animals↗
Adaptation of fetal pulmonary blood flow to local infusion of tolazoline.
Although tolazoline is the most commonly used drug in the treatment of neonatal pulmonary hypertension, its mode of action and efficacy remain incompletely understood. In order to study the effects of tolazoline on a high resistance pulmonary circulation and to better understand mechanisms that control pulmonary vascular tone and reactivity in the fetus, we infused tolazoline either continuously or as bolus into the left pulmonary artery of 15 chronically instrumented, normoxic fetal lambs during late gestation. The vasodilatory effects of bolus injections of tolazoline (2.5 mg) were inhibited by the prior administration of the histaminergic receptor blockers, cimetidine (56%), diphenhydramine (56%), or both (100%). During the continuous infusion of tolazoline (4.5 mg/h for 9 min), pulmonary blood flow to the left lung increased from 61 +/- 6 ml/min (mean +/- SE; control) to 100 +/- 10 (peak) at 30 min (p less than 0.001). However, following this initial vasodilatation, pulmonary blood flow steadily decreased toward control values by 90 min, despite the continued infusion of tolazoline (p less than 0.001). Although the calcium channel blocker, verapamil, and the alpha-adrenergic blocker, phentolamine, had little effect on fetal pulmonary blood flow when infused alone, both drugs increased the vasodilatory response to tolazoline (p less than 0.001). We conclude that tolazoline effects pulmonary vasodilatation by a histaminergic mechanism and that subsequent refractoriness to the drug is a calcium-dependent process which may be partially mediated by an alpha-adrenergic mechanism.
Animals↗
Prognosis in early carcinoma of the bladder based on chromosomal analysis.
In 53 cases of non-invasive or submucosal invasive well differentiated carcinoma of the bladder observed for 4 to 101 months cytogenetic analysis by the direct technique (non-culture) has been performed repeatedly. Markers, abnormal chromosomes, have been found in 33 patients and recurrence has developed in 32 of these 33 patients, resulting in 9 deaths. All but 1 of the 20 patients without markers have been observed for up to 8 years and have remained free of recurrence. In this 1 recurrence, 8 months post-diagnosis, the mode changed from 69 to 92, evidence of dedifferentiation and development of a new tumor in a bladder prone to neoplasia. Based on our over-all cytogenetic experience with 165 patients with carcinoma of the bladder a simplified classification is presented. This classification, built on measurable characteristics of early carcinoma, including the presence or absence of marker chromosomes, allows accurate prognostication and, thus, provides the foundation for development of standard therapy.
Adult↗