Biomedical subjects
Publications and source records attributed to R D Gilbert.
A thirteen-year-old boy presented with acute renal tubular dysfunction after an infection with salmonella enteritidis. The child recovered following treatment with ciprofloxacin for a week.
The effects of high blood pressure on growth are not fully understood and while hypertension may be associated with failure to thrive, hypertension causing failure to thrive in children is poorly documented. We describe four children presenting with failure to thrive due to hypertension consequent to various aetiologies. Control of hypertension with appropriate therapy resulted in improved growth. The exact pathogenesis of failure to thrive in hypertensive children is not known. These cases demonstrate the importance of careful measurement of blood pressure in children with failure to thrive.
Invasive bacterial infection in children infected with the human immunodeficiency virus (HIV) is common. South African data on this problem are limited. Over 1 year we prospectively studied 108 HIV-infected children hospitalized for 136 presumed infective episodes. Blood culture was positive in 24.8% of episodes. Streptococcus pneumoniae predominated (14/30 positive blood cultures); one-third of isolates showed resistance to penicillin. Acute lower respiratory tract infection accounted for 44% of clinical diagnoses, a bacterial cause being established for 23.8% of these. Age and stage of HIV infection did not influence the likelihood of a positive culture. A high proportion of presumed infective episodes requiring hospitalization of young HIV-infected children have a bacterial cause. Blood culture appears to be a useful method of obtaining the microbiological information required to focus antibiotic therapy.
In the present study, we examined the direct cytotoxic effects of cocaine on fetal cardiac myocytes. Cocaine treatment of cultured fetal rat (21 days) myocardial cells (FRMCs) induced a time- and concentration-dependent increase in apoptotic cells in FRMCs. Cocaine induced surface exposure of phosphatidylserine in FRMCs at 12-h treatment and increased apoptotic cells up to 96 h. Corresponding DNA fragmentation induced by cocaine in these cells was demonstrated in situ by terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling assay and by electrophoresis of labeled DNA fragments, showing the characteristic apoptotic ladders. The pD(2) and maximum increase of cocaine-induced apoptosis in FRMCs were 4.3 and 3.2-fold, respectively. Both caspase-9 and caspase-3 inhibitors (Z-LEHD-FMK and Ac-DEVD-CHO, respectively) blocked cocaine-induced apoptosis. In addition, cyclosporin A inhibited cocaine-induced apoptosis in a concentration-dependent manner with an IC(50) value of 0.1 microM. The maximum of 86% inhibition was obtained with 3 microM cyclosporin A. Cocaine induced the release of cytochrome c from the mitochondria and increased its levels in the cytosol by 3.1-fold. In accordance, the level of cytochrome c in the mitochondria fraction decreased by approximately 60%. Cocaine-induced translocation of cytochrome c was inhibited by cyclosporin A. The results indicate that cocaine has a direct cytotoxic effect on fetal cardiomyocytes by inducing apoptosis in the cells. Furthermore, the release of cytochrome c from the mitochondria and its subsequent activation of caspase-9 and caspase-3 play a key role in cocaine-induced apoptosis.
Studies have suggested that when chlorine dioxide is contained in a mouthrinse, it neutralizes volatile sulfur compounds in mouth air. The efficacy of a chlorine dioxide-containing mouthrinse in the reduction of oral malodor was evaluated in a randomized, controlled, double-blind, parallel group study of 31 men and women. Subjects with a maximum odor pleasantness score of < or = -1 (slightly unpleasant/stale) on a 7-point ordinal scale at both screening and baseline were randomized to treatment with the chlorine dioxide-containing rinse (n = 16) or distilled water (negative control) (n = 15). Oral malodor was evaluated at baseline (prerinse) and at 2, 4, 8, 24, 48, 72, and 96 hours postrinse by both a trained, previously calibrated panel of organoleptic judges and a factory-calibrated portable sulfide monitor. The sulfide monitor measured concentrations of volatile sulfur compounds in the subjects' mouth air 3 minutes after completion of the organoleptic assessment at each time point. The correlation between the organoleptic assessments and log-transformed sulfide monitor values was evaluated. With the chlorine dioxide mouthrinse, a statistically significant improvement in odor pleasantness, reduction in odor intensity, and reduction in oral volatile sulfur compound concentrations compared to the water control were evident at 2 hours postrinse and persisted through 8 hours postrinse. The mean (+/- SD) odor pleasantness improved from -1.25 +/- 0.31 at baseline to -0.73 +/- 0.33 at 2 hours postrinse in the chlorine dioxide group compared to -1.40 +/- 0.38 at baseline to -1.31 +/- 0.67 at 2 hours in the control group (P < 0.01). Odor pleasantness reached its maximum change from baseline to 0.63 +/- 0.45 at 8 hours postrinse. The mean (+/- SD) log-transformed sulfide monitor measurement decreased from 5.40 +/- 0.29 at baseline to 5.17 +/- 0.13 at 2 hours postrinse in the chlorine dioxide group, but increased from 5.47 +/- 0.40 at baseline to 5.56 +/- 0.54 at 2 hours in the control group (P < 0.01). As measured by the sulfide monitor, the mean volatile sulfur compound concentration in the chlorine dioxide group reached its minimum level at 8 hours postrinse (change from baseline in the log-transformed Halimeter measurement of -0.35 +/- 0.31). Thus, this study demonstrates that a one-time use of a chlorine dioxide-containing mouthrinse significantly improves mouth odor pleasantness, reduces mouth odor intensity, and reduces volatile sulfur compound concentrations in mouth air for at least 8 hours after use.
PURPOSE: To evaluate the safety and efficacy of the Braun Oral-B OxyJet (MD15) Oral Irrigator when used as an adjunct to manual brushing. MATERIALS AND METHODS: 64 subjects with mild-to-moderate gingivitis entered this randomized, parallel-group, examiner-blind 8-week study. Subjects were assigned to use either the MD15 and a manual brush, or a manual brush alone. Both groups brushed twice daily; the MD15 subjects, in addition to brushing, also used the irrigator in the evening. Subjects were scored at baseline, week 4 and week 8 at up to 168 oral sites for gingival inflammation (modified gingival index), gingival bleeding (angular bleeding index), and plaque (modified plaque index). RESULTS: No adverse events related to study treatment were reported. Use of the MD15 in conjunction with manual brushing resulted in significant (P < 0.05) decreases from baseline in the plaque index at week 8, the gingival index at week 4, and the bleeding index at weeks 4 and 8. The gingival index was also decreased from baseline at week 8, but this was not statistically significant (P = 0.069). The control group also showed significant decreases from baseline for the gingival index at week 8 and the bleeding index at weeks 4 and 8, but plaque scores were not significantly reduced. Although use of the MD15 plus brushing significantly reduced plaque levels from baseline, while brushing alone did not, the difference between the two groups did not achieve statistical significance (P = 0.065). Differences between the groups with respect to the gingival and bleeding indices were also not statistically significant. It is concluded that use of the OxyJet Oral Irrigator in conjunction with manual brushing is safe, reduces plaque and improves gingival health.
In order to determine the effects of chronic, high-altitude hypoxia on the ovine fetal heart, we exposed pregnant ewes to 3,820 m beginning at 30 days gestation. We previously showed that following approximately 110 days of hypoxia the fetal heart showed significant reduction in cardiac output (76% of control) and contractility, and elevated levels of citrate synthase and lactate dehydrogenase. To investigate ultrastructural influences on these observed physiologic changes at altitude, we hypothesized that the volume densities of myofibrils and mitochondria, and glycogen content would be reduced in the ovine fetal heart and that this may contribute to contraction and cardiac output deficits in hypoxia. Mitochondria and myofibril volume density were determined by standard point-counting techniques and glycogen content was determined by biochemical analysis. The glycogen content from the hypoxic right ventricle (4.8 +/- 0.3%) was significantly lower than in control right ventricle (6.8 +/- 0.5%) and both left ventricles (hypoxia, 7.2 +/- 0.5; control, 7.8 +/- 0. 4%). Total mitochondrial volume density was also significantly reduced following hypoxia (15.5 +/- 0.7%) compared to controls (16.9 +/- 0.4%). As is common in the ovine fetal heart, the myofibril volume density of the right ventricle from both groups was significantly higher than the left ventricle (RV, 58.6 +/- 1.6; LV 54.3 +/- 0.9%). However, it was not different between control and high altitude. In support of our hypothesis, we may speculate that deficits in the quantity of myocyte glycogen and mitochondria contribute to the observed reduction in cardiac output and contractility, despite the upregulation of citrate synthase and lactate dehydrogenase. In contrast, myofibril volume density was unchanged.
To determine the effect of chronic hypoxia on myocardial capillarity, we exposed pregnant ewes to an altitude of 3,820 m from day 30 to day 139 of gestation and compared the fetus to low-altitude (approximately 300 m) controls. We hypothesized that capillarity would increase in the hypoxic myocardium to optimize oxygen and metabolite flux to hypoxic tissues. Fetal hearts were fixed by retrograde aortic perfusion and processed for microscopy and stereological evaluation. Fiber cross-sectional area and capillary density were measured and standardized to sarcomere length. Capillary volume density and capillary diameter were measured, capillary-to-fiber ratio and capillary length density were calculated, and the capillary anisotropy coefficient was obtained from a table of known values. Capillary-to-fiber ratio, capillary volume density, and the capillary anisotropy coefficient were not different between hypoxia and control groups. Capillary diameter was significantly larger in the right compared with the left ventricle of hypoxic but not control hearts; fiber cross-sectional area tended to be larger in the right ventricle of both groups, but this was not significant. As a result of larger fiber size, capillary density and capillary length density were significantly smaller in the right ventricle of hypoxic but not control fetal hearts. Contrary to our hypothesis, the ovine fetus does not show morphological adaptation in the myocardium after approximately 109 days of high-altitude hypoxic stress.
In fetal sheep subjected to high altitude hypoxemia for 110 days beginning on day 30 of gestation, cardiac output was decreased 24% compared to normoxic control fetuses. This decrease was due to a 33% reduction in right ventricular output, with only a 14% reduction in left ventricular output. There were no changes in preload or heart rate, but approximately 7% of the reduction in cardiac output could be explained by an increase in arterial blood pressure (afterload). In papillary muscle isolated from long-term hypoxemic fetal hearts, maximum developed tension in response to increasing concentrations of calcium was reduced in both the right and left ventricles, but sensitivity to calcium was increased in both. This finding suggests alterations in the calcium pathway for excitation-contraction coupling in the hypoxemic fetal hearts may be responsible for the reduction in contractility. The mechanism for the decrease in contractility could not be explained by changes in sarcolemmal L-type calcium channel number or sarcoplasmic reticulum calcium release channel number. In addition, there were no changes in the calcium-induced calcium release mechanism involving the sarcoplasmic reticulum, which could explain the reduced contractility. We speculate that the decreased calcium response may be due to other factors, such as the amount of calcium stored in the sarcoplasmic reticulum, myofilament calcium sensitivity, or cellular content of myofilaments.
Explore the source record for details and available documents.
We studied myocardial contractility in fetal sheep from ewes exposed to approximately 112 days of hypoxia at high altitude (3,820 m). We measured the inotropic response to extracellular Ca2+ concentration ([Ca2+]o, 0.2-10 mM) and ryanodine (10(-10) to 10(-4) M) in isometrically contracting papillary muscles and quantified dihydropyridine (DHPR) and ryanodine (RyR) receptors. In hypoxic fetuses, curves describing the force-[Ca2+]o relationship were shifted left, and the top plateaus were decreased by approximately 35% in both left and right ventricles. In normoxic and hypoxic fetuses, ryanodine (10(-4) M) reduced maximum active tension (Tmax) to approximately 25-40% of baseline values, indicating that the sarcoplasmic reticulum was the chief source of activator Ca2+ and that Ca2+ influx alone was not sufficient to activate a contraction of normal amplitude. Hypoxia resulted in a lower Tmax in the right ventricle and a lower maximum rate of rise in the left ventricle after treatment with ryanodine. DHPR number did not change, but RyR number and the RyR/DHPR in both ventricles were higher in hypoxic fetuses. We conclude that hypoxia decreases contractility, possibly by reducing the availability of activator Ca2+. Further studies are needed to directly measure the Ca2+ current and intracellular Ca2+ transient and to examine myofilament protein and adenosinetriphosphatase activity.
In this study, we hypothesized that a reduction in beta-adrenergic receptor number or a decrease in functional coupling of the receptor to the adenylate cyclase system may be responsible for the blunted inotropic response to isoproterenol observed in fetal sheep exposed to high altitude (3,820 m) from 30 to 138-142 days gestation. We measured the contractile response to increasing doses of isoproterenol and forskolin in papillary muscles from both ventricles, estimated beta-adrenergic receptor density (Bmax) and ligand affinity (Kd) using [125I]iodocyanopindolol, and measured adenosine 3',5'-cyclic monophosphate (cAMP) levels before and after maximally stimulating doses of isoproterenol and forskolin. Left ventricular wet weight was unchanged, but right ventricular weight was 20% lower than controls. At the highest concentration of isoproterenol (10 microM), maximum active tension was 32 and 20% lower than controls in hypoxemic left and right ventricles, respectively. The contractile response to forskolin was severely attenuated in both hypoxemic ventricles. Bmax was unchanged in the left ventricle, but increased by 55% in the hypoxemic right ventricle. Kd was not different from controls in either ventricle. Basal cAMP levels were not different from controls, but isoproterenol-stimulated and forskolin-stimulated cAMP levels were 1.4- to 2-fold higher than controls in both hypoxemic ventricles. The results suggest mechanisms downstream from cAMP in the beta-adrenergic receptor pathway are responsible for the attenuated contractile responses to isoproterenol.
Resistance to methyl parathion insecticide has evolved in the tobacco budworm, Heliothis virescens, and several biochemical mechanisms have been identified in various strains. Reduced sensitivity of acetylcholinesterase to inhibition by methyl paraoxon, the active metabolite of the insecticide, is controlled by a single autosomal locus, AceIn. We report that AceIn is genetically linked to methyl parathion resistance, which is expressed as a dominant gene. Methyl parathion-resistant and -susceptible strains were intercrossed and the resulting mixed colony was heterozygous at AceIn. Pair matings from the mixed colony were chosen, on the basis of AceIn genotype only, to establish strains Ace-S and Ace-R, homozygous for AceInSS and AceInRR, respectively. The Ace-R strain was 15.9-fold resistant compared to AceInSS, while hybrid progeny expressed 24.6-fold resistance, demonstrating dominant inheritance of resistance. When progeny of the backcross (Ace-S x Ace-R) to Ace-S were exposed to a discriminating dose of methyl parathion, 24.5% survived as predicted by the model of a single resistance gene. Survivors displayed only the AceInRS genotype, demonstrating a linkage disequilibrium which was highly significant. Assuming that no other resistance genes are linked closely to AceIn, it would appear that AceIn is a powerful gene for resistance, conferring a resistance proportional to the slower rate of inhibition in the resistant enzyme. The contribution of AceIn to resistance relative to detoxicative genes and the possible interaction of resistance genes are discussed.
Abdominal aortic aneurysms are rare in children. Causes include mycotic aneurysms, vasculitides (eg, Takayasu's arteritis), connective tissue diseases (eg, Marfan's syndrome, Ehlers-Danlos syndrome, and tuberous sclerosis) and traumatic false aneurysms. Four cases are described. Case 1 was a 12-year-old boy who presented with an acute unheralded rupture of the subdiaphragmatic aorta accompanied by lower limb paralysis and ischemia. Attempted repair failed because of extensive friability of the large arteries. Histological evaluation confirmed cystic medial necrosis despite Marfanoid phenotype. Cases 2 and 3 were boys aged 12 and 11 with Takayasu's arteritis who presented with hypertensive encephalopathy and heart failure. Although both had involvement of the origins of the renal arteries, one aneurysm was predominantly suprarenal and the other infrarenal. Currently both children are being managed successfully with antihypertensive therapy. Case 4 was a 5-year-old girl who presented with hypertension and a pulsatile abdominal mass after treatment of infective endocarditis 18 months previously. Arteriography and three-dimensional computed tomography confirmed an aneurysm (6 x 5 x 4 cm) arising from the aorta and involving the right renal artery. Aneurysmectomy, removal of a small ischemic right kidney, and Gore-Tex grafting resulted in cure of the hypertension and uneventful recovery. The present series confirms that rupture is a fatal complication, renovascular complications are common, and medical control of hypertension is an essential part of management. Management strategies need to be highly individualized, and may be successful without surgical intervention. Close clinical and ultrasound follow-up of those managed nonoperatively is essential.
To quantify and compare blood flow in maxillary mucogingival flaps, a total of 16 cats (32 mucogingival specimens) were divided into two groups. In group I the blood flow in attached or reflected maxillary tissues were measured. In Group II the effects on blood flow were measured in reflected tissues after the injection of the following solutions: (1) saline solution; (2) 2% lidocaine plain; (3) 2% lidocaine with 1:50,000 epinephrine; (4) no injection. After an injection of 153 Gadolinium microspheres into the left ventricle of the heart, the tissues were harvested and placed in a gamma counter. Group I had a mean blood flow value of 34.4 ml/min/100 gm of tissue for the unreflected samples and 152.3 ml/min/100 gm of reflected tissue. The levels of blood flow in tissue samples in group II results were: no injection (control), 41.2 ml/min/100 gm; saline solution, 46.8 ml/min/110 gm; 2% lidocaine with 1:50,000 epinephrine, 60.6 ml/min/100 gm; and 2% lidocaine plain, 90.2 ml/min/100 gm. On the basis of these results it appears that reflection of gingival tissue and injection of 2% lidocaine plain induces increased blood flow 90 minutes postoperatively.
To elucidate the effects of chronic hypoxia on alpha 1-adrenergic receptor-mediated contractions of the uterine artery, we examined norepinephrine-induced contractions in tissues obtained from near-term (approximately 140 days gestation) pregnant ewes maintained near sea level (approximately 300 m) and at high altitude (3,820 m) from 30 days gestation. Compared with the sea-level controls, contractions induced by norepinephrine in main and fourth-branch uterine arteries of the high-altitude animals were significantly depressed. The norepinephrine dose-response curves were shifted to the right and the concentrations at which 50% of the maximal response was attained were increased 3.2- and 5.7-fold in the main and fourth-branch uterine arteries, respectively. The maximal responses were decreased 22 and 36% in main and fourth-branch uterine arteries, respectively. The dissociation constants of norepinephrine were increased from 0.77 to 1.53 microM and from 0.72 to 2.05 microM in main and fourth-branch uterine arteries, respectively. Radioligand binding studies with [3H]prazosin revealed a decrease in the density of alpha 1-adrenergic receptors in both vessels from high-altitude animals. We conclude that chronic hypoxia depresses alpha 1-adrenergic receptor-induced contractions of conduit- and resistance-type uterine arteries. The depressed contractility is mediated, at least in part, by decreases in alpha 1-adrenergic receptor density and agonist binding affinity.
We exposed fetuses to high-altitude (3,820 m) hypoxemia from 30 to 130 days gestation, when we measured fetal heart rate, right and left ventricular outputs with electromagnetic flow probes, and arterial blood pressure during an isoproterenol dose-response infusion. We also measured the distribution of cardiac output with radiolabeled microspheres during the maximal isoproterenol dose. Baseline fetal arterial blood pressure was higher in long-term hypoxemic fetuses (50.1 +/- 1.3 vs. 43.4 +/- 1.0 mmHg) but fell during the isoproterenol infusion to 41.3 +/- 1.4 and 37.5 +/- 1.4 mmHg, respectively, at the highest dose. Heart rate was the same in both groups and did not differ during isoproterenol infusion. Baseline fetal cardiac output was lower in the hypoxemic group (339 +/- 18 vs. 436 +/- 19 ml.min-1.kg-1) due mainly to a reduction in right ventricular output. During the isoproterenol infusion, right ventricular output increased to the same extent in both hypoxemic and normoxic fetuses (approximately 35%); however, left ventricular output increased only approximately 15% in the hypoxemic group compared with approximately 40% in the normoxic group. The percent change in individual organ blood flows during isoproterenol infusion in the hypoxemic groups was not significantly different from the normoxic group. All of the mechanisms that might be responsible for the differential response of the fetal left and right ventricles to long-term hypoxia are not understood and need further exploration.
We measured pyruvate kinase (PK), citrate synthase (CS), and lactate dehydrogenase (LDH) activities in the right and left ventricles of fetal, maternal, and nonpregnant adult sheep exposed to high altitude (3,820 m) for 112 days and compared them with control groups of animals kept at sea level. Enzymes were assayed by the spectrophotometric appearance of reaction products specific to each enzyme, and activity was expressed as micromoles per minute per gram of wet weight of tissue. In control sheep, CS activity was significantly higher in both ventricles of the pregnant and nonpregnant adult compared with the fetus. However, LDH and PK activities were only higher in the left ventricle of the nonpregnant adult compared with the fetus. Long-term hypoxemia significantly increased LDH activities in fetal (57 and 53%), pregnant adult (29 and 27%), and non-pregnant adult (25 and 24%) right and left ventricles, respectively. CS activities also increased in fetal (90 and 97%), pregnant adult (43 and 39%), and nonpregnant adult (46 and 48%) right and left ventricles, respectively. However, PK activity was not affected by altitude in any group of animals. In the fetal heart, which uses lactate as its primary metabolic fuel, these enzyme changes may help enhance aerobic energy production during hypoxemia. In the adult heart, which relies on free fatty acids as well as glucose for energy production, the significance of these enzyme changes is less clear.