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Biomedical subjects

C E Miller

Publications and source records attributed to C E Miller.

At least 55 records · Page 3Linked to original sources

A murine antibody to Shigella dysenteriae type 1 employs V-genes that contain a rearranged codon for the lambda light chain.

The cDNA coding for a hybridoma anti Shigella dysenteriae type 1 antibody (3707 E9) has been cloned, and sequenced. Binding patterns with fragments of the bacterial polysaccharide antigen had already been studied in detail. The VH sequence utilizes the VH441 gene, first identified amongst beta-(1,6)galactan-binding antibodies, while the VL is closely related to the V lambda 1 gene. We found that the VL3707 E9 gene employed a VL-J combinatorial joining leading to a rare Trp-->Leu substitution at position L96.

Amino Acid Sequence↗

Low-dose glucocorticoids after in vitro fertilization and embryo transfer have no significant effect on pregnancy rate.

OBJECTIVE: To determine the effect on pregnancy rate (PR) of low-dose glucocorticoid treatment in cycles without micromanipulation. DESIGN: Randomized, prospective, double-blinded, placebo-controlled trial. SETTING: One university-based tertiary infertility center and two private infertility centers. PATIENTS: All patients receiving standard stimulation IVF-ET or transfer of cryopreserved embryos at the participating facilities from January to September 1993 were asked to participate in this study. Patients having micromanipulation were excluded from this study. INTERVENTIONS: Participating patients were randomized to either 16 mg oral 6-alpha-methylprednisolone for four evenings starting the evening of retrieval or the evening before thawing cryopreserved embryos or to placebo administered in an identical fashion. Both groups were treated with 250 mg oral tetracycline four times per day starting with initiation of the study medication and continuing for 4 days. Cryopreservation and stimulation cycles were managed according to pre-established protocols for all patients. A clinical pregnancy was confirmed by an appropriately rising hCG titer and a gestational sac on ultrasound. RESULTS: A total of 206 stimulation patients and 61 cryopreservation patients were randomized and had an ET. Patient characteristics were similar between groups. The clinical pregnancy and implantation rates between placebo and glucocorticoid groups were 35.9% versus 40.8% and 12.8% versus 11.7% for stimulation cycles and 30.3% versus 25% and 9.9% versus 7.4% for cryopreservation cycles, respectively. None of these differences were statistically significant. CONCLUSIONS: Glucocorticoid plus antibiotic treatment at these doses for transfers of nonmicromanipulated embryos does not appear to have a significant effect on pregnancy or implantation rates.

Adult↗

Flow-induced dilation in newborn intestine.

The goal of these experiments was to determine the presence and mechanistic basis of flow-induced dilation in mesenteric artery from 3-d-old swine. In the first experiment, in vitro gut loops were perfused from a blood-filled reservoir under controlled-flow conditions, and flow was progressively increased from approximately 40% to approximately 170% in six increments by manipulation of pump speed. Under control conditions, vascular resistance significantly decreased after each step increase in flow rate. NG-Monomethyl-L-arginine (LNMMA; 10(-4) M), an arginine analog that blocks nitric oxide production, eliminated this flow-induced dilation, but only for the step increases in flow at rates above the baseline flow rate. For step increases below the baseline rate, LNMMA caused a simple parallel shift of the resistance-flow rate curve upward. Phenylephrine (10(-6) M), an alpha 1-agonist which has no effect on nitric oxide production or half-life, did not eliminate flow-induced dilation, but instead caused a simple parallel shift of the resistance-flow rate curve upward across the entire range of flows studied. In the second experiment, a 3-cm segment of mesenteric artery was perfused with Krebs buffer at two flow rates: 10 and 25 mL/min. The effluent from the mesenteric artery segment was suffused onto a deendothelialized, phenylephrine-precontracted ring of swine carotid artery; relaxation of this bioassay vessel served as an index of release of relaxing factors from the mesenteric artery segment. Under control conditions, increase in the mesenteric artery flow rate caused a 60% relaxation of the bioassay vessel. This effect was eliminated by the addition of LNMMA to the buffer (10(-4) M), but not by the addition of indomethacin (10(-5) M). Flow-induced dilation occurs in the mesenteric artery of 3-d-old swine. This vascular phenomenon appears to be mediated by nitric oxide, but only at flows above the baseline flow rate. The mechanism(s) responsible for this phenomenon at lower flow rates is not clear.

Animals↗

Reform and primary care.

The success of Canada's health care reform depends on nurses' participation. No one can dispute that nurses are the largest single group of health care providers. Nurses are also experienced players in primary health care-health care's new direction.

Canada↗

Characterization of organophosphorus hydrolases and the genetic manipulation of the phosphotriesterase from Pseudomonas diminuta.

There are a variety of enzymes which are specifically capable of hydrolyzing organophosphorus esters with different phosphoryl bonds from the typical phosphotriester bonds of common insecticidal neurotoxins (e.g. paraoxon or coumaphos) to the phosphonate-fluoride bonds of chemical warfare agents (e.g. soman or sarin). These enzymes comprise a diverse set of enzymes whose basic architecture and substrate specificities vary dramatically, yet they appear to be ubiquitous throughout nature. The most thoroughly studied of these enzymes is the organophosphate hydrolase (opd gene product) of Pseudomonas diminuta and Flavobacterium sp. ATCC 27551, and the heterologous expression, post-translational modification, and genetic engineering studies undertaken with this enzyme are described.

Animals↗

Elevated maternal serum AFP and normal ultrasound: what next?

Given the discovery of intracranial changes observed in fetuses with open spina bifida, the wisdom of routinely performing amniocentesis on persons with unexplained maternal serum alpha-fetoprotein elevations is now being questioned. The detection rate for spina bifida with a targeted ultrasound examination is greater than 95%. Yet one must also consider the sensitivity of ultrasound in detecting other anomalies, such as ventral wall defects and fetal karyotype anomalies. Although the sensitivity of ultrasound for neural tube defects has improved dramatically in recent years, it cannot detect all chromosome or structural anomalies that may be detected by amniocentesis. Therefore, patients should be made aware of their specific risks following a targeted ultrasound and offered the option of amniocentesis.

Amniocentesis↗

Regulation of capillary exchange capacity in postnatal swine intestine.

To determine whether intrinsic regulation of capillary exchange capacity is age-dependent during early postnatal life, we measured the capillary filtration coefficient (Kf,c), an index of capillary exchange capacity, within isolated perfused intestine from 3- and 35-day-old swine at different arterial pressures. Kf,c was determined gravimetrically, by means of the flow-equilibration technique. During baseline perfusion at age-appropriate pressures, Kf,c averaged 0.203 +/- 0.020 vs. 0.361 +/- 0.040 ml.min-1 x mmHg-1 x 100 g in 35- vs. 3-day-old intestine. In older animals, a progressive rise in Kf,c was noted as arterial pressure was lowered: Kf,c increased 14, 35, and 98% above baseline when pressure was reduced 20, 40, and 60% below baseline, respectively. An inverse linear correlation between Kf,c and blood flow was demonstrated in this group. Kf,c also increased in 3-day-old intestine during progressive hypotension, but these changes were of less magnitude: Kf,c averaged 19, 17, and 23% above baseline when pressure was reduced 20, 40, and 60% below baseline, respectively. In contrast to the circumstance noted in older animals, the relationship between Kf,c and blood flow was not significant within 3-day-old intestine. Intraarterial infusion of 1 microgram/min of isoproterenol, an agent known to increase capillary exchange capacity, caused Kf,c to increase 80% within 3-day-old intestine group. We conclude that Kf,c increases to a greater extent in 35- than 3-day-old swine intestine in response to arterial pressure reduction. However, intestine from younger animals is capable of increasing capillary exchange capacity in response to stimuli other than arterial hypotension, as evidenced by its response to isoproterenol.

Aging↗

Effects of ischemia and reperfusion on intrinsic vascular regulation in the postnatal intestinal circulation.

The purpose of these experiments was to determine the effect of 1 h of total ischemia followed by 2 h of reperfusion on intrinsic vascular regulation within intestine from 3- and 35-d-old swine. Intrinsic vascular regulation was defined as the ability of in vitro segments of small intestine to bring about adjustments of blood flow and the arteriovenous O2 content difference across the intestinal segment of sufficient magnitude to preserve tissue O2 uptake in response to a 35% reduction in arterial perfusion pressure. This response was elicited before (control conditions) and after ischemia-reperfusion (post-I/R). In older subjects, the efficacy of blood flow regulation was attenuated post-I/R, insofar as blood flow fell in response to pressure reduction. However, this group demonstrated a rise in arteriovenous content difference after pressure reduction under control and post-I/R conditions that were of sufficient magnitude to preserve tissue O2 uptake. In younger subjects, blood flow regulation was absent under control conditions and post-I/R. The arteriovenous O2 content difference increased in response to pressure reduction under control conditions but failed to do so post-I/R; consequently, tissue oxygenation decreased in response to arterial pressure reduction post-I/R in 3-d-old intestine. We conclude that ischemia-reperfusion affects intrinsic vascular regulation in postnatal intestine and that this effect is age-dependent. Intestine from older subjects maintains the intrinsic capacity to preserve tissue oxygenation in response to a hypotensive challenge despite the insult of ischemia-reperfusion, whereas intestine from younger subjects does not maintain this capacity.

Animals↗

Effect of increased tissue oxygen uptake on autoregulation in postnatal intestine.

To determine whether the rate of tissue oxygen utilization affects pressure-flow autoregulation in an age-dependent fashion in postnatal swine intestine, in vitro gut loops from 3- and 35-day-old swine were subjected to a 35% step reduction in arterial pressure under control conditions, during intra-arterial infusion of 2,4-dinitrophenol (DNP), and 30 min after luminal instillation of predigested artificial swine milk. Autoregulation was quantitated by determining the effect of pressure reduction on vascular resistance, and also by calculating Gf, a flow-controlling gain factor that relates pressure and flow. DNP infusion increased oxygen uptake 77 and 58% in gut from 3- and 35-day-old swine, respectively, whereas feeding increased oxygen uptake approximately 50% in both groups. Under control conditions, arterial pressure reduction had no effect on vascular resistance in either group. During DNP infusion and 30 min after feeding, however, intestine from 35- but not from 3-day-old swine demonstrated significant vasodilation in response to pressure reduction. Gf averaged -0.06 +/- 0.11 vs. 0.21 +/- 0.08 (P < 0.05) before vs. DNP infusion, and 0.06 +/- 0.03 vs. 0.22 +/- 0.06 (P < 0.05) before vs. 30 min after feeding in intestine from 35-day-old swine; these increases in Gf indicate that the intensity of the pressure-flow response increased during experimental treatments. In contrast, Gf averaged -0.11 +/- 0.07 vs. -0.23 +/- 0.08 before vs. DNP infusion, and -0.23 +/- 0.06 vs. -0.23 +/- 0.09 before vs. 30 min after feeding in intestine from 3-day-old swine.(ABSTRACT TRUNCATED AT 250 WORDS)

2,4-Dinitrophenol↗

Drug therapy of ventricular tachycardia: a cost comparison of randomized noninvasive and invasive approaches.

OBJECTIVE: Economic evaluation of noninvasive (suppression of ventricular arrhythmias detected by ambulatory monitoring) and invasive (suppression of arrhythmias induced by programmed stimulation) approaches to antiarrhythmic drug selection for ventricular tachyarrhythmias. DESIGN/SETTING: Randomized clinical trial/tertiary-care hospital. PATIENTS: Of 124 consecutive patients referred for treatment of symptomatic ventricular tachyarrhythmias, 57 consenting patients were eligible to have drug therapy selected by either noninvasive or invasive approaches. MEASUREMENTS: Costs of initial and follow-up (26 +/- 15 months) admissions for the two groups were compared. This economic evaluation also considered relative efficacies of the approaches using the primary outcome variable of symptomatic, sustained ventricular tachyarrhythmia recurrence (including sudden death). RESULTS: Initial hospitalization for therapy selection was less costly by the noninvasive approach ($6,869 +/- 4,019) than by the invasive approach ($13,164 +/- 6,740) (P less than 0.001). However, the noninvasive approach generated higher follow-up hospital costs ($9,204 +/- 9,217) than the invasive approach ($3,784 +/- 4,944) (P = 0.01). Thus, total hospital costs of the noninvasive ($16,073 +/- 9,423) and invasive approaches ($16,949 +/- 7,174) were equivalent. The two-year actuarial probability of a recurrent, sustained, symptomatic ventricular tachyarrhythmia was greater in noninvasive (0.50 +/- 0.10) than in invasive (0.20 +/- 0.08) approach patients (P = 0.02). CONCLUSIONS: The lower initial hospital costs of the noninvasive approach are offset by greater follow-up costs. Within two years the costs of the two approaches are equivalent. Thus, greater antiarrhythmic efficacy can be achieved by the invasive approach to drug selection without increasing total hospital costs.

Anti-Arrhythmia Agents↗

Periodontal status of individuals in early stages of human immunodeficiency virus infection.

The purpose of this study was to evaluate the association of periodontal health and human immunodeficiency virus infection among individuals in the early stages of disease who were participating in randomized placebo-controlled clinical trials of zidovudine. Previous reports have described a rapidly progressive periodontitis and atypical gigivitis associated with late stages of infection by the human immunodeficiency virus. A health history was completed by each subject. Baseline oral examinations were completed on 97 asymptomatic patients and nine with AIDS-related complex (ARC) during their regular clinic visit. Follow-up examinations were conducted at 3-month intervals throughout the 48 weeks of the oral study. Evaluations of plaque, calculus, gingival abnormalities, caries, and periodontal disease were conducted. Periodontal measurements included plaque index (PI), gingival index (GI), bleeding index (BI), probing depth (PD), and observation for cratering, necrosis, and tooth mobility on six teeth in each patient. More than half of the subjects had visited their dentist during the previous year and had had an oral prophylaxis; less than 25% of them had had either restorative work or extractions. The mean scores for periodontal indices averaged over the course of the study in asymptomatic and ARC respectively were: PI: 0.9 (SE 0.04) and 0.9 (SE 0.08), 0.818; GI: 1.0 (SE 0.04) and 0.9 (SE 0.07), P = 0.412; BI: 0.6 (SE 0.04) and 0.4 (SE 0.07), P = 0.278; PD: 2.9 (SE 0.05) and 2.6 (SE 0.10), P = 0.140. There was no evidence of cratering, necrosis, or tooth mobility in either group. Few had calculus or dental caries. There were no clinically significant differences detected between ARC versus asymptomatic patients. Dental histories and oral examinations showed that two groups of patients in early stages of HIV-disease were in good periodontal health.

AIDS-Related Complex↗

Tributyltin-resistant bacteria from estuarine and freshwater sediments.

Resistance to tributyltin (TBT) was examined in populations from TBT-polluted sediments and nonpolluted sediments from an estuary and from fresh water as well as in pure cultures isolated from those sediments. The 50% effective concentrations (EC50s) for populations were higher at a TBT-polluted freshwater site than at a site without TBT, suggesting that TBT selected for a TBT-resistant population. In contrast, EC50s were significantly lower for populations from a TBT-contaminated estuarine site than for those from a site without TBT, suggesting that other factors in addition to TBT determine whether populations become resistant. EC50s for populations from TBT-contaminated freshwater sediments were nearly 30 times higher than those for populations from TBT-contaminated estuarine sediments. We defined a TBT-resistant bacterium as one which grows on trypticase soy agar containing 8.4 microM TBT, a concentration which prevented the growth of 90% of the culturable bacteria from these sediments. The toxicity of TBT in laboratory media was influenced markedly by the composition of the medium and whether it was liquid or solid. Ten TBT-resistant isolates from estuarine sediments and 19 from freshwater sediments were identified to the genus level. Two isolates, each a Bacillus sp., may be the first gram-positive bacteria isolated from fresh water in the presence of a high concentration of TBT. There was a high incidence of resistance to heavy metals: metal resistance indices were 0.76 for estuarine isolates and 0.68 for freshwater isolates.(ABSTRACT TRUNCATED AT 250 WORDS)

Copper↗

Effect of sustained mesenteric nerve stimulation on intestinal oxygenation in developing swine.

The effects of sustained mesenteric nerve stimulation on intestinal oxygenation were determined in 3- and 35-day-old swine. Studies were conducted in pentobarbital-anesthetized animals during free-flow or constant-flow perfusion. Square-wave stimuli sufficient to induce maximal resistance vessel constriction were applied to postganglionic periarterial mesenteric nerves and each stimulation was sustained until measured variables reached steady state. When vascular resistance data were analyzed without data transformation, autoregulatory escape of intestinal vascular resistance was more complete in 3- than in 35-day-old animals when the escape process was complete; however, expression of these data as escape indexes revealed a similar degree of escape in both age groups. In 35-day-old animals, (a-v)O2 increased during sustained nerve stimulation under free-flow conditions; under constant-flow conditions, (a-v)O2, 86Rb extraction, and capillary permeability-surface area product were lower at completion of the escape process compared with baseline. In 3-day-old swine, these variables remained unchanged from baseline. Intestinal O2 uptake was compromised by sustained nerve stimulation, and this effect was similar in both age groups. We conclude that sustained nerve stimulation reduces intestinal oxygenation to a similar degree in 3- and 35-day-old swine. It is important to note, however, that the response of 3-day-old swine may be dissimilar from that which occurs during immediate postnatal life; indeed, the intestinal hemodynamic response of swine less than or equal to 1 day old should not be extrapolated from the response of 3-day-old animals.

Aging↗

Effects of hypoxia and ischemia on autoregulation in postnatal intestine.

Pressure-flow autoregulation was quantified within in vitro intestine from 3- and 35-day-old swine before and after lowering arterial PO2 (hypoxia) or lowering baseline blood flow by means of norepinephrine infusion (ischemia). Autoregulation was elicited by reducing arterial pressure approximately 33% from an age-appropriate baseline pressure. In 3-day-old intestine, autoregulation was unaffected by hypoxia or ischemia: vascular resistance was unchanged after pressure reduction, while Gf averaged -0.33 +/- 0.15 vs. -0.26 +/- 0.05 under control vs. hypoxic conditions, and -0.48 +/- 0.15 vs. -0.46 +/- 0.11 under control vs. ischemic conditions, respectively. In 35-day-old intestine, autoregulation was enhanced by hypoxia and ischemia. Under both experimental conditions, vasodilation was noted in response to pressure reduction: Gf averaged -0.04 +/- 0.14 vs. 0.38 +/- 0.08 under control vs. hypoxic conditions, and -0.12 +/- 0.10 vs. 0.28 +/- 0.08 under control vs. ischemic conditions, respectively. Regression analysis revealed a significant inverse linear correlation between Gf and venous PO2 in older, but not younger, subjects. Significant relationships between Gf and blood flow were not demonstrated in either group under any experimental condition. We conclude that autoregulation is enhanced within in vitro intestine from 35-, but not 3-day-old, swine during hypoxia or ischemia, and that reduction of venous PO2 is the principal factor responsible for the effect noted in older subjects.

Analysis of Variance↗

Effect of O2 availability on intrinsic vascular response to venous pressure elevation in postnatal swine intestine.

The goal of these experiments was to determine whether the intrinsic vascular response of postnatal intestine to acute venous pressure elevation was dependent on the preexisting level of oxygen availability. To this end, acute venous hypertension was applied to denervated loops of small intestine from 3- and 35-day-old swine anesthetized with pentobarbital during free-flow and controlled-flow perfusion. During controlled-flow perfusion, the base-line blood flow rate was set slightly above (+5%; high flow) or significantly below (-50%; low flow) the rate noted during free-flow perfusion so as to directly alter intestinal oxygen availability. The vascular response to venous hypertension noted under controlled high-flow perfusion was similar in both age groups and generally consistent with that noted under free-flow perfusion. In contrast, the response noted during low-flow perfusion was clearly age dependent. In the older group, vascular resistance decreased (27%), while arteriovenous oxygen content difference [(a-v)O2] and tissue oxygen uptake remained unchanged. In the younger group, vascular resistance remained unchanged, whereas (a-v)O2 and oxygen uptake decreased (14%). We conclude that the intrinsic vascular response to venous pressure elevation is dependent on the preexisting level of oxygen availability in intestine from 35- but not from 3-day-old swine. We speculate that the local metabolic vascular response to venous hypertension is more effective in intestine from older than from younger swine.

Aging↗