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Biomedical subjects

M D White

Publications and source records attributed to M D White.

At least 19 recordsLinked to original sources

Reproducibility of relationships between human ventilation, its components and oesophageal temperature during incremental exercise.

For human exercise at intensities greater than approximately 70 to 85% of maximal levels of exertion, ventilation (V E) increases proportionately to core temperature (T C) following distinct T C thresholds. This suggested T C in humans could be a modulator of exercise-induced ventilation. This study tested the reproducibility of relationships between oesophageal temperature (T oes) ventilation and its components during incremental exercise. On two nonconsecutive days, at an ambient temperature of 22.1+/-0.3 degrees C and RH of 45+/-5%, seven untrained adult males of normal physique pedaled on a seated cycle ergometer in an incremental exercise protocol from rest to the point of exhaustion. In each exercise session, ventilatory equivalents for oxygen consumption (VE.VO2 (1-)) and carbon dioxide production (VE.VCO2 (1-)) plus the components of V E, tidal volume (V T) and frequency of respiration (f), were expressed as a function of T oes. Results indicated the reproducibility criteria of Bland and Altman were met for the relationships between T oes and both (VE.VO2 (1-)) and (VE.VCO2 (1-)) as well as for relationships between T oes and each of V T and f. Intraclass correlation coefficients (R) for between-trial T oes thresholds for (R=0.91, P<0.05) and (R=0.88, P<0.05) were also high and significant. In both trials, after T oes increased by approximately 0.3 degrees C, V T demonstrated a distinct plateau point at a reproducible T oes (R=0.93, P<0.05) and f demonstrated a distinct and reproducible T oes threshold (R=0.84, P<0.05). In conclusion, the results illustrate that for humans, ventilation has a significant and reproducible relationship with core temperature during incremental exercise.

Adolescent↗

Tympanic temperature reflects intracranial temperature changes in humans.

The purpose of the study was to identify extracranial locations in which temperature changes in humans reflect those of intracranial temperature in a reliable and repeatable way. This was achieved by subjecting 14 non-anaesthetized patients after neurosurgery to face fanning while intracranial and extracranial temperatures were continuously measured. In all patients the cranium was closed and the group included both febrile and non-febrile as well as hyperthermic and normothermic patients. The patients' faces were fanned for 20-30 min, with a small fan at an air speed of 3.25 m s(-1). This gave intracranial temperature changes measured in the subdural space ( T(sd)) that were highly and significantly correlated ( r=0.91, P<0.05, n=14) with changes in tympanic temperatures ( T(ty)). A low, statistically insignificant correlation ( r=0.40, P>0.05, n=12) was found between T(sd) and oesophageal temperatures. In conclusion, intracranial temperature changes, induced by face fanning, were reliably reflected by the changes in T(ty).

Adult↗

The reproducibility of power spectrum analysis of heart rate variability before and after a standardized meal.

We tested the reproducibility of the heart rate variability (HRV) measurements before and after a standardized meal. Heart rate recordings were obtained in 14 healthy subjects tested in a reclining position before and after a standardized meal on two separated occasions, apart by a 1-2-week interval. We measured three components of HRV: sympathetic activity (SYMP), parasympathetic activity (PSYMP) and the ratio of SYMP/PSYMP under controlled breathing and noncontrolled breathing conditions. We observed that all components were reproducible during noncontrolled breathing condition, whereas only PSYMP was reproducible during controlled breathing condition. Our results thus indicate that HRV measurements could be a useful, noninvasive and nonexpensive method to provide SYMP and SYMP/PSYMP in feeding behavior studies when measured under noncontrolled breathing conditions. Nonetheless, using a controlled breathing condition may be relevant when assessing the effect of various interventions or drugs on parasympathetic activity.

Adult↗

Impaired mucosal immunity in L-selectin-deficient mice orally immunized with a Salmonella vaccine vector.

Lymphocyte trafficking in the gastrointestinal tract is primarily mediated by interactions with the mucosal addressin cell adhesion molecule 1 and its lymphocyte ligand, alpha(4)beta(7), and partly by L-selectin (L-Sel) interactions with peripheral node addressin coexpressed on some mucosal addressin cell adhesion molecule 1. We inquired whether intestinal responses in mice lacking L-Sel would be enhanced. L-Sel-deficient (L-Sel(-/-)) mice were orally immunized with either Salmonella vaccine vector or Salmonella vector-expressing colonization factor Ag I (CFA/I) from enterotoxigenic Escherichia coli. In L-Sel(-/-) mice, mucosal IgA anti-CFA/I fimbrial responses were greatly reduced, and systemic IgG2a anti-CFA/I fimbrial responses were 26-fold greater compared with C57BL/6 (L-Sel(+/+)) mice. L-Sel(-/-) Peyer's patch (PP) CD4(+) Th cells revealed IFN-gamma-dominated responses and an unprecedented absence of IL-4, whereas the expected mixed Th cell phenotype developed in L-Sel(+/+) mice. PP CD4(+) Th cell anti-Salmonella responses were nearly nonexistent in L-Sel(-/-) mice immunized with either Salmonella vaccine. Splenic CD4(+) Th cell anti-Salmonella responses were reduced but did show cytokine production in Ag restimulation assays. Increased colonization of PP and spleen was noted only with the Salmonella vector in L-Sel(-/-) mice, resulting in increased splenomegaly, suggesting that the Salmonella-CFA/I vaccine was not as infectious or that the presence of the fimbriae improved clearance, possibly because of reduced neutrophil recruitment. However, sufficient anti-Salmonella immunity was induced, because Salmonella vector-immunized L-Sel(-/-) mice showed complete protection against wild-type Salmonella challenge, unlike L-Sel(+/+) mice. This evidence shows that L-Sel is important for development of mucosal immunity, and absence of L-Sel is protective against salmonellosis.

Administration, Oral↗

Effective parameters for two-phase flow in a porous medium with periodic heterogeneities.

Computational simulations of two-phase flow in porous media are used to investigate the feasibility of replacing a porous medium containing heterogeneities with an equivalent homogeneous medium. Simulations are performed for the case of infiltration of a dense nonaqueous phase liquid (DNAPL) in a water-saturated, heterogeneous porous medium. For two specific porous media, with periodic and rather simple heterogeneity patterns, the existence of a representative elementary volume (REV) is studied. Upscaled intrinsic permeabilities and upscaled nonlinear constitutive relationships for two-phase flow systems are numerically calculated and the effects of heterogeneities are evaluated. Upscaled capillary pressure-saturation curves for drainage are found to be distinctly different from the lower-scale curves for individual regions of heterogeneity. Irreducible water saturation for the homogenized medium is found to be much larger than the corresponding lower-scale values. Numerical simulations for both heterogeneous and homogeneous representations of the considered porous media are carried out. Although the homogenized model simulates the spreading behavior of DNAPL reasonably well, it still fails to match completely the results form the heterogeneous simulations. This seems to be due, in part, to the nonlinearities inherent to multiphase flow systems. Although we have focussed on a periodic heterogeneous medium in this study, our methodology is applicable to other forms of heterogeneous media. In particular, the procedure for identification of a REV, and associated upscaled constitutive relations, can be used for randomly heterogeneous or layered media as well.

Models, Theoretical↗

Search for correlates of protective immunity conferred by anthrax vaccine.

Vaccination by anthrax protective antigen (PA)-based vaccines requires multiple immunization, underlying the need to develop more efficacious vaccines or alternative vaccination regimens. In spite of the vast use of PA-based vaccines, the definition of a marker for protective immunity is still lacking. Here we describe studies designed to help define such markers. To this end we have immunized guinea pigs by different methods and monitored the immune response and the corresponding extent of protection against a lethal challenge with anthrax spores. Active immunization was performed by a single injection using one of two methods: (i) vaccination with decreasing amounts of PA and (ii) vaccination with constant amounts of PA that had been thermally inactivated for increasing periods. In both studies a direct correlation between survival and neutralizing-antibody titer was found (r(2) = 0.92 and 0.95, respectively). Most significantly, in the two protocols a similar neutralizing-antibody titer range provided 50% protection. Furthermore, in a complementary study involving passive transfer of PA hyperimmune sera to naive animals, a similar correlation between neutralizing-antibody titers and protection was found. In all three immunization studies, neutralization titers of at least 300 were sufficient to confer protection against a dose of 40 50% lethal doses (LD(50)) of virulent anthrax spores of the Vollum strain. Such consistency in the correlation of protective immunity with anti-PA antibody titers was not observed for antibody titers determined by an enzyme-linked immunosorbent assay. Taken together, these results clearly demonstrate that neutralizing antibodies to PA constitute a major component of the protective immunity against anthrax and suggest that this parameter could be used as a surrogate marker for protection.

Animals↗

The school-police partnership. Identifying at-risk youth through a truant recovery program.

A substantial amount of research has established that truancy is a consistent at-risk indicator of future criminality. This article studies the experiences of 178 juveniles targeted by the Truant Recovery Program, a collaborative and nonpunitive school-law enforcement effort, and considers questions regarding its impact through examination of juvenile justice and school information in the years before and after the truancy sweep. In particular, the article suggests that intensive cooperative efforts between school and police may be effective in identifying troubled youth and raises questions about appropriate school and justice system responses for children who demonstrate at-risk behavior.

Absenteeism↗

Endogenous fat oxidation during medium chain versus long chain triglyceride feeding in healthy women.

OBJECTIVE: To compare the effect of medium chain triglycerides (MCT) vs long chain triglycerides (LCT) feeding on exogenous and endogenous oxidation of long chain saturated fatty acids (LCSFA) in women. SUBJECTS: Twelve healthy female subjects (age 19-26 y, body mass index (BMI) 17.5-28.6 kg/m2) DESIGN AND MEASUREMENTS: In a randomized cross-over design, subjects were fed weight maintenance diets providing 15%, 45% and 40% of energy as protein, carbohydrate and fat, respectively, with 80% of this fat comprising either a combination of butter and coconut oil (MCT) or beef tallow (LCT). Following 6 days of feeding, subjects were given daily oral doses of 1-(13)C labelled-myristic, -palmitic and -stearic acids for 8 days. Expired 13CO2 was used as an index of LCSFA oxidation with CO2 production assessed by respiratory gas exchange. RESULTS: No difference in exogenous LCSFA oxidation was observed as a function of diet on day 7. On day 14, greater combined cumulative fractional LCSFA oxidation (16.9 +/- 2.5%/5.5 h vs 9.1 +/- 1.2%/5.5 h, P < 0.007), net LCSFA oxidation (2956 +/- 413 mg/5.5 h vs 1669 +/- 224 mg/5.5 h, P < 0.01), and percentage dietary LCSFA contribution to total fat oxidation (16.3 +/- 2.3%/5.5 h vs 9.5 +/- 1.5%/5.5 h; P < 0.01) were observed in women fed the MCT vs LCT diet. With the MCT diet, but not the LCT diet, combined cumulative fractional LCSFA oxidation (P < 0.03), net LCSFA oxidation (P < 0.03), and percentage dietary LCSFA contribution to total fat oxidation (P < 0.02) were increased at day 14 as compared to day 7. Day 14 results indicated increased endogenous LCSFA oxidation during MCT feeding. CONCLUSION: The capacity of MCT to increase endogenous oxidation of LCSFA suggests a role for MCT in body weight control over the long term.

Adult↗

Assessing the impact of administrative policy on use of deadly force by on- and off-duty police.

Deadly force research typically does not distinguish between shootings by on-duty and off-duty police. This article uses Philadelphia police shooting data from two time periods (1970-1978 and 1987-1992) and a unique quasi-experimental design to examine the comparative effects upon on- and off-duty police shootings of an administrative policy that limited police shooting discretion but that did not address questions of police weapons carrying and access to firearms. The article draws important distinctions between when to shoot and carry administrative policies and considers their impact on deadly force by on- and off-duty police.

Adult↗

Sacral nerve stimulation for the management of voiding dysfunction.

Voiding dysfunction is common, and patients with urge incontinence, frequency/urgency syndromes, and chronic urinary retention are challenging to treat once conservative therapies (such as pharmacologic agents, pelvic floor rehabilitation, and intermittent catheterization) have been exhausted. Sacral nerve stimulation (SNS) is a new, minimally invasive, reversible therapy for the management of refractory voiding dysfunction and provides an attractive therapeutic alternative for patients with this condition. In this review, the role of SNS in the management of voiding dysfunction is examined critically, and the efficacy, risks, and benefits of this new modality are evaluated.

Journal Article↗

Components of total energy expenditure in healthy young women are not affected after 14 days of feeding with medium-versus long-chain triglycerides.

OBJECTIVE: To examine the effect of consumption of medium-chain triglycerides (MCT) vs. long-chain triglycerides (LCT) on total energy expenditure (TEE) and its components in young women during the second week of a 2-week feeding period. RESEARCH METHODS AND PROCEDURES: Twelve healthy lean women (age: 22.7+/-0.7 years, body mass index [BMI]: 21.5+/-0.8 kg/m2) were fed weight maintenance diets containing 15% of energy as protein, 45% as carbohydrate, and 40% as fat, 80% of which was treatment fat, for 2 weeks in a randomized cross-over design separated by a 2-week washout period. Dietary fat was composed of triglycerides containing either 26% medium-chain fatty acids (MCFA) and 74% long-chain fatty acids (LCFA), or 2% MCFA and 98% LCFA. Free-living TEE was measured from day 7 to 14 on each dietary treatment using doubly labeled water (DLW). Basal metabolic rate (BMR) and thermic effect of food (TEF) were measured on days 7 and 14 using respiratory gas exchange analysis (RGE) for 30 minutes and 330 minutes, respectively. Activity-induced energy expenditure (AIEE) was derived as the difference between TEE and the sum of BMR and TEF. RESULTS: The average TEE while consuming the MCT diet (2246+/-98 kcal/day) did not differ from that of the LCT diet (2186+/-138 kcal/day. BMR was significantly higher on the MCT diet on day 7 (1219+/-38 kcal/day vs. 1179+/-42 kcal/day), but not on day 14; there was no effect of diet on TEF. There were no differences in BMR, TEF, or AIEE between diets when expressed as percentages of TEE. On average, BMR, TEF, and AIEE represented 54.6%, 8.2%, and 37.2%, respectively, of TEE. DISCUSSION: Results suggest that between day 7 and day 14 feeding of MCT vs. LCT at these levels, TEE is not affected and that increases seen in energy expenditure following MCT feeding may be of short duration. Thus, compensatory mechanisms may exist which blunt the effect of MCT on energy components over the longer term.

Adult↗

Experimental utilization of the holmium laser in a model of ureteroscopic lithotripsy: energy analysis.

BACKGROUND AND OBJECTIVE: Medical lasers have rapidly expanded in both indications and utilization. We have developed a simple model for the investigation of various modalities of lithotripsy using readily available silicate stones of uniform mass. MATERIALS AND METHODS: The holmium:YAG VersaPulse Select (Coherent, Palo Alto, CA) was used in these experiments to define the relation between fiber diameter and efficacy of stone fragmentation. For each fiber, lithotripsy was performed in an incremental fashion at 0.6, 0.8, and 1.0 J at a frequency of 10, 16, and 20 pulses per second at each energy level. RESULTS: Total kilojoules did not differ between any fibers investigated, supporting the consistency of our methodology. The power density of the holmium laser energy, as expressed as total kJ/area, decreases in proportion to increasing fiber diameter. We expected an increase in fragmentation success as fiber diameter decreased (at equal energy output). However, peak lithotripsy occurred with the 365- and 550-microm fibers, whereas neither the 200- nor the 1000-microm fibers was effective. CONCLUSION: This model utilizing a silicate stone phantom supports our clinical observation that the 365-microm fiber (and additionally the 550-microm fiber) provides the best method for efficient intracorporeal lithotripsy.

Humans↗

Enhanced postprandial energy expenditure with medium-chain fatty acid feeding is attenuated after 14 d in premenopausal women.

BACKGROUND: Medium-chain triacylglycerols (MCTs) are reported to enhance human energy expenditure (EE), although few studies have involved women and the duration of such effects is only known for periods of approximately 7 d. OBJECTIVE: This study was conducted to determine whether women consuming mixed, MCT-enriched or long-chain triacylglycerol (LCT)-enriched diets showed changes in EE or substrate oxidation after 7 and 14 d. DESIGN: Twelve nonobese, premenopausal women were fed isoenergetic mixed diets enriched in either MCTs or LCTs during separate, 14-d feeding periods. Each meal contained 40% of energy as fat (80% of which was the treatment fat), 45% as carbohydrate, and 15% as protein. On days 7 and 14 of each trial, basal metabolic rate (BMR, kJ/min), total energy expenditure (TEE, kJ/min), and thermic effect of feeding (deltakJ/min) after a standardized breakfast were measured by respiratory gas exchange. RESULTS: On day 7, the mean (+/-SEM) BMR (3.58+/-0.11 kJ/min) with the MCT diet was greater (P = 0.0003) than that with the LCT diet (3.43+/-0.11 kJ/min). The mean postprandial TEE on day 7 was significantly greater (P = 0.04) with the MCT diet (4.36+/-0.04 kJ/min) than with the LCT diet (4.23+/-0.04 kJ/min); by day 14, postprandial TEE was still greater with the MCT diet, but not significantly so. No significant differences in the thermic effect of feeding were evident between diets. CONCLUSIONS: Results from this longest controlled MCT feeding study to date suggest that short-term feeding of MCT-enriched diets increases TEE, but this effect could be transient with continued feeding.

Adolescent↗

Direct cooling of the human brain by heat loss from the upper respiratory tract.

This study is the first report on human intracranial temperature in conscious patients during and after an upper respiratory bypass. Temperatures were measured in four subjects subdurally between the frontal lobes and cribriform plate (T(cr)) and on the vault of the skull (T(sd)). Further measurements were taken in the esophagus (T(es)) and on the tympanic membrane. Reinstitution of airflow in the upper respiratory tract under conditions of mild hyperthermia gave a rapid drop in T(cr) of 0.4-0.8 degrees C. In three patients the intracranial temperature at the basal aspect of the frontal lobes fell below T(es). Thus local selective cooling of the brain surface below that of the trunk temperature was shown to occur. Intensive breathing by the patients after extubation for a 3-min period produced a cooling at the site of T(cr) measurement at a rate of up to 0.1 degrees C/min, and this response could be evoked on demand. The results support the view that cooling of the upper airway can directly influence human brain temperature.

Adult↗

Cytokeratin expression in breast cancer: phenotypic changes associated with disease progression.

Transition from a normal to a cancerous state is marked by alterations in the cytoskeletal structure of those cells involved. We have examined such changes to determine if these transitions are markers of disease progression. Cytokeratin (CK) protein and messenger RNA (mRNA) expression were examined in malignant and benign breast tissues. Flow cytometric results demonstrated a significant correlation between cytokeratin protein expression detected by 5D3 antibody, specific for cytokeratins 8, 18, and 19 and axillary node metastasis (P = 0.01). A threshold of positivity of 338,000 molecules/cell was determined and reflected the wide range in cytokeratin levels expressed by normal or benign tissues. Examination of cytokeratins 8, 18, and 19 revealed a consistent pattern of expression with respect to tumor grade. Only cytokeratin 19 showed significant correlation with increasing tumor size (P = 0.006). mRNA expression for cytokeratin 8 was significantly higher in node-positive compared with node-negative disease (P = 0.02). Cytokeratin 18 mRNA levels were significantly lower in both node-negative (P = 0.03) and node-positive (P = 0.02) patients when compared with benign samples. Increased levels of cytokeratin 18 mRNA showed an inverse relationship with protein expression (P = 0.05). The results indicate that cytokeratin expression in breast cancer may be associated with tumor progression. Furthermore, the alteration in the expression of individual cytokeratins deserves further investigation to determine the consequences of these changes with respect to cellular function.

Adult↗

Dietary fat composition and human adiposity.

OBJECTIVES: This study was undertaken to investigate the relation between dietary fat composition and adiposity in adult men. SUBJECTS: A sample of 128 male subjects who participated in Phase 2 of the Québec Family Study. DESIGN: The association between adiposity and total dietary fat intake (TFI), saturated fat intake (SFA), monounsaturated fat intake (MUFA) and polyunsaturated fat intake (PUFA) was analyzed in the overall sample. A comparison of body fatness was also performed between consumers of high (4th quartile) and low amounts (1st quartile) of TFI, SFA, MUFA and PUFA. RESULTS: Significant positive correlations were found between the percentage of dietary energy as total fat and body fatness. Men in the upper quartile of TFI displayed significantly more adiposity than those in the lower quartile. Significant differences were also observed when quartiles were established using SFA and MUFA. However, higher intakes of PUFA had no statistical effects on adiposity. CONCLUSION: These results confirm the notion that high fat diets might lead over time to excess body fat deposition. SFA and MUFA intake also seem to be predictors of actual adiposity markers while high PUFA intake seems to exert no effect on these markers.

Adipose Tissue↗