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Biomedical subjects

M D White

Publications and source records attributed to M D White.

At least 37 records · Page 2Linked to original sources

Evaluation of retropulsion caused by holmium:YAG laser with various power settings and fibers.

The ideal intracorporeal lithotriper would comminute all types of calculi into small readily excreted particles. It would be small and flexible with an energy source safe for the uroepithelium. It should not break, should be inexpensive, and should not retropulse the stone up the urinary tract. This investigation was designed to quantify the last quality for the holmium:YAG laser. The mechanism of action of the pulsed Ho:YAG laser (wavelength 2100 nm) is the generation of a gas plasma at the stone-fluid interface causing a shockwave. The holmium laser was employed for lithotripsy of model stones composed of silicate with a ferrous coating. Stones were selected with a mass of 2 mg +/- 0.1 mg. We sequentially investigated three variables: energy (0.6, 0.8, and 1.0 J), frequency (10, 16, and 20 Hz), and fiber diameter (200, 365, 550, and 1000 microm). Ten stone trials were performed with each of the 36 possible combinations of energy, pulse frequency, and fiber diameter. Our model ureter consisted of a clear rigid polymer tube filled with 0.9% saline. The system was closed and permitted intertrial flushing of generated air bubbles. The laser fiber was maintained at constant extension from the ureteroscope, with stones positioned at the fiber tip before each trial. Laser energy was applied for 2 seconds, with maximum and net retropulsion recorded in millimeters. Each measurement series was recorded in a database for paired Student t-tests. Net retropulsion was then compared by statistically holding each of the three variables constant (fiber size constant with power and frequency varying; frequency constant with power and fiber size varying; and power constant with fiber size and frequency varying). Most retropulsion occurred with the 365-microm and 550-microm fibers. Most comminution was also noted with these fiber sizes. There was no statistical correlation between observed retropulsion and efficiency of comminution. This self-contained model for laser lithotripsy allowed us to measure retropulsion accurately. Silicate stones are not chemically similar to human uroliths but are of uniform composition. The irregular surface characteristics are similar to human stones, making them ideal for retropulsion investigations.

Evaluation Studies as Topic↗

Endoscopic subcutaneous neurovascular lower-extremity myofascial flap harvesting for genitourinary reconstruction.

Neurovascular myofascial flaps have been widely utilized when healthy tissues outside the anatomic confines of the pelvis are necessary for complex genitourinary reconstructions. Myofascial flaps have great potential in providing support and tone to the bladder neck in a model of total urinary incontinence. Two muscles were evaluated for minimally invasive harvesting utilizing an adult rabbit and human cadaveric model: the gracilis, because of its neurovascular supply and length, and the sartorius, because of its location. Three adult New Zealand White rabbits were prepared and draped in sterile fashion after general anesthesia. Bilateral 2-cm incisions were made over the origins of the gracilis and sartorius muscles. Dissection times were entered in a database on a personal computer for paired Student t-tests. Special techniques for dissection included utilization of a 5-mm subcutaneous dissector/retractor and reticulated scissors and dissector. Once the tissues were harvested, rotational angles of the functional arcs around the origins of the gracilis and sartorius flaps were measured, as were the lengths of the muscular flaps from the proximal pedicle to the free distal end. Initial positioning of the myofascial flap at the bladder neck was investigated in this nonsurvival study. Blood loss was estimated before the animals were humanely sacrificed. The possibilities of minimally invasive genitourinary reconstruction are numerous. Both flaps can be dissected endoscopically and have rotational angles allowing transfer to more cephalad positions in the groin or intra-abdominally. Further studies are needed to establish the efficacy of the myofascial graft for minimally invasive genitourinary reconstructions.

Animals↗

Ethanol ingestion prolongs orthostatic intolerance in hyperthermic humans.

BACKGROUND: Both ethanol ingestion and hyperthermia contribute to orthostatic intolerance (OI). HYPOTHESIS: Since ethanol has been cited as a major risk factor for hyperthermia-related deaths, we hypothesized that ethanol exacerbates OI induced by hyperthermia. METHODS: There were seven subjects (four males, three females) rendered hyperthermic (esophageal temperature = 39 degrees C) in a 40 degrees C water bath on two separate days: Condition 1) Control (juice ingestion); and Condition 2) Ethanol [ethanol (1 ml x kg(-1) body mass) and juice ingestion]. To test for OI, 5-min supine periods were followed by 5-min 63 degrees head-up tilts prior to and following immersion. BPs, heart rate and esophageal temperatures were monitored throughout the experiments. RESULTS: For first and second post-immersion tilts, mean arterial BP (MAP) during tilting increased by 5.9 +/- 3.6 (SE) and 9.8 +/- 2.6 mm Hg in the control condition, while it decreased by 7.9 +/- 5.8 and 0.6 +/- 4.3 mm Hg in the ethanol condition. This gave significantly lower MAP (ethanol vs. control) of 63.6 +/- 3.1 vs. 71.8 +/- 4.5 mm Hg (p < 0.05) for the first and 79.6 +/- 2.3 vs. 86.7 +/- 4.4 mm Hg (p < 0.05) for the second post-immersion tilts. These values were all significantly less (p < 0.05) than normothermic tilted values of 94.7 +/- 4.7 mm Hg in the ethanol and 93.6 +/- 2.9 mm Hg in the control condition. Prior to warm water immersion, subjects tolerated all head-up tilts. In the control condition, only one subject experienced orthostatic intolerance following the first post-heating tilt and no intolerance was experienced following 30 min post-heating. However, during the ethanol condition, 4 subjects experienced orthostatic intolerance following the first tilt with episodes of intolerance lasting as long as 80 min (8 supine/tilt cycles). CONCLUSION: Ethanol ingestion prolonged and increased the magnitude of OI in hyperthermic subjects. This may at least partly explain why ethanol is a major risk factor in hyperthermia-related deaths.

Adult↗

Energy and macronutrient balances for humans in a whole body metabolic chamber without control of preceding diet and activity level.

OBJECTIVE: To examine the relationships between 24 h energy and macronutrient balances in a whole body metabolic chamber subsequent to periods when subjects maintained their normal food intake and physical activity levels. SUBJECTS: Thirteen males and 17 females were studied for two 24 h sessions while consuming an estimated isocaloric diet with a food quotient of 0.85. MEASUREMENTS: Energy expenditure and macronutrient oxidation rates were measured twice for 24 h in whole body indirect calorimeter. RESULTS: Positive and significant correlations were evident between energy and lipid balances (r = 0.38, P < 0.05 and r = 0.54, P < 0.01, respectively) and differences between the two sessions for energy and lipid balances were also significantly correlated (r = 0.40, P < 0.05). Accounting for carbohydrate or protein balances improved the strength of each of these associations. CONCLUSION: These results indicate that for subjects in a small but significant positive energy balance, with uncontrolled diet and activity preceding their metabolic chamber sessions, that 24 h energy balance is positively correlated with lipid balance. Accounting for associations between lipid, carbohydrate, protein and energy balances, improved the strength of the association between 24 h lipid and energy balances. The implications of these results are that in these conditions modifications to lipid balance are important for weight maintenance.

Adult↗

Acute effect of exercise and low-fat diet on energy balance in heavy men.

OBJECTIVE: To quantify the acute effect of the exercise-low-fat diet combination on energy balance compared with sedentarity and a high fat diet in overweight individuals. DESIGN AND MEASUREMENTS: We assessed the acute effect of exercise and ad libitum intake of low-fat foods on daily energy balance. Six heavy men participated in two randomly assigned sessions which required a 24 h stay in a whole body indirect calorimeter. Sessions were preceded by either a 60 min aerobic exercise at 50% VO2 max or a 60 min rest. Subjects were fed a low-fat diet (mean FO = 0.89) after exercise and a mixed diet (mean FQ = 0.85) after the resting period. RESULTS: The difference in energy balance between the two conditions was 7.3 MJ. About half of the effect was attributable to the energy surplus expended during exercise whereas the remaining fraction was explained by the difference in post-exercise energy balance. CONCLUSION: In heavy men, the combination of a low-fat diet and exercise has a strong acute effect on energy balance compared to a rest-mixed diet condition.

Adult↗

Interleukin-4-specific signal transduction events are driven by homotypic interactions of the interleukin-4 receptor alpha subunit.

Interleukin-4 (IL-4) exerts its effects through a heterodimeric receptor complex (IL-4R), which contains the IL-4R(alpha) and gamma(c) subunits. IL-4R(alpha) also functions with other partner subunits in several receptor types, including the IL-13 receptor. To examine the roles of the individual subunits within IL-4R complexes, we employed a chimeric system that recapitulates native IL-4R function as verified by the activation of the kinases, JAK1 and JAK3, and induction of STAT-6. When a mutant gamma(c) subunit in which the four cytoplasmic tyrosines were converted to phenylalanine was paired with the cytoplasmic domain of the IL-4R(alpha) chain, specificity within the JAK-STAT pathway was not altered. Signaling events were examined further in cells expressing the IL-4R(alpha) chimera alone without the gamma(c) chimera. Ligand-induced homodimerization of these receptors activated the IL-4 signaling program despite the absence of gamma(c), including induction of JAK1 and STAT-6, phosphorylation of the insulin-related substrate 1 and cellular proliferation. Thus, homotypic interactions of the IL-4R(alpha) subunit are sufficient for the initiation and determination of IL-4-specific signaling events, and such interactions may be integral to signaling through IL-4R complexes.

Animals↗

Cell adhesion molecules in bladder cancer: soluble serum E-cadherin correlates with predictors of recurrence.

Sera from 40 patients with newly diagnosed bladder cancer (28 superficial tumours (pTa and pT1) and 12 muscle-invasive tumours) were assessed by enzyme-linked immunosorbent assay (ELISA) to determine the concentrations of soluble E-cadherin (sE-cadherin), soluble E-selectin (sE-selectin), soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1). Corresponding frozen sections of primary tumour were analysed for E-cadherin expression using the monoclonal antibody, HECD-1 and standard immunohistochemistry. Patients with bladder cancer had significantly higher concentrations of sE-cadherin compared with a control group (P = 0.017). No difference was found between the two groups with regard to sE-selection (P = 0.403), sVCAM-1 (P = 0.942) and sICAM-1 (P = 0.092). High levels of sE-cadherin were related to poor histological grade (P = 0.009), number of superficial tumours at presentation (P = 0.008) and a positive 3 month check cytoscopy in superficial disease (P = 0.036). Abnormal E-cadherin expression was associated with increasing tumour stage (P = 0.009) and grade (P = 0.03). There was no correlation between high levels of soluble E-cadherin in sera and abnormal E-cadherin expression by the tumour (P = 0.077). Elevated levels of sE-cadherin are found in sera of patients with bladder cancer and correlate with known prognostic factors.

Aged↗

Reproducibility of 24-h energy expenditure and macronutrient oxidation rates in an indirect calorimeter.

The maintenance of weight and adipose tissue mass in humans appears to be related to a balance between the rates of oxidation and consumption of macronutrients; yet, little evidence is available on the reproducibility of 24-h macronutrient oxidation rates and how this relates to diet in the days preceding a chamber session. This study examined the reproducibility of 24-h macronutrient oxidation rates, 24-h energy expenditure (EE), and respiratory quotient (RQ) in 30 adults who ate their habitual diets before two 24-h whole body indirect calorimeter sessions. Results showed that the within-subject coefficients of variation (CVws) for 24-h EE and RQ were 2.8 and 2.6%, respectively. CVws for macronutrient oxidations ranged from approximately 15 to 25%. Means comparisons of 24-h EE, RQ, and macronutrient oxidation rates between sessions showed no significant differences, and all variables had significant positive intraclass correlation coefficients (P < 0.05). In conclusion, macronutrient oxidations all showed significant reproducibility for the group and a significant but lower reproducibility for individuals when habitual diet and activity preceded the experimental sessions.

Adipose Tissue↗

Eucapnic hypoxia lowers human cold thermoregulatory response thresholds and accelerates core cooling.

Hypoxia lowers the basic thermoregulatory responses of animals and humans. In cold-exposed animals, hypoxia increases core temperature (Tco) cooling rate and suppresses shivering thermogenesis. In humans, the experimental effects of hypoxia on thermoregulation are equivocal. Also, the effect of hypoxia has not been separated from that of hypocapnia consequent to hypoxic hyperventilation. To determine the isolated effects of hypoxia on warm and cold thermoregulatory responses and core cooling during mild cold stress, we examined the Tco thresholds for sweating, vasoconstriction, and shivering as well as the core cooling rates of eight subjects immersed in 28 degrees C water under eucapnic conditions. On 2 separate days, subjects exercised on an underwater cycle ergometer to elevate Tco above the sweating threshold. They then rested and cooled until they shivered vigorously. Subjects inspired humidified room air during the control trial. For the eucapnic hypoxia trial, they inspired 12% O2-balance N2 with CO2 added to maintain eucapnia. Eucapnic hypoxia lowered the Tco thresholds for vasoconstriction and shivering by 0.14 and 0.19 degrees C, respectively, and increased core cooling rate by 33% (1.83 vs. 1.38 degrees C/h). These results demonstrate that eucapnic hypoxia enhances the core cooling rate in humans during mild cold stress. This may be attributed in part to a delay in the onset of vasoconstriction and shivering as well as increased respiratory heat loss during hypoxic hyperventilation.

Adult↗

Exercise hyperpnea and hyperthermia in humans.

The problem of the relative hyperpnea occurring at high levels of exercise remains unresolved. This study examined whether the hyperpnea observed in humans during exercise at approximately 70% of maximal work capacity was related to cranial (tympanic) and thoracic (esophageal) temperatures. Six trained male subjects pedaled at approximately 60 revolutions/min on an electrically braked cycle ergometer in a climatic chamber at 25 degrees C and approximately 35% relative humidity in two sessions. The subjects pedaled until exhaustion in two sessions. In one session work rate was increased by 40 W every 2 min and in the other session by 20 W every 2 min. In both exercise sessions, core temperature thresholds for ventilation were evident and subsequently tympanic and esophageal temperatures diverged. This suggested that the hyperpnea in humans observed after approximately 70% of an individual's maximal work rate was determined, in part, by core temperatures and revealed supportive evidence for selective brain cooling in humans.

Adult↗

Physical dilatation of the nostrils lowers the thermal strain of exercising humans.

Increased nasal air flow during exercise was examined as a possible heat loss avenue contributing to selective brain cooling in hyperthermic humans. On 2 separate days, eight subjects [mean (SE) age, 26.4 (1.2) years] exercised on a cycle ergometer in a warm room [28 (0.2) degrees C; 28 (5)% relative humidity] to induce a moderate level of hyperthermia. In one session the nostrils were physically dilatated [average dilatation 1.55 (0.17) times] and in the other they were not (control). Both sessions started with a 5-min resting period; then subjects pedaled at 60 W for 5 min, 100 W for 15 min, and 150 W for 20 min. During dilatation both tympanic temperature (Tty) and forehead skin blood flow, estimated by laser doppler velocimetry, were significantly lower than during the control exercise of 150 W. Rates of increase of Tty during the 100-W exercise were the same in both conditions; however, during the 150-W exercise with dilatated nostrils Tty increased at a rate significantly lower than during control [1.1 (0.3) degrees C.h-1 vs 1.5 (0.4) degrees C.h-1]. The change in the rate of increase of Tty between conditions was significantly correlated to the degree of nostril dilatation (r = -0.77, P = 0.02), suggesting that the lower Tty observed was due to nostril dilatation. Facial skin temperature was not significantly different between sessions. The results suggest that the nasal cavity may act as a heat exchanger in selective brain cooling of exercising humans.

Adult↗

Nasal mucosal vasodilatation in response to passive hyperthermia in humans.

The present study was conducted to measure nasal mucosal blood flow (NMBF) during body warming. Five subjects [mean (SD) 24 (2) years], wearing only shorts and a thick felt hat with ear flaps, were immersed to the neck in a bath at 40 (0.5) degrees C. Tympanic (Tty), esophageal (Tes), mean unweighted skin (Tsk), nose skin and ear pinna skin were recorded at 1-min intervals. NMBF on the lower septal wall was estimated using a laser Doppler flow meter. At rest Tty and Tes were both 36.5 degrees C. Tty dropped significantly below Tes during body warming, despite impeded heat loss from the head due to the felt hat. Tty increased to 37.3 degrees C and Tes increased to 37.5 degrees C during the immersion. During the immersion all skin temperatures were steady or increasing, ruling out the possibility of a contamination of Tty from Tsk. Body warming significantly (P = 0.001) increased NMBF by approximately three times from resting values at the end of immersion. During the period of increasing core temperatures NMBF was significantly correlated to Tty (r = 0.93, P = 0.0001) and Tes (r = 0.97, P = 0.0001), suggesting the blood flow change in this tissue was a thermoregulatory response. The increased NMBF during hyperthermia supports the hypothesis of respiratory cooling involvement in selective brain cooling of humans.

Body Temperature Regulation↗

Core temperature thresholds for hyperpnea during passive hyperthermia in humans.

Humans have higher ventilation when they are hyperthermic but it is not known whether core temperature thresholds for ventilation exist, nor has a physiological rationale been presented for this response. To examine this question, ventilation was studied in relation to core temperatures in humans rendered hyperthermic in a warm bath. Seven subjects [mean (SE), 23.3 (1.4) years] wearing only shorts and a thick felt hat with ear flaps were immersed to the neck in a bath at 41 (0.5) degrees C for 25 min. Tympanic (Tty), esophageal (Tes), thigh skin and forehead skin temperatures, heart rate, inspired minute ventilation (V1 at body temperature and pressure, saturated), ventilation frequency and oxygen consumption (VO2 at standard temperature and pressure, dry) were recorded at 30-s intervals. At immersion V1 briefly increased to 18.6 (3.0) l.min-1, returned to about the pre-immersion value, and significantly increased to 19.3 (3.0) l.min-1 by the end of immersion. VO2 increased significantly from the pre-immersion value of 0.27 l.min-1 to 0.67 l.min-1 by the first 0.5 min of immersion, but then returned to its pre-immersion value. Tty increased to 38.7 (0.2) degrees C and Tes increased to 39.0 (0.2) degrees C by the end of immersion. Core temperature thresholds for increases in V1 were evident at 38.1 degrees C when expressed against Tty and at 38.5 degrees C when expressed against Tes. The results indicated that during body warming core temperature thresholds for V1 are reached and subsequently a hyperpnea was evident, despite VO2 remaining at a resting value.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Isolated effects of peripheral arm and central body cooling on arm performance.

BACKGROUND: Whole body cooling impairs manual arm performance. The independent contributions of local (peripheral) and/or whole body (central) cooling are not known. Therefore, a protocol was developed in which the arm and the rest of the body could be independently cooled. METHODS: Biceps temperature (Tmus), at a depth of 20 mm, and esophageal temperature (Tes) were measured. Six subjects were immersed to the clavicles in a tank (body tank) of water under 3 conditions: 1) cold body-cold arm (CB-CA); 2) warm body-cold arm (WB-CA); and 3) cold body-warm arm (CB-WA). In the latter two conditions, subjects placed their dominant arm in a separate (arm) tank. Water temperature (Tw) in each tank was independently controlled. In conditions requiring cold body and/or cold arm, Tw in the appropriate tanks was 8 degrees C. In conditions requiring warm body and/or warm arm, Tw in the appropriate tanks was adjusted between 29 and 38 degrees C to maintain body/arm temperature at baseline values. A battery of 6 tests, requiring fine or gross motor movements, were performed immediately before immersion and after 15, 45, and 70 minutes of immersion. RESULTS: In CB-CA, Tes decreased from an average of 37.2 to 35.6 degrees C and Tmus decreased from 34.6 to 22.0 degrees C. In WB-CA, Tmus decreased to 18.1 degrees C (Tes = 37.1 degrees C), and in CB-WA, Tes decreased to 35.8 degrees C (Tmus = 34.5 degrees C). By the end of immersion, there were significant decrements (43-85%) in the performance of all tests in CB-CA and WB-CA (p < 0.0002); scores for each test were similar in these two conditions. There was no significant change in scores throughout the CB-WA condition. In both conditions with arm cooling (i.e., WB-CA and CB-CA), Tmus accounted for 85-98% of the variance in all tests. When the core was cooled in the CB-WA condition, Tes was significantly correlated to scores in only two tests (accounted for 90 and 93% of the variance) although the actual effect was small. In the CB-CA condition, partial correlations indicated that Tes accounted for 4-10% of the variance in scores of 4 tests. CONCLUSIONS: We conclude that cooling of the body and/or the arm elicits large decrements in finger, hand and arm performance. The decrements are due almost entirely to the local effects of arm tissue cooling.

Adult↗

The relationship between directly measured human cerebral and tympanic temperatures during changes in brain temperatures.

The present study was performed to investigate the relationship between noninvasive measurements of core temperature and intracranial temperature measurements in humans. At 2-3 weeks following minor subarachoid haemorrhage, five patients were studied during open brain surgery. All patients were fully conscious and free of neurological symptoms at the time of surgery. During craniotomies in the frontotemporal region, temperatures between the dura and brain surface were on average 0.58 (SD 0.51) degrees C lower than those near the mesencephalon. During the 60-90 min following the initial exposure of the brain surface to the ambient temperature of 24 degrees C, subdural temperature at the convexity decreased by 0.72 (SD 0.43) degrees C and subdural temperature at the basis decreased by 0.36 (SD 0.17) degrees C. During the same period, mesencephalon temperature decreased by 0.22 (SD 0.10) degrees C. The decreases of cerebral temperatures were followed by a similar decrease in tympanic temperature of 0.28 (SD 0.10) degrees C but by an increase in rectal temperature of 0.22 (SD 0.13) degrees C and an increase in oesophageal temperature of 0.20 (SD 0.20) degrees C. The maximal shift of frontal skin temperature during the same period amounted to +0.04 (SD 0.21) degrees C. The findings would seem to support the thesis that a direct relationship does exist between tympanic and brain temperatures in humans and that of the externally accessible body temperatures, tympanic temperatures giving the best approximation of average cerebral temperature.

Body Temperature↗