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Biomedical subjects

D C Winter

Publications and source records attributed to D C Winter.

At least 55 records · Page 3Linked to original sources
PubMed1999

Berberine inhibits ion transport in human colonic epithelia.

The effects of berberine on ion transport in both human colonic mucosal epithelia and an intestinal epithelial cell line (T84) were examined. Berberine (concentration range 0-500 microM) reduced both basal and stimulated ion transport responses in human colonic mucosae in a manner which was non-specific for Ca2+ -or cAMP-mediated signals. Similarly, in cultured intestinal epithelial monolayers, berberine inhibited Ca2+ -and cAMP-mediated responses indicating an inhibitory activity directly at the level of the epithelium rather than an indirect effect through other mucosal element(s). Berberine did not alter the rate of generation of cAMP by adenylyl cyclase or the activity of protein kinase A, the effector enzyme of the cAMP pathway. Berberine inhibited carbachol-stimulated 86Rb+ efflux from T84 monolayers. Berberine also inhibited K+ conductance in apically-permeabilised re-sected mucosae. These results indicate i) that berberine exerts an anti-secretory action directly upon epithelial cells and ii) the mechanism of action may be at the level of blockade of K+ channels.

Berberine↗
PubMed1999

Nitric oxide synthetase and Helicobacter pylori in patients undergoing appendicectomy.

BACKGROUND: This study was designed to determine whether Helicobacter pylori forms part of the normal microenvironment of the appendix, whether it plays a role in the pathogenesis of acute appendicitis, and whether it is associated with increased expression of inducible nitric oxide synthetase (iNOS) in appendicular macrophages. METHODS: Serology for H. pylori was performed on 51 consecutive patients undergoing emergency appendicectomy. Appendix samples were tested for urease activity, cultured and stained for H. pylori, graded according to the degree of inflammatory infiltrate, and probed immunohistochemically for iNOS expression. RESULTS: The mean age of the patients was 21 (range 7-51) years. Seventeen patients (33 per cent) were seropositive for H. pylori but no evidence of H. pylori was found in any appendix specimen. However, an enhanced inflammatory cell infiltration was observed in seropositive patients (P < 0.04) and the expression of macrophage iNOS in the mucosa of normal and inflamed appendix specimens was increased (P < 0.01). CONCLUSION: H. pylori does not colonize the appendix and is unlikely to be a pathogenic stimulus for appendicitis. Priming effects on mucosal immunology downstream from the foregut may occur after infection with H. pylori.

Adolescent↗
PubMed1997

Chylothorax.

BACKGROUND: Chylothorax is a condition that is debilitating to the point of threatening life. There is controversy over its management, in particular the relative merits of conservative measures and the timing of surgical intervention. METHOD: The literature is reviewed from the basic sciences of chyle composition and flow, to diagnostic approaches, the complications of chyle loss and appropriate management strategies. RESULTS AND CONCLUSION: Prompt diagnosis is essential to institute an effective therapeutic regimen. Surgery achieves fast, safe and effective reversal of this dire situation. Minimally invasive thoracoscopic techniques are gaining wide recognition. Early intervention, which should be aggressive and complete to avoid the immune and nutritional consequences of extended chyle depletion, is recommended.

Chylothorax↗
PubMed1994

Long-term partial liquid ventilation (PLV) with perflubron in the near-term baboon neonate.

PURPOSE: The feasibility and safety of continuous long-term (4-5 day) partial liquid ventilation (PLV) using perflubron was demonstrated in newborn baboons. PLV, a potential therapy for adult and neonatal respiratory distress syndrome (RDS), is conventional mechanical ventilation (CMV) with the lung filled to about functional residual capacity with perfluorochemical liquid. PROTOCOL: As a pilot trial for a larger preclinical study focused on the safety of extended duration PLV, three near term baboons were studied. The animals were delivered by cesarean section, anesthetized, intubated and placed on CMV. The animals were given intratracheal perflubron (30 ml/kg) and maintained on PLV for 96 hours. The transition back to gas ventilation occurred, after draining, over the fifth day (hrs 96-120). RESULTS: Two of the animals were born with normal pulmonary function, while the third developed respiratory distress prior to PLV. All the animals were adequately supported with PLV using moderate ventilator settings and low concentrations of oxygen. Perflubron distribution was enhanced by periodic rotation of the animals. Preliminary histology show vacuolated alveolar macrophages and no evidence of edema or other significant changes in the lungs. Pulmonary function in the RDS animal, after PLV treatment, showed normal gas exchange and lung mechanics. CONCLUSIONS: Three near term baboons, one with clinical RDS, tolerated 4 days of PLV followed by 1 day of CMV without complications using practical clinical management methods.

Animals↗
PubMed1991

Arterial tonometry for noninvasive, continuous blood pressure monitoring during anesthesia.

Arterial tonometry is a technique used to measure arterial blood pressure noninvasively. The authors developed a new tonometer system containing an array of 15 piezoresistive pressure transducers, a mechanical positioning system, signal conditioning and multiplexing electronics, and a display and control console. The authors evaluated the accuracy, reliability, and clinical acceptability of this system by comparing tonometric blood pressure measurements with intraarterial blood pressure measurements in 60 anesthetized patients. Blood pressure was measured intraarterially in either the right or left radial artery by a Gould P23XL calibrated transducer, whereas blood pressure was measured by tonometer at the radial artery of the other arm. The tonometric waveform was similar to the intraarterial waveform. Simultaneous tonometer and intraarterial systolic blood pressures of the 60 patients (3,036 data sets) had an overall regression coefficient, r = 0.97, and an equation, regression equation = 0.95X + 5.8. Similar values were obtained for mean and diastolic pressures. Regression analyses of the paired tonometric and intraarterial blood pressure values showed good correlations in both sexes and in ages ranging from 8 to 82 yr (r = 0.94-0.97). Mean absolute values of error (precision) for the systolic, mean, and diastolic measurements did not differ significantly among the five systolic, five mean, and four diastolic pressure groups and ranged from 3.6 to 6.6 mmHg, with negligible bias, with intraarterial pressure used as the reference. Bias for the various pressure groups was small: -0.9-3.6 mmHg for systolic; -3.0-0.7 mmHg for mean; and -2.1-4.5 mmHg for diastolic. The "limits of agreement" (mean difference +/- two standard deviations) were within an acceptable range for clinical anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Blood pressure measurement by arterial tonometry in controlled hypotension.

A newly developed arterial tonometer enabled us to measure the blood pressure waveforms in addition to determining systolic and diastolic pressures noninvasively and continuously. Twenty-eight adult patients undergoing orthopedic surgery under controlled hypotension were studied. Systolic blood pressure was reduced to two-thirds of baseline values with an infusion of nitroglycerin during nitrous oxide/enflurane anesthesia. Intraarterial blood pressures were simultaneously measured in either the right or the left radial artery with a cannula and a Gould P23XL calibrated transducer; tonometric monitoring was performed on the contralateral radial artery using a Colin CBM-3000 instrument. The outputs of the two blood pressure measurement instruments were recorded for later data analysis. The shape of the tonometric pressure waveform was nearly identical to the waveform recorded intraarterially even during controlled hypotension. Regression analyses of 2039 paired tonometric and intraarterial blood pressure values during the hypotensive period showed good correlations (r = 0.78 for systolic, r = 0.81 for mean, and r = 0.70 for diastolic pressures). The accuracy of systolic, mean, and diastolic readings was from 4 to 7 mm Hg with negligible bias and did not differ significantly among six systolic, four mean, and four diastolic pressure groups. Our results indicate that arterial tonometry can provide accurate, reliable, and real-time monitoring of blood pressure even during controlled hypotension.

Adult↗
PubMed1990

Proximal, tracheal, and alveolar pressures during high-frequency oscillatory ventilation in a normal rabbit model.

To study the effect of different high-frequency oscillatory ventilation parameters on airway pressure, we measured oscillatory pressure amplitude ([Paw[) and mean airway pressure (Paw) at three sites in open-chested normal rabbits: proximal, trachea, and alveolus. Five animals were studied to test a new pleural capsule design, which was then used in two groups of animals to measure right upper (n = 4) or middle (n = 5) lobe alveolar pressures. Animals were randomly sequenced through combinations of frequency (10, 15, and 20 Hz) and fractional inspiratory time (Ti) (0.3 and 0.5) while normoxic and eucapnic. During capsule testing, we noted that alveolar pressures increased (p less than 0.05) with increasing capsule mass, suggesting that compressive forces from the capsule may alter the capsule measurement. We thus used a low-mass (430 mg) transducer system in the rabbit high-frequency oscillatory ventilation experiments. Using multifactorial analysis of variance, we found significant main effects of Ti on Paw, and of measurement site on both [Paw[ and Paw (all p less than 0.009). Frequency did not influence variations in either [Paw[ or Paw. For both Ti settings, alveolar upper lobe Paw was lower compared with that of the middle lobe (p less than 0.0005). Lengthening Ti (0.3 to 0.5) increased tracheal Paw in each capsule group (p less than 0.0005). At Ti = 0.5, tracheal Paw exceeded Paw measured proximally (p less than 0.05). Our data support in vivo alveolar Paw inhomogeneity and demonstrate significant changes in pressures within the lung related to Ti during high-frequency oscillatory ventilation.

Analysis of Variance↗
PubMed1989

Role of lung injury in the pathogenesis of hyaline membrane disease in premature baboons.

To test the hypothesis that hyaline membrane disease (HMD) has a multifactorial etiology in which barotrauma plays a major role, we compared the immediate institution of high-frequency oscillatory ventilation (HFOV; 15 Hz, n = 5) with positive-pressure ventilation with positive end-expiratory pressure (PPV; n = 7) in premature baboons (140-days gestation) with HMD. Measurements of ventilation settings and physiological parameters were obtained and arterial-to-alveolar O2 (PaO2-to-PAO2) ratio and oxygenation index [(PaO2/PAO2)-to-mean airway pressure ratio (IO2)] were calculated. At death (24 h), static pressure-volume (PV) curves were performed, and phospholipids (PL) and platelet-activating factor (PAF) were measured in lung lavage fluid. Morphological inflation patterns were analyzed using a panel of standards. By design, mean airway pressure was initially higher (19 vs. 13 cmH2O) in the HFOV animals. PaO2-to-PAO2 ratio and IO2 progressively deteriorated in the PPV animals and then stabilized at significantly lower levels than with HFOV. PV curves from HFOV animals had significant increases in lung volume at maximum distending pressure, deflation volume at 10 cmH2O, and hysteresis area compared with PPV, which showed no hysteresis. Seven of seven PPV and only one of five HFOV animals had morphological findings of HMD. PL amount and composition in both groups were consistent with immaturity, even though the quantity was significantly greater in the PPV group. PAF was present (greater than or equal to 0.10 pmol) in six of seven PPV and in the only HFOV animal with HMD. We conclude that HFOV protected PL-deficient premature baboons from changes in gas exchange, lung mechanics, and morphology typical of HMD in this model.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Influence of ventilatory technique on pulmonary baroinjury in baboons with hyaline membrane disease.

To assess the influence of ventilatory technique on pulmonary baroinjury in experimental hyaline membrane disease, we randomized 24 premature baboons to six treatment groups according to ventilator (PPV, positive pressure ventilator; HFO, high frequency oscillator; HFI, high frequency flow interrupter) and O2 therapy FIO2 as clinically indicated, or FIO2 1.0). PaCO2 was adjusted by varying pressure amplitude, and for PPV, also by rate (less than 60/min). HFO and HFI were set at a frequency of 10 Hz. Animals were cared for with standard NICU techniques until death or sacrifice at 11 days. One animal died at delivery and was excluded from data analysis. There were no intergroup differences in Paw, Pa/AO2, PaCO2 or oxygenation index (IO2 = [Pa/AO2]/Paw) prior to death of the first study animal at 13 h. Animals who subsequently developed airleak had higher Paw, lower Pa/AO2 and lower IO2 during this period. The degree of airleak was significantly less with HFO compared to PPV or HFI. The effect of O2 exposure did not appear different with respect to the degree of airleak or the frequency of severe tracheal injury, although survival was shortened. Severe tracheal injury was more frequent with HFI compared to PPV or HFO. BPD was found only in 100% O2 exposed animals surviving greater than 1 wk. Management of premature baboons with HFO and appropriate O2 resulted in less severe airleak, 100% survival, and no evidence of severe tracheal injury or BPD. These outcomes were not achieved with clinically similar strategies using PPV or HFI.

Animals↗
PubMed1985

Elastic properties of collapsing and expanding trachea.

The compliance of the canine trachea under positive and negative transmural pressures was measured in an in-vivo preparation. The average compliance values found in eight animals were 11.7 X 10(-6) (dynes/cm2)-1 at zero transmural pressure and 4.9 and 6.9 X 10(-6) (dynes/cm2)-1 at -20 and +20 X 10(3) dynes/cm2 transmural pressure, respectively. These compliances were significantly lower than those measured by others in excised preparations. Stress relaxation was noted at all pressure levels.

Animals↗
PubMed1985

An acoustic plethysmograph to measure total infant body volume.

An acoustic plethysmograph intended to measure the body volume of premature infants has been developed using the principle of the Helmholtz resonator, in which the resonance frequency is dependent on the volume of the resonating cavity. A prototype system was built and used to measure the volume of inanimate objects and newborn miniature pigs. Results for inanimate objects agree within 1 percent with comparable measurements by water displacement. Results of the animal body volume measurements compare favorably (within an average of 1.1 percent) with those obtained using hydrostatic weighing.

Acoustics↗
PubMed1985

Use of resonating cavity to measure body volume.

A technique to estimate the body volume of newborns has been developed using the principle of the Helmholtz resonator. The change in the resonance frequency of a small cavity after an infant is placed inside can be used to determine the body volume of the infant. A prototype system, termed an acoustic plethysmograph, was built and used to measure the volume of newborn miniature pigs. Results of the animal body volume measurements compare favorably (within an average of 1.1%) with body volumes measured by hydrostatic weighing.

Animals↗
PubMed1984

Turbulence in pulsatile flows.

Turbulence during pulsatile flow has been suggested as a possible mechanism to enhance the transport of gases during high-frequency ventilation. Experimental studies on oscillatory flow in straight, circular tubes have identified three types of flow: (a) laminar; (b) conditionally turbulent, in which high-frequency disturbances occur during the decelerating phase of the flow cycle but relaminarize by the beginning of the subsequent accelerating phase; and (c) fully turbulent flow, in which disturbances occur throughout the flow cycle. Fully turbulent flow has been observed only when a mean flow is present, and only laminar or conditionally turbulent flow has been observed for purely oscillatory flow. A critical Reynolds number based on the Stokes layer can be defined, and transition Reynolds numbers between 400 and 550 have been experimentally determined for purely oscillatory flow in a circular tube, although lower values are expected for physiological flows. There are some indications that the structure of oscillating turbulent flow is similar to steady turbulent flow, and preliminary work in our laboratory shows that the spectral content of flows during high-frequency ventilation is similar to that in steady turbulent flow.

Animals↗
PubMed1978

Estimating central and peripheral respiratory resistance.

An analytic approach for fractionating total respiratory resistance into central (Rc) and peripheral (Rp) components is presented. In the analysis, linear regression equations relating the logarithm of the measured total resistance to the logarithm of frequency are derived for data spanning the frequency range 1-16 Hz. The computed slope and intercept are used to obtain estimates of the fraction of the resistance in the periphery (Fp) and of Rp and Rc. Data from anesthetized, closed-chested dogs in a control state and with an external resistor (1.37 cmH2O.1-1.s) were used to test the approach. Mean values +/- SE's for control data were: Fp = 0.400 +/- 0.039, Rp = 1.37 +/- 0.16 cm H2O.1-1.s, and Rc = 1.98 +/- 0.10 cmH2O.1-1.s. Mean values of Rp obtained with and without added resistance were not significantly different (P less than 0.1). The increase in the mean values of Rc represented 85% of the value of the added resistance but was significantly different from the known value of the external resistance (P less than 0.05). These data suggest that it may be possible to fractionate total respiratory resistance into central and peripheral components using the frequency dependence of forced oscillatory resistance.

Airway Resistance↗
PubMed1976

Ultrasonic detection of cardiovascular flow disturbances.

Blood flow that is disturbed or turbulent may have a significant effect on the development of cardiovascular disease. A method is presented here for detecting periods of disturbed flow using autocorrelograms of the audio signal from a pulsed ultrasound Doppler velocity meter (PUDVM). Autocorrelograms describe quantitatively how the form of a signal changes over time. We produced steady laminar and turbulent pipe flow in a hydraulic test tank, and computed autocorrelograms of the audio signal of the centerline velocity as detected by the PUDVM using fast Fourier transform techniques. We have shown that the autocorrelation coefficient averaged over a short length of time (64 ms) is significantly higher for laminar than for turbulent flow. We have also produced pulsatile flow in our hydraulic tank and computed the mean autocorrelation coefficient at different phases of the flow cycle. The regions of disturbed and undisturbed flow were predicted from the steady flow results. The disturbed flow first appears during the period of the highest forward velocities. These results indicate that the mean autocorrelation coefficient can serve as an indicator of the presence of flow disturbances.

Cardiovascular Diseases↗