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Biomedical subjects

K Davis

Publications and source records attributed to K Davis.

At least 217 records · Page 12Linked to original sources
PubMed1993

The roles of von Willebrand factor and factor VIII in arterial thrombosis: studies in canine von Willebrand disease and hemophilia A.

We have studied the roles of von Willebrand factor (vWF) and factor VIII in arterial thrombosis in four canine phenotypes: normal (n = 6), hemophilia A (n = 11), von Willebrand disease (vWD) (n = 9), and hemophilia A/vWD (n = 1). vWF activity was determined by botrocetin-induced agglutination of fixed human platelets and vWF antigen (vWF:Ag) by Laurell electroimmunoassay and crossed immunoelectrophoresis. Plasma from normal dogs and those with hemophilia A had vWF activity, vWF:Ag, and a full range of vWF:Ag multimers on gel electrophoresis equivalent to normal canine plasma pool. Platelet cytosol contents were isolated by freezing and thawing, triton X-100 solubilization, or sonication of washed platelets with and without protease inhibitors and inhibitors of platelet activation. Washed platelets were also stimulated with calcium ionophore and MgCl2. There was no measurable vWF activity or vWF:Ag in platelet lysates or releasates in any dog regardless of phenotype. All dogs were studied using a standard arterial stenosis and injury procedure to induce arterial thrombosis. Thromboses were detected by cyclic reductions in Doppler blood flow velocity. Vessels were examined by light and scanning electron microscopy. Thrombosis developed in the arteries of normal (9 of 10) and hemophilia A dogs (16 of 16) but in none of the vWD dogs (0 of 10). Infusion of canine vWF cryoprecipitate into vWD dogs markedly shortened bleeding time but did not support thrombosis as seen in dogs with vWF in the plasma and subendothelium. Thrombosis, then, fails to occur when vWF is absent from the plasma and subendothelial compartments or present only in the plasma compartment. These data are consistent with the hypothesis that vWF in the plasma and subendothelium supports thrombosis. Neither plasma FVIII nor platelet vWF is essential for thrombosis in this model.

Animals↗
PubMed1993

Airway pressure release ventilation.

BACKGROUND: Elevated airway pressures during mechanical ventilation are associated with hemodynamic compromise and pulmonary barotrauma. We studied the cardiopulmonary effects of a pressure-limited mode of ventilation (airway pressure release ventilation) in patients with the adult respiratory distress syndrome. METHODS: Fifteen patients requiring intermittent mandatory ventilation (IMV) and positive end-expiratory pressure (PEEP) were studied. Following measurement of hemodynamic and ventilatory data, all patients were placed on airway pressure release ventilation (APRV). Cardiorespiratory measurements were repeated after a 2-hour stabilization period. RESULTS: During ventilatory support with APRV, peak inspiratory pressure (62 +/- 10 vs 30 +/- 4 cm H2O) and PEEP (11 +/- 4 vs 7 +/- 2 cm H2O) were reduced compared with IMV. Mean airway pressure was higher with APRV (18 +/- 5 vs 24 +/- 4 cm H2O). There were no statistically significant differences in gas exchange or hemodynamic variables. Both cardiac output (8.7 +/- 1.8 vs 8.4 +/- 2.0 L/min) and partial pressure of oxygen in arterial blood (79 +/- 9 vs 86 +/- 11 mm Hg) were essentially unchanged. CONCLUSIONS: Our results suggest that while airway pressure release ventilation can provide similar oxygenation and ventilation at lower peak and end-expiratory pressures, this offers no hemodynamic advantages.

Adult↗
PubMed1993

Continuous duodenal feeding restores gut blood flow and increases gut oxygen utilization during PEEP ventilation for lung injury.

Positive end-expiratory pressure (PEEP) improves oxygenation but, at moderate levels, limits portal blood flow (PBF) and may cause relative splanchnic ischemia. Under these conditions, methods of supporting gut physiology may prevent the sequelae of gut ischemic damage. Enteral feeding is known to cause splanchnic hyperemia in uninjured animals. In order to study the effects of continuous enteral feeding on gut hemodynamics in a flow-limited environment, six dogs underwent the insertion of arterial, pulmonary artery, and portal and hepatic vein catheters. Splenectomy and duodenostomy were performed, and the hepatic artery and portal vein were encircled with flow probes. Lung injury (LI) was undertaken with intravenous oleic acid (0.08 mL/kg), followed by incremental additions of PEEP totaling 10 cm H2O to correct shunt. Continuous elemental feeding (1 kcal/mL, 3 mL/kg/hr) was started through the duodenostomy. Cardiac index (CI), PBF, and gut oxygen delivery and consumption (GO2D, GO2C) were measured at baseline (T0), 1 hour after LI and PEEP (T1), and 1 hour after drip feeding was begun (T2). Lung injury and PEEP significantly decreased CI, PBF, and GO2D without changing GO2C. Feeding returned PBF and GO2D to baseline levels without changing CI. GO2C increased significantly compared with baseline levels. Based on prior studies, these changes do not represent recovery of the injured model. Continuous enteral feeding, therefore, redistributed CI to the portal circulation. The improved gut hemodynamics documented in this model may preserve splanchnic integrity and prevent gut-derived complications.

Animals↗
PubMed1993

The effect of respiratory and lactic acidosis on diaphragm function.

The relative effects of respiratory and metabolic acidosis on diaphragm function are not known. To determine these effects, we compared the effects of respiratory and lactic acidosis on the contractile properties of the diaphragm. We estimated diaphragmatic performance from the change in transdiaphragmatic pressure after supramaximal stimulation of the phrenic nerves in an open-chested, casted-abdomen dog. Similarly, we stimulated the gastrocnemius motor nerve and examined force production and relaxation rate to determine if there was a difference in the response of this skeletal muscle. There was a fall in diaphragm performance with respiratory acidosis (77.1 +/- 16.9 cm H2O versus 93.8 +/- 15.0 cm H2O baseline), but not with lactic acidosis (96.7 +/- 15.7 cm H2O versus 93.8 +/- 15.0 cm H2O baseline); and the gastrocnemius was unaffected by either acidosis. The changes with respiratory acidosis were similar to those seen with diaphragmatic fatigue and had similar relaxation rate changes, suggesting that intracellular pH may play a mechanistic role in respiratory muscle fatigue. In addition, the absence of a respiratory acidosis effect on a non-diaphragmatic skeletal muscle's function represents another physiologic difference between the diaphragm and other skeletal muscles.

Acidosis, Lactic↗
PubMed1993

The addition of sighs during pressure support ventilation. Is there a benefit?

The purpose of this study was to determine if sigh breaths delivered during pressure support ventilation (PSV) were beneficial in maintaining arterial oxygenation (PaO2) and pulmonary mechanics. Ten patients being weaned from mechanical ventilation in the PSV mode were studied. All patients were ventilated for 4 h without sighs, 4 h with sighs, and again for 4 h without sighs. During each 4-h period, continuous measurements of ventilatory volumes and airway pressures were accomplished. At the end of each 4-h period, an arterial blood gas determination was obtained. There were no statistically significant differences in any of the measured variables during the different periods of ventilation. We conclude that the sigh breath is of no benefit during PSV.

Adult↗
PubMed1993

The pathophysiologic changes following bile aspiration in a porcine lung model.

Aspiration of bile is an underpublicized aspiration syndrome. Using a porcine lung model, the physiologic response and the histopathology of lung tissue were evaluated after the intratracheal instillation of sublethal doses of bile. Twenty-one domestic swine (11 to 19 kg) were the studied population. Three groups of five swine were evaluated: a control group received intratracheal physiologic saline (pH 7.45); study group 1 received strained gastric contents (pH 2.24); and study group 2 received strained bile (pH 7.19). All animals received the solutions at 0.5 ml/kg intratracheally. Lungs of six additional animals were studied (two gastric, two bile, and two physiologic saline) after aspiration by scanning electron microscopy (SEM). A seventh untreated animal was used as the SEM control. The physiologic data were analyzed using analysis of variance for repeated measures. The SEM and histopathologic results were graded by an observer blinded to the groups and were analyzed using the analysis of variance (ANOVA) and Scheffe tests. The group with bile aspiration was consistently characterized by significant deterioration of PaO2, the alveolar-arterial (A-a) gradient, shunt fraction, and static compliance (p < 0.01); and the light histopathologic and SEM findings demonstrated pathologic changes in the bile-exposed lung (p < 0.05) greater than the gastric- or saline-exposed lungs. It is concluded that bile aspiration produces a severe chemical pneumonitis leading to noncardiac pulmonary edema.

Animals↗
PubMed1993

Humidification in the intensive care unit. Prospective study of a new protocol utilizing heated humidification and a hygroscopic condenser humidifier.

STUDY OBJECTIVE: Determine the utility of a proposed algorithm in allowing safe, efficient humidification in mechanically ventilated patients using both a hygroscopic condenser humidifier (HCH) and heated humidifier (HH). DESIGN: A prospective study using an algorithm to chose humidification devices based on physical examination and sputum characteristics. SETTING: All patients admitted to the surgical ICU. PATIENTS: One hundred twenty consecutive patients requiring mechanical ventilation (MV) were studied. INTERVENTIONS: Patients were examined by the attending respiratory care practitioner and given either an HCH or HH. If patients demonstrated any of the following--thick or tenacious secretions, core temperature < 32 degrees C, or bloody secretions--they were given an HH. All others used an HCH. If any of the above conditions occurred during HCH use, the patient was given an HH. MEASUREMENTS AND RESULTS: Duration of ventilation, incidence of nosocomial pneumonia, ventilator circuit colonization, and mortality were determined for patients in each group. Cost of humidification devices, number of suctioning procedures per day, and volume of saline solution instilled were also recorded. Initially, 27 percent (32/120) of patients used an HH and 73 percent (88/120) used an HCH. During the study, ten patients required changing to an HH during HCH use. Patients in the HH group were more likely to have preexisting lung disease and had a longer duration of ventilation (83 +/- 21 h) and higher mortality (21 percent). Patients in the HCH group were more likely to be postoperative, had shorter durations of ventilation (38 +/- 14 h), and lower mortality (9 percent). There was no difference in the incidence of nosocomial pneumonia between the two groups (9 percent vs 6 percent) and endotracheal tube occlusion did not occur in either group. Circuit colonization was common in the HH group (64 percent) but rate in the HCH group (5 percent). Cost per day was significantly less for the HCH group ($4 vs $19.80). Patients who required a change from HCH to HH did so at a mean of 5 days. CONCLUSION: The proposed algorithm resulted in cost-efficient and safe application of humidification devices in patients in the surgical ICU.

Adult↗
PubMed1993

The effect of manipulation on range of movement at the ankle joint.

Manipulation is commonly used by physiotherapists in the treatment of musculoskeletal disorders; however, there have been few studies evaluating its use in peripheral joints. The purpose of this study was to investigate the effect of manipulation on dorsiflexion range of movement at the ankle joint. Twenty asymptomatic subjects participated, one ankle acting as the experimental ankle and receiving the manipulation intervention, while the other ankle acted as the control. The manipulation studied was a longitudinal talocrural manipulation. Dorsiflexion range of movement was measured at 5 consecutive torque levels pre and post manipulation intervention in the experimental ankle and pre and post no intervention in the control ankle. These values were compared using analysis of trend within an analysis of variance framework. There was no statistically significant change in dorsiflexion range of movement following manipulation. It was concluded that in the case of asymptomatic subjects these results did not provide support for the experimental hypothesis that a single talocrural manipulation alters dorsiflexion range of movement. It was suggested that future research investigate the effects of manipulation in a symptomatic population.

Adult↗
PubMed1993

Acid phosphatase activity in senile plaques and cerebrospinal fluid of patients with Alzheimer's disease.

The origin of the various components of senile plaques in Alzheimer's disease (AD) continues to be a focus of intense research scrutiny. Lysosomal enzyme activity within the plaques is of particular interest because of its possible relevance to a presumed abnormal processing of precursor molecules that may lead to the formation of plaque amyloid. Histochemical evidence of acid phosphatase (ACP), a lysosomal hydrolase, activity in senile plaques has been documented long before many of the current biochemical data regarding plaque pathogenesis became available. Recent evidence suggests the presence of neuronal membrane abnormalities that may allow "leakage" of some intracellular molecules, including enzymes, into the perineuronal environment and from there, possibly, to the cerebrospinal fluid (CSF). In the course of investigating this hypothesis, we decided to readdress the issue of ACP activity in AD by assaying the enzyme both in brain tissue sections as well as in CSF samples from neuropathologically confirmed cases of AD and from normal control subjects. Brain frozen sections from five cases with AD and five control subjects were histochemically stained for ACP using the alpha-naphthylphosphate hydrolysis method. Frozen CSF samples from 15 cases with AD and 19 control subjects were assayed for ACP activity using the thymolphthalein monophosphate hydrolysis method. In all cases studied, CSFs were cytologically unremarkable. Neurons in normal and AD brains were strongly positive for ACP. In AD, numerous senile plaques showed strong ACP activity with both granular and diffuse patterns. The CSFs from six of 15 AD cases (40%) showed ACP activity with values ranging from 0.04 to 0.4 U/L. No ACP activity was detected in any of the 19 control CSFs analyzed. The exact source of ACP in senile plaques and CSF of patients with AD cannot be established based on these data alone but the ACP may have originated from neurons with oxidative stress or oxygen free radical-mediated membrane damage. The data encourage further investigation of this hypothesis.

Acid Phosphatase↗
PubMed1992

A comparison of the enzymological and biophysical properties of two distinct classes of dehydroquinase enzymes.

This paper compares the biophysical and mechanistic properties of a typical type I dehydroquinase (DHQase), from the biosynthetic shikimate pathway of Escherichia coli, and a typical type II DHQase, from the quinate pathway of Aspergillus nidulans. C.d. shows that the two proteins have different secondary-structure compositions; the type I enzyme contains approx. 50% alpha-helix while the type II enzyme contains approx. 75% alpha-helix. The stability of the two types of DHQase was compared by denaturant-induced unfolding, as monitored by c.d., and by differential scanning calorimetry. The type II enzyme unfolds at concentrations of denaturant 4-fold greater than the type I and through a series of discrete transitions, while the type I enzyme unfolds in a single transition. These differences in conformational stability were also evident from the calorimetric experiments which show that type I DHQase unfolds as a single co-operative dimer at 57 degrees C whereas the type II enzyme unfolds above 82 degrees C and through a series of transitions suggesting higher orders of structure than that seen for the type I enzyme. Sedimentation and Mr analysis of both proteins by analytical ultracentrifugation is consistent with the unfolding data. The type I DHQase exists predominantly as a dimer with Mr = 46,000 +/- 2000 (a weighted average affected by the presence of monomer) and has a sedimentation coefficient s0(20,w) = 4.12 (+/- 0.08) S whereas the type II enzyme is a dodecamer, weight-average Mr = 190,000 +/- 10,000 and has a sedimentation coefficient, s0(20,w) = 9.96 (+/- 0.21) S. Although both enzymes have reactive histidine residues in the active site and can be inactivated by diethyl pyrocarbonate, the possibility that these structurally dissimilar enzymes catalyse the same dehydration reaction by the same catalytic mechanism is deemed unlikely by three criteria: (1) they have very different pH/log kcat. profiles and pH optima; (2) imine intermediates, which are known to play a central role in the mechanism of type I enzymes, could not be detected (by borohydride reduction) in the type II enzyme; (3) unlike Schiff's base-forming type I enzymes, there are no conserved lysine residues in type II amino acid sequences.

Bacterial Proteins↗
PubMed1992

Axillary node dissection for early breast cancer: some is good, but all is better.

Optimal management of the axillary lymphatics in breast cancer patients remains a contentious subject. Axillary recurrence, while infrequent, may have very significant clinical consequences in the affected patient. Axillary sampling, partial and total axillary lymphadenectomy, radiotherapy, and surgery plus radiotherapy are discussed with attention to efficacy in prevention of axillary recurrence, accuracy of nodal staging, and morbidity. The incidence of axillary recurrence decreases and accuracy of staging increases with the number of lymph nodes resected. There is little difference in incidence of morbidity between partial and total axillary lymphadenectomy. Radiotherapy is not as effective as lymphadenectomy for regional disease control and, when administered following a surgical staging procedure, increases the risk of lymphedema of the ipsilateral upper extremity and, in patients undergoing breast-conserving surgery, the ipsilateral breast. We believe that total axillary lymphadenectomy provides optimal regional disease control and axillary staging with morbidity comparable to that of partial lymphadenectomy.

Axilla↗
PubMed1992

Gut feeding and hepatic hemodynamics during PEEP ventilation for acute lung injury.

Mechanical ventilation with positive end-expiratory pressure (PEEP) limits hepatic blood flow (HBF) and oxygen delivery (HO2D). Early gut feeding may augment hepatic hemodynamics and avoid relative ischemia in this flow-limited environment. To examine these effects, canines were instrumented with arterial, pulmonary artery, portal, and hepatic vein catheters. Splenectomy and gastrostomy were performed and the hepatic artery and portal vein were encircled with flow probes. All animals underwent lung injury with oleic acid (0.08 ml/kg) followed by the addition of 10 cm H2O PEEP to correct shunt. One group (fed) was then given a bolus elemental feeding (1 kcal/ml, 10 ml/kg) and the Control group, sterile water. Cardiac index (CI), HBF, hepatic oxygen delivery (HO2D), and hepatic oxygen consumption (HO2C) were measured at baseline (T0), after PEEP (T1), and 1 (T2) and 2 hr (T3) after feeding. Data were tested for significant changes between time points in the same group by ANOVA and significant differences were subjected to t testing. PEEP significantly decreased CI, HBF, and HO2D compared to baseline. Subsequently, gut feeding increased HBF to baseline levels and improved HO2D. HO2C also increased but hepatic O2 extraction was unchanged. There was little change noted in the control group over this same period. We conclude that gut feeding augments HBF and HO2D in this flow-limited state and may preserve splanchnic integrity in critical illness.

Acute Disease↗
PubMed1992

Sterility of refrigerated injectable collagen syringes after injection of patient.

BACKGROUND: Injectable collagen has been used for more than 15 years to correct soft tissue cosmetic defects. After injection, the collagen remaining in the syringe is often refrigerated for later use in the same patient, despite manufacturer and Food and Drug Administration recommendations to discard the unused collagen. OBJECTIVE: This study examined the incidence of bacterial contamination of stored collagen. METHODS: Syringe needle tips and collagen from 50 previously used syringes containing either Zyderm I, Zyderm II, or Zyplast were cultured separately under aerobic and anaerobic conditions. Bacterial isolates were identified. RESULTS: Propionibacterium acnes was cultured from 7 of 50 needle tips. One positive needle tip culture grew both P. acnes and Staphylococcus aureus. Bacteria were isolated from only one collagen sample that grew a nonhemolytic streptococcus that may have represented a laboratory contaminant. CONCLUSION: Syringes of collagen stored for repeated use rarely become contaminated with bacteria despite frequent contamination of their needle tips. Skin abscesses after collagen injection should be cultured under anaerobic, as well as aerobic, conditions so that infections caused by P. acnes will not be missed.

Collagen↗