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K Davis

Publications and source records attributed to K Davis.

At least 19 recordsLinked to original sources

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

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

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

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

To smile again.

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Adaptation, Psychological

Monoethylglycinexylidide production parallels changes in hepatic blood flow and oxygen delivery in lung injury managed with positive end-expiratory pressure.

Mechanical ventilation with high levels of positive end-expiratory pressure (PEEP) decreases hepatic blood flow (HBF) and hepatic oxygen delivery (HO2D). Noninvasive methods of detecting decreased HBF might prevent hepatic ischemia and dysfunction. Monoethylglycinexylidide (MEGX) is a hepatic metabolite of lidocaine, used clinically to determine graft function following hepatic transplantation. In order to test the hypothesis that MEGX production would be affected by changes in hepatic hemodynamics associated with lung injury, 12 dogs were instrumented with femoral and pulmonary artery catheters. Splenectomy was performed and the portal and hepatic veins cannulated. The hepatic artery and portal vein were encircled with flow probes. Lung injury was induced in six animals (INJURED group) with oleic acid (0.08 mL/kg) and 10 cm H2O PEEP was added to correct subsequent shunt. Levels of MEGX were measured 15 minutes after injection of intravenous lidocaine (1 mg/kg). Levels of HBF, HO2D, and MEGX were measured at BASELINE, after lung injury (INJURY time point), and after addition of PEEP (PEEP time point). CONTROL animals (n = 6) were studied at the same time points but without lung injury or PEEP. Hepatic blood flow and hepatic oxygen delivery were significantly decreased after lung injury and further decreased after PEEP. Levels of MEGX were unchanged in the CONTROL group but were significantly reduced by lung injury and PEEP in the INJURED group. Decreased MEGX production may be a useful clinical indicator of reduced hepatic flow and oxygen supply in critical illness.

Animals

Cost and complications during in-hospital transport of critically ill patients: a prospective cohort study.

We prospectively studied transport of a group of 100 surgery/trauma patients and a matched control group in the ICU. APACHE II scores for the two groups were 23 +/- 6 and 20 +/- 8. During transport both groups had ECG, heart rate, blood pressure, and oxygen saturation continuously monitored. We also determined the cost and results of transport for those patients requiring diagnostic testing. There were six diagnostic tests performed: CT scan of the abdomen (39%), CT scan of the head (31%), CT scan of the chest (8%), CT scan of the cervical spine (4%), angiography (14%), and tomography (4%). Average transport time was 74 +/- 16 minutes with a range of 20-225 minutes. Physiologic changes defined as a BP +/- 20 mm Hg, heart rate +/- 20 beats/min, respiratory rate +/- 5 breaths/min, or oxygen saturation +/- 5% for 5 minutes duration occurred in 66% of transported patients and 60% of ICU patients. There were no differences in arterial blood gas levels before and during transport. In 39% of transports, the results of diagnostic testing produced a change in patient management within 48 hours. Abdominal CT scanning and angiography were associated with the highest percentage of tests leading to a management change (51% and 57%). The average charge to the patient was $612.00 and the average cost to the hospital $452.00. Our results suggest that while physiologic changes are frequent during transport, they are also frequent in ICU patients as a consequence of the severity of illness.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Impaired acetylcholine release in the inflamed rat intestine is T cell independent.

We investigated mechanisms underlying the suppression of [3H]acetylcholine ([3H]ACh) release from myenteric plexus-longitudinal muscle preparations of rats infected 6 days previously with Trichinella spiralis. There was a 73% suppression of KCl-evoked release of [3H]ACh in the jejunum, and a 76% suppression was observed in the worm-free ileum, indicating that the local presence of the parasite in the lumen is not prerequisite for the suppression of ACh release from the myenteric plexus. Treatment of rats with betamethasone (3 mg.kg-1.day-1 ip) during the infection prevented the acute inflammatory response and attenuated the suppression of [3H]-ACh release (from 73 to 22%) in the jejunum of infected rats. This finding is consistent with the hypothesis that the suppression of ACh release occurs as a result of the inflammatory process. Marked suppression of [3H]ACh release was also seen in T. spiralis-infected nude athymic rats, which were shown to lack functioning T lymphocytes. Thus changes in ACh release are not dependent on T lymphocytes. Taken in conjunction with our previously published study showing that altered muscle function in this model is T cell dependent, the results of the present study indicate that different components of the inflammatory response mediate changes in smooth muscle and myenteric nerves in the T.spiralis infected rat.

Acetylcholine

Balloon mitral commissurotomy after previous surgical commissurotomy. The National Heart, Lung, and Blood Institute Balloon Valvuloplasty Registry participants.

BACKGROUND: Mitral restenosis after surgical mitral commissurotomy often occurs within 5-15 years, necessitating a repeat procedure. Balloon mitral commissurotomy (BMC) has been advocated as an alternative to repeat surgery for mitral restenosis. METHODS AND RESULTS: The purposes of this study are to determine the short- and intermediate-term outcomes of patients undergoing BMC after previous surgical commissurotomy, to compare these patients with those undergoing balloon mitral commissurotomy as an initial procedure, and to elucidate the multivariate determinants of acute procedural and clinical outcome. Of 738 patients undergoing BMC as part of the National Heart, Lung, and Blood Institute Balloon Valvuloplasty Registry, 133 underwent BMC after previous surgical mitral commissurotomy. Prospective data obtained included demographic, hemodynamic, echocardiographic, and clinical follow-up. BMC after previous surgical commissurotomy produced a significant reduction in transvalvular gradient from 13 +/- 5 to 6 +/- 3 mm Hg (p less than 0.0001) and an increase in mitral valve area from 1.0 +/- 0.3 to 1.8 +/- 0.8 cm2 (p less than 0.0001). BMC as an initial procedure increased valve area from 1.0 +/- 0.4 to 2.0 +/- 0.8 cm2 (p less than 0.0001) (p = 0.03 versus prior surgery). Baseline characteristics including mitral valve echo score were similar for both groups. Comparing 6-month status in patients with prior surgery to those without, 80% versus 90% were New York Heart Association (NYHA) functional class I or II (p = 0.004). Mortality was similar. In patients with previous mitral valve surgery, multivariate predictors of improvement in 6-month clinical status included the experience of the center (p = 0.006), lower echocardiographic score (p = 0.001), and lower left ventricular end-diastolic pressure (p = 0.008). Multivariate determinants of a final mitral valve area greater than or equal to 1.5 cm2 were a lower baseline NYHA functional class (p = 0.003) and lower mitral valve echocardiographic score (p = 0.008). CONCLUSIONS: BMC after previous surgical mitral commissurotomy results in similar hemodynamic changes as in patients undergoing BMC as an initial procedure. Symptomatic improvement at 6 months is slightly less frequent in prior commissurotomy patients. Patients with favorable valvular morphology and preserved left ventricular function who undergo BMC in experienced centers are most likely to achieve symptomatic improvement after previous surgical commissurotomy. In general, BMC is an effective treatment for mitral restenosis after previous surgical commissurotomy.

Catheterization

The injured duodenum.

Duodenal injuries are relatively infrequent. A high index of suspicion is required because the retroperitoneal location of the duodenum makes the diagnosis of injuries difficult. Physical findings may be subtle and nonspecific. Contrast studies are often required to make the diagnosis. Options for operative management are outlined. Morbidity and mortality are related to associated injuries and delay in diagnosis.

Abdominal Injuries

Expanding Medicare and employer plans to achieve universal health insurance.

This article presents a proposal for expanding Medicare and employer-based health insurance plans to achieve universal health insurance. Under this proposed health care financing system, employees would provide basic health insurance coverage to workers and dependents, or pay a payroll tax contribution toward the cost of their coverage under Medicare. States would have the option of buying all Medicaid beneficiaries and other poor individuals into Medicare by paying the Medicare premiums and cost sharing. Other uninsured individuals would be automatically covered by Medicare. Employer plans would incorporate Medicare's provider payment methods. This proposal would result in incremental federal governmental outlays on the order of $25 billion annually. These new federal budgetary costs would be met through a combination of premiums, employer payroll tax, income tax, and general tax revenues. The principal advantage of this plan is that it draws on the strengths of the current system while simplifying the benefit and provider payment structure and instituting innovations to promote efficiency.

Costs and Cost Analysis

Total axillary lymphadenectomy in the management of breast cancer.

The optimal extent of axillary dissection in patients with breast cancer remains unclear. We report 278 total axillary lymphadenectomies (levels I, II, and III and Rotter's [interpectoral] nodes) that were performed in 264 closely followed up private patients. There have been no axillary recurrences to date (mean follow-up, 50 months). If only level I and II nodes had been removed, the false-negative staging error would have been only 2.6%. However, 29 (31.5%) of 92 pathological node-positive axillae contained apical and/or Rotter's metastases. The incidence of complications was comparable with that reported for partial lymphadenectomy. Arm lymphedema developed in 6% of nonirradiated patients; postoperative radiotherapy and gross nodal disease were significant risk factors for lymphedema. Total axillary lymphadenectomy largely prevents axillary, recurrence, eliminates the small staging error inherent in partial lymphadenectomy, and has acceptable morbidity, provided radiotherapy to the regional nodal areas is avoided.

Adult

The effect of low dose dopamine on gut hemodynamics during PEEP ventilation for acute lung injury.

Mechanical ventilation with positive end-expiratory pressure (PEEP) diminishes gut and hepatic blood flow and redistributes cardiac output away from the splanchnic circulation. This flow-limited environment can aggravate underlying hypoperfusion and ischemia in the postinjury setting. To examine the effects of low dose dopamine on a lung injury PEEP model of gut hypoperfusion, six anesthetized, splenectomized canines were instrumented with arterial, pulmonary artery, portal vein, and hepatic vein catheters. Electromagnetic flow probes were placed around the hepatic artery and portal vein for continuous flow measurements. Gut and hepatic blood flow, oxygen delivery, oxygen consumption, and extraction ratio were calculated at four time points: baseline, 1 hr after lung injury with oleic acid, 1 hr after ventilation with 10 cm H2O PEEP, and 1 hr after the continuous infusion of dopamine. Portal flow and gut oxygen delivery fell significantly with the infusion of PEEP. These values returned to near baseline levels with the addition of dopamine. Gut oxygen extraction increased from 16 +/- 2% to 35 +/- 3% with PEEP but returned to near baseline with dopamine (20 +/- 4%, P less than 0.01 compared to PEEP). We conclude that dopamine improves blood flow and oxygen delivery to the gut in this flow-limited model. This may preserve splanchnic physiology during PEEP ventilation for acute lung injury.

Animals

Migration to rural areas by HIV patients: impact on HIV-related healthcare use.

OBJECTIVE: To evaluate the impact of patient migration on human immunodeficiency virus (HIV)-related healthcare use in a rural setting. DESIGN: Data were collected on all patients seeking medical care related to HIV infection at The University of Iowa HIV/acquired immunodeficiency syndrome (AIDS) clinic. Information was collected related to patient care, stage of illness, prior and current residence, and clinic and hospital use. SETTING: An outpatient clinic in a university hospital offering primary and consultative medical care for persons with HIV infection. PATIENTS: All patients scheduled into clinic reported a previous positive HIV serologic test. RESULTS: Forty-five percent (81 of 181) of patients reported moving to Iowa, yet no more than 11% (n = 20) moved out of the state during the same period of observation. Of patients meeting the Centers for Disease Control criteria for AIDS, 24% were diagnosed prior to moving to Iowa (18 of 74). Twenty-seven percent of AIDS-related inpatient days of hospitalization and 19% of AIDS-related outpatient clinic visits were used by persons diagnosed in another state. Lifetime charges totalled for eight patients ranged from $24,873 to $232,556, with a mean of $109,934. CONCLUSIONS: A substantial portion of HIV-related healthcare in our rural area was used by individuals who had migrated to or back to Iowa. Further understanding of the reasons for and the extent of HIV patient migration to rural areas is needed.

Adult

Atrial natriuretic peptide suppresses osmostimulated vasopressin release in young and elderly humans.

Atrial natriuretic peptide (ANP) may suppress vasopressin release, but the dynamics of this interaction as well as the influence of age have not been defined. We studied six or seven young (19-40 yr old) and seven elderly volunteers (65-83 yr old) under two circumstances: 1) after infusion of 5% saline (0.04 ml.kg-1.min-1) for 2 h and 2) after the same infusion given with simultaneous synthetic human ANP (0.05 micrograms.kg-1.min-1). Hypertonic saline alone produced a progressive rise in plasma vasopressin with increasing serum sodium. During hypertonic saline alone, vasopressin levels began to rise at an increment in serum sodium of 1.67 +/- 0.35 mM in the young and 1.43 +/- 0.32 mM in the elderly and rose linearly with increasing serum sodium. When ANP was infused with hypertonic saline (with peak ANP levels of approximately 1,000 pM), vasopressin levels began to rise at an increment in serum sodium of 4.43 +/- 0.67 mM in the young and 4.57 +/- 0.43 mM in the elderly (P less than 0.01 vs. saline alone). Furthermore, the vasopressin response for any given serum sodium was significantly reduced in both young and elderly subjects, resulting in a rightward displacement of the curve relating vasopressin response to sodium concentration (P less than 0.001). In conclusion, ANP not only suppresses vasopressin but raises the threshold for release of vasopressin in response to osmotic stimulation in both young and elderly individuals. High circulating ANP levels may be responsible in part for the suppression of vasopressin levels and water diuresis seen during states of volume expansion.

Adult