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Biomedical subjects

C L Davis

Publications and source records attributed to C L Davis.

At least 37 records · Page 2Linked to original sources
PubMed2000

Prostaglandin E2-induced sensitization of bradykinin-evoked responses in rat dorsal root ganglion neurons is mediated by cAMP-dependent protein kinase A.

Primary cultures of neonatal rat dorsal root ganglion (DRG) neurons were used to examine the mechanisms underlying both the direct activation and the sensitization of sensory neurons by prostanoids. Prostaglandin E2 (PGE2) elevated cytosolic calcium concentration ([Ca2+]i) in a subpopulation of small (< 19 microm) diameter, capsaicin-sensitive DRG neurons. PGE2 also stimulated substance P (SP) release from DRG cultures. In contrast to bradykinin, PGE2 did not stimulate phosphoinositidase C (PIC) and the PGE2-evoked increase in [Ca2+]i was dependent on extracellular calcium. Pre-treatment with PGE2 potentiated bradykinin-evoked increases in [Ca2+]i in small diameter neurons and increased the number of cells that responded to low concentrations of bradykinin. A similar effect was seen with prostaglandin I2 (PGI2) but not prostaglandin F2alpha (PGF2alpha). PGE2 pretreatment also potentiated bradykinin-evoked release of SP, inducing a leftward shift in the bradykinin concentration-response curve and an increase in the maximum response. PGE2 stimulated adenylyl cyclase activity in DRG cultures, at concentrations and times consistent with those required to observe both the direct and sensitizing effects of the prostanoid on [Ca2+]i responses. Furthermore, the direct and sensitizing effects of PGE2, on both [Ca2+]i responses and SP release, were mimicked by the membrane permeant cAMP analogue dibutyryl cAMP and inhibited by H89, an inhibitor of cAMP-dependent protein kinase A (PKA). These observations are consistent with the hypothesis that both direct activation and sensitization of sensory neurons by prostanoids, such as PGE2, are mediated by PKA-dependent phosphorylation mechanisms.

Adenylyl Cyclases↗
PubMed2000

Efficacy of alkaline washing for the decontamination of orange fruit surfaces inoculated with Escherichia coli.

The effectiveness of washing treatments to decontaminate orange fruit surfaces inoculated with Escherichia coli was evaluated. Washing on roller brushes with fruit cleaners or sanitizers followed by potable water rinse reduced E. coli by 1.9 to 3.5 log cycles. Prewetting fruit for 30 s before washing provided no significant benefit in most cases. Additional sanitizing treatments either with chlorine or acid sanitizers did not enhance the results of alkaline washing. In general, high pH washing solutions (pH 11.8) applied with an adequate spray volume effectively reduced the surface contamination of fruit that lowered the microbial load of fresh juice as well.

Animals↗
PubMed1999

Recurrent and de novo glomerular disease after renal transplantation: a report from Renal Allograft Disease Registry (RADR).

INTRODUCTION: Short-term and long-term results of renal transplantation have improved over the past 15 years. However, there has been no change in the prevalence of recurrent and de novo diseases. A retrospective study was initiated through the Renal Allograft Disease Registry, to evaluate the prevalence and impact of recurrent and de novo diseases after transplantation. MATERIALS AND METHODS: From October 1987 to December 1996, a total of 4913 renal transplants were performed on adults at the Medical College of Wisconsin, University of Cincinnati, University of California at San Francisco, University of Louisville, University of Washington, Seattle, and Washington University School of Medicine. The patients were followed for a minimum of 1 year. A total of 167 (3.4%) cases of recurrent and de novo disease were diagnosed by renal biopsy. These patients were compared with other patients who did not have recurrent and de novo disease (n=4746). There were more men (67.7% vs. 59.8%, P<0.035) and a higher number of re-transplants (17% vs. 11.5%, P<0.005) in the recurrent and de novo disease group. There was no difference in the rate of recurrent and de novo disease according to the transplant type (living related donor vs. cadaver, P=NS). Other demographic findings were not significantly different. Common forms of glomerulonephritis seen were focal segmental glomerulosclerosis (FSGS), 57; immunoglobulin A nephritis, 22; membranoproliferative glomerulonephritis (GN), 18; and membranous nephropathy, 16. Other diagnoses include: diabetic nephropathy, 19; immune complex GN, 12; crescentic GN (vasculitis), 6; hemolytic uremic syndrome-thrombotic thrombocytopenic purpura (HUS/TTP), 8; systemic lupus erythematosus, 3; Anti-glomerular basement membrane disease, 2; oxalosis, 2; and miscellaneous, 2. The diagnosis of recurrent and de novo disease was made after a mean period of 678 days after the transplant. During the follow-up period, there were significantly more graft failures in the recurrent disease group, 55% vs. 25%, P<0.001. The actuarial 1-, 2-, 3-, 4, and 5-year kidney survival rates for patients with recurrent and de novo disease was 86.5%, 78.5%, 65%, 47.7%, and 39.8%. The corresponding survival rates for patients without recurrent and de novo disease were 85.2%, 81.2%, 76.5%, 72%, and 67.6%, respectively (Log-rank test, P<0.0001). The median kidney survival rate for patients with and without recurrent and de novo disease was 1360 vs. 3382 days (P<0.0001). Multivariate analysis using the Cox proportional hazard model for graft failure was performed to identify various risk factors. Cadaveric transplants, prolonged cold ischemia time, elevated panel reactive antibody, and recurrent disease were identified as risk factors for allograft failure. The relative risk (95% confidence interval) for graft failure because of recurrent and de novo disease was 1.9 (1.57-2.40), P<0.0001. The relative risk for graft failure because of posttransplant FSGS was 2.25 (1.6-3.1), P<0.0001, for membranoprolifera. tive glomerulonephritis was 2.37 (1.3-4.2), P<0.003, and for HUS/TTP was 5.36 (2.2-12.9), P<0.0002. There was higher graft failure (64.9%) and shorter half-life (1244 days) in patients with recurrent FSGS. CONCLUSION: In conclusion, recurrent and de novo disease are associated with poorer long-term survival, and the relative risk of allograft loss is double. Significant impact on graft survival was seen with recurrent and de novo FSGS, membranoproliferative glomerulonephritis, and HUS/TTP.

Adult↗
PubMed1999

Elevated basal and thapsigargin-stimulated intracellular calcium of platelets and lymphocytes from bipolar affective disorder patients measured by a fluorometric microassay.

BACKGROUND: A number of investigators have reported finding elevated basal and stimulated intracellular calcium levels in the platelets or lymphocytes of bipolar disorder patients. METHODS: Intracellular calcium was measured by a micro fura-2 fluorometric method in the platelets and lymphocytes of 30 affective disorder patients and 14 control subjects. RESULTS: We observed significantly elevated basal calcium concentrations in bipolar patient platelets and lymphocytes compared to control subjects. Bipolar patient platelet calcium responses to thrombin, serotonin, and thapsigargin were also significantly greater than control subjects. The peak calcium levels of lymphocytes of bipolar patients were greater than control subjects only when stimulated by thapsigargin. There were significant differences between bipolar and unipolar patients in basal and thapsigargin-stimulated calcium measures but not between bipolar I and bipolar II patients. Unmedicated versus medicated calcium measures were not significantly different. We also found little correlation between calcium measures and the severity of mood rating. CONCLUSIONS: Using this method, we were able to confirm and extend the work of others, indicating altered intracellular calcium homeostasis in the blood cells of bipolar disorder patients. In addition, our data suggest that storage operated calcium channels may be the source of the elevated intracellular calcium in platelets and lymphocytes of bipolar patients.

Adult↗
PubMed1999

Diagnosing pneumonia by physical examination: relevant or relic?

BACKGROUND: The reliability of chest physical examination and the degree of agreement among examiners in diagnosing pneumonia based on these findings are largely unknown. OBJECTIVES: To determine the accuracy of various physical examination maneuvers in diagnosing pneumonia and to compare the interobserver reliability of the maneuvers among 3 examiners. METHODS: Fifty-two male patients presenting to the emergency department of a university-affiliated Veterans Affairs medical center with symptoms of lower respiratory tract infection (cough and change in sputum) were prospectively examined. A comprehensive lung physical examination was performed sequentially by 3 physicians who were blind to clinical history, laboratory findings, and x-ray results. Examination findings by lung site and whether the examiner diagnosed pneumonia were recorded on a standard form. Chest x-ray films were read by a radiologist. RESULTS: Twenty-four patients had pneumonia confirmed by chest x-ray films. Twenty-eight patients did not have pneumonia. Abnormal lung sounds were common in both groups; the most frequently detected were rales in the upright seated position and bronchial breath sounds. Relatively high agreement among examiners (kappa approximately 0.5) occurred for rales in the lateral decubitus position and for wheezes. The 3 examiners' clinical diagnosis of pneumonia had a sensitivity of 47% to 69% and specificity of 58% to 75%. CONCLUSIONS: The degree of interobserver agreement was highly variable for different physical examination findings. The most valuable examination maneuvers in detecting pneumonia were unilateral rales and rales in the lateral decubitus position. The traditional chest physical examination is not sufficiently accurate on its own to confirm or exclude the diagnosis of pneumonia.

Adult↗
PubMed1999

Idiopathic edema.

Idiopathic edema is a syndrome of real or perceived excessive weight gain. This article reviews what is known about the possible causes, evaluation, and treatment. Although the cause is unknown but often thought to be due to secondary hyperaldosteronism, primary abnormalities of the hypothalamus, thyroid, dopaminergic release or renal dopaminergic metabolism, vascular basement membrane, or capillary sphincter control could perhaps contribute in some patients. The diagnosis requires careful attention to possible abnormalities of the liver, heart, kidneys, gastrointestinal tract, thyroid, and pancreas. The history must include an evaluation for risks of bulimia and purging; diuretic and laxative screening should be performed. Specific records of daily weights, urinary outputs, and menstral cycle dates are useful. Treatment may include dietary counseling to provide weight control and a constant carbohydrate intake, treatments for depression, compression stockings, spironolactone, amiloride, angiotensin II inhibitors, or sympathomimetic agents, depending on the severity and timing of the patient's symptoms. Unfortunately, idiopathic edema may be a multifactorial disorder that has not been completely delineated. Further research into possible causative mechanisms is required before a more useful algorithm for evaluation and treatment is available.

Capillary Permeability↗
PubMed1999

Collapsing glomerulopathy in renal allografts: a morphological pattern with diverse clinicopathologic associations.

We reviewed the clinical and pathological characteristics of seven patients with collapsing glomerulopathy (CG) in renal allograft biopsy specimens. All patients underwent biopsies for graft dysfunction. Two patients had nephrotic proteinuria (protein, >3.5 g/24 h), whereas all others had only modest or insignificant proteinuria. In five of seven patients, additional pathological processes, including microvascular injury, acute rejection, recurrent diabetic nephropathy, and immune complex glomerulonephritis, were present, each of which likely contributed to graft dysfunction and proteinuria. None of the patients in this series had nephrotic syndrome solely attributable to CG. Three biopsy specimens had features consistent with chronic rejection. The development of CG in renal allograft biopsy specimens was associated with graft dysfunction and a high rate of graft loss. These findings emphasize the prognostic significance of CG in renal allografts and suggest that CG may result from diverse pathogenic mechanisms.

Adult↗
PubMed1999

Unique changes in interstitial extracellular matrix composition are associated with rejection and cyclosporine toxicity in human renal allograft biopsies.

Renal allograft loss from chronic rejection or cyclosporine toxicity (CsAT) is characterized by progressive interstitial fibrosis, yet the protein composition of these lesions is unknown. The normal tubular basement membrane (TBM) contains laminin (LM), collagen IV (containing collagen IV alpha chain 1 [COL4A1] and COL4A2), thrombospondin (TSP), and fibronectin (FN). Only TSP and FN extend beyond the TBM into the interstitial space. Very scanty amounts of interstitial collagens (I and III) are detected in the interstitium. In a pilot study of human renal allograft biopsy specimens, three patterns of extracellular matrix (ECM) composition were identified. Pattern 1 showed no change in ECM composition; pattern 2 showed generalized accumulation of collagens I and III in the interstitium; and pattern 3 showed new expression of COL4A3 and LM-beta2 in the proximal TBM. Criteria were established for the clinicopathological diagnosis of CsAT and rejection. These diagnoses were correlated with the ECM composition in 22 renal allograft biopsy specimens. Control groups were examined in a similar manner and included native kidney biopsy specimens from patients with other allografts (n = 7), renal biopsy specimens from patients with glomerular disease (n = 9), and renal allograft biopsy specimens from patients without clinicopathological evidence of renal disease. These data show that rejection is associated with pattern 3 and CsAT is associated with pattern 2. Thus, detection of ECM composition may be a useful adjunct to standard microscopy in distinguishing rejection from CsAT in renal allograft biopsy specimens. These data suggest that interstitial fibrosis associated with rejection and CsAT result from different pathogenic mechanisms.

Biopsy↗
PubMed1999

Numerous length polymorphisms at short tandem repeats in human cytomegalovirus.

We show the presence of numerous short tandem repeats in the human cytomegalovirus (HCMV) genome and assess their usefulness as molecular markers. The genome is shown to contain at least 24 microsatellite regions that exhibit length polymorphisms. Insertion-deletion polymorphisms at these short tandem repeats are common (80% of repeats examined are polymorphic among two laboratory strains and 10 clinical isolates). This is the first report of widespread microsatellite length polymorphism in a viral genome. Some regions are highly polymorphic: one was revealed by DNA sequencing to contain length variants at five closely linked sites, which combined resulted in 10 variants for this region among the 12 strains and isolates examined. This study not only provides a new molecular marker system for this virus but also extends our understanding of microsatellite polymorphism in two important ways. First, variable-length repeats in HCMV can be considerably shorter than polymorphic repeats previously found in other organisms. Second, highly variable microsatellite repeats are not confined to prokaryotes and eukaryotes, as previously assumed. This variation provides a useful marker system for distinguishing viral isolates, and similar markers are also likely to be found in other large-genome DNA viruses.

Cytomegalovirus↗
PubMed1999

Acute renal failure after cardiopulmonary bypass in related to decreased serum ferritin levels.

Acute renal failure (ARF) requiring dialysis occurs in up to 4% of patients after cardiopulmonary bypass (CPB). CPB leads to the generation of intravascular free hemoglobin, resulting in increased endothelial and renal tubular cell free iron, which is associated with renal injury. Conversely, renoprotection is conferred by processes that upregulate heme and iron sequestration pathways, such as ferritin. This study evaluates the influence of free hemoglobin generation during CPB and the capacity to sequester free iron on the occurrence of post-CPB renal insufficiency. Thirty consecutive patients undergoing CPB were enrolled in the study. Serum creatinine, free hemoglobin, and ferritin were measured preoperatively, at the end of bypass, and 24 and 48 h after surgery. Renal injury, as determined by an increase in the serum creatinine of > or =25% (ARF) by 48 h after surgery, occurred in 40% (12 of 30) of patients, and dialysis was necessary in 6.6% (2 of 30). Free hemoglobin levels increased in all patients but did not correlate with postoperative ARF. However, patients with preoperative serum ferritin levels < or =130 microg/L, the median value for the group, had a sixfold greater likelihood of developing ARF compared to patients with levels above this value (P = 0.03). Lower serum ferritin levels appear to be associated with the development of ARF. Serum ferritin levels may signify intravascular as well as endothelial and renal epithelial cell ability to bind free iron generated during CPB-induced hemolysis, and thus may help provide information regarding the risk for ARF.

Acute Kidney Injury↗
PubMed1999

Enhancing microbiological safety of fresh orange juice by fruit immersion in hot water and chemical sanitizers.

Trials were conducted with hot water and chemicals to sanitize Valencia oranges contaminated by natural microflora or inoculated with Escherichia coli. Microbial loads and sensory quality of fresh juice extracted from surface-heated fruit were also evaluated. E. coli on fruit surfaces was reduced by either hot water or chemical treatments. An estimated 5-log reduction of E. coli was attained by immersing inoculated fruit in hot water at 80 degrees C for 1 min or 70 degrees C for 2 min. Immersing inoculated fruit in various chemical solutions at about 30 degrees C for 8 min only reduced E. coli by about 1.8- to 3.1-log cycles on nonstem-scar surfaces of the fruit. In general, both hot water and chemical treatments were less effective at removing microflora from the stem-scar area. Rapid hot-water immersions at 80 degrees C for 1 min and 70 degrees C for 2 min reduced both fruit-surface and initial juice microbial loads without altering original sensory quality of fresh juice.

Beverages↗
PubMed1998

Recombinant human tumor necrosis factor receptor Fc fusion protein therapy in kidney transplant recipients undergoing OKT3 induction therapy.

BACKGROUND: Initial doses of OKT3 are associated with a cytokine-induced acute clinical syndrome (ACS). This study assessed the safety of a recombinant human tumor necrosis factor receptor fusion protein (TNFR:Fc) given to minimize OKT3-ACS symptoms in renal allograft recipients undergoing induction therapy. METHODS: Sixteen patients were randomized into treatment or control groups. Treated patients received TNFR:Fc 1 hr before OKT3 on days 0 and 3. Patients were monitored after transplant for OKT3-ACS symptoms. Levels of cytokines, serum creatinine, and C-reactive protein were followed. RESULTS: Patients receiving TNFR:Fc had lower OKT3-ACS symptoms as measured by a scoring system. There was a higher incidence of infection in treated patients (10/12) compared to controls (1/4) in the 3 months after transplant, but the etiology of this difference was unclear. There were no significant differences in cytokine profiles. CONCLUSIONS: TNFR:Fc is well tolerated by renal transplant patients receiving OKT3 induction therapy and modestly decreases the symptoms associated with OKT3-ACS.

Acute Disease↗
PubMed1998

Interferon-alpha treatment of posttransplant lymphoproliferative disorder in recipients of solid organ transplants.

Posttransplant lymphoproliferative disorder (PTLD) has been treated with decreased immunosuppression, antiviral medications, anti-B lymphocyte agents, radiation therapy, and/or chemotherapy. However, a standardized stepwise approach to treatment has not been previously evaluated. In the present study, 19 consecutive patients presenting to a single institution with newly diagnosed PTLD were treated according to a sequential protocol that consisted of (1) a reduction in immunosuppressive medications plus, if feasible, resection or definitive radiation therapy of localized disease, (2) interferon-alpha, and (3) systemic chemotherapy. Of the 3 patients presenting exclusively with localized disease, two were treated with resection of pulmonary parenchymal nodules and one was treated with radiation therapy to a paraspinous mass, without evidence of recurrence at a mean follow-up of 31 months (range, 8 to 46 months). Sixteen patients presented with PTLD not amenable to local therapy, and they were treated daily with 3x10(6) units/m2 subcutaneous interferon-alpha. Total regression of PTLD (defined as disappearance of the tumor mass by physical examination or computed tomography scanning) was found in 8 of 14 patients who received at least 3 weeks of interferon therapy. Interferon-alpha therapy was continued for 6 to 9 months in the eight patients judged to be responders. None of these patients have relapsed to date with the same neoplastic clone. Two patients, however, developed new neoplastic clones. Seven patients received systemic chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) (n=1), EPOCH (etoposide, vincristine, and doxorubicin administered as a continuous infusion, with an intravenous bolus of cyclophosphamide and oral prednisone) (n=4), or EPOCH followed by DHAP (dexamethasone, cytarabine, and cisplatin) (n=2) after failure of interferon-alpha; five patients had a complete response. Only 1 of the 19 patients died of uncontrolled PTLD. These results suggest that the majority of solid organ transplant recipients who develop PTLD can be safely and successfully treated using a sequential approach to therapy.

Adult↗
PubMed1998

Successful treatment of severe hepatitis C-associated pulmonary vasculitis in a liver transplant recipient.

BACKGROUND: We report the clinical course of a patient who developed fever, hypoxia, and bilateral pulmonary infiltrates two and a half years after orthotopic liver transplantation (OLT) for cirrhosis due to hepatitis C. The patient had a history of hepatitis C-associated vasculitis manifested by purpuric skin rashes, renal abnormalities, and elevated cryoglobulins, and was receiving interferon-alpha at the time of presentation. RESULTS: The results of bronchoscopy with bronchoalveolar lavage were unrevealing, and open lung biopsy revealed active small vessel vasculitis. The patient responded dramatically to plasmapheresis and the addition of high-dose corticosteroids with resolution of hypoxia, pulmonary infiltrates, and glomerulonephritis. This is, to our knowledge, the first report of the successful treatment of hepatitis C-associated pulmonary vasculitis after OLT. CONCLUSIONS: We conclude that hepatitis C-associated pulmonary vasculitis should be included in the differential diagnosis of a patient presenting with fever, hypoxia, and pulmonary infiltrates after OLT for hepatitis C. Treatment with plasmapheresis and high-dose corticosteroids may be effective in patients with this disorder.

Adrenal Cortex Hormones↗