Multiskilling and multicredentialing of the health professional: role of the cardiac sonographer. Sonographer Council of the American Society of Echocardiography.
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Credentialing↗
Biomedical subjects
C L Davis
Publications and source records attributed to C L Davis.
Expression of PDGF alpha-receptor in renal arteriosclerosis and rejecting renal transplants.
Platelet-derived growth factor (PDGF) plays an important role in renal disease. We have recently demonstrated that in healthy mature human kidney, PDGF alpha-receptor expression is largely restricted to interstitial cells. The study presented here assesses the expression of PDGF alpha-receptor in 18 mature adult kidneys with arteriosclerosis from individuals with no clinically evident history of renal disease other than localized neoplasia, in 13 kidneys with irreversible transplant rejection, and in a series of renal transplant biopsies composed of examples of both severe and absent rejection, by in situ hybridization and immunocytochemistry. Strong focal or diffuse expression of PDGF alpha-receptor mRNA and protein was noted in some intimal cells of intrarenal arterial vessels exhibiting signs of arteriosclerosis and/or vascular rejection. By double immunostaining, it could be shown that these cells were neither endothelial cells nor infiltrating leukocytes. The cells were most often identified as smooth muscle by colabeling for the smooth muscle cell-specific protein SM22alpha and less commonly for alpha-smooth muscle actin. There was also a population of PDGF alpha-receptor-expressing cells that failed to colabel with any of these markers, and hence remain of uncertain histogenesis. These intimal cells were generally negative for several other markers of differentiated smooth muscle cells, i.e., calponin and desmin. Near these PDGF alpha-receptor-positive intimal cells, expression of PDGF A-chain, an alpha-receptor ligand, was demonstrated in endothelial, intimal, and/or medial cells. Prominent PDGF alpha-receptor mRNA and protein expression also was noted in areas of interstitial fibrosis and in some glomeruli, in particular those with segmental glomerulosclerosis or fibrotic crescents. Double immunolabeling for PDGF alpha-receptor and alpha-smooth muscle actin confirmed that most of these latter PDGF alpha-receptor-positive cells were interstitial myofibroblasts or mesangial cells, or both. In summary, these data demonstrate widespread expression of PDGF alpha-receptor in renal cell types involved in fibrotic and sclerosing processes. The data also show that PDGF alpha-receptor expression identifies a unique population of phenotypically altered vascular smooth muscle cells, which appear to be involved in the vascular response to injury.
Adult↗
ABC of palliative care. Breathlessness, cough, and other respiratory problems.
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Cough↗
Association of hepatitis C virus infection with mortality and graft survival in kidney-pancreas transplant recipients.
BACKGROUND: Although most studies have not demonstrated decreased patient or graft survival in kidney-alone allograft recipients infected with hepatitis C virus (HCV), the impact of HCV infection on patient and graft survival in HCV-infected kidney-pancreas recipients has not been studied. METHODS: We undertook a retrospective cohort analysis of 137 kidney-pancreas transplant recipients who were transplanted between January 1989 and May 1996. HCV infection was determined by a positive polymerase chain reaction. Relative risk of death and graft failure was calculated using the Cox proportional hazards model with time-dependent covariates. Relative risks were adjusted (aRR) to control for the number of OKT3-treated rejections and cytomegalovirus status of the recipient at the time of transplantation. RESULTS: Mean length of follow-up was 30.4 months in the HCV-infected patients compared with 31.7 months in noninfected patients. Seven (5.1%) patients were infected with HCV before transplant, one (1%) relapsed after transplantation, and four (2.9%) acquired the infection after transplantation. The HCV-infected group had a 3.7-fold (95% confidence interval [CI], 1.0-13.5) increased risk of death after transplant compared with the HCV-negative group, with an aRR of 5.5 (95% CI, 1.5-20.0). Death in the HCV-infected group (n=3) was generally the result of liver failure and sepsis, whereas death for those in the uninfected group (n=11) was primarily of cardiovascular origin. Patients infected with HCV were 3.4-fold (95% CI, 1.1-10.1) more likely to develop kidney graft failure than HCV-negative patients with an aRR of 5.1 (95% CI, 1.7-15.4). The risk of pancreatic allograft failure was not significantly increased. CONCLUSIONS: We conclude that HCV infection in kidney-pancreas transplant patients results in a significantly increased risk of kidney allograft failure and death.
Adult↗
Renal disease in hepatitis C-positive liver transplant recipients.
Glomerular abnormalities are frequent in patients undergoing liver transplantation; however, renal dysfunction following transplantation is mainly attributed to cyclosporine toxicity. Membranoproliferative glomerulonephritis (MPGN) is seen in patients infected with hepatitis C virus (HCV), the virus responsible for 30% of the end-stage liver disease leading to liver transplantation. To determine the incidence of renal abnormalities in liver transplant recipients and the association with HCV, we undertook a longitudinal study in HCV-positive (n=91) and HCV-negative (n=106) liver transplant recipients. Mean creatinine clearance before transplantation was 94 ml/min/1.73 m2 in HCV+ patients and 88 ml/min/1.73 m2 in HCV- patients. By 3 months after transplantation, the mean creatinine clearance decreased by approximately one third in both groups. A greater proportion of HCV+ patients excreted >2 g protein/day after transplantation (P=0.05) and had renal biopsies showing MPGN than did HCV- recipients (4/10 HCV+ patients vs. 0/7 HCV- patients; P=0.1). In the HCV+ group, proteinuria was not associated with recurrent HCV hepatitis, DQ matching, posttransplant diabetes, or hypertension. Treatment of HCV-related MPGN with interferon-alpha2b appeared to stabilize proteinuria and renal function but did not reverse renal dysfunction nor cause liver allograft rejection. After transplantation, HCV+ patients had similar renal function over 3 years after transplantation, compared with HCV- patients, but they had an increased risk of proteinuria and occurrence of MPGN that was only partially responsive to interferon.
Adult↗
Utilization of supplemental triglycerides or free fatty acids by calves from 4 to 10 weeks of age.
Our objectives were 1) to determine the effects of increased availability of 2-monoglycerides from triglyceride digestion on absorption of free fatty acids (FFA) and utilization of nutrients by calves of weaning age and 2) to determine whether absorption of FFA increased with age. Thirty-two male Holstein calves were fed milk replacer until d 28 of age and then were assigned, to one of four treatments: 1) control, 80 g/d of whey protein concentrate in 2 L of water; 2) control plus 120 g/d of lard triglycerides; 3) control plus 90 g/d of lard triglycerides plus 30 g/d of lard FFA (low FFA); and 4) control plus 60 g/d of triglycerides plus 60 g/d of lard FFA (high FFA). Treatments were fed by nipple pail twice daily to maintain closure of the esophageal groove. Intake of calf starter (available continuously) was decreased by supplemental fats and tended to be lower for calves fed high FFA than for those fed low FFA. Digestibilities of total C18 fatty acids and total fatty acids were lower for calves fed triglycerides than for calves fed FFA, but digestibilities were not affected by age. Energy digestibility was greater for fat treatments than for controls and was greater for FFA treatments than for triglycerides, but intakes of digestible energy and metabolizable energy did not differ. Absorbed N was greater for calves on the control treatment than for those on the fat treatments, but retained N and average daily gain did not differ. Digestibility of fatty acids was greater for calves fed mixtures of triglycerides and FFA than for those fed triglycerides alone, but digestibility did not change during wk 6 to 10 of age.
Aging↗
Relation between general practitioners' prescribing of antibacterial drugs and their use of laboratory tests.
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Anti-Bacterial Agents↗
Cyclosporine-associated thrombotic microangiopathy/hemolytic uremic syndrome following kidney and kidney-pancreas transplantation.
Cyclosporine-associated thrombotic microangiopathy (CsA-TMA) is characterized by anemia, acute renal failure, and renal TMA. We report a case-control study of 13 patients (seven kidney-alone transplant recipients and six kidney-pancreas transplant recipients) who developed TMA (12 CsA, 1 FK506). Once CsA-TMA was identified, CsA or FK506 was discontinued and isradipine, aspirin, and pentoxifylline were started. Cyclosporine was reinstituted in all patients once serum creatinine reached the previous baseline value. Patients developing further decreases in renal function on rechallenge with CsA were converted to FK506 (n = 3). Rechallenge with CsA was successful in nine of the 13 patients (69%), with three (23%) converted to FK506 for a total salvage rate of 92%. The creatinine clearance at 6 months, 1 year, and 2 years following transplantation was 73.2 +/- 25.7 mL/min, 54.7 +/- 18.8 mL/min, and 57.0 +/- 32.0 mL/min, respectively, for patients successfully rechallenged with CsA compared with 67 +/- 17 mg/min, 71.8 +/- 21.2 mL/min, and 69 +/- 19 mg/min, respectively, for controls (P = NS). The average creatine clearance for patients converted to FK506 was 44.7 +/- 31.2 mL/min at 6 months following transplantation (n = 3) and 27.0 +/- 11.3 mL/min at 1 year. In this case-controlled retrospective series of renal transplant patients with documented CsA-TMA, the triple-drug combination of isradipine, aspirin, and pentoxifylline allowed for the successful reinstitution of CsA or conversion to FK506 in the setting of TMA, and resulted in increased transplant survival compared with previous reports.
Adolescent↗
B1 bradykinin receptors and sensory neurones.
1. The location of the B1 bradykinin receptors involved in inflammatory hyperalgesia was investigated. 2. No specific binding of the B1 bradykinin receptor ligand [3H]-des-Arg10-kallidin was detected in primary cultures of rat dorsal root ganglion neurones, even after treatment with interleukin-1 beta (100 iu ml-1). 3. In dorsal root ganglion neurones, activation of B2 bradykinin receptors stimulated polyphosphoinositidase C. In contrast, B1 bradykinin receptor agonists (des-Arg9-bradykinin up to 10 microM and des-Arg10-kallidin up to 1 microM) failed to activate polyphosphoinositidase C, even in neurones that had been treated with interleukin-1 beta (100 iu ml-1), prostaglandin E2 (1 microM) or prostaglandin I2 (1 microM). 4. Dorsal root ganglion neurones removed from rats (both neonatal and 14 days old) that had been pretreated with inflammatory mediators (Freund's complete adjuvant, or carrageenan) failed to respond to B1 bradykinin receptor selective agonists (des-Arg9-bradykinin up to 10 microM and des-Arg10-kallidin up to 1 microM). 5. Bradykinin (25 nM to 300 nM) evoked ventral root responses when applied to peripheral receptive fields or central terminals of primary afferents in the neonatal rat spinal cord and tail preparation. In contrast, des-Arg9-bradykinin (50 nM to 500 nM) failed to evoke ventral root depolarizations in either control rats or in animals that developed inflammation following ultraviolet irradiation of the tail skin. 6. The results of the present study imply that the B1 bradykinin receptors that contribute to hypersensitivity in models of persistent inflammatory hyperalgesia are located on cells other than sensory neurones where they may be responsible for releasing mediators that sensitize or activate the nociceptors.
Animals↗
Acupuncture for the relief of cancer-related breathlessness.
The palliation of cancer-related breathlessness is challenging and complex. An open pilot study was conducted, exploring the safety and efficacy of acupuncture in 20 patients who were breathless at rest and whose breathlessness was directly related to primary or secondary malignancy. Sternal and LI4 acupuncture points were used. Outcome measures included pulse, respiratory rate, oxygen saturation and patient-rated visual analogue scales of breathlessness, pain, anxiety and relaxation. At each time point the mean values of the variables were calculated and compared to their pretreatment levels (Student's t-test). Seventy per cent (14/20) of patients reported marked symptomatic benefit from treatment; there were significant changes in VAS scores of breathlessness, relaxation and anxiety at least up to 6 hours post acupuncture which were measured to be maximal at 90 minutes (p < 0.005, p < 0.001, respectively). There was a significant reduction in respiratory rate, which was sustained for 90 minutes post acupuncture (p < 0.02). The therapeutic value of acupuncture in the management of breathlessness requires further evaluation.
Acupuncture Points↗
Identification of platelet-derived growth factor A and B chains in human renal vascular rejection.
Platelet-derived growth factor (PDGF) exists as a dimer composed of two homologous but distinct peptides termed PDGF-A and -B chains, and may exist as AA, AB, and BB isoforms. The PDGF-B chain has been implicated as a mediator of renal vascular rejection by virtue of up-regulated expression of its receptor, PDGF beta-receptor, in affected arteries. A role for PDGF-A chain in mediating intimal proliferation has been suggested in human atherosclerosis (Rekhter MD, Gordon D: Does platelet-derived growth factor-A chain stimulate proliferation of arterial mesenchymal cells in human atherosclerotic plaques? Circ Res 1994, 75:410), but no studies of this molecule in human renal allograft injury have been reported to date. We used two polyclonal antisera to detect expression of PDGF-A chain and one monoclonal antibody to detect PDGF-B chain by immunohistochemistry in fixed, paraffin-embedded tissue from 1) normal adult kidneys, 2) a series of renal transplant biopsies chosen to emphasize features of vascular rejection, and 3) allograft nephrectomies. Immunohistochemistry was correlated with in situ hybridization on adjacent, formalin fixed tissue sections from nephrectomies utilizing riboprobes made from PDGF-A and -B chain cDNA. PDGF-A chain is widely expressed by medial smooth muscle cells of normal and rejecting renal arterial vessels of all sizes by immunohistochemistry and in situ hybridization. PDGF-A chain is also expressed by a population of smooth muscle cells (shown by double immunolabeling with an antibody to alpha-smooth muscle actin) comprising the intima in chronic vascular rejection. In arteries demonstrating acute rejection, up-regulated expression of PDGF-A chain by endothelial cells was detected by both immunohistochemistry and in situ hybridization. In contrast, PDGF-B chain was identified principally in infiltrating monocytes within the rejecting arteries, similar to its localization in infiltrating monocytes in human atherosclerosis. Although less prominent than the case for PDGF-A chain, PDGF-B chain also was present in medial and intimal smooth muscle cells in both rejecting and nonrejecting renal arteries. PDGF-A and -B chains have now been localized at both the mRNA and protein levels to the intimal proliferative lesions of vascular rejection. These peptides, which are known stimuli for smooth muscle cell migration and proliferation in experimental vascular injury, may have similar stimulatory effects on smooth muscle cells in an autocrine and/or paracrine manner to promote further intimal expansion and lesion progression in this form of human vasculopathy.
Blotting, Western↗
Attitude: the cornerstone of a winner.
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Attitude of Health Personnel↗
Bone pain that responds to calcium channel blockers. A retrospective and prospective study of transplant recipients.
A severe episodic bone pain syndrome of unknown cause was first described in renal transplant recipients in France and associated with the use of cyclosporine. We have retrospectively and prospectively evaluated this pain syndrome in our transplant patients. This pain is bilateral, of acute onset and episodic, primarily involving the knees and/or ankles. It usually occurs at night or with recumbency, and is often relieved with elevation or walking. Physical examination of the affected areas is unrevealing. Kidney, liver, pancreas, heart, lung and combined organ transplant recipients on cyclosporine were available from the University of Washington Transplant Services and were retrospectively evaluated by chart review (n = 351) or prospective clinical evaluation (n = 38) for evidence of this clinical syndrome. In the retrospective chart review, 19.1% of patients had episodes of bone pain. The highest prevalence occurred in renal transplant recipients (27.7%). The bone pain syndrome was documented in the charts of 14 patients who subsequently developed significant osteonecrosis. Prospectively, 21 of 22 patients with the bone pain syndrome experienced complete relief of this pain upon treatment with calcium channel blockers (95.4% response rate). The pathophysiology of this bone pain syndrome is unknown, although its response to the vasodilatory effects of calcium channel blockers suggests a vascular etiology.
Bone and Bones↗
Frameshift mutations in Salmonella induced by the extracts of medicinal herbs Lannea edulis (Sond.) Engl. and Monotes glaber Sprague.
Lannea edulis and Monotes glaber have been prescribed for various affectations in the traditional medical practice of Zimbabwe and other parts of Africa. Mutagenicity testing using Salmonella typhimurium strains TA97a, TA98, and TA100, indicated that the aqueous extracts of these plants induced frameshift mutations in Salmonella. The extract of L. edulis displayed marginal mutagenicity in strain TA97a while that of M. glaber showed a significant dose-dependent mutagenicity in both strains TA97a and TA98. There was no mutagenic effect observed in strain TA100. Two other plant extracts, those of Lannea discolor and Dolichos kilimandscharicus, were nonmutagenic in all three strains.
Dose-Response Relationship, Drug↗
Hepatitis C--associated glomerular disease in liver transplant recipients.
Hepatitis C virus (HCV) infection may be associated with extrahepatic illness including renal disease. We investigated the clinical and virological characteristics of three patients who developed a mesangial proliferative and sclerosing glomerulopathy alone or in association with membranoproliferative glomerulonephritis after liver transplantation for end-stage liver disease secondary to HCV infection. Using polymerase chain reaction technology and the IgM RIBA assay, viral load, genotype and IgM antibody response to HCV in the setting of glomerulonephritis was evaluated. Within 1 year of transplantation, the patients showed decreased renal function, proteinuria and recurrent hepatitis C liver disease. Likewise, HCV viral load increased following transplantation, whereas the viral genotypes remained unchanged. Although the first patient presented with classic type II cryoglobulinemia in association with glomerulonephritis, the second patient developed an IgM directed specifically against the hepatitis C core antigen. The third patient developed a low-titered IgM directed against the hepatitis C core antigen with rheumatoid factor activity but without cryoglobulinemia. All of the patients show IgM in glomerular capillary walls by biopsy. One patient has shown a clinical response to interferon (IFN) alfa-2b therapy without evidence of hepatic allograft rejection. The second and third patients have not responded to IFN or developed hepatic rejection. This study suggests that HCV-associated glomerulonephritis may complicate liver transplantation in conjunction with the production of increased amounts of IgM of variable specificity. The posttransplant setting may provide a unique situation in which to investigate the specific requirements for the onset of renal disease.
Adult↗
Mitoxantrone and cytosine arabinoside as treatment for acute myeloblastic leukemia in older patients.
The majority of patients with acute myeloid leukemia (AML) are elderly, and their response to chemotherapy is poorer than that of younger patients. The combination of mitoxantrone (MTN) and cytosine arabinoside (Ara-C) is a possible alternative to an anthracycline/Ara-C combination for the treatment of AML in these patients. Of 52 older patients (> 59 years) referred over a 3.5-year period, 33 patients (age range 60-78 years, median 67 years) received MTN and Ara-C as therapy for newly diagnosed AML. MTN was administered at a dose of 12 mg/m2/day, intravenously, for 3 days (23 patients), or 10 mg/m2/day for 5 days (10 patients), and Ara-C at a dose of 100 mg/m2 twice daily, intravenously, for 7 days. Complete remission (CR) was achieved in 16/33 patients (48%). The median remission duration was 6 months (range 1-37 months). The median survival was 14 months for those who achieved CR compared with 9 months for those with resistant disease. Two patients remain in first CR after 13 and 37 months, but three patients died whilst receiving consolidation therapy. In selected elderly patients with AML, the combination of MTN and Ara-C provides an acceptable alternative to an anthracycline/Ara-C regimen, with a higher CR rate than historical controls. However, the CR rate and remission duration remain low compared with those of younger patients, supporting the need to investigate new approaches to treatment in this population.
Age Factors↗
Glomerulonephritis in renal allografts associated with hepatitis C infection: a possible relationship with transplant glomerulopathy in two cases.
Chronic infection with hepatitis C virus (HCV) has been identified as a cause of type I membranoproliferative glomerulonephritis (MPGN). HCV infection is common in patients with end-stage renal disease and may persist in renal allograft recipients. MPGN in the allograft may therefore be a manifestation of persistent HCV infection. We report two cases of glomerulopathy with features of both MPGN and transplant glomerulopathy in renal transplant patients chronically infected with HCV. We discuss the course of interferon alfa therapy in both patients as well as a possible relationship of HCV infection with transplant glomerulopathy.
Chronic Disease↗
Nimodipine increases CSF somatostatin in affectively ill patients.
Preliminary evidence suggests that nimodipine, an L-type calcium channel blocker, is effective in treating some patients with rapidly cycling affective disorders and some phases of Alzheimer's disease, i.e., two syndromes associated with transient or permanent reductions in cerebrospinal fluid (CSF) somatostatin, respectively. CSF somatostatin (SRIF) was measured in 14 affectively ill patients while they were medication-free and during chronic nimodipine treatment. CSF somatostatin significantly increased in patients during active nimodipine treatment compared with ones in the medication-free state. The current findings raise the possibility that nimodipine-induced increases in CSF somatostatin could potentially contribute to its spectrum of efficacy on neuropsychiatric disorders associated with cognitive or affective impairment. Further clinical and preclinical studies are indicated to elucidate the potential mechanisms involved in the elevation of CSF SRIF, whether it is reflected in regional changes in brain, and its possible relevance to nimodipine's clinical actions.
Adult↗