Insulin resistance in patients with adult polycystic kidney disease.
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Biomedical subjects
Publications and source records attributed to A Hartmann.
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BACKGROUND: In order to assess the immediate renal function after living donor transplantation, renal function was compared in eight renal allograft recipients and their living related kidney donors during the first 24 h after transplantation. METHODS: Substantial and comparable intraoperative volume loading with Ringer's acetate and mannitol was performed together with the administration of frusemide. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were estimated by the clearances of inulin and p-aminohippurane, respectively. Tubular reabsorptive function and injury were estimated from the clearance of lithium, the fractional excretion of sodium and the urinary excretion of N-acetyl-beta-glucosaminidase. RESULTS: One hour after completion of surgery, GFR (54 +/- 7 ml/min) and ERPF (294 +/- 35 ml/min) were only 30% lower in the grafts than in the remaining donor kidneys, increasing to similar levels within 3 h. Only minor tubular dysfunction and injury were revealed in the grafted kidneys, and these tended to normalize within 24 h. CONCLUSIONS: By the present transplantation procedure comprising short ischaemia time and substantial volume expansion combined with mannitol and frusemide administration, kidneys from living donors regain nearly normal function within a few hours after transplantation.
BACKGROUND: A single bolus dose of LMW heparin at the start of haemodialysis effectively prevents clot formation in the dialyser and bubble trap. However, there are few studies on the appropriate dosage of LMW heparins in haemodialysis. Therefore we examined the relationship between the anticoagulant effect of dalteparin and clinical clotting during haemodialysis. METHODS: We performed an open, prospective study on the effect of decreasing doses of dalteparin in 12 haemodialysis patients during a total of 84 sessions (4-4.5 h). The normally applied dose of dalteparin in each patient was reduced by 25% for each session down to 50% of initial dose if no clotting was observed. Clinical clotting (grade 1-4) was evaluated by visual inspection after blood draining of the air trap every hour and by inspection of the dialyser after each session and compared to corresponding values for anti-FXa activity and dialysis time. Blood flow and ultrafiltration rate were kept within narrow limits throughout the study. RESULTS: No episodes of grade 4 clotting occurred, and no session was interrupted. Eighteen episodes of grade 3 clinical clotting (11%) were observed in patients without warfarin treatment, none with an anti-FXa activity >0.43 IU/ml. Oral warfarin treatment reduced the clinical clotting, and only one grade 3 episode was observed in patients on warfarin therapy. Anti-FXa activity and haemodialysis time were the only factors independently correlated to clotting in a logistic regression model. CONCLUSION: An anti-FXa activity above 0.4 IU/ml after 4 h of dialysis inhibits significant clotting during haemodialysis. A bolus dose of dalteparin of 70 IU/kg usually seems appropriate, but may be reduced in patients on warfarin treatment. Dialysis time is an independent risk factor for clinical clotting.
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OBJECTIVE: Extremely high flow through arteriovenous malformations (AVMs) may limit the safety and effectiveness of endovascular glue therapy. To achieve a more controlled deposition of glue, we used transient but profound systemic hypotension afforded by an intravenously administered bolus of adenosine to induce rapidly reversible high-degree atrioventricular block. METHODS AND CASE REPORT: A patient with a large high-flow occipital AVM fed primarily by the posterior cerebral artery underwent n-butyl cyanoacrylate glue embolization. Nitroprusside-induced systemic hypotension did not adequately reduce flow through the nidus, as determined by contrast injection in the feeding artery. In a dose-escalation fashion, boluses of adenosine were administered to optimize the dose and verify that there was no flow reversal in the AVM and no other unexpected hemodynamic abnormalities by arterial pressure measurements and transcranial Doppler monitoring of the posterior cerebral artery feeding the AVM. Thereafter, 64 mg of adenosine was rapidly injected as a bolus to provide 10 to 15 seconds of systemic hypotension (approximately 20 mm Hg). Although there were conducted beats and some residual forward flow through the AVM during this time, the mean systemic and feeding artery pressures were roughly similar and remained relatively constant. A slow controlled injection of n-butyl cyanoacrylate glue was then performed, with excellent filling of the nidus. CONCLUSION: Adenosine-induced cardiac pause may be a viable method of partial flow arrest in the treatment of cerebral AVMs. Safe, deep, and complete embolization with a permanent agent may increase the likelihood of endovascular therapy's being curative or may further improve the safety of microsurgical resection.
OBJECTIVE: Ultrasonographic assessment of carotid artery plaque morphology is widely used to identify patients at high risk for stroke. However, the reliability of plaque analysis in high-grade stenosis is uncertain. We determined the interrater reliability of sonographic plaque morphology analysis in patients with severe carotid artery stenosis. MATERIALS AND METHODS: Duplex Doppler was performed on 114 patients with 80-99% stenosis of the internal carotid artery using a Siemens Quantum 2000 D with a handheld 7.5 MHz transducer. B-mode pictures with and without color coding were printed on a Sony color video printer UP-5000 W. Three raters independently evaluated plaque echolucency, heterogeneity, calcification, and surface structure. Interrater agreement was calculated by a jackknife procedure generating kappa values and two-sided 95% confidence intervals. RESULTS: Kappa values and 95% confidence intervals were 0.05 (-0.07 to 0.16) for plaque surface structure, 0.15 (0.02 to 0.28) for plaque heterogeneity, 0.18 (0.09 to 0.29) for plaque echogenicity, and 0.29 (0.19 to 0.39) for plaque calcification. The upper bounds of all of the confidence intervals were below the 0.40 level suggested for minimal reliability. CONCLUSION: The low interrater agreement indicated that unaided visual assessment of static B-mode pictures to assess plaque morphology in patients with severe carotid artery stenosis is not reliable. Other evaluation procedures and standardized criteria, as yet undeveloped, are needed to improve reliability.
A pair of primers and a gene probe for the amplification and detection of the Bacillus cereus neutral protease gene (NPRC) were developed. Specificity for the npr genes of the B. cereus group members B. cereus, B. mycoides, and B. thuringiensis was shown. Restriction polymorphism patterns of the PCR products confirmed the presence of the NPRC gene in all three species.
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BACKGROUND: Recent data provide evidence of a systemic inflammatory response in severe acute pancreatitis; in contrast, the exact immune mechanisms underlying chronic pancreatitis remain unclear. METHODS: To investigate the immune response in the clinical features of chronic pancreatitis, we investigated the gene expression of tumor necrosis factor-alpha (TNF-alpha), tumor necrosis factor receptor (TNFR)-p55 and -p75 and inducible nitric oxide synthase (iNOS) in peripheral blood mononuclear cells (PBMC) of 18 patients with late-stage alcoholic chronic pancreatitis of different disease activity (Balthazar criteria). RESULTS: Semiquantitative reverse transcriptase-polymerase chain reaction revealed a significantly enhanced gene expression of TNF-alpha (P < 0.05), TNFR-p55 (P < 0.05) and TNFR-p75 (P < 0.01) in unstimulated PBMC of patients with advanced chronic pancreatitis (11/18 with calcifications) compared to healthy controls (n = 8). No significant difference was found between patients with mild acute pancreatitis and patients with an inactive quiescent pancreatitis. Moreover, no expression of inducible nitric oxide synthase was detectable. CONCLUSIONS: The enhanced gene expression of TNFR-p75, TNFR-p55 and TNF-alpha in unstimulated PBMC demonstrates an enhanced leucocyte activation in patients with late-stage chronic pancreatitis and suggests a pathogenetic role of the cytotoxic TNF-alpha pathway in the clinical features of alcoholic chronic pancreatitis. The pathogenetic role of nitric oxide in chronic pancreatitis remains to be fully elucidated.
OBJECTIVE: To investigate whether the degree of glomerular structural lesions in young patients with type 1 diabetes and microalbuminuria was associated with urinary albumin excretion rate (AER) 6 years later and whether the AER level was influenced by blood glucose control, blood pressure, or glomerular filtration rate (GFR). RESEARCH DESIGN AND METHODS: There were 17 young adults with type 1 diabetes and microalbuminuria, 8 men and 9 women with mean age 20 years (95% CI: 18-22) and duration of diabetes of 11 years (10-13), who participated in a 6-year prospective study. Kidney biopsies (measurements of basement membrane thickness [BMT] and mesangial and matrix volume fractions) and GFR were performed at baseline. AER and HbA1c were measured at least three times a year and blood pressure once a year. RESULTS: In a multivariate analysis, baseline BMT and mean 6-year HbA1c contributed significantly to AER at the end of the study (R2 = 0.69, P < 0.01). When mesangial volume fraction replaced BMT as the independent variable, this parameter and AER at baseline predicted the AER at 6 years (R2 = 0.55, P < 0.55). Mesangial volume fraction and BMT (in separate analysis) contributed significantly to change in AER during the study. During the study, neither AER (30 micrograms/min [19-40] to 16 micrograms/min [7-90]) nor blood pressure (96 mmHg [92-102] to 95 mmHg [91-98]) changed significantly in the group. However, HbA1c was reduced from 10.3 (9.6-11.0) to 8.4% (7.8-9.1) (P < 0.01). CONCLUSIONS: In young patients with microalbuminuria, the long-term urinary AER was predicted by the degree of glomerular structural changes and associated with blood glucose control, but not with blood pressure or GFR.
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The early 4 French (Fr), pre-formed, Judkins coronary catheters had unsatisfactory maneuverability due to reduced torque stability. Technical innovations have led to improved 4 Fr catheters. This prospective study evaluates the safety and feasibility of the 4 Fr Quick Care Infinity catheter (Cordis, Miami, Florida). Within a series of 2,366 patients investigated for suspected coronary artery disease, 302 were selected for outpatient treatment according to the guidelines for outpatient catheterization. Fluoroscopy time was 2.8 +/- 2.5 minutes. It was not necessary to change to larger catheters in any patient. After sheath removal, hemostasis was achieved within 14 +/- 8 minutes. Strict bed rest lasted 181 +/- 65 minutes; patients were discharged 303 +/- 76 minutes after arterial puncture. Sixteen of the 302 patients (5.3%; 95% confidence interval (CI): 3.1-7.9%) changed to inpatient treatment for reasons unrelated to the arterial access. Eight patients (2.6%; CI: 1.1-5.1%) required one night of hospitalization for control of hematoma. The following morning, vessel murmur, pain, and large hematoma (more than 10 cm diameter) occurred in 1 (0.3%), 6 (2.0%), and 6 (2.0%) patients, respectively. This necessitated hospital admission in 2 patients (0.7%; CI: 0.0-2.3%) for up to 2 days. Major entry site complications requiring blood transfusion or surgery did not occur (CI: 0.0-0.3%). It was concluded that outpatient catheterization for coronary artery disease using the new 4 French catheters is feasible and can be rapidly and safely performed in a selected patient population.
HISTORY AND CLINICAL FINDINGS: A 48-year-old man with advanced light-chain plasmacytoma was admitted because of severe dyspnoea and tachycardia. Physical examination revealed peripheral cyanosis and signs of right heart failure. INVESTIGATIONS: The partial pressure of oxygen and CO2 in arterial blood were both reduces (72 mm Hg and 33 mm Hg, respectively). Liver enzyme activities were increased, there was right heart enlargement radiologically and the ECG showed low voltage and typical signs of right heart strain. Echocardiography revealed cardiac metastases of the plasmacytoma with subtotal right ventricular outflow tract obstruction (RVOTO), without any signs of pulmonary emboli. TREATMENT AND COURSE: Palliative radiotherapy to the heart reduced the intracardiac tumor size and improved the patients' general condition. The signs of the RVOTO were markedly reduced in both the ECG and the echocardiogram. But after this initial improvement pneumonia developed, of which the patient died. Autopsy revealed radiation pneumonia with extensive fibrosis as the immediate cause of death. CONCLUSION: In patients with advanced neoplasia cardiac metastasis should be included in the differential diagnosis of dyspnoea, tachycardia or hypotension of uncertain etiology. Echocardiography is the diagnostic tool of choice.
BACKGROUND: Azathioprine (AZA) is widely used in organ transplantation. Common practice is to adjust dose according to body weight only, despite documented pharmacokinetic variability. The purpose of this study was to investigate whether high-dose AZA treatment monitored by 6-thioguanine nucleotides (6-TGN) levels reduces the incidence of rejection episodes in renal transplantation without a corresponding increase in myelotoxicity. METHODS: Patients receiving cyclosporine, steroids, and AZA were randomized into either the low-dose AZA group (3 mg/kg on day 0, then 2 mg/kg/day the first week and 1 mg/kg/day thereafter) or the high-dose AZA group. In the latter, AZA was started at 5 mg/kg/day and then adjusted to keep 6-TGN concentrations (measured twice weekly) between 100 and 200 pmol/8 x 10(8) RBCs. RESULTS: A total of 360 transplant recipients were included in the final analysis. The cumulative incidence of first rejection episodes was reduced by 21%, from 62.8% in the low-dose group to 49.4% in the high-dose group (difference: 13.3%; 95% confidence interval: 3.2-23.5). Similar results were found in subgroups according to HLA-DR match. The 6-TGN concentration was significantly higher in the high-dose AZA group during the first month, and the reduction in rejection episodes was achieved in the same period. A larger proportion of patients in the high-dose group had nadir white blood cell count below 2.0 x 10(9) leukocytes/L (13.3% vs. 4.4%; difference: 8.9%; confidence interval: 3.1-14.7). CONCLUSIONS: High-dose AZA therapy in a triple-drug regimen, monitored by 6-TGN, will keep myelotoxicity within acceptable limits with the benefit of a reduction in acute rejection episodes.
Chromosomal instability and persistent reproductive cell death show a significant correlation after cells are exposed to ionizing radiation. To examine the possible role of apoptosis in persistent reproductive cell death, we analyzed subsets of chromosomally stable and unstable clones for relationships between chromosome stability, reproductive integrity, and apoptosis. All clones were generated from the GM10115 cell line and derived from single progenitor cells surviving 10 Gy of X-rays, and all measurements were made approximately 60-80 generations after irradiation. The incidence of apoptosis, as measured by both annexin V binding of phosphatidylserine residues and terminal deoxynucleotidyl transferase labeling of DNA strand breaks, was significantly higher in chromosomally unstable clones than it was in chromosomally stable clones (P < 0.05; ANOVA and Student's t test). Furthermore, statistical analyses of the biological end points of persistent reproductive cell death and apoptosis were consistent, showing R2 values of 0.78 and 0.76, respectively. These results suggest that persistent reproductive cell death can, in part, be explained by the predisposition of a fraction of the clonal population to undergo apoptosis or necrosis. Immunological blot analyses of protein levels and DNA bandshift assays confirmed the mutant status of p53 in the host cell line, implying an apoptotic pathway that is independent of p53. Induction of apoptosis by agents such as actinomycin D, etoposide, and staurosporine and induction of necrosis by sodium azide were accompanied by an increase in the level of intracellular peroxy radicals and lipid peroxidation products, two independent end points that are typically associated with oxidative stress. Similar findings were observed in several subclones showing persistent apoptosis. These results suggest that the elevated levels of free radical damage that we detected were derived from the fraction of cells dying by apoptotic or necrotic processes. Possible mechanisms whereby oxidative stress may contribute indirectly to the perpetuation of chromosomal instability are discussed.
DNA double-strand breaks can lead to chromosomal rearrangements at the first mitosis after exposure to the DNA strand-breaking agent. The evidence suggests a number of different pathways for DNA double-strand break rejoining in mammalian cells, but it is unclear what factors determine the fate of the induced break and whether or not it will lead to chromosomal rearrangement. If a cell does survive and proliferate after DNA cleavage, delayed chromosomal instability can be observed in the clonal descendants of the exposed cell. Most, but not all DNA double-strand breaking agents are effective at inducing this delayed chromosomal instability. In this paper, we review the evidence for the role of the DNA double-strand break in directly induced and delayed chromosomal rearrangements.
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