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Biomedical subjects

A Hartmann

Publications and source records attributed to A Hartmann.

At least 289 records · Page 16Linked to original sources
PubMed1996

Five years' follow-up of renal glomerular and tubular functions in heart transplant recipients.

BACKGROUND: Many studies have shown that cyclosporine A may have detrimental long-term effect on kidney function. However, few prospective long-term studies have assessed both glomerular and tubular functions of the kidneys in heart transplant recipients METHODS: We examined 10 heart transplant recipients prospectively for 5 years. Hemodynamic data were obtained by standard heart catheterization technique, and glomerular filtration rate and blood flow were calculated as clearance of inulin and paraaminohippuran, respectively. Tubular functions were assessed by renal excretion of enzymes and albumin and by the lithium clearance method. All patients received cyclosporine A, azathioprine, and prednisolone as immunosuppressive regimen. The dose of cyclosporine averaged 3.9 +/- 0.3 during the first year and 3.2 +/- 0.3 mg/kg up to 5 years. RESULTS: All patients completed the study. Four received rejection therapy. Six were treated for hypertension. Cardiac output remained unchanged and averaged 5.5 +/- 0.9 L/min at baseline. No change ws found in any of the measured or calculated central hemodynamic parameters except a tendency toward an increased systemic peripheral resistance with time. Glomerular filtration remained constant at 66 +/- 22 ml/min, renal plasma flow showed a tendency to decline averaging 361 +/- 133 at baseline and 254 +/- 68 ml/min at 5 years (p = 0.08). Albumin excretion rate increased from 22 +/- 27 to the 102 +/- 100 micrograms/min between 1 and 5 years ( p < 0.05). The excretion of tubular enzymes, N-acetyl-6-glucosaminidase and alkaline phosphatase, and the renal handling of lithium remained unchanged. CONCLUSIONS: Cyclosporine therapy over 5 years did not progressively impair glomerular or tubular functions. However, the occurrence of microalbuminuria may be caused by therapy with cyclosporine itself or associated hypertension.

Albuminuria↗
PubMed1996

[Hyperbaric oxygenation (HBO) in the treatment of radiogenic side effects].

AIM: Many reports show that late complications of radiotherapy can be successfully treated by hyperbaric oxygen (HBO). This synopsis attempts to review the literature to identify areas of clinical use and further research. PATIENTS AND METHODS: Clinical and experimental data about HBO treatment of radiation late effects are analysed. Mechanisms of hyperbaric oxygen in the treatment of late radiation side effects are discussed. RESULTS: There is evidence in the literature that HBO is beneficial in the treatment of radiation cystitis, osteoradionecrosis of the mandible, hemorrhagic proctitis, soft tissue necrosis and neurologic deficits. The prophylactic use of HBO has shown to prevent the development of osteoradionecrosis after tooth removal and the loss of titanium implants in irradiated facial bones. The physiologic basis of HBO can be referred to induction of neoangiogenesis and revascularisation. CONCLUSIONS: Clinicians can be encouraged to use hyperbaric oxygen for the treatment of radiation cystitis, osteonecrosis of the mandible, hemorrhagic proctitis, soft tissue necrosis and neurologic deficits following radiation therapy.

Animals↗
PubMed1995

[ACE inhibitors and early diabetic nephropathy].

At present we are able to disclose diabetic nephropathy in the very early stages, i.e. when urinary albumin excretion is only slightly increased (20-200 micrograms/min = microalbuminuria). Good blood glucose control and active antihypertensive treatment may stop or retard the further development towards renal failure. Angiotensin-converting-enzyme (ACE)-inhibitors seem to have a renoprotective effect. In this article we suggest guidelines for the use of ACE-inhibitors in patients with type 1 diabetes and early diabetic nephropathy. Special concerns are included in respect of adolescents, pregnant women and persons with type 2 diabetes.

Albuminuria↗
PubMed1995

Pretransplant plasma exchange or immunoadsorption facilitates renal transplantation in immunized patients.

Patients with preformed antibodies against HLA molecules accumulate on renal transplant waiting lists and have inferior graft survival compared with nonsensitized patients. One hundred patients were included in a program of pretransplant removal of antibodies by plasma exchange (n = 90) or immunoadsorption (n = 10) in addition to prednisolone and cyclophosphamide medication. After plasma exchange, the panel reactivity and the antibody titer were reduced in about half of the patients, and after immunoadsorption the panel reactivity fell in 6 of 10 patients. Of the 83 patients who received grafts, 17 received a graft from a living donor (LD) and 66 received a graft from a cadaver donor (CD). Patients with a positive crossmatch against their LD were included in the program and were thus grafted with a recent positive, current negative crossmatched organ. Fifteen CD graft recipients had a pretreatment positive crossmatch toward their donor. No episodes of hyperacute rejection were seen. One- and 4-year graft survival rates in LD transplants with a recent positive and current negative crossmatch were 77% and 64%, respectively. At 1 and 4 years, graft survival rates were 70% and 57% in pretreated first CD graft recipients (n = 27) and 61% and 47% in pretreated regrafted patients (n = 39), respectively. In this program, a high rate of transplantation among the sensitized patients was achieved. Graft survival was inferior to that seen in nonsensitized patients, but was comparable to graft survival in sensitized patients at other centers.

Adult↗
PubMed1995

Effect of fluvastatin for safely lowering atherogenic lipids in renal transplant patients receiving cyclosporine.

The lipophilic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been associated with rhabdomyolysis in cyclosporine-treated treated patients, indicating an interaction of drugs. We therefore studied the safety and efficacy of the hydrophilic HMG-CoA reductase inhibitor fluvastatin in 14 cyclosporine-treated renal transplant patients. To qualify for inclusion, total cholesterol after dietary stabilization had to be > 240 mg/dL. Prior to starting active medication, patients underwent a 4-week placebo period. Fluvastatin was given in a dose of 20 mg once daily for 12 weeks, which was increased to 20 mg twice daily for a further 8 weeks. Fluvastatin reduced total and low density lipoprotein cholesterol in all patients at both dosages whereas no effect on high density lipoprotein cholesterol was observed. Triglyceride levels were lowered at week 20. Incremental dosages of fluvastatin did not affect cyclosporine concentration and no adjustment of cyclosporine dosage was necessary. The higher doses of fluvastatin also had no effect on renal function as judged by serum creatinine levels. Creatine phosphokinase remained unchanged throughout the study. No serious side-effects were observed. In conclusion, the hydrophilic HMG-CoA reductase inhibitor fluvastatin at either 20 or 40 mg/day appears to be both safe and effective in lowering atherogenic lipids in renal transplant patients.

Adolescent↗
PubMed1995

Chronic angiotensin-converting enzyme inhibition may improve sodium excretion in cardiac transplant hypertension.

Cyclosporine-associated hypertension (CAH) may be mediated in part by sodium and volume retention. To investigate this issue, we studied the effects of a calcium antagonist, nitrendipine (NIT, 10-20 mg b.i.d.), and a converting enzyme inhibitor, lisinopril (LIS, 10-20 mg o.d.), on blood pressure (office BP, 24 hr ambulatory BP), excretion of an acute sodium load (200 mmol/2 hr i.v.), glomerular filtration rate (insulin clearance), cumulative dopamine excretion, plasma atrial natriuretic peptide (ANP), and endothelin excretion in 8 patients with CAH after cardiac transplantation in a double-blind, randomized, crossover trial for 6 weeks. Five patients received a diuretic during the trial at a constant dose. Office diastolic BP (DBP) decreased significantly with LIS from 97 +/- 6 to 87 +/- 9 mmHg and with NIT from 96 +/- 7 to 92 +/- 12 mmHg. Ambulatory 24 hr DBP decreased significantly from 96 +/- 7 mmHg to 86 +/- 10 mmHg (LIS) and to 84 +/- 11 mmHg (NIT). Ambulatory DBP during the day was lowered significantly from 98 +/- 11 mmHg to 87 +/- 10 mmHg (LIS) and to 88 +/- 9 mmHg (NIT) and during the night from 95 +/- 9 mmHg to 86 +/- 8 mmHg (LIS) and to 79 +/- 7 mmHg (NIT). Cumulative sodium excretion 6 hr after an acute sodium load increased to 52 +/- 39 mmol (placebo), 96 +/- 44 mmol (LIS, P < 0.05 vs. placebo), and 71 +/- 34 mmol (NIT). Glomerular filtration rate, cumulative dopamine excretion, ANP, and endothelin excretion did not differ between either treatment group. We conclude, that: (1) both drugs were similar in lowering office BP and during the day, but NIT tended to be more effective during the night; and (2) cumulative sodium excretion during LIS was significantly increased compared with placebo. There was a similar trend during NIT also. Therefore, it is possible that chronic angiotensin-converting enzyme inhibition and possibly calcium antagonists might improve the sodium-retaining state in CAH independent of differences in blood pressure, ANP, dopamine, or renal function.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

p53 gene mutations inside and outside of exons 5-8: the patterns differ in breast and other cancers.

Most studies of mutations in the p53 tumor suppressor gene in tumors have examined only exons 5-8. Our laboratory previously found 64 mutations in exons 5-8 of the p53 gene in 194 primary breast cancers. Herein, we report 18 additional mutations found outside of exons 5-8. Mutations are present in exons 4, 9 and 10, and flanking splice junctions, but not in the promotor region or in exons 1, 2, 3 and 11. No missense mutations are found outside of exons 5-8. Instead, there is a predominance of frameshift mutations with lesser numbers of nonsense and splice site mutations. In contrast, the majority of mutations in exons 5-8 in this sample are missense changes and all of these are at amino acids that are identical in the 11 known p53 sequences that represent about 1.6 billion years of evolutionary divergence. The difference in mutational pattern between these two regions of the p53 gene is due to a lack of missense mutations and inframe microdeletions outside of exons 5-8. A review of our database of p53 mutations (De Vries et al., in preparation) shows that the patterns of mutation inside and outside of exons 5-8 differ in other types of cancers as well. The paucity of missense mutations in exons 2-4 and 9-11 in breast and other cancers (even at amino acids identical throughout p53 gene evolution) suggest that at least some missense mutations result in a phenotype other than malignant transformation. These data also illustrate the importance of examining identical exons when comparing the pattern of p53 gene mutations in different populations.

Adult↗
PubMed1995

DNA-damaging effect of cyclophosphamide on human blood cells in vivo and in vitro studied with the single-cell gel test (comet assay).

The single-cell gel (SCG) test was used to study the induction and persistence of DNA damage by cyclophosphamide (CP) in human blood cells after treatment in vitro and in vivo. S9-mix-activated CP (from 0.1 mM upward) induced DNA effects in a concentration-dependent manner in the in-vitro SCG test. Blood cells from various donors showed considerable intra- and interindividual variability. Incubation of CP-treated blood samples at 37 degrees C caused a rapid decrease in DNA effects, but DNA migration was still significantly increased 1 hr after the end of the CP treatment. Comparative studies with the in vitro sister chromatid exchange (SCE) test were performed that demonstrated that much lower CP concentrations (about 100 times) were required for a significant induction of SCEs. A group of 11 patients who suffered from vasculitis/collagen disease and were treated with low CP doses (50-200 mg/day) exhibited an elevated level of DNA damage in the SCG test with peripheral blood cells, compared with a group of 11 control persons or 5 patients without chemotherapy. Increases in DNA damage were variable and not clearly related to the CP dose. SCE tests could successfully be performed with 5 out of the 11 CP-treated patients; all showed significantly increased SCE frequencies. For six patients no result could be obtained with the SCE test due to a failure of lymphocyte proliferation. Three multiple sclerosis patients who received high doses of CP were investigated with the SCG test before, during, and after the treatment. The results indicate that CP-induced DNA effects that are detectable with the SCG test persist in vivo for a period of several days, but for less than 2 weeks. The results of our study provide information with regard to the use of the SCG test in human monitoring. The advantages and limitations of the test are discussed.

Adult↗
PubMed1995

Sympathetic re-innervation after heart transplantation: dual-isotope neurotransmitter scintigraphy, norepinephrine content and histological examination.

Cardiac transplantation entails surgical disruption of the sympathetic nerve fibres from their somata, resulting in sympathetic denervation. In order to investigate the occurrence of sympathetic re-innervation, neurotransmitter scintigraphy using the norepinephrine analogue iodine-123 metaiodobenzylguanidine (MIBG) was performed in 15 patients 2-69 months after transplantation. In addition, norepinephrine content and immunohistochemical reactions of antibodies to Schwann cell-associated S100 protein, to neuron-specific enolase (NSE) and to norepinephrine were examined in 34 endomyocardial biopsies of 29 patients 1-88 months after transplantation. Anterobasal 123I-MIBG uptake indicating partial sympathetic re-innervation could be shown in 40% of the scintigraphically investigated patients 37-69 months after transplantation. In immunohistochemical studies 83% of the patients investigated 1-72 months after transplantation showed nerve fibres in their biopsies but not positive reaction to norepinephrine. Significant norepinephrine content indicating re-innervation could not be detected in any biopsy. It was concluded that in spite of the lack of norepinephrine content there seemed to be immunohistological and scintigraphic evidence of sympathetic re-innervation. An explanation for this contradictory finding may be the reduced or missing norepinephrine storage ability compared to the restored uptake ability of regenerated sympathetic nerve fibres.

3-Iodobenzylguanidine↗
PubMed1995

Enhanced cyto- and genotoxicity of tetracycline in Wilson disease fibroblasts.

Tetracycline (TC) exerts DNA damaging properties which are accelerated in the presence of copper(II). Thereby, reactive oxygen species are generated. We investigated, if copper-accumulating cells show a higher sensitivity to TC compared to normal cells. Fibroblasts with an increased copper content were derived from patients of two genetic disorders, Wilson disease (WD) and Menkes disease (MD). Cytotoxic and genotoxic effects of TC were investigated in different human fibroblasts. The inhibition of cell growth by TC was measured in two normal fibroblast lines, fibroblast lines of two patients with WD and one patient with MD. While TC inhibited cell growth at similar concentrations in normal fibroblasts and the MD fibroblasts, the WD cells were much more sensitive. Furthermore, an increased inhibition of DNA synthesis and an enhanced induction of unscheduled DNA synthesis (UDS) was found in WD cells after a TC-treatment compared to normal cells.

Cell Division↗
PubMed1995

Vitamin E prevents exercise-induced DNA damage.

The single cell gel test (SCG test or comet assay) was used to study DNA damage in peripheral white blood cells (WBC) of humans after a single bout of exhaustive exercise and the effect of vitamin supplementation. Human subjects were asked to run on a treadmill until exhaustion and blood samples were taken before and 24 h after the run. A clear increase in DNA strand breakage was observed in the 24-h sample of all probands. A short-term application of multivitamin pills or vitamin E (3 x 800 mg) resulted in a significantly smaller increase of DNA effects in WBC of some probands. When the volunteers were given a supplement of vitamin E (1200 mg daily) for 14 days prior to a run, exercise-induced DNA damage was clearly reduced in all probands. In four out of five subjects, vitamin supplementation completely prevented the induction of DNA damage after exhaustive exercise. Intake of vitamin E for 14 days led to a clear increase in vitamin E serum concentrations. Malondialdehyde (MDA), a marker of lipid peroxidation, was measured in the serum of probands in tests with and without vitamin supplementation for 14 days. MDA concentrations were significantly decreased following vitamin E supplementation but not significantly changed 15 min and 24 h after a run. Our results demonstrate that vitamin E prevents exercise-induced DNA damage and indicate that DNA breakage occurs in WBC after exhaustive exercise as a consequence of oxidative stress.

Adult↗
PubMed1995

Genotoxic effects of chemicals in the single cell gel (SCG) test with human blood cells in relation to the induction of sister-chromatid exchanges (SCE).

In a comparative study, benzo[a]pyrene (BaP), cyclophosphamide (CP), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and tetrachloroethylene (PER) were tested for their ability to induce genotoxic effects in the single cell gel (SCG) test and the sister-chromatid exchange (SCE) test with human blood cells. MNNG as well as S9 mix activated BaP- and CP-induced DNA effects in both tests in a dose-dependent manner. While the range of concentrations which induced DNA migration or SCE was the same for MNNG and for BaP, much higher CP concentrations were necessary for a positive response in the SCG test than in the SCE test. PER was tested in the absence and in the presence of S9 mix and neither induced DNA migration nor increased SCE frequencies. In these experiments, a clear cytotoxic effect of PER was observed. To investigate a possible influence of DNA repair on the effects in the SCG test, cells were treated for 2 h and further incubated for 1 h after removal of the test substance. This procedure caused a clear decrease in induced DNA migration in experiments with BaP and CP, whereas no reduction was found with MNNG. This modified protocol did not lead to the detection of DNA effects after treatment with PER. The results indicate that the SCG test responds to various DNA lesions and does not seem to be sensitive to non-genotoxic cell killing. Its sensitivity obviously depends on the type(s) of induced DNA lesions and the effects can be modified by DNA repair processes in a complex manner. For the detection of genotoxic properties of chemicals with the in vitro SCG test, a single evaluation at the end of the exposure period seems to be sufficient.

Benzo(a)pyrene↗
PubMed1995

Changes in late auditory evoked potentials induced by growth hormone-releasing hormone (GHRH) but not somatostatin (SRIF) after peripheral administration in male controls.

To investigate possible influences of growth hormone-releasing hormone (GHRH) and somatostatin (SRIF) on auditory perceptional processes, 12 subjects received either placebo (sodium chloride 0.9%), GHRH (50 micrograms), or SRIF (100 micrograms) on different days. Late auditory evoked potentials (AEP) were computed and further analyzed by using the brain electric source analysis (BESA) method. Reduced late AEP latencies were observed following GHRH administration. In contrast, SRIF had no significant effects on the AEP. The changes in late auditory processing seen after administration of GHRH were most likely induced by a direct central nervous action.

Acoustic Stimulation↗
PubMed1995

Long-term habituation of brain evoked potential responses and pituitary-adrenal secretion with repeated (placebo) testing.

To study whether changes in late auditory evoked potentials (AEPs) and/or in stress-sensitive hormones of the hypothalamic-pituitary-adrenal (HPA) system take place between a first and a second placebo experiment and if so, whether these changes are possibly related to each other, we conducted two identical placebo sessions (2 ml 0.9% saline) and one cortisol session (50 mg) with 10 subjects on three different days. Plasma cortisol concentrations were significantly higher at the beginning of the first placebo experiment than the second, with a concordant decrease of plasma adrenocorticotropin hormone (ACTH) concentrations. In the AEP domain, a consistently lower P2 amplitude was observed in the first session. Since the change in late auditory processing could not be demonstrated after exogenous administration of cortisol, a direct mediation through an elevation of plasma cortisol concentrations or indirect mediation through a decrease of plasma ACTH concentrations seems unlikely. We rather propose that other stress-sensitive mechanisms, such as CCK, might account for the novelty-induced P2 amplitude lowering.

Acoustic Stimulation↗
PubMed1995

The use of immunological methods to detect and identify bacteria in the environment.

Immunological detection methods have become increasingly important in microbial ecology for the tracking of specific microorganisms and for community analysis. For a reliable application of these techniques, the monoclonal antibodies or polyclonal antisera used have to fulfill several quality criteria. Cross reactivity, cellular localization of the antigenic determinant, affinity characteristics and the expression of the antigenic determinant at environmental conditions have to be determined. Immunological methods can be used for the identification, quantification and enrichment of specific bacteria in extracts as well as for the visualization of cells in situ. The sensitivity of advanced immunological methods can be compared to PCR techniques. Using image processing of epifluorescence micrographs or confocal laser scanning microscopy, the immunofluorescence approach can now be applied to study complex environmental samples.

Journal Article↗
PubMed1995

Contralateral cerebellar diaschisis 7 hours after MCA-occlusion in primates.

2,3,5-triphenyltetrazoliumchloride (TTC) as an indicator of mitochondrial function in combination with regional cerebral blood flow measurements was used in six baboons 6.9 +/- 1.2 h after permanent occlusion of the left middle cerebral artery. Staining with TTC was compared with blood flow data obtained during normocapnia using the microsphere method. Five animals showed a focal area of unstained tissue in the left middle cerebral artery territory. Mean blood flow in the unstained area was 28.3 +/- 15.4 ml min-1 100 g-1. Five of 6 animals showed a significant decrease of contralateral cerebellar blood flow in the presence of normal TTC staining. We conclude that at this early stage of infarction contralateral cerebellar diaschisis is caused by functional deactivation.

Animals↗
PubMed1995

Single-dose pharmacokinetics of fluconazole in patients with liver cirrhosis.

The pharmacokinetics of a single 100 mg i.v. dose of fluconazole were studied in parallel groups of ten normal subjects and nine patients with liver cirrhosis, a condition with a high risk of life-threatening fungal infection. The following mean pharmacokinetic parameters were found for the patient group: terminal elimination constant 0.0101/h (normal 0.0214/h); mean residence time 134 h (normal 46.7h); area under the curve 200 h.mg/L(normal 69.4 h.mg/L); plasma clearance 0.96 L/h.kg(normal 2.16 L/h.kg). All these differences were statistically significant (P < 0.05). The majority of the patients were being concomitantly treated with duretics (frusemide and spironolactone). It is suggested that the known slight interaction between such drugs and fluconazole was intensified by the disease state. These results emphasize the need for caution in the treatment with fluconazole of patients with severe liver disease. Nevertheless, in view of the wide range of values found in the patients, and low toxicity of fluconazole, a dosage reduction in cirrhosis does not seem to be justified in the present state of knowledge.

Adult↗