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Biomedical subjects

M Mihatsch

Publications and source records attributed to M Mihatsch.

At least 55 records · Page 3Linked to original sources

[Acquired cystic renal changes--a clinically relevant problem in long-term dialysis].

While dialysis patients survive renal failure for years and even decades, multiple morphologic alterations take place in their kidneys. One of these (so to speak) "postmortem" changes is the formation of secondary renal cysts. A patient with end stage renal failure due to amyloidosis is described who was dialysed at home for 9 years. Intravenous pyelography and renal biopsy in the predialysis period likewise documented the presence of amyloidosis and the absence of cystic disease. Ultrasonography of both kidneys, a suspicious increase in hematocrit and the autopsy finding of numerous large cysts also showed the presence of acquired cystic disease. The frequency and complications of this newly recognized disease in longterm dialysed patients are discussed. Recommendations are given concerning follow-up of these patients, with a view to early detection of tumor development within the cysts.

Amyloidosis↗

Value of urinary sediment in the diagnosis of interstitial rejection in renal transplants.

The occurrence of lymphocyturia, or a sharp increase in preexisting lymphocyturia, has been found to correlate with immunological rejection. In most studies time-consuming staining techniques or counting chambers have been used. A new staining technique, with prestained slides, is investigated as a predictor of cellular rejection and to distinguish between cellular rejection and cyclosporine (CsA) toxicity, or other causes of renal function impairment. In 18 consecutive renal transplant recipients, treated with CsA, urinary sediments were analyzed almost daily for two months, and prediction of cellular rejection was related to renal biopsies and retrospective clinical evaluation. In addition 24 transplant biopsies were compared with urinary sediment prediction; in both parts of the study a lymphocyturia of more than 20% and polymorphs less than 55% (of 100 nucleated cells, excluding squamous epithelial cells) were considered to suggest interstitial rejection. Episodes of lymphocyturia (greater than 20%), with simultaneous increase of the number of epithelial cells, resulting in a relative decrease of polymorphs (less than 55%), were found 10 times. Of these, 9 corresponded well with biopsy or clinical evaluation and 1 was false-positive. Correlating urinary sediment analysis with biopsy histology (n = 24), 19 were accurate, 3 equivocal, and 2 false; this corresponds to a sensitivity of 77% and a specificity of 91%. In conclusion, the analysis of urinary sediments with prestained slides is a quick and simple method to diagnose cellular rejection and to distinguish it from toxic of ischemic renal damage. Results are comparable to those of the fine-needle aspiration technique without invasive insult to the patient.

Adult↗

Cyclosporine alone or in combination with prednisone in cadaveric renal transplantation.

One hundred recipients of first cadaveric kidney transplants were treated with three different immunosuppressive regimens: (1) conventional immunosuppression, (2) CsA alone, and (3) low-dose CsA in combination with low-dose prednisone, with rapid adjustment to give CsA whole blood trough levels of 300 to 800 ng/mL. One-year graft survival in the aza + pred group was 76%, and in the CsA alone group 75%. Graft survival at two and six months in the CsA-pred group was 94%. The dose of CsA in the CsA-pred group in the first two months posttransplant was only about half that given to the CsA-alone group. Surprisingly, the reduction in the CsA dose also reduced the number of methylprednisolone pulses given for treating rejection by greater than 50%. The incidence of nephrotoxicity and extrarenal side effects also fell considerably. Withdrawal of prednisone in the CsA-pred group after five months led to reversible rejection in two cases. In conclusion, (1) the rapid reduction in the CsA dosage is beneficial and has no drawbacks, and (2) our guidelines for withdrawing prednisone (timing of withdrawal, rate of reduction in dosage) still need further refinement.

Adult↗

Cyclosporin A used alone or in combination with low-dose steroids in cadaveric renal transplantation.

The actual survival rate of 25 primary cadaveric kidney grafts in recipients treated initially with cyclosporin A (CyA) alone was 84%. The survival rate in 37 patients under conventional immunosuppression was 76%. The mean number of dialyses required in the first 4 weeks after transplantation was 1.2 per patient in both groups. At 15-28 months posttransplant, mean serum creatinine levels have remained stable at 175 mumol/l in the CyA group. The mean daily dose of steroids (including methylprednisolone i.v.) in the first two months was 2.07 mg/kg/d in patients under conventional immunosuppression and 0.76 mg/kg/d in the patients receiving CyA (p less than 0.001). The combination of CyA with low-dose steroids enabled the dose of CyA to be rapidly tapered off in once-weekly steps. CyA levels were monitored by determination of whole blood trough concentrations (target level: 300-800 ng/ml). At 60 days posttransplant the average dose of CyA was 6.0 +/- 0.5 mg/kg/d compared with an average daily dose of 11.4 +/- 0.9 as recommended for CyA alone in the protocol for the European multicentre study. This more rapid reduction in the CyA dose reduced nephrotoxicity (serum creatinine levels 174 +/- 14 as compared with 289 +/- 31 mumol/l) (p less than 0.05) and almost halved the number of methylprednisolone pulses given up to the end of the second month. We conclude from these results (1) that previously the dosage of CyA administered at this centre was probably too high, and (2) early adjustment of dose levels on the basis of blood concentrations and with low-dose prednisone cover appears to be safe and effective, but requires further verification.

Azathioprine↗

The role of tubuloglomerular feedback in acute impairment of renal function in obstructive jaundice.

Acute renal functional impairment not infrequently accompanies liver dysfunction and, particularly with bile duct obstruction, may be extremely severe. Recent studies suggest that tubuloglomerular feedback (TGF) activated by circulating non-electrolyte factors which occur during liver dysfunction may contribute to the intense renal vasoconstriction thought to be central to the functional renal impairment. In this study, serum from two patients with obstructive jaundice (OJ) and renal impairment, and from rats with OJ due to bile duct ligation were either dialysed or treated with furosemide, known to block electrolyte-mediated TGF. These sera, when perfused into loops of Henle in rat nephrons, induced a significant fall of 28% in stop-flow pressure, an indirect measure of glomerular capillary pressure thus implying arteriolar vasoconstriction. These findings are consistent with the hypothesis that circulating, non-electrolyte factors, which stimulate TGF, occur in cases of obstructive jaundice and that these may contribute to the renal impairment.

Acute Kidney Injury↗

Experimental approach to the correlation of hemodynamic changes with increases in urinary lactate dehydrogenase as a new parameter reflecting serious renal tissue damages.

From previous investigations with nephroptotic patients increased urinary LDH was assumed to be a reliable marker indicating a renal tissue defect due to the organs descent in erect position. Animal experiments now allowed correlation of this enzymatic activity with controlled changes of anatomical and physiological parameters. Changes of the renal hemodynamics or urinary flow induced in acute experiments in dogs simulated kidney displacement in nephroptotic patients. Both ureters were cannulated for separate urine collection and one kidney was manipulated. The renal arterial or venous flow was reduced or the ureter was occluded under electromagnetic blood-flow control. Arterial constriction alone (30%/15 min) selectively caused a drastic decrease (approximately 80%) of Xenon wash-out (= nutrient-flow) in the renal cortex. Under the same conditions radio-labeled microspheres injected intracardially showed a centralization of the renal capillary blood flow from the outer cortex to the juxtamedullary zone. Urinary LDH activities increased up to 800% immediately after arterial constriction. In accordance with total LDH activity the percentage distribution of isoenzymes changed: LDH-I increased and the LDH-V decreased. Neither constriction of the renal vein nor ureteral occlusion had similar effects. In long-term experiments backward fixation of one kidney in rats would reflect the effects of kidney displacement over years in nephroptotic patients: animals were unilaterally nephrectomized and the remaining kidney was dislocated backwards (approximately 2,5 vertebrae) and fixed to the lateral pelvic wall. "Ptotic" rats showed during the following examinations a constant increase of urinary LDH up to 50% by 26 weeks postoperatively. In accordance with increased LDH the isotope nephrogram was pathological and arteriographies showed a stretched and narrowed renal artery. In a number of rats "ptotic" fixation was not effective enough. All these animals showed normal LDH, isotope nephrograms and arteriographies. Both animal experiments documented that reduced flow/hypoxia is essentially responsible for the tissue damage in the kidney manifested by increased release of urinary LDH.

Animals↗

Diagnostic relevance of urinary lactate dehydrogenase determination in nephroptosis and for the indication to nephropexy.

Previously reported experiments with animals suggested that reduced renal arterial flow might be the actual cause for the pathogenicity of nephroptosis. Clinical studies now give evidence that measurements of urinary LDH may be a criterion equal to the isotope nephrogram (ING) in considering this disease. Patients with a "mobile" kidney verified by i.v. pyelography were examined by an ING and a 1-day test for urinary LDH. In accordance with periodic kidney displacement total urinary LDH activities were measured in a 8-h urine volume in the supine position and a 8-h urine volume in the erect position of the patients. Evaluations were all expressed as percentage increase of LDH activity of the patient in the erect versus supine position and correlated with his ING-pattern. Among 45 nephroptotic individuals 34 showed, in accordance with a pathological ING, a mean LDH increase of more than a 100%. Eleven individuals had normal INGs and less than 20% increase equal to a group of 16 normal controls. We postulated a 30% increase as the upper limit between normal and pathological urinary LDH. The percentage distribution of isoenzymes was also altered within the pathological LDH range: LDH-I, which increases in normal controls, now decreased in nephroptotic patients. LDH-IV and V, which decrease in controls, now increased. Homomeric isoenzymes obviously show reciprocal behavior. The degree of kidney descent in cm does not correlate with percentage increase of urinary LDH, i.e. it is not a criterion for pathogenicity. Biopsies taken during nephropexy revealed that from an anamnestic duration of 50 weeks onwards the kidney is significantly affected and tissue damages become evident. If patients were re-investigated after nephropexy they showed normal i.v. pyelograms and normal LDH and no longer had clinical symptoms.

Humans↗

[Anti-HBc within the framework of hepatitis B virus infection: correlation to the form of inflammation and to the viral expression].

168 HBAg seropositive and 105 HBAg seronegative liver biopsies were studied for correlations between anti-HBc titers (indirect immunofluorescence method) and tissue expression of HBsAg and HBcAg (immunofluorescence), Dane particles in blood (immune electron microscopy) and inflammatory reaction. 98.8% of the HBAg seropositive patients were positive for anti-HBc. The mean titers showed statistically significant differences mainly between chronic aggressive hepatitis (1:2(11.3)) versus lobular hepatitis (1:2(10.1)), chronic persistent hepatitis (1:2(9.9)) and nonspecific reactive hepatitis (1:2(7.6)). Due to the considerable deviation of titers within the histological groups, however, titers below 1:2(11) are of low diagnostic relevance, whereas titers above 1:2(12) are mainly indicative of chronic aggressive hepatitis, although acute lobular hepatitis with signs of possible transition to chronicity or chronic persistent hepatitis with strong inflammatory activity may occur. Among HBAg seronegative patients 20% were positive for anti-HBc (mean titer = 1:2(7.7)). Among 78 patients also tested for anti-HBs, 10.2% were positive for both anti-HBc and anti-HBs. In an additional 12.8%, anti-HBc was the only marker of past hepatitis B virus infection. Anti-HBs was the only marker in a further 33%. In none of the HBAg seronegative patients and in only 59% of all HBAg seropositive patients, there was an association of anti-HBc with complete virus synthesis as measured by the demonstration of HBcAg in tissue or Dane particles in blood. It is concluded that anti-HBc is not a criterion of infectiosity but a specific, although non-characteristic, marker for HBAg seropositive acute and chronic hepatitis as well as for terminated HBV infection of all possible inflammatory and HBAg expression types.

Antibodies, Viral↗

[Preoperative immunosuppression in the kidney-transplanted dog in connection with specific antigenic pre-treatment].

Postoperative, nonspecific routine immunosuppressive therapy fails in up to 50% in human cadaver renal transplantation. Donorspecific preoperative immunological conditioning of the host is harder to induce in dogs than in some rodents. In a pilot study 2 i.v. donorblood injections on days -18 and -11 followed by a 6-day preoperative pulse without any postoperative therapy induce a significant albeit limited prolongation of graft function.

Animals↗

[Clinical aspects and therapy of candidiasis in pneumological patients].

13 cases of deep candidiasis (two or more positive blood cultures or histological evidence) are reported. The patients were hospitalized because of respiratory problems (pneumonia, neuromuscular respiratory failure, bronchial carcinoma, brochiectasis, chronic bronchitis and acute laryngitis). Frequency, clinical signs and symptoms and therapy are discussed. The importance of early diagnosis is stressed.

Acidosis↗

[Complications of surgery in cirrhosis].

Extraabdominal operations are relatively well tolerated by the cirrhotic patient. However abdominal and thoracic surgery are followed by a very high morbidity and a mortality reaching 50% in these patients. Aggravating factors such as a decompensated cirrhosis and an alcoholic or viral hepatitis bear a catastrophic prognosis. The decision to perform surgery should as much as possible imply a knowledge of the histological nature of the cirrhosis and an intensive pre-operative preparation of the patient particularly in the respiratory and cardiac field.

Abdomen↗

[Ultrastructural studies on an animal model of epiphyseolysis. Cells and matrix in the proximal growth plate of the rat tibia after administration of DL-serine(3,4,5-trihydroxybenzyl)-hydrazide] (author's transl)

After administration of DL-serine-(2,3,4-trihydroxybenzyl-)hydrazide, the growth plate of rat tibia, and most of all the zone of hypertrophic cartilage, is much widened. Numerous chondrocytes become necrotic, and their columnar arrangement disappears. There is no zone vascular invasion. Spontaneous epiphyseolyses occur frequently, The ergastoplasm is damaged most; it is dilated and forms giant and/or collapsed cisternae. At a later stage it is reduced to a few vesicles. It is assumed that the chondrocytic synthesis and secretion are disturbed. The loss of cytoplasmic processes also confirms this. In the cartilage matrix there are broad collagen fibres of an axial periodicity of 650 A, which are atypical of hyaline cartilage. Possible pathogenetic mechanisms of the distrubed fibrillogenesis are discussed in conncetion with the epiphyseolysis.

Animals↗