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Biomedical subjects

M J Mihatsch

Publications and source records attributed to M J Mihatsch.

At least 19 recordsLinked to original sources
PubMed1992

[Pathology of myxoid mitral valve degeneration: literature review and personal results].

Mitral prolapse is a parachute-like protrusion of the value into the left atrium. Almost always a myxoid degeneration of the valve is the base of such a prolapse. Myxoid degeneration is understood as dissolution of the collagenous fibrous layer and its replacement by acid glucosaminoglycans. An alteration of collagen is suspected as primary defect in this sometimes also inherited disorder. The electron microscope reveals fragmentation of collagen fibrils and elastic fibers and, within the myxoid material, free lysosomes, so called "matrix-vesicles". An isolated disturbance of collagen types I and III could not be detected by immunohistochemistry. Studies could also to date not demonstrate mutations in the genes coding for collagens.

Aged↗
PubMed1992

Risk factors for cyclosporine-induced nephropathy in patients with autoimmune diseases. International Kidney Biopsy Registry of Cyclosporine in Autoimmune Diseases.

BACKGROUND: Cyclosporine is an immunosuppressive drug that is used to treat patients with autoimmune disease as well as patients who have received allografts. The drug can cause renal damage, but the incidence of and risk factors for nephropathy in patients treated with cyclosporine for autoimmune or inflammatory diseases are not known. METHODS: We analyzed data from renal biopsies performed in 192 patients (129 adults and 63 children) who had been treated with cyclosporine for insulin-dependent diabetes mellitus of recent onset, uveitis, psoriasis, Sjögren's syndrome, or polychondritis. The mean (+/- SD) initial dose of cyclosporine was 8.2 +/- 2.8 mg per kilogram of body weight per day, and the duration of treatment was 4 to 39 months (median, 13). RESULTS: Forty-one patients (37 adults and 4 children) had cyclosporine-induced nephropathy, defined as at least moderate focal interstitial fibrosis with tubular atrophy, arteriolar alterations, or both. As compared with patients in whom nephropathy did not develop, these patients received a larger initial dose of cyclosporine (9.3 +/- 2.8 vs. 8.0 +/- 2.8 mg per kilogram per day), had a larger maximal increase in the serum creatinine concentration above base-line values (101 +/- 77 percent vs. 50 +/- 33 percent), and were older (31 +/- 13 vs. 23 +/- 12 years). These three variables were shown by multivariate logistic-regression analysis to be significant risk factors. The duration of the elevation in the serum creatinine concentration and the occurrence of elevated blood pressure were not additional risk factors. CONCLUSIONS: Nephropathy is an important potential effect of cyclosporine therapy. The risk of its development in patients with autoimmune diseases who are treated with cyclosporine can be minimized by allowing a dose no higher than 5 mg per kilogram per day and avoiding increases in serum creatinine of more than 30 percent above the patient's base-line value.

Adolescent↗
PubMed1992

[Anorectal malignant melanoma].

Primary malignant anorectal melanoma is a rare disease. A wide variety of different treatment modalities--local excision, rectal amputation, exenteration of the pelvis with or without lymph node dissection--are proposed and represent the limited experience of the individual clinic. Mean survival of between 7 and 32 months and a 5-year survival between 0% and 12% are reported. The need for histological examination of every pathologic formation of the anorectum is stressed. Local excision is preferable provided the tumor is small, complete excision is possible and tumor thickness is less than 2 mm. Inguinal lymph node dissection can be dispensed with for prophylactic purposes but is standard when metastases are proven. Four own cases are presented and discussed.

Aged↗
PubMed1992

Serial kidney biopsies in patients with nephrotic syndrome treated with cyclosporin.

A total of 21 patients with severe steroid-resistant or steroid-dependent nephrotic syndrome have been treated with cyclosporin (CsA) over a period of 6 to 71 months. A permanent treatment was started in patients with complete [c] (proteinuria less than 0.3 g/day) or partial [p] (0.3 to less than 3.0 g/day) remission. In four cases proteinuria was markedly reduced but still greater than 3 g/day. Informed consent was obtained and all patients agreed to further control biopsies. Out of 14 patients treated for longer than 6 months, a fall in creatinine clearance was seen in three cases, including two patients with focal sclerosis who required dialysis treatment. Control biopsies were performed once in 11 and twice in seven patients. In two cases definite CsA-related damage was diagnosed after 1 and 24 months of treatment. Possible CsA-induced damage could not be excluded in three additional cases. In all other biopsies no CsA-related alterations could be demonstrated up to 47 months of treatment. The mean values of the creatinine clearance showed no deterioration. The drop off in a few cases has been related to the basic disease.

Adolescent↗
PubMed1992

The efficacy and tolerability of cyclosporine G in human kidney transplant recipients.

Twelve consecutive first cadaveric kidney transplant recipients received cyclosporine G (CsG)(initial dose 12 mg/kg per day) as basic immunosuppressive treatment along with prednisone (initial dose 0.5 mg/kg per day) for the first three months after transplantation. Thereafter CsG was replaced by Sandimmun (cyclosporine, CsA). Evaluation of the immunosuppressive efficacy and assessment of possible side effects of CsG was made and compared with the results in 38 historical control patients starting with the same dose of CsA as part of the same immunosuppressive dosage schedule. Statistically, there was no difference in patient survival at three (91% in CsG group versus 95% in CsA group) and twelve months (91% in CsG group versus 92% in CsA group), or in graft survival at three (75% in CsG group versus 89% in CsA group) and twelve months (75% in CsG group versus 84% in the CsA group). At equivalent oral doses of CsG and CsA significantly higher blood levels of CsG were observed (2P less than 0.05). Nephrotoxicity assessed by graft biopsy could be demonstrated to a similar extent in both groups, whereas hepatotoxicity was more pronounced during CsG treatment. Sequential measurements of bilirubin revealed a significant increase in all patients but median values were significantly higher in the CsG patients. A pronounced and concordant elevation of liver enzymes occurred during CsG treatment in three out of 12 patients. Liver biopsies performed in these patients revealed histological alterations consistent with toxic liver injury. Thus, in human kidney transplant recipients CsG and CsA appeared to be equally immunosuppressive and nephrotoxic but more hepatotoxic. On the basis of this limited experience we conclude that in human kidney transplant recipients CsG has no advantage over CsA.

Adult↗
PubMed1992

Consensus conference on cyclosporin A for psoriasis February 1992.

Human studies using oral cyclosporin A (CyA; Sandimmun) therapy for psoriasis have been in progress for nearly 9 years. Cumulative data of the clinical effects of this therapy in 1000 patients have been collected, and are derived from multiple open and controlled studies. The efficacy of this treatment in psoriasis is well recognized, and the relative safety of up to 2 years of therapy is also established, provided that the guidelines are observed. However, there is concern regarding the long-term safety of CyA treatment of psoriasis as experience is still limited. Careful monitoring of all CyA-treated patients is therefore mandatory, and CyA should only be used by dermatologists who have expertise in its use. During treatment, co-operation with an experienced nephrologist is strongly recommended.

Cyclosporine↗
PubMed1992

Thromboxane mediates glomerular haemodynamics in a model of chronic glomerular disease.

In order to evaluate a possible haemodynamic role of cyclooxygenase products in chronic renal disease, a model of chronic glomerular injury was induced in nephritic rats by unilateral nephrectomy and high dietary protein intake. Eight weeks after induction of an in situ immune complex glomerulonephritis (CGN), rats subjected to high protein (HP) intake (42% protein) and uninephrectomy revealed a significantly lower glomerular filtration rate (GFR; 485 +/- 53 microliters min-1 100 g-1 body weight (BW)) compared with uninephrectomized rats with ICGN which were on low protein (LP) diet (6% protein) (825 +/- 155 microliters min-1 100 g-1 BW) (P less than 0.01). The glomerular thromboxane B2 (TxB2) formation in uninephrectomized rats with ICGN on either LP or HP intake was not significantly different (HP: 473 +/- 61; LP: 493 +/- 63 pg mg-1 min-1), but was significantly higher when compared with non-nephritic controls on either diet. Glomerular prostaglandin E2 (PGE2) production in rats on HP diet was higher compared with rats with LP intake (HP: 617 +/- 67; LP: 351 +/- 76 pg mg-1 min-1) (P less than 0.01). The thromboxane receptor blocker daltroban significantly elevated suppressed GFR in ICGN rats on HP diet (ICGN+vehicle: 426 +/- 69; ICGN+daltro: 689 +/- 66 microliters min-1 100 g-1 BW) (P less than 0.01). Thromboxane receptor blockade had no effect on glomerular haemodynamics in ICGN animals receiving LP diet (ICGN+vehicle: 771 +/- 24; ICGN+daltro: 684 +/- 85 microliters min-1 100 g-1 BW).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Renal graft rejection or cyclosporin toxicity? Early diagnosis by a combination of Papanicolaou and immunocytochemical staining of urinary cytology specimens.

A method is described for distinguishing between graft rejection and cyclosporin nephrotoxicity in renal allograft recipients by analyzing fresh morning urine samples. The technique combines classic Papanicolaou with immunocytochemical staining and was performed in urine specimens from a series of 42 patients. Early-stage cyclosporin toxicity was usually associated with increased numbers of proximal tubular cells only, whereas in rejection and late-stage toxicity there were increases in both tubular cells and in lymphocytes and monocytes (greater than 2000 cells/ml urine). Differentiation between these two clinical conditions was achieved by immunostaining, which revealed that increased numbers of CD25+ and CD8+ cells, as well as an increase in the HLA-DR/Lu5 ratio, were typical of rejection. CD25 positivity proved to be the best indicator of rejection, with a sensitivity and specificity of more than 90%. A cytodiagnostic algorithm is presented that is based on cell numbers and types, including immunophenotypes. The proposed method has the advantage of being noninvasive and appears to represent a reliable and rapid adjunct for the monitoring of graft function, especially in high-risk patients on cyclosporin immunosuppression.

Adolescent↗
PubMed1992

Immunosuppression and cancer: the ciclosporin case.

Experimental and clinical data relevant for the evaluation of the carcinogenic potential of the immunosuppressant ciclosporin are reviewed. Ciclosporin binds reversibly to the cytosolic receptor protein ciclophilin. Ciclophilin is likely involved in the blockade of lymphocyte activation-induced gene transcription of various growth factors, especially interleukin-2. The drug has no effect on the transcription of housekeeping genes nor does it activate any gene. Ciclosporin may inhibit tumor cell growth, notably those which are growth factor dependent. At high concentration virus-transformed cells, especially Epstein-Barr-infected B-lymphocytes, may escape the control of specific cytotoxic T-lymphocytes. Ciclosporin has no genotoxic activity, and has no DNA-binding property. In experimental studies ciclosporin did not cause cancer in the absence of an initiating event (e.g. chemical mutagen). However, by its immunosuppressive property, the drug may allow the growth of initiated tumor cells in vivo, an effect which is dose-dependent. In clinical use ciclosporin immunosuppression is associated with an increased incidence of lymphoproliferative disorders and other malignancies particularly of the skin when compared with a normal, not immunosuppressed population. Conventional immunosuppression (azathioprine, antilymphocyte globulin, prednisone) also demonstrates comparable risks to develop tumors. Lymphoproliferative lesions regress after dose reduction or cessation of treatment. Furthermore, combinations of various immunosuppressants with associated 'over-immunosuppression' may result in a higher incidence of viral infection and malignancy. In summary, chemical immunosuppression carries the intrinsic risk of tumor growth. In the case of ciclosporin this effect is dose dependent. Thus, the risk may be reduced by low dosage and by avoiding combination therapies with additional immunosuppressants.

Animals↗
PubMed1992

Studies on morphological outcome of cyclosporine-associated arteriolopathy after discontinuation of cyclosporine in renal allografts.

Cyclosporine (CSA)-associated arteriolopathy (CAA) is the second most frequent morphological diagnosis in renal allografts and its final outcome remains unclear. The present study was performed to clarify the morphological outcome of CAA by follow-up histological analysis after stopping CSA. Furthermore, the clinical management of patients showing CAA is discussed. Most of the patients came from our early experience with CSA between 1981-1983 when CSA doses and trough levels were high. Twenty recipients were divided into two groups according to the presence of CAA after stopping CSA: group A (n = 9) showed persistent CAA and group B (n = 11) showed no CAA. The majority of the patients, including five incomplete remission in group A, showed obvious improvement of CAA even if the arterioles were severely affected. Improvement of CAA was noted a few months after stopping CSA or after lower dose CSA therapy. There were no significant differences in CSA blood levels or duration of CSA therapy between the groups. The severity of preexistent CAA was significantly greater in group A. Only two patients who died from malignant tumor showed exacerbation of CAA. Eight patients died and eight grafts were lost, seven due to vascular rejection and one to hemolytic uremic syndrome-like CAA. Poor renal function was also noted in four cases with functioning graft owing to vascular rejection even though the improvement of CAA was evident. The complete regression of CAA and the remodelling of arterioles showing well preserved vascular patency were frequently found after stopping or reducing the dose of CSA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Kidney biopsy findings in cyclosporine-treated patients with insulin-dependent diabetes mellitus.

Renal biopsy specimens of 40 patients with recent-onset insulin-dependent diabetes mellitus treated with cyclosporine (CSA) for 6-29 months were examined. Cyclosporine-associated chronic vascular interstitial toxicity of moderate intensity was found in 10 patients (25%). The most prominent lesions were interstitial fibrosis and tubular atrophy. Arteriolopathy was less pronounced and glomerular damage unremarkable. A significant correlation exists between the extent of tubular atrophy and CSA trough whole blood levels. These data indicate that the development of CSA-associated chronic nephropathy is dose-dependent.

Adolescent↗
PubMed1991

Cardiac myxomas: immunohistochemical study of benign and malignant variants.

Immunohistochemical investigation of 11 cardiac myxomas (CMs) including one malignant metastasizing CM showed a co-expression of epithelial (lu-5 and CAM 5.2), mesenchymal (vimentin) and neuroendocrine antigens (neuron-specific enolase) in all tumour cells. Factor VIII was found in the endothelial cells of capillaries only. In the subendocardium of fetal heart tissue close to the foramen ovale myofibroblasts reacting with the panepithelial antibody lu-5 were detected. We conclude that CMs are neoplasms that may develop from embryonic cell remnants.

Adult↗
PubMed1991

Control of hypertension by verapamil enhances renal damage in a rat remnant kidney model.

The effect of calcium channel blockers on the progression of renal failure is controversial. In contrast with earlier studies, we recently reported that moderately large doses of verapamil significantly accelerated chronic renal failure in the rat remnant kidney model. Studies reporting beneficial effects of verapamil were characterised by a much lower dose of verapamil and by the start of treatment immediately after renal ablation, which potentially interfered with the initial phase of remnant kidney hypertrophy. We therefore studied the effects of a high, fully antihypertensive oral dose of verapamil (100-150 mg/kg/per day; group Vera high) and a low, haemodynamically almost ineffective dose (10-15 mg/kg per day; group Vera low), on the progression of chronic renal failure in female Wistar rats with 5/6 nephrectomy. The treatment was started no earlier than 5 weeks after renal ablation, and matched groups of 20 animals were followed for 16 weeks thereafter. High-dose verapamil reduced systolic blood pressure to median values of 130-140 mmHg throughout the experimental period, whereas blood pressure in Vera low animals remained elevated at median values of 165-172 mmHg similar to non-treated rats with 172-185 mmHg median systolic blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Surface charge distribution is a determinant of antigen deposition in the renal glomerulus: studies employing 'charge-hybrid' molecules.

The deposition of antigens and immune complexes (IC) in the renal glomerulus is charge-dependent. The demonstration that molecules of net anionic charge, but with discrete positively charged regions, exhibit affinity for the glomerular basement membrane (GBM) extends this concept. Charge hybrid (polar) molecules were constructed by covalently coupling small polycations (lysozyme or linear poly-L-lysine chains with a mean of 17 and 20 residues) to larger polyanions (ovalbumin or human serum albumin (HSA]. Although the products were of overall net anionic charge they still bound to glomerular structures. Immunofluorescence studies performed after i.v. injection of the samples into rats revealed that HSA:poly-L-lysine had the highest affinity. Radioisotopic measurements showed uptake of HSA:poly-L-lysine to be a function of the number of lysine residues; binding of HSA:poly-L-lysine20 was 2.5 times higher than HSA:poly-L-lysine17 (P less than 0.01). Prior injection of a small competing polycation (polyethyleneimine 1200) reduced uptake of HSA:poly-L-lysine by 75%, indicating the charge-based nature of the interaction. HSA:poly-L-lysine20 alone was effectively eliminated from the glomeruli within 72 h. Administration of HSA:poly-L-lysine followed by anti-HSA antibody induced immune complex formation in the capillary wall, giving rise to a granular immunofluorescence pattern and discrete subendothelial and subepithelial deposits. Molecules with polar structure do occur naturally and may contribute to immune complex formation in glomerulonephritis.

Analysis of Variance↗
PubMed1991

Collagen type III glomerulopathy: a new idiopathic glomerular disease.

A new type of idiopathic glomerular disease is reported in a 49-year-old Italian woman who presented with uncharacteristic renal symptoms, i.e., hypertension and slight proteinuria. Clinical investigation excluded a familial renal disease and more specifically nail-patella syndrome. Diagnostic renal biopsy by light microscopy showed a picture similar to membranoproliferative glomerulonephritis. The enlarged glomeruli were lobulated, the peripheral basement membranes were thickened by the deposition of light-microscopically undefined material, cell proliferation was lacking. By electron microscopy, the material was nonhomogenous, partly granular partly fibrillar, containing typical collagen fibers. The latter were identified as collagen type III, to a lesser extent collagen type I. Review of the literature resulted in 12 similar or identical cases reported from Japan and one additional case reported in a white American female. Evidence of systemic disease is lacking. Etiology and pathogenesis are elusive. A progressive deterioration of renal function must be expected. Collagen type III glomerulopathy is suggested as term of this new type of idiopathic glomerular disease.

Biopsy↗