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Biomedical subjects

M Mihatsch

Publications and source records attributed to M Mihatsch.

At least 37 records · Page 2Linked to original sources

Induction of experimental allergic arthritis with outer surface proteins of Borrelia burgdorferi.

OBJECTIVE: The arthritogenic potential of the cationic outer surface proteins (Osp) from Borrelia burgdorferi was tested in rats. METHODS: Water-soluble Osps were prepared by butanol extraction and were administered by intraarticular injection. Tissue injury was assessed by scintigraphy and histology. RESULTS: A mild arthritis was seen in naive rats. Preimmunized animals had more severe, longer lasting bouts of inflammation. CONCLUSION: The Osps of Borrelia burgdorferi are potent arthritogens in rats. These immunodominant antigens may play a role in the development of Lyme arthritis in humans.

Animals↗

Long-term benefits and risks of cyclosporin A (sandimmun)--an analysis at 10 years.

To evaluate long-term benefits and risks of CyA therapy in renal transplantation, we analyzed the 10-year experience with all 59 patients who had received a first cadaveric renal graft until August 1983 and were immunosuppressed with CyA. We compared their actual graft survival with that of all 213 patients who had received a first cadaveric graft from 1967 until August 1983, but were immunosuppressed initially with azathioprine and prednisone (AzaP). For comparison of p-creatinine, proteinuria, blood pressure, lipids, uric acid and skin malignancies we evaluated the patients staying unchanged on initial therapy for 10 years (CyA = 12, AzaP = 53). RESULTS. (1) Actual graft survival at 10 years was 34% (20/59) with CyA and 27% (58/213) in AzaP treated patients (intention to treat) (P = .09 = ns). At 1 to 5 years, graft survival was 15% superior with CyA, but after 7 years the survival curve of the CyA-group has closely joined the chronic decline seen in the AzaP group. This behaviour could neither be explained by chronic CyA-nephrotoxicity nor by chronic rejection after switching from CyA to AzaP. (2) P-creatinine at 10 years was significantly (P < .03), but mildly elevated under CyA (130 +/- 52; AzaP = 109 +/- 65). (3) Proteinuria (g/d) at 10 years was not significantly different (CyA = 0.41 +/- 0.58, versus AzaP = 0.83 +/- 1.61). (4) Systolic blood pressure was higher at 10 years under CyA (152 +/- 19) than under AzaP (136 +/-) (P < .02), but diastolic pressure was not (89 +/- 10 versus 84 +/- 12; ns). Antihypertensive drug/patient was twice as high under CyA (1.25 versus 0.64 P < .02). (5) Cholesterol, triglyceride, HDL were not different. 75% of the CyA-patients were steroid free at 10 years, none of the AzaP-patients. (6) P-uric acid was not significantly different in both groups (494 +/- 192 vs 400 +/- 124), but 42% of CyA-patients were on uric acid lowering drug (given after at least one gout attack) as compared to 9% under AzaP (P < .006). (7) Seventeen percent of patients under CyA for 10 years had at least one skin cancer, not different from 15% of AzaP-patients. CONCLUSIONS. The main benefit of CyA was the better graft survival up to 5 years and the chance to stay free of steroids. The main risks of CyA were nephrotoxicity, hypertension and symptomatic hyperuricemia. No difference was found for hyperlipidemia and skin-malignancies.

Antihypertensive Agents↗

Telepathology with an integrated services digital network--a new tool for image transfer in surgical pathology: a preliminary report.

We describe a low-cost telepathology system working via a commercial integrated services digital network (ISDN) and consisting of modular software and hardware elements. The main elements are Apple Macintosh workstations; a software program for the simultaneous transfer of pictures, voice, and data; and procedures for image processing and general administration of all the information generated. Additionally, the system allows remote control of any peripheral instruments by a "picture-instrument manager." The transfer rate is currently 64 kbit/s; it will be extended to 128 kbit/s (ISDN basic rate) in the near future and to 2 Mbit/s (ISDN primary rate) in the next 2 years. The system was tested by the regional hospital in Samedan, Switzerland, and the Department of Pathology, University of Basel, Basel, Switzerland, a distance of 250 km, by offering a remote frozen section service to the regional hospital in 16 cases. Fifty-four to 58 seconds were needed for the transfer of a diagnostic 8-bit grey-level image containing 341 (median value) +/- 26.1 (standard error) kbytes (n = 13) or a diagnostic 24-bit color image containing 165 (median value) +/- 16.9 (standard error) kbytes (n = 3). The time required for a diagnostic session was between 25 and 35 minutes.

Adult↗

[Complications of immunosuppression].

In the near future several new immunosuppressive substances will be available: Cyclosporin G, IMM125 (both are new derivates of Cyclosporin A), FK506, Rapamycin, Leflunomid, Mycophenolic acid (RS-61443), Bredinin (Mizorinin), Brequinar, Deoxyspergualin and several new monoclonal antibodies (anti-CD4, anti-II-2-Receptor, anti-CD8, anti-CD45, anti-ICAM1 and others). Side-effects of immunosuppressants are classified in 1) relative drug-specific or 2) unspecific effects of over-immunosuppression (infections and malignancies). Nephrotoxicity of Cyclosporin A and guidelines for its prevention are covered in more detail. The authors fear, that the proliferation of new immunosuppressive drugs will make it more difficult, to carefully evaluate their side-effects.

Cyclosporine↗

Risks and benefits of graft biopsy in renal transplantation under cyclosporin-A.

261 patients who received a kidney transplant under cyclosporin-A immunosuppression were reviewed in order evaluate the benefits and the risks of renal graft biopsies. 240 graft biopsies were performed in 124 of the 261 patients. The biopsy diagnoses were 103x rejection, 90x cyclosporin-A toxicity, 8x acute tubular necrosis, 8x glomerulonephritis, 9x different biopsy results, and 12 cases of normal renal tissue. In 214 cases the clinical course was well explained by the biopsy result. The histological results led to therapeutical changes in 199 cases. 221 of the 240 biopsies were performed without any complications. There was only one biopsy with irreversible and there were 19 biopsies with reversible complications.

Biopsy↗

[Donor allopurinol treatment improves organ preservation of the kidney also when using UW solution].

Kidney function following hypothermic preservation with Eurocollins (EC) was previously shown to be improved by donor treatment with Allopurinol (AP) [1]. The University of Wisconsin organ preservation solution (UW), however, contains Allopurinol (1 mM). A syngeneic rat kidney transplant model was used to investigate concurrent Allopurinol donor-pretreatment (40 mg/kg b.w.). Kidney graft function resulted to be improved by AP pretreatment following organ preservation with both EC or UW as evidenced by significant reduction in serum creatinine values. On day two following transplantation the respective serum creatinine values (mumol/l) with and without AP-pretreatment were 424 +/- 39 and 662 +/- 25 for EC, and 259 +/- 48 and 387 +/- 48 for UW organ preservation. Furthermore survival- and histology-data were also superior for recipients of kidney grafts from AP-pretreated donors. We conclude that Allopurinol concentration in the UW solution might be to low or that adding AP into an organ storage solution is not the best application modality.

Adenosine↗

Cyclosporine and the renin-angiotensin system.

Much is known about the renin-angiotensin system during cyclosporine treatment: plasma renin or prorenin activity seems to be raised in man and animals; hyperplasia of the juxtaglomerular apparatus has been reported in man and animals; renin concentration is known to be increased in animal kidneys; renin-angiotensin-like alterations in vascular contractility have been identified in animal vessels. Since the major functional side effects of cyclosporine are systemic vasoconstriction and renal vasoconstriction, the renin-angiotensin system could be involved. Also, an infrequent complication in man, vasculopathy, develops only in the afferent arteriole, where renin production is most abundant. Hence, this information is now reviewed and incorporated into a single pathophysiological concept, with the implication that renin activation plays a central role in the pathogenesis of cyclosporine-induced functional and structural lesions, merits further attention.

Animals↗

Does microinvasion of the capsule and/or micrometastases in regional lymph nodes influence disease-free survival after radical prostatectomy?

Since 1976, 126 patients with clinically localised carcinoma of the prostate have been managed by radical retropubic prostatectomy. All patients with tumour spread beyond the capsule or metastasis in lymph nodes received radiotherapy. Tumour category pT3 was divided into invasion of the capsule or infiltration of the seminal vesicle. The disease-free 10-year survival rate in patients with minimal invasion of the capsule was 72% and in patients with infiltration of the seminal vesicles it was 26%. Unilateral lymph node metastases were classified as microscopic disease or macroscopic infiltration. The disease-free 10-year survival rate in patients with metastasis in 1 lymph node (micro- and macro-metastasis) was 65% in contrast to 0% in patients with bilateral disease.

Aged↗

[The long-term management of heart transplant patients].

The long-term care of patients following heart transplantation is characterized by the problems associated with long-term immunosuppression. In addition, a specific form of coronary atherosclerosis develops within years in many patients requiring coronary angiography on a yearly basis. The examination of patients after heart transplantation does not reveal characteristic findings, as long as the transplanted heart functions properly and a normally functioning graft allows a functionally almost normal life. The dependence on a specialized center, which may be more or less depending on the clinical course, and the ever present knowledge of the potentially lethal consequences of a graft failure present a severe psychic stress to the patient. This stress is handled more or less well and requires special attention by the treating physicians and, ideally, an intact social environment. The care of patients in a center close to their place of living is less time consuming for the patient and relieves the burden of the transplanting center.

Follow-Up Studies↗

[Problems with long-term immunosuppression following organ transplantation].

Long-term immunosuppression is followed by an increase of malignancies (skin cancer, lymphomas and Kaposi's sarkoma). Among the infectious complications an incidence of bacteraemia up to 48% is found, a relative increase of infection with listeria and salmonella, and viruses from the herpes group. The major side effect of azathioprine is haematologic, whereas Cyclosporin A is nephrotoxic. Three classes of renal functional impairment by Cyclosporine are defined: 1. renal dysfunction, 2. acute nephrotoxicity and 3. chronic nephrotoxicity. Appropriate ways to handle chronic nephrotoxicity are discussed.

Humans↗

Comparison of immunofluorescent findings in kidney after snap-freezing and formalin fixation.

Two types of tissue preparation for immunofluorescent staining were compared with sections of the same kidney. In one, formalin-fixed paraffin-embedded kidney sections were incubated with pronase (IF-PRON). The optimal pronase exposure for bright, specific IF and a mild background IF, suitable for the whole set of antisera was determined (pronase 0.75 g/l of Tris buffer for 60 min) and this was used for the subsequent steps of the study. Snap-frozen sections were also stained (IF-FROZ). Positive and negative cases, IF intensity, distribution and location in IgA nephropathy, membranous nephropathy, proliferative lupus nephritis were compared by the 2 methods. The main antigens for each disease were adequately revealed by IF-PRON, so that a correct diagnosis was possible in all cases. IF-PRON was also applied to sections before and after prolonged storage of blocks in the files, to see whether or not retrospective analysis is possible. Only minor differences were found between the 2 series of sections. Finally, the exposure of the sections to the continuous fluorescent light showed that IF fading was less in fixed sections. We conclude that IF-PRON is a reliable method for renal pathology with some advantages over the IF-FROZ.

Dose-Response Relationship, Drug↗

[Renal manifestations of sarcoidosis].

Renal manifestations of sarcoidosis are rare. In addition to calcium nephropathy, granulomatous interstitial nephritis and glomerulo-nephritis (GN) account for most cases. The latter two manifestations are described in 4 patients and in a detailed review of the literature. In comparison to a nonselected population of sarcoidosis patients, granulomatous interstitial nephritis is found more frequently in male patients above 40 years of age; it is associated more frequently with other extrathoracic manifestations of sarcoidosis; and it causes renal insufficiency of varying degree, which is at least partially reversible with steroid therapy. Predominant findings are silent microhematuria, sterile pyuria, mild proteinuria and a variety of tubular functional disorders. Glomerulonephritis (39 observations) has been described with increasing frequency in sarcoidosis. Because of the well known immunological abnormalities of sarcoidosis, frequent association of sarcoidosis with GN could be expected but this association has not yet been proven statistically. Sarcoidosis-associated GN includes a variety of histological forms, viz. membranous, proliferative and sclerosing GN. Glomerulonephritis may appear before sarcoidosis. Conversely, both diseases may appear simultaneously, or GN may follow all other manifestations of sarcoidosis with a latency period of many years.

Aged↗

The angiotensin converting enzyme inhibitor enalapril in acute ischemic renal failure in rats.

The influence of the renin-angiotensin system on renal hemodynamics, tubular pressure and tubulo-glomerular feedback was investigated with the angiotensin converting enzyme inhibitor MK 421 (enalapril), in uninephrectomized rats with and without ischemia-induced acute renal failure. In animals with normal renal function proximal tubular pressure and tubulo-glomerular feedback response were lowered by enalapril long-term treatment, whereas glomerular filtration rate and renal blood flow were not influenced by the drug. After 45 and 70 minutes ischemia there was no difference between treated and untreated animals in the severely impaired glomerular filtration rate. Renal blood flow remained unaffected by the treatment. The histological damage due to ischemia (tubular casts, tubular necrosis and medullary capillary congestion) was not influenced by enalapril. As tubulo-glomerular feedback had been significantly inhibited during renin-angiotensin inhibition, its importance in mediating acute renal failure remains doubtful; other factors such as tubular obstruction and medullary congestion may be crucial.

Acute Kidney Injury↗