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Biomedical subjects

H Starklint

Publications and source records attributed to H Starklint.

At least 55 records · Page 3Linked to original sources

Keratin patterns in prostatic hyperplasia and adenocarcinoma.

Keratin patterns in benign prostatic hyperplasia and prostatic adenocarcinoma were evaluated using frozen and formalin-fixed tissue. Five different commercially available antibodies were used. In frozen tissue basal cells of benign acinic and ductal structures stained with PKE, and to a lesser degree with MCA 144, CAM 5.2 and RCK 102. Luminal cells stained with MCA 144, CAM 5.2, RCK 102 and to a lesser degree with PKE. In formalin-fixed tissue basal cells stained exclusively with Z622, predominantly with PKE and RCK 102, and to lesser degree with MCA 144 and CAM 5.2. Luminal cells stained with MCA 144 and CAM 5.2 and to some degree with PKE and RCK 102, while Z622 stained luminal cells of ductal epithelium weakly, but acinic cells not at all. Luminal phenotype dominated in prostatic adenocarcinomas which were stained with MCA 144 and CAM 5.2 irrespective of differentiation, and independently of whether frozen or formalin-fixed tissue was used. However, the different keratin phenotype of benign and malignant prostatic epithelium depends to some degree on the immunohistochemical procedures used. In diagnostic pathology Z622 may be able to separate intraluminal neoplastic lesions from invasive carcinoma, a problem particularly seen when cribriform growth pattern is found.

Adenocarcinoma↗

Long-term cyclosporin nephrotoxicity in the rat: effects on renal function and morphology.

This long-term study elucidates the development and reversibility of functional and morphological cyclosporin (CsA) nephropathy. Sprague-Dawley rats were given CsA (12.5 or 25 mg/kg per day) for 4, 8 or 16 weeks, or CsA during the first half of the 8- or 16-week period, and vehicle during the second half. Controls were given CsA vehicle throughout the study. Renal function was investigated with clearance methods (inulin, lithium, sodium and potassium). CsA-treated rats developed a focal renal interstitial fibrosis, the severity of which correlated to the accumulated CsA dose given (Kendall's tau = 0.56, P less than 0.0001). This renal lesion was not reversible. CsA reduced GFR and lithium clearance, and increased proximal fractional reabsorption. There was significant correlation (P less than 0.0001) between accumulated CsA dose and severity of functional impairment. Renal function improved following drug withdrawal, but in the compiled material, low-grade nephrotoxicity was evident 4 to 8 weeks after CsA withdrawal: GFR was decreased to 84% (P less than 0.02) of control levels. This indicates that CsA-induced renal focal interstitial fibrosis is progressive during treatment, and is not reversible, while functional CsA nephropathy is progressive but partly reversible if CsA is withdrawn.

Absorption↗

Activation of fibrinolysis during xenoperfusion.

Ten rabbit kidneys were perfused at 80 mm Hg, 37 degrees C, with oxygenated recirculating heparinized human blood. These experiments were compared to another ten perfusion experiments where 1 unit/ml porcine plasmin was added to the human blood one hour before the perfusion, at which time the fibrinolytic activity was significant and the fibrinogen concentration under the detection limit. Rejection, determined as time until blood flow decreased to 2 ml/min, was not significantly delayed by addition of plasmin. At the end of the experiments, the fibrinolytic activity in the control experiment had increased above the activity in the plasmin added experiments, although the fibrinogen concentration was almost unchanged. Histological examinations demonstrated a decreased platelet deposition and the fall in platelet count was smaller in the plasmin experiments. C3d determinations revealed a slight activation of complement upon addition of plasmin, but the activation by xenoperfusion was much more pronounced and, at the end of the experiment, the C3d concentration was the same in the two groups.

Animals↗

Nephrotoxicity of cyclosporin A in humans: effects on glomerular filtration and tubular reabsorption rates.

The contention that cyclosporin A (CyA) nephrotoxicity may be due to renal afferent arteriolar constriction was inferred from rat studies showing CyA to increase renal vascular resistance, to reduce glomerular filtration rate (GFR) and delivery of tubular fluid from the end of the proximal tubule to the loop of Henle (Vprox), and to increase proximal fractional reabsorption. In order to test whether the mechanism of human CyA nephrotoxicity is similar to its rat analogue, and whether CyA treatment causes prolonged renal malfunction after drug withdrawal, renal function was investigated with clearance techniques including lithium clearance (CLi) as a measure of Vprox. The subjects were patients (n = 11) with previously normal renal function, given CyA in the treatment of ocular manifestation of extrarenal disease, or bone-marrow transplant recipients. Nine out of these eleven patients were investigated before and during CyA treatment: GFR (P less than 0.05) and Vprox (P less than 0.005) decreased while proximal fractional reabsorption increased (P less than 0.01). In six patients investigated before CyA was given, and re-examined a mean of 273 days (range 84-384 days) after CyA withdrawal, CLi was reduced (P less than 0.05) while mean GFR was not significantly lowered (0.5 greater than P greater than 0.2). In one of these six patients GFR was reduced to a subnormal value of 26 ml min-1 (1.73 m2 body surface)-1. In conclusion, human and rat CyA nephrotoxicity have the same pattern of renal functional deterioration. Cyclosporin A nephrotoxicity was evident in patients investigated a mean of 9 months after CyA withdrawal.

Absorption↗

Cataractogenic effect of cyclosporin A: a new adverse effect observed in the rat.

In a study designed to test the long-term nephrotoxic effects of cyclosporin A (CyA), 11 of 13 rats given CyA, 25 mg/kg per day for 8 months, developed cataract. None of the 15 rats given CyA 12.5 mg/kg per day, nor of the controls given vehicle only (n = 10), developed this lesion. In a subsequent study, 15 rats were given CyA 25 mg/kg per day, 15 were given 12.5 mg/kg per day, and 10 controls were given the vehicle only. After 16 weeks, three rats of the group on CyA 25 mg/kg per day had developed cataract. The SPF Sprague-Dawley rats were maintained on a controlled breeding diet (Ewos R3). Perforating eye lesions or infections were not observed, but one rat without opacity of the lens had antibodies against sialodacryoadenitis virus. Thus, in the rat, high-dose CyA has significant cataractogenic effects when administered for 15%-25% of the rat life-span.

Animals↗

Platelet aggregation is not essential for xenograft rejection.

Five rabbit kidneys were perfused at 80 mm Hg with heparinized human blood, five with platelet poor human blood, and five with human blood added prostacyclin. Time until blood flow decreased to 2 ml/min was significantly delayed by removal of platelets or addition of prostacyclin. Histological examination did not reveal any difference between the groups. It is concluded that platelets play an enhancing role, but they are not essential for xenograft rejection.

Animals↗

Excessive hypercalcaemia and mixed connective tissue disease.

A 23-year-old female with extreme hypercalcaemia was treated with calcitonin, mitramycin and parathyroidectomy and normocalcaemia was achieved after 4 weeks. Nevertheless, the patient later died of cutaneous necrosis, impaired circulation and multiple organ failure. Serum immunoreactive parathyroid hormone was in the normal range and parathyroid tissue normal. Mixed connective tissue disease was diagnosed on the basis of high titers of antibody to extractable nuclear antigen, moderately elevated levels of antibody to nuclear antigen and only marginal elevation of anti-double standed DNA. The role of Cl. difficile toxin in the blood and an acinic cell tumour is unclear.

Adult↗

Nephrotoxicity of cyclosporin A. A lithium clearance and micropuncture study in rats.

Renal function was studied in rats treated with cyclosporin A (CyA). Peroral CyA 25 mg kg-1 day-1 depressed glomerular filtration rate (GFR) from 1284 +/- 429 to 500 +/- 228 microliters min-1 g-1 kidney weight (KW) (P less than 0.01). Absolute rate of proximal tubular reabsorption (APR) decreased from 1075 +/- 437 to 468 +/- 203 microliters min g KW-1 (P less than 0.01). Proximal tubular fractional reabsorption (PFR) was 67.7 and 68.5% measured with the TT/OT and fractional lithium-clearance methods, respectively. Amiloride had no effect on lithium-clearance in CyA treated rats. Acute isotonic volume expansion increased GFR and APR towards normal, while PFR remained increased. Increased sodium clearance did not normalize renal function. CyA intravenously (12.5 mg kg-1) depressed GFR and APR acutely, while PFR increased. Proximal intratubular pressures were low normal (mean 11.6 mmHg). Proximal transit times were prolonged (mean 25.2 s, P less than 0.01). Renal morphology was normal. The data are evidence against a primary tubular damage of CyA, and makes it less likely that the major lesion is located to the glomerular membrane. The results suggest that CyA nephrotoxicity mainly is due to a haemodynamic effect.

Amiloride↗

Antagonist capacities of nifedipine, captopril, phenoxybenzamine, prostacyclin and indomethacin on cyclosporin A induced impairment of rat renal function.

Experimental evidence indicates that cyclosporin A (CyA) nephrotoxicity is due to renal arteriolar constriction, reducing renal blood flow, glomerular filtration rate (GFR), and delivery of tubular fluid from the end of the proximal tubule to the loop of Henle. The proximal tubular fractional reabsorption (PFR) is increased. Therefore, the impact on renal function of vasodilating agents was studied in rats given CyA. Conscious catheterized rats and clearance techniques were used. In acute experiments a preexisting CyA-nephrotoxicity was resistant to infusion of phenoxybenzamine, prostacyclin, captopril, nifedipine and indomethacin. Concomitant treatment with captopril and CyA did not improve renal function, while concomitant treatment with CyA and nifedipine improved GFR to 1.13 +/- 0.34 ml min-1 g-1 kidney weight (gKW) (n = 19, P less than 0.05), as compared to CyA and placebo treated controls (n = 12, 0.83 +/- 0.32 ml min-1 g-1 KW). Nifedipine also reduced FPR (88.6 +/- 5.1% vs. 83.2 +/- 5.6%. P less than 0.01), and increased lithium clearance from 99 +/- 54 to 184 +/- 64 microliters min-1 g-1 KW (P less than 0.001). The results are further evidence that CyA nephrotoxicity includes renal vasoconstriction, and indicates that calcium entry blockade is nephroprotective in the case of CyA toxicity.

Animals↗