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Biomedical subjects

H Starklint

Publications and source records attributed to H Starklint.

At least 73 records · Page 4Linked to original sources

On the role of platelets and leucocyte in renal xenoperfusion.

Five rabbit kidneys were perfused with heparinized human blood, five with platelet-rich, leucocyte-poor blood, five with platelet-poor, leucocyte-rich blood, and five with platelet-poor, leucocyte-poor, heparinized human blood. The kidneys were perfused at a constant pressure of 80 mm Hg and the time until the flow decreased to 2 ml/min was determined. Removal of platelets from the blood significantly delayed rejection. The effect of removing leucocytes was insignificant. Morphologically all groups revealed platelet aggregates, endothelial damage and ischemic changes of distal tubular epithelium.

Animals↗

Indications for and timing of removal of non-functioning kidney transplant.

The clinical indications for and the timing of removal of non-functioning cadaver kidney transplants were studied in 49 of 58 kidneys which had never functioned or which ceased to function in the period 1979-1982. The reason for graftectomy was rejection in 32 cases, rejection and graft infection in eight, surgical complications in eight cases and infection in one case. Nine of the 58 failed kidney grafts were not removed. Graftectomy was performed within a week after diagnosis of graft failure in 24 of the 49 cases. The clinical indications for graftectomy were compared with the morphologic observations in the grafts. Discrepancy was greatest in regard to diagnosis of rejection and primary renal artery thrombosis. Severe complications related to graft failure aggravated the condition in 17 patients and resulted in eight deaths. Based on the findings, a management schedule is proposed. It facilitates postponement or avoidance of graftectomy and minimizes the risk of complications relating to failure of graft function.

Graft Rejection↗

Cyclosporine A: effectiveness and toxicity in a rat model.

In an effort ot elucidate the effectiveness of Cyclosporine A (CyA) relative to the toxicity, Lewis to Sprague-Dawley first and second set skin transplantation and evaluation of the renal function with clearance methods was performed. CyA 12.5 mg/kg/day delayed first set rejection from 12.3 to 15.4 days (p less than 0.001), and second set from 10.5 to 12.1 days (p less than 0.05); 25 mg/kg/day prolonged the survival times to 18.3 (p less than 0.01) and 19.5 (p less than 0.002) days, respectively. The majority of the skin grafts were still not rejected at the end of the 3 weeks CyA 25 mg/kg/day treatment in contrast to the results during 12.5 mg/kg; the second set skin graft survival was significantly better (p less than 0.01) during the higher dosage. It is concluded, that CyA is not fully immunosuppressive at the 12.5 mg/kg/day dosage. In the doses 12.5 and 25 mg/kg GFR (inulin clearance [Cin]) was reduced to 80 and 48%, respectively, of the control value; the lithium clearance (CLi) was reduced to 69 and 27%. Proximal fractional reabsorption, as calculated from 1-CLi/Cin, was increased from a control value of 82% to 86 and 92% (p less than 0.02) in the 12.5 and 25 mg/kg/day group, respectively, suggesting that CyA nephrotoxicity is due to a decrease in the glomerular ultrafiltration pressure rather than being secondary to proximal tubular damage. In conclusion, in this model there does not seem to exist a therapeutic window between nephrotoxicity and the immunological effectiveness of CyA.

Animals↗

Ketoconazole and cyclosporine A: combined effects on rat renal function and on serum and tissue cyclosporine A concentration.

The effects of ketoconazole (Kcnz) on cyclosporine A (CyA) serum levels and CyA-nephrotoxicity were studied. To rats later anesthetized with pentobarbital sodium, CyA 12.5 and Kcnz 20 mg/kg/day (n = 20), or CyA 12.5 mg/kg and Kcnz-vehicle (n = 21), was dosed. To rats anesthetized with etomidate (n = 14), CyA 12.5 mg/kg and Kcnz-carrier was dosed. S-CyA was monitored during 14 days, and then the rats were investigated with clearance (C) methods (inulin [(in), lithium (Li)], sodium, and potassium), and liver (L) and kidney (K) CyA was measured. Kcnz increased S-CyA, L-CyA and K-CyA (+50 -80%). There were significant (p less than 0.05) correlations between S- and L- or K-CyA. Kcnz increased CyA nephrotoxicity: Mean Cin was 1.012 ml/min/gKW (kidney weight) after CyA treatment (a subnormal value), but decreased to 0.556 ml/min/gKW in the group also given Kcnz (p less than 0.001). CLi decreased from 0.135 to 0.048 ml/min/gKW (p less than 0.001), and absolute proximal tubular reabsorption decreased from 0.877 to 0.508 ml/min/gKW (p less than 0.001), while the fractional reabsorption in the proximal tubule (FPR), expressed as a percentage of GFR, increased from 86.9 to 91.6% (p less than 0.005). Thus, after Kcnz treatment to rats given CyA 12.5 mg/kg/day, their renal function was indistinguishable from that in rats given CyA 25 mg/kg/day.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

Glomerulotubular function in cyclosporine A treated rats.

A total of 178 rats treated with Cyclosporine A (CyA, dose range 0-50 mg/kg/day) during 14 days were investigated with clearance methods (inulin, lithium, sodium and potassium), serum CyA and plasma renin concentration (PRC). Inulin clearance (Cin) decreased to a mean of 68% of the control value in the 12.5 mg/kg/day group, 44% in the 25 mg/kd/day group and 47% in the 50 mg/kg/day group, respectively. Lithium clearance (CLi) was reduced in all CyA treated groups, while the absolute proximal tubular reabsorption as calculated from Cin-CLi was decreased during increased fractional proximal reabsorption (1-CLi/Cin). As proximal intratubular hydrostatic pressure has been shown to be low in the normal range (excluding tubular obstruction) these findings are considered due to a decrease in ultrafiltration pressure. Furthermore we found the reabsorption of sodium distal to the proximal tubule to be decreased, both absolute (PNa X (CLi-CNa)) and fractional to the delivery from the end of the proximal tubule (1-CNa/CLi). Also the distal potassium reabsorption was decreased PK X (CLi-CK). These findings were not primary, but rather secondary, to the altered proximal function, since it has been shown that i.v. CyA immediately produces increased fractional proximal reabsorption. PRC was increased from a mean of 2.5 to 4.9 and 5.3 X 10(-4) Goldblatt units (GU)/ml (12.5 and 25 mg/kg group, respectively), to be explained by the decreased sodium delivery to the macula densa region and/or by a direct CyA effect. In conclusion CyA reduces the net ultrafiltration pressure, and due to an insufficient decrease in absolute proximal tubular reabsorption, fractional proximal reabsorption increases.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Chronic granulomatous disease associated with chronic glomerulonephritis.

A boy with chronic granulomatous disease (CGD) developed glomerulonephritis at the age of 12 years. The glomerulonephritis progressed to terminal uraemia at age 15 when maintenance haemodialysis was started. The clinical course was complicated by pulmonary aspergillosis and Pseudomonas septicaemia from which he eventually died. The glomerulonephritis was of unknown origin, and a possible relationship between CGD and glomerulonephritis is discussed.

Adolescent↗

Xeno- and auto-perfusion of rabbit kidney. Machine perfusion with blood at 37 degrees C.

Five rabbit kidneys were perfused with human blood and another five with their own blood in a re-circulating oxygenated system at 37 degrees C. The flow decreased to 2 ml/min. within 30 min. in all xenoperfusions, while none of the autoperfused had decreased to this level by 60 min. Endothelial damage, exudation, and IgG deposits along the basement membrane of the glomerular capillaries were the discriminative features of the xenoperfusion. In these experiments, we were unable to demonstrate any major role of platelets in the process leading to decreased blood flow.

Animals↗

Two cases of malakoplakia of the prostate.

2 further cases of malakoplakia of the prostate are reported, so that a total of 23 cases have now been described. The histological picture, as well as the methods of staining for the demonstration of the pathognomonic Michealis-Gutmann bodies are reviewed. The presence of Escherichia coli as a possible factor in the etiology is discussed. A description is given of the symptoms and physical findings in cases of prostatic malakoplakia, and the differential diagnosis, with particular reference to cancer of the prostate, is reviewed. Histology alone can provide the correct diagnosis. Finally it is emphasized that malakoplakia can be treated with long-term antibiotic therapy.

Aged↗

Glomerulotubular function in cyclosporine-treated rats. A lithium clearance, occlusion time/transit time and micropuncture study.

Sprague-Dawley rats treated with cyclosporine (Cys) and appropriate controls were investigated with inulin, lithium and sodium clearances. It was found that Cys depressed glomerular filtration rate (GFR) and absolute proximal tubular reabsorption, while fractional proximal reabsorption was increased. As a normal proximal tubular reabsorptive capacity was found after volume expansion, and the intratubular pressure was normal, tubulotoxicity or obstruction of the tubular system by Cys was excluded. Increased fractional proximal reabsorption was also found with the occlusion time/transit time method. Intravenous Cys resulted in instantaneous renal functional changes qualitatively identical to those of prolonged Cys treatment. It was concluded that Cys nephrotoxicity is due to decreased ultrafiltration pressure, most probably due to a reversible spasm in the afferent glomerular arteriole.

Animals↗

Effect of cooling and warming rate on glycerolized rabbit kidneys.

Cooling and warming rates are known to be important determinants of viability for cryopreserved cells, but optimal rates have not previously been determined for any whole organ. In this study, rabbit kidneys, permeated with 2 M glycerol were cooled to -80 degrees C at four rates varying from 1 degrees C/hr to 3.1 degrees C/min and then rewarmed at four rates from 1 degrees C/hr to 4.2 degrees C/min, giving 16 experimental treatments. After gradual deglycerolization at 10 degrees C, each kidney was autografted and observed for 30 min. Assessment was by measurement of vascular resistance, immediate post-thaw lactate dehydrogenase (LDH) release, gross appearance, light- and electron microscopy, and tissue K+/Na+ ratio 30 min after transplantation. The best results were obtained after cooling at 1 degrees C/hr; warming rate had little apparent influence on the criteria used to assess function with the exception of LDH release, which indicated a preferred warming rate around 1 degrees C/min. Histological studies revealed extensive vascular damage, notably to the glomerular capillaries, that was minimized by very slow cooling. Freeze substitution, carried out on samples removed at -80 degrees C, demonstrated extensive ice formation in the interstitial space and, at the faster cooling rates, in the glomerular capillaries. Intracapillary ice formation was reduced in the kidneys cooled at 1 degrees C/hr.

Animals↗

Testicular germ cell tumours in Denmark 1976-1980. Pathology of 1058 consecutive cases.

In the first five-year period of the Danish Testicular Carcinoma Study (DATECA) 1058 consecutive testicular germ cell tumours were examined. Of these, 554 were seminomas comprising 515 of typical type, 26 anaplastic and 13 spermatocytic; 497 were non-seminomas comprising 145 pure tumours and 352 mixed tumours of various types. Among the various subtypes of non-seminomas embryonal carcinoma (EC) was recorded in 87 per cent, endodermal sinus tumour (yolk sac tumour; EST) in 22 per cent, teratoma (T) in 55 per cent and choriocarcinoma (CC) in 17 per cent. Only very few tumours were pure EST or pure CC. Five tumours were recorded as 'others or uncertain'. The tumours were graded with regard to various histologic features. Moderate and severe necrosis, bleeding, and a large number of mitoses were significantly more frequent in non-seminomas. The presence of tumour tissue at the resection margin was also more frequent in non-seminomas. Tumours with a largest diameter of less than 2.5 cm had already caused metastases in 16 per cent of the seminomas and 29 per cent of the non-seminomas. Increasing size of the tumours was associated with increasing frequency of metastatic disease but this association was not directly proportional. Distribution of the various histologic types according to the stage of disease varied. Thus, 78 per cent of the seminomas presented in stage I while 54 per cent of the non-seminomas had localized disease. Anaplastic seminomas were distributed similarly to the non-seminomas while all spermatocytic seminomas, with one exception, were recorded as stage I. Of non-seminomatous subtypes pure EC was associated with the highest frequency of stage III, followed by mixed tumours containing CC components. Although the present series is large the heterogeneity of germ cell tumours demands further investigation of larger numbers to confirm some of the findings.

Adult↗

The survival of pig to rabbit renal xenografts during inhibition of thromboxane synthesis.

Five rabbits treated with the thromboxane synthetase inhibitor Dazoxiben and five control rabbits received pig renal xenografts. Plasma albumin, complement factor C3, TXB2, 6-keto-PGF1 alpha, and serum TXB2 and 6-keto-PGF1 alpha were determined before and 1/2 hour after transplantation. The xenograft survival was significantly decreased in the Dazoxiben treated animals compared to the placebo treated animals determined as time to total cyanosis of the graft, total urine production, and time to stop of urine production. Lack of TXB2 production during blood coagulation confirmed inhibition of platelet thromboxane synthesis. The other determined variables showed no significant differences between the treated and the placebo animals.

6-Ketoprostaglandin F1 alpha↗

Pinacidil--effects on function and perfusion of normal kidneys and renal xenografts.

Pinacidil is a new vasodilating compound claimed to increase renal perfusion and function. A preliminary study showed that pinacidil did not sustain renal perfusion through a period of increasing renal vascular resistance in pig-to-rabbit renal xenotransplantation. Accordingly, the effect of pinacidil on renal function in conscious catheterized rats was studied. Pinacidil 0.12-0.18 mg/kg i.v. caused a moderate reduction in mean arterial blood pressure (14-17 mmHg), a decrease in inulin and PAH clearances (50-65%), and sodium and water retention. The sodium clearance/lithium clearance ratio decreased, suggesting increased sodium reabsorption in the distal nephron during pinacidil administration. Thus the results are in accord with those obtained with several other vasodilators, but not with those obtained in mongrel dogs during pinacidil administration.

Animals↗

Ultrastructural visualization of concanavalin A binding receptor sites in neoplastic and non-neoplastic transitional cell epithelium of the human urinary bladder.

Concanavalin A binding receptor sites in non-neoplastic and neoplastic transitional cell epithelium from tumour-bearing human urinary bladders were mapped ultrastructurally following successive incubation of vibratome slices with concanavalin A, peroxidase and diaminobenzidine. In the normal epithelium the reaction product was found in the plasma membranes of the basal cells. Some areas of the endoplasmatic reticulum and the discoid vesicles were reacting in all cell layers. In the neoplastic epithelium, reaction product was localized to the plasma membranes throughout the epithelium, irrespective of the grade of malignancy. The intracellular distribution was similar to that in normal epithelial cells. The topographical distribution suggests that concanavalin A binding glycoproteins are found in the transitional cell epithelium in immature membranes.

Binding Sites↗