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Biomedical subjects

I Karlberg

Publications and source records attributed to I Karlberg.

At least 55 records · Page 3Linked to original sources

Kidney transplantation in type 1 (insulin-dependent) diabetic patients. Early glomerulopathy.

The development of diabetic glomerulopathy in kidneys transplanted to diabetic patients was estimated in transplant biopsies and evaluated in relation to suspected clinical risk factors for diabetic nephropathy. Surgical biopsies were taken at baseline and at 24-36 months post-transplantation in 16 Type 1 (insulin-dependent) diabetic patients and 8 non-diabetic control subjects with a glomerular filtration rate more than 30 ml.min-1 at follow-up. Immunosuppressive therapy included cyclosporine in all but one case. Stereological methods were used to assess basement membrane thickness, volume fraction of mesangium per glomerulus, and volume fraction of matrix per mesangium. The volume fraction of interstitial tissue per cortex was estimated by light microscopy. After 2 years the basement membrane thickness had increased by 55 nm (SD 58 nm) in the diabetic group. This change was significantly different from that of 2 nm (SD 37 nm) in control subjects (p = 0.02). Mesangial volume fraction increased significantly by 0.04 (SD 0.03) in diabetic patients, and this change was significantly different from that of -0.01 (SD 0.04) in non-diabetic patients (p = 0.009). No change was detectable in the matrix expressed as fraction of mesangial volume. An increase in interstitial volume fraction from baseline to 2 years was observed, but was significant only in the diabetic group (p = 0.04). The changes in structural parameters did not correlate with mean values during follow-up of glycated haemoglobin or estimated protein intake, nor was any pattern discernible in the relationship to graft tissue types.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Biochemical effect of liver transplantation in two Swedish patients with familial amyloidotic polyneuropathy (FAP-met30).

Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant inherited disorder characterized by progressive peripheral and autonomic neuropathy, associated with neural and systemic amyloid deposits. The amyloid fibrils contain a variant transthyretin (TTR) molecule (TTR met30), over 90% of which is produced in the liver. After liver transplantation in two patients with severe symptomatic FAP, only normal TTR was detectable in circulation. The two patients are being monitored at regular intervals, and, although in one patient there was no evidence of reduction in the quantity of amyloid present at 6 months, there had been no further progression of the neuropathy.

Adult↗

Effect of rearterialization on short-term graft function in orthotopic rat liver transplantation.

The orthotopic liver transplant model in rats has been very useful for immunological studies. However, differing opinions exist as to whether rearterialization of the graft is necessary for such experiments. Therefore, in this study we evaluated the short-term allograft function when rearterialized was compared to restored venous portal flow only and in situ hepatic artery ligation. The technique of orthotopic liver transplantation in the rat with and without rearterialization of the graft is described in detail. In addition, we evaluated the technical feasibility of sutured vascular anastomosis as compared to the traditional cuff technique. Urea synthesis rate was used as a sensitive marker of integrated liver function, including uptake, synthesis and excretion. Standard liver test of bilirubin, plasma aspergine aminotransferase and alanine aminotransferase were measured. We found no significant differences in the biochemical markers between allografts with portal venous flow only compared to the combination with arterial flow. Autopsy was performed after the biochemical studies at day 14. Histopathological analyses revealed no differences between the two groups of transplanted rats. The patency of sutured anastomoses was in our hands found to be superior to that of the cuff technique, with a success rate of more than 90% in rats with portal venous flow. This rat model in which vascular anastomosis is performed with a running suture technique and without rearterialization seems to be excellent for short-term studies of preservation and liver function after orthotopic liver transplantation.

Anastomosis, Surgical↗

Acute and long-term changes in plasma levels of atrial natriuretic factor in patients with renal replacement therapy.

In 14 patients on hemodialysis who received kidney grafts from living related donors, plasma levels of immunoreactive atrial natriuretic factor (Ir-ANF) were determined in a sequence covering the last hemodialysis treatment, the day of transplantation, and a follow-up period of 6-12 months. The geometric mean value before dialysis was 196 pg/ml, the range 32-634. Weight loss during dialysis was 1.5 +/- 1.1 kg (mean +/- SD), but only a nonsignificant reduction in Ir-ANF levels occurred. On the day of transplantation, plasma Ir-ANF levels increased from 143 pg/ml before to 391 post-transplantation (P = 0.02, n = 12), probably in response to deliberate volume expansion. Post-transplant Ir-ANF levels correlated significantly to diuresis during the first 24 h, which ranged from 3.7 to 17.81 (mean 6.6; r = 0.65, P = 0.02). On day 2, mean 24 h diuresis decreased to 3.3 +/- 1.41. Most patients had reached their true dry weight by day 5, but Ir-ANF levels remained high, the geometric mean being 180 pg/ml. During further follow-up and preserved graft function (GFR range 34-88 ml/min per 1.73 m2 body surface area), Ir-ANF levels declined to a geometric mean of 63 pg/ml by 2-6 months and to 36 at 12 months post-transplant. We conclude that plasma Ir-ANF levels are chronically elevated in patients with chronic renal failure but may be further stimulated by acute overhydration. Transplanted kidneys initially respond to the increased levels but adapt within a day. Even with good graft function, normalization of plasma Ir-ANF requires several weeks or months.

Adolescent↗

Survival after liver transplantation of patients with primary biliary cirrhosis in the Nordic countries. Comparison with expected survival in another series of transplantations and in an international trial of medical treatment.

Until December 1988, 38 patients with primary biliary cirrhosis (PBC) had been transplanted in the Nordic countries. The observed survival probability in accordance with Kaplan-Meier analysis was around 75% 2-3 months after surgery, with few deaths during the next 3 years. The observed survival curve was compared with the expected survival calculated from the experience of a recent English PBC transplant series; the patterns are very similar. Secondly, the observed survival was compared with the expected survival curve, calculated from the survival experience of an international trial of medical treatment--that is, the expected survival had the patients not been transplanted; after the first 2-3 months the observed survival stayed better than the expected survival. Finally, the merits of transplantation for each particular patient was evaluated by means of the ratio of probability of survival when transplanted to probability of survival when medically treated 3, 6, and 8 months after surgery. The ratio increased with time, indicating a relative increase in the benefit of transplantation with time after surgery.

Denmark↗

Renal transplantation in patients with systemic lupus erythematosus: increased risk of early graft loss.

The outcome of primary renal transplantation in 31 SLE patients was evaluated in relation to two contemporary controls per patient, matched for age, sex and immunosuppressive therapy. The proportion of living donors was one third in both groups. Patient survival did not differ, but graft survival at 6 and 12 months post transplantation was significantly reduced in SLE patients (p less than 0.001). When divided into groups using either azathioprine and steroids or combinations including cyclosporin A (14 and 17 SLE patients in each group), graft survival was significantly reduced for the azathioprine-treated SLE patients, 36% vs. 82% for their controls at one year. For cyclosporin-treated SLE patients, one-year graft survival was 59% vs. 85% for their controls, and 6 out of 17 grafts in the cyclosporin-treated group were lost within the first month vs. only 4 out of 34 controls. These differences were, however, not statistically different. Most failed grafts were lost from rejection, with a high proportion of acute vascular rejection, isolated or in combination with cellular rejection. There was no apparent association between rejection and HLA-matched or presence of HLA antibodies. Retransplantation was successful in 6 out of 7 cases. We conclude that SLE patients have an increased risk of early graft rejection, but that this may be overcome by more powerful immunosuppressive therapy.

Adolescent↗

Circulating levels of selenium and zinc in relation to nutritional status in patients with head and neck cancer.

There is evidence that selenium and zinc are involved in malignant neoplasia. The exact role of these trace elements, however, is not completely understood. For this reason, we studied circulating levels of selenium and zinc in relation to food intake and nutritional status in 14 patients with head and neck cancer. Six patients without cancer served as controls. The patients with cancer were in different stages of disease. They were untreated or in an initial phase of oncologic treatment. Five of these patients were severely cachectic according to weight loss and nutritional status, which included body mass index, anthropometric values, and serum albumin level. These patients also demonstrated decreased circulating levels of selenium and zinc. Plasma glutathione peroxidase (selenium-dependent enzyme) activity, however, was not significantly different when the cachectic patients with cancer were compared with controls. We found that the plasma selenium level was positively correlated to both short-term and long-term selenium intake when all 20 patients were accounted for. However, no significant correlation could be shown between plasma selenium and serum albumin levels. Although only one patient demonstrated a plasma value below the reference value, serum zinc was positively correlated to the serum albumin level. We conclude that plasma selenium concentrations are essentially related to food intake but not necessarily to weight loss. Low circulating levels of zinc are, rather, associated with the catabolic state of the patient with cancer.

Adult↗

Induction of sister-chromatid exchanges by direct and indirect mutagens in human lymphocytes, co-cultured with intact rat liver cells. Effect of enzyme induction and preservation of the liver cells by freezing in liquid nitrogen.

An in vitro assay system using intact rat hepatocytes and human peripheral lymphocytes is described which has been developed with the aim of bringing test conditions closer to in vivo conditions, thereby broadening the available battery of simple in vitro assays. A culture vessel, which contains an inner chamber with a semipermeable bottom, has been designed to allow easy removal of the hepatocytes. Determination of sister-chromatid exchange rate was used as the experimental end point. For validation, a series of chemicals were used which have been tested previously in a large interlaboratory investigation of short-term test methods. Our study supplies complementary information to this investigation in as much as some chemicals could be correctly assigned as positive or negative, in contrast to what was found in the earlier tests. Furthermore, we show that the metabolic capacity of both normal and induced liver cells can be preserved in liquid nitrogen for long periods.

Animals↗

Whole body gas exchange: amino acid and lactate clearance as indicators of initial and early allograft viability in liver transplantation.

A method for the rapid assessment of liver allograft circulation and function after liver transplantation is described. In 12 patients undergoing liver transplantation continuous recording of whole body energy production was made on the basis of gas exchange measurements during the surgical procedure. Oxygen consumption decreased rapidly by 25% when the blood supply to the native liver was interrupted. After the anhepatic period, there was a sharp increase of oxygen consumption with successful reperfusion of the allograft. Carbon dioxide production fell by 14% and returned to preanhepatic values after successful declamping. In two cases with suboptimal reperfusion the return of gas exchange values was slow and incomplete. Results from the studies of whole body energy production were compared with biochemical measurements. No significant accumulation of amino acids occurred during the anhepatic period, but in the two patients with incomplete revascularization, clearance of amino acids, after the anhepatic phase, was impaired and plasma amino acids accumulated. The same pattern was found for plasma lactate levels. By the techniques described in this article, rapid and reliable assessment of initial and early graft function in hepatic transplantation is possible. This is of great value for the intraoperative and early postoperative assessment and planning of surgical and anesthesiologic strategies.

Adolescent↗

Human organ transplantation.

In terms of rehabilitation and extended years of survival, transplantation is a good treatment if vital organs are affected by end-stage disease. Rejection is one of the most serious complications, although advances in molecular biology may well lead to specific immunosuppression with few or no side-effects. The unique metabolic functions of the heart, liver and kidney make it doubtful whether artificial replacements will become available in the foreseeable future. In the present state of knowledge, metabolic feedback between artificial organs probably cannot be accomplished, and organ transplantation is therefore likely to remain an evolving technology for many years to come.

Costs and Cost Analysis↗