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Biomedical subjects

J Nordenström

Publications and source records attributed to J Nordenström.

At least 19 recordsLinked to original sources
PubMed2005

Influence of trauma on plasma elimination of exogenous fat and on lipoprotein lipase activity and mass.

BACKGROUND: Trauma is followed by an increased plasma clearance and oxidation of exogenous fat but the underlying mechanism is not fully understood. AIM: To examine the influence of a surgical trauma on the plasma elimination of exogenous triglycerides (TG) and its relationship with lipoprotein lipase (LPL) activity and LPL mass. METHODS: Nine patients underwent a hypertriglyceridaemic clamp and a lipolytic capacity test before and after open abdominal surgery. The infusion rate was adjusted to maintain a stable TG concentration of 4 mmol x l(-1) during 180 min. The lipolytic capacity was determined as the change in LPL activity and mass following a bolus dose of 100 IU x kg BW(-1) heparin sodium. RESULTS: Postoperatively, the plasma elimination rate of fat was 2.6 times higher (P<0.001). Infusion of lipids in the postoperative state was followed by a smaller rise in free fatty acids (P<0.05) in comparison with the preoperative situation. The postoperative basal fasting LPL activity was half of that in the preoperative state and the LPL activity rose almost two-fold during the clamp. The heparin-induced rises in LPL activity and LPL mass were similar (n.s.) before and after surgery. CONCLUSIONS: A moderate surgical trauma is accompanied by a greater than two-fold rise in plasma elimination rate of exogenous fat despite a lower basal LPL activity and a virtually unchanged LPL pattern during infusion of lipids. Our study demonstrates that although trauma may substantially enhance the fat elimination capacity a significant proportion of the infused fat is not utilized for metabolic purposes.

Abdomen↗
PubMed2001

Survival of macroencapsulated allogeneic parathyroid tissue one year after transplantation in nonimmunosuppressed humans.

The use of immunoisolation devices may allow transplantation without need for immunosuppression and could widen the indications for cell transplantation. In this study, we evaluated the survival of encapsulated parathyroid tissue in nonimmunosuppressed humans. Autologous parathyroid implants: Seven patients undergoing parathyroidectomy had devices containing small pieces of their own parathyroid tissue implanted SC. These devices were explanted after 2-4 weeks for histological evaluation. Allogeneic parathyroid implants: Four patients with chronic hypoparathyroidism were transplanted with one to three large (40 microl) and one small (4.5 microl) device filled with meshed parathyroid tissue and implanted SC. The small devices were explanted at 4 weeks, while the large ones were explanted 8.5 to 14 months after implantation. In both studies, control implants were placed in nude mice. Autologous study results: At explantation, the grafts consisted of 22 +/- 6% endocrine tissue and 63 +/- 7% fibrosis, while 15 +/- 5% of the grafts were necrotic. Allogeneic study results: In devices explanted from the patients at 4 weeks, fibrosis dominated and only 1%, 5%, and 23% of the grafts consisted of endocrine tissue. A similar histological appearance was found in grafts from nude mice. In devices explanted at 8.5-14 months, histologically intact endocrine tissue was found in all patients. However, nearly all the tissue consisted of fibrosis. There was no detectable increase in the parathormone (PTH) level in all patients. Macroencapsulated human allogeneic parathyroid tissue can survive up to 1 year after transplantation into nonimmunosuppressed patients. However, marked fibroblast overgrowth occurred, especially in the allogeneic implant study, using meshed parathyroid tissue. This was probably not related to the allo-response, because similar findings were observed in the nude mouse implants. In future studies, better tissue preparation and improvements in the physiological milieu inside the device may help to reduce fibroblast overgrowth and increase survival of the parathyroid cells.

Animals↗
PubMed1999

Phagocyte-induced lipid peroxidation of different intravenous fat emulsions and counteractive effect of vitamin E.

Unsaturated fatty acids, a major component of fat emulsions used in parenteral nutrition, are prone to peroxidation which is an important feature of oxygen-associated tissue damage. We used the nitroblue tetrazolium (NBT) reduction test to measure the production of superoxide radicals by stimulated polymorphonuclear neutrophils (PMN) in the presence of different fat emulsions: Intralipid (containing 100% long-chain triacylglycerols, LCT), Vasolipid (a physical mixture of 50% LCT and 50% medium-chain triacylglycerols, MCT) and Structolipid (structured triacylglycerols containing 63% LCT and 37% MCT). We measured the amount of malonaldehyde (MDA) and 4-hydroxyalkenal to determine the lipid peroxidation of the three fat emulsions in the presence of stimulated neutrophils. Further, we investigated the role of vitamin E (alpha-tocopherol) in preventing lipid peroxidation in vitro. The results showed that the values of NBT reduction of PMN were significantly decreased in each of the three fat emulsions and that increasing concentrations of fat emulsions were associated with decreased values of NBT reductions, in a dose-dependent way (P<0.001). There were, however, no statistically significant differences between the values of the three different types of fat emulsions (P>0.05). Lipid peroxidation increased significantly in the presence of all three types of fat emulsions, and was more pronounced for Intralipid than for Vasolipid and Structolipid after 1 and 2 h of incubation with resting as well as with stimulated phagocytes. The increased lipid peroxidation of the fat emulsions was markedly reduced by vitamin E, and the inhibition was concentration dependent. In conclusion, lipid peroxidation in vitro is more pronounced when PMNs are incubated with fat emulsions. This increase in lipid peroxidation can be reduced by adding vitamin E to the fat emulsions.

Adolescent↗
PubMed1999

Portfolio of qualifications: a tool for evaluating academic productivity at the Karolinska Institutet.

A Portfolio of Qualifications for academic appointments at the Karolinska Institutet has been developed to define more clearly the competence and qualifications which are given high priority for academic appointments at the Karolinska Institutet. The major fields of application are for new appointments and promotions, providing guidelines for the individual for improving his/her proficiency, and as a basis for determining individual salary rates. Four portfolios have been developed, a pedagogical, a clinical, a scientific, and a leadership, development and workplace relations portfolio. Attached to the portfolios are assessment forms. We consider the Qualifications Portfolio to be a reflection of changes in attitudes and values at the Karolinska Institutet. The system offers a method for the recognition of faculty productivity in different dimensions. This may be beneficial for the university in view of the increasing diversity and complexity of academic institutions. The Qualifications portfolio can be obtained from the world wide web, http:/(/)www.ki.se/ki/merit.se.html (in Swedish), http:/(/)www.ki.se/ki/merit.html (in English).

Dental Research↗
PubMed1998

Muscle strength and endurance after surgery for primary hyperparathyroidism.

OBJECTIVE: To evaluate the effect of surgery on muscular strength and endurance in patients with primary hyperparathyroidism (HPT). DESIGN: Prospective open study. SETTING: University hospital, Sweden. SUBJECTS: Nine patients undergoing HPT surgery and nine matched patients undergoing thyroid resection who acted as controls. INTERVENTIONS: Concentric and eccentric endurance was evaluated with a test comprising 100 repeatedly executed muscle action at 90 degrees.s-1. Blood samples obtained before and after operation were analysed for calcium, phosphate, thyroid stimulating hormone (TSH), and parathyroid hormone (PTH) concentrations. MAIN OUTCOME MEASURES: Peak torque during maximum voluntary concentric and eccentric muscle actions at 90 degrees.s-1 before, three months and one year after operation. RESULTS: There were no differences in concentric and eccentric peak torque before and after operation either within or between groups. Concentric and eccentric endurance were similar in the HPT group and controls before as well as after operation. The return of calcium and PTH concentrations to their reference ranges after parathyroidectomy did not correlate with changes in concentric and eccentric peak torque. CONCLUSIONS: The subjective improvement in muscle endurance which is often encountered in patients with HPT after operation is not associated with an objective increase in muscle strength or endurance as measured by isokinetic muscle performance.

Calcium↗
PubMed1998

Bone mineral recovery after parathyroidectomy in patients with primary and renal hyperparathyroidism.

Patients with hyperparathyroidism (HPT) generally display reduced bone mass due to excessive PTH activity. The effect of parathyroidectomy on bone mass changes in different types of HPT, however, is not well understood. Bone mineral density (BMD) was measured in the distal radius, total body, femoral neck, and lumbar spine by dual energy x-ray absorptiometry in four groups of patients with different hyperparathyroid conditions: primary symptomatic HPT (n = 54), primary asymptomatic (mild) HPT (n = 24), HPT associated with hemodialysis (n = 20), and HPT associated with renal transplant (n = 30). Subsets of patients with primary symptomatic HPT (n = 52), HPT associated with hemodialysis (n = 19), and HPT associated with renal transplant (n = 15) underwent parathyroidectomy, and bone density was measured longitudinally for 3 yr. Patients with primary asymptomatic (mild) HPT did not undergo surgery and were followed prospectively. Before surgery, all groups showed a greater reduction of bone mineral density in cortical bone (distal radius) than in predominantly trabecular bone (lumbar spine). In primary symptomatic HPT, the BMD z-score of the distal radius was -1.80 +/- 0.21 (+/-SEM), and the corresponding figures for the total body, femoral neck, and lumbar spine were -0.60 +/- 0.15, -0.54 +/- 0.14, and -0.53 +/- 0.18 compared with those of an age- and sex-matched reference group. In renal HPT BMD z-scores were -2.51 +/- 0.38 (hemodialysis patients) and -2.83 +/- 0.43 (renal transplant patients) for the distal radius and between -0.81 and -1.46 for the other measured sites. After parathyroidectomy, BMD increased by 1-8% at all sites in patients with primary symptomatic HPT and HPT associated with renal transplant. The largest increase in bone mass was observed in patients with HPT associated with hemodialysis, in whom the improvement amounted to 7-23%. In patients with primary HPT and HPT associated with hemodialysis, this increase in bone density resulted in virtual recovery from their preoperative bone loss. The majority of patients with asymptomatic primary HPT disease (n = 21) maintained their bone density during the follow-up period and have not shown evidence of increases in serum calcium or PTH levels, but three patients followed conservatively underwent parathyroidectomy due to progressive deterioration of BMD. We conclude that, regardless of the etiology, a large proportion of HPT patients show reduced bone density. In patients with primary symptomatic HPT and patients with HPT associated with hemodialysis, bone density increases after parathyroidectomy to an extent that largely restores the preoperative bone loss. However, no anabolic effect of parathyroidectomy on bone mass was observed in patients with HPT associated with renal transplant, probably because of their immunosuppressive therapy.

Bone Density↗
PubMed1998

Familial isolated hyperparathyroidism maps to the hyperparathyroidism-jaw tumor locus in 1q21-q32 in a subset of families.

Approximately 70 families with familial isolated hyperparathyroidism (FIHP) have been reported. Whether it is a separate entity or a variant of multiple endocrine neoplasia type 1 (MEN1 at 11q13) or hyperparathyroidism-jaw tumor (HPT-JT or HRPT2 at 1q21-32) syndrome is not known. We describe here 3 unreported families with familial primary hyperparathyroidism and evaluate their clinical, pathological, and genetic profiles. Biochemical and radiological screenings for MEN1 were negative for all families. In 2 families with a total of 10 affected cases and 3 female obligate carriers, there is no evidence of jaw or renal lesions despite careful radiological investigations. In both families the disease was linked to the 1q21-q32 region with the maximum logarithm of the odds (lod) scores of 3.10 and 3.43 for markers D1S222 and D1S249 respectively, at recombination fraction of 0. In 1 family 2 types of parathyroid pathology were found: 3 of chief cell type and 1 of oxyphil/oncocytic cell type. Two chief cell tumors and 1 oxyphil tumor were found to have loss of heterozygosity (LOH) involving loss of the wild-type alleles for chromosome 1q markers. In the third family, with 4 affected siblings, a parathyroid carcinoma and 2 cases of polycystic kidney disease were found. The parathyroid carcinoma also showed loss of heterozygosity in the 1q region. In conclusion, we found that the hyperparathyroidism traits in a subset of FIHP families are linked to the 1q21-32 markers in the HRPT2 region. We describe the spectrum of parathyroid disease in 1q-linked families involving 3 different types of pathology and demonstrate for the first time loss of wild-type alleles in these parathyroid tumors. Taken together, the results suggest that some of the FIHP are a variant of HPT-JT and that the gene involved is a tumor suppressor gene.

Adult↗
PubMed1998

[The merit profile--an instrument for the evaluation of academic achievement].

The concept of a merit profile has been evolved at Karolinska Institute in Stockholm, whereby not only research achievements but also teaching, administrative and clinical skills and experience are each given merit ratings to produce an individual profile. This approach is based on the notion that all of these fields of activity constitute integregal facets of a scat of higher learning in medicine, and that a candidate's relative merits in each of these areas should be seen not only in relation to the overall academic goals but also to practical, professional considerations. The merit profile is intended to be used in selection for appointments and promotion, and as a basis for the continued enhancement of individual competence, and salary review.

Academic Medical Centers↗
PubMed1997

Serum immunoreactive leptin concentration and its relation to the body fat content in chronic renal failure.

Leptin, secreted from fat cells, functions as a lipostat mechanism through modulation of satiety signals. The role of leptin in humans has been only partly revealed. However, obese patients have markedly elevated levels of this hormone, and in both normal-weight and obese subjects there is a direct correlation between serum leptin levels and the percentage of body fat. The aim of the present study was to investigate the role of leptin and its relation to body fat content in chronic renal failure (CRF), a disorder associated with decreased appetite. Serum leptin levels and body composition (dual-energy x-ray absorptiometry) were measured in a cohort of 59 patients with terminal CRF (creatinine clearance rate, 8 +/- 1 ml/min). Sixteen of the patients were re-evaluated after 12 mo of peritoneal dialysis treatment, and eight patients were re-evaluated after 12 mo of hemodialysis treatment. The mean serum leptin concentrations were markedly higher (mean +/- SEM) in patients with CRF than in healthy control subjects matched for gender and body mass index (25.7 +/- 5.2 ng/ml versus 8.4 +/- 0.9 ng/ml; P < 0.001). Patients with ongoing signs of inflammation (C-reactive protein > 10 mg/L) demonstrated higher serum leptin levels (41.9 +/- 13.7 ng/ml versus 18.6 +/- 4.2 ng/ml; P < 0.05) than patients with normal C-reactive protein. A strong positive correlation (rho = 0.83; P < 0.0001) was found between serum leptin concentrations and the percentage of body fat. After 12 mo of peritoneal dialysis, the amount of body fat increased markedly (19.0 +/- 1.5 to 25.1 +/- 2.2 kg; P < 0.001), and the changes in serum leptin concentrations correlated significantly (rho = 0.69; P < 0.01) to the changes in the body fat content. In contrast, no significant changes in either body fat content or serum leptin levels were recorded in the eight patients that were re-evaluated after 12 mo of hemodialysis. Serum leptin concentrations are approximately three times higher in patients with CRF compared with healthy control subjects with a similar body mass index. In this study, it is also demonstrated that serum leptin is a good marker for the body fat content in CRF patients and correlates strongly to changes in body fat during 12 mo of peritoneal dialysis. These findings suggest that serum leptin could serve as a valuable clinical marker for the body fat content in patients with CRF. Further studies are needed to verify the hypothesis that increased serum leptin concentrations may contribute to uremic anorexia.

Adipose Tissue↗
PubMed1997

Allelic loss on chromosome 11 is uncommon in parathyroid glands of patients with hypercalcaemic secondary hyperparathyroidism.

OBJECTIVE: To test the hypothesis that progression of secondary hyperparathyroidism from normocalcaemia to hypercalcaemia occurs because of development of monoclonal parathyroid tumours after the inactivation of a tumour suppressor gene on chromosome 11q13. DESIGN: Experimental study. SETTING: University hospital, Sweden. SUBJECTS: 13 Patients with secondary hypercalcaemic hyperparathyroidism. INTERVENTIONS: 48 Parathyroid glands were removed, 39 of which were analysed using Southern blot hybridisation and polymerase chain reaction. MAIN OUTCOME MEASURES: Loss of heterozygosity on several loci on chromosome 11, including 11q13, which carries the presumed gene for multiple endocrine neoplasia type 1 (MEN1). RESULTS: Monosomy for chromosome 11 was found in one tumour. CONCLUSIONS: It seems unlikely that the MEN1 gene is of importance in the progression of secondary hyperparathyroidism.

Adolescent↗
PubMed1996

Microdialysis of adipose tissue during surgery: effect of local alpha- and beta-adrenoceptor blockade on blood flow and lipolysis.

The adrenergic regulation of adipose tissue lipolysis and blood flow was investigated in nonobese patients (10 men and 23 women) undergoing cholecystectomy. Two microdialysis probes were inserted into the scadipose tissue and microdialyzed in the absence or presence of 10(-4) mol/L of either nonselective beta-adrenoceptor blocker propranolol or nonselective alpha-adrenoceptor blocker phentolamine. The catecholamines increased rapidly after intubation and subsequent surgery and extubation (P = 0.0001; F = 11-13). In the middle of surgery, the elevations of the noradrenaline and adrenaline levels were almost 3 times the basal value. At the end of surgery, they dropped in parallel, but increased again, only to reach their absolute maximum in connection with extubation (10- and 3-fold elevation, respectively). Plasma glycerol and free fatty acids started to increase about 30 min after plasma catecholamines. These increases in catecholamines were paralleled by an increase in the dialysate glycerol level (lipolysis index). Propranolol inhibited by two thirds (P = 0.003) and phentolamine further stimulated by 25% (P = 0.04) the increase in glycerol in the tissue dialysate induced by the operation. There was a transient decrease in tissue blood flow (ethanol escape from the microdialysis probe; P < 0.001) at the beginning of the surgical procedure. This was not affected by propranolol or phentolamine. In conclusion, during anesthesia and surgical trauma, endogenous catecholamines modulate adipose tissue lipolysis via alpha- and beta-adrenoceptors. However, the vasoconstriction induced by these procedures seems to be independent of the adrenergic system.

Adipose Tissue↗
PubMed1996

Bone demineralization after renal transplantation: contribution of secondary hyperparathyroidism manifested by hypercalcaemia.

BACKGROUND: Renal transplantation patients often present signs and symptoms of bone disease. METHODS: In a cross-sectional study, dual-energy X-ray absorptiometry was used to examine bone mineralization in kidney transplantation patients. The contribution of secondary hyperparathyroidism manifested by hypercalcaemia was assessed. Twenty transplantation patients with long-standing (> 6 months) hypercalcaemia (> 2.6 Ca mmol/l) after transplantation, 21 normocalcaemic transplantation patients, and 20 healthy controls were examined. RESULTS: Bone mass density (BMD) was significantly less in the hypercalcaemic (1.00 +/- 0.1 g/cm2) and in the normocalcaemic groups (1.11 +/- 0.15 g/cm2) compared to the healthy controls (1.17 +/- 0.11 g/cm2). Decreased bone mineralization was evident shortly after transplantation and may well have been present before surgery. Females had less BMD compared to males and their BMD decreased further with age. CONCLUSION: Kidney transplantation patients with persistent hypercalcaemia comprise a risk group with regard to bone demineralization.

Adult↗
PubMed1995

[High-dose chemotherapy in breast cancer. Promising results in combination with stem cell support].

Thirty-three women with breast cancer have undergone high dose chemotherapy with autologous stem cell support at Huddinge Hospital. Twenty-eight patients had stage IV disease while five patients had disease stage II or III with involvement of > 10 axillary lymph nodes. Patients who received peripheral stem cells had a shorter duration of neutropenia than patients who received autologous bone marrow (p < 0.001). The transplant related mortality was 3 per cent. The calculated progression free survival was 39 per cent at 24 months after high dose therapy in women with stage IV chemosensitive breast cancer. Patients who got a complete remission after standard dose chemotherapy had a better survival rate than patients who got a partial remission. All women with refractory disease progressed within five months from therapy. Four out of five patients with disease stage II or III are progression free with the longest follow-up time of 46 months. High dose chemotherapy with stem cell support can be given with acceptable toxicity. The follow-up time is short but the results are promising, in particular for women who obtain a complete remission before the high dose therapy starts.

Adult↗