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Biomedical subjects

K Lundholm

Publications and source records attributed to K Lundholm.

At least 19 recordsLinked to original sources
PubMed1992

Age-standardized incidence of ruptured aortic aneurysm in a defined Swedish population between 1952 and 1988: mortality rate and operative results.

The incidence and mortality rate of ruptured aortic aneurysm in a defined and stable Swedish population was determined for the period 1952-1988. The annual rupture rate of abdominal aneurysm rose significantly from 0.9 per 100,000 inhabitants in the 1950s to 6.9 in the 1980s. After standardization for age, the mortality rate increased between 1960 and 1988 by 2.4 per cent annually (95 per cent confidence interval 1.2-3.6 per cent, P = 0.0004). Comparable figures from the UK during the 1980s have been reported to be two to three times higher. The mortality rate of ruptured thoracic aneurysm in the Swedish population did not increase when adjusted for age. In the 1980s the overall mortality rate of ruptured abdominal aneurysm was 85 per cent. Death occurred outside surgical clinics in 52 per cent of cases; 37 per cent of the total number of patients with ruptured aneurysm reached the operating table but only 30 per cent underwent aortic reconstruction. Patients treated by vascular surgeons had lower blood loss and transfusion needs, shorter aortic clamp time and operation time, and lower mortality rate than patients treated by non-specialized general surgeons. Specialized vascular surgeons also completed the reconstruction, and used straight grafts, in a higher proportion of cases than general surgeons.

Age Factors↗
PubMed1992

Prevalence of carnitine depletion in critically ill patients with undernutrition.

The aim of this study was to evaluate to what extent secondary carnitine deficiency may exist based on the prevalence of subnormal carnitine status in patients with critical illness and abnormal nutritional state. Healthy control patients (n = 12) were investigated and compared with patients with possible secondary carnitine deficiency, ie, patients with overt severe protein-energy malnutrition (PEM, n = 28), postoperative long-term (greater than 14 days) parenteral glucose feeding (250 g glucose/d, n = 7), severe liver disease (n = 10), renal insufficiency (n = 7), and sustained septicemia with increased metabolic rate (n = 8). Nutritional status, energy expenditure, creatinine excretion, and blood biochemical tests were measured in relationship to free and total carnitine concentrations in plasma and skeletal muscle tissue, as well as urinary excretion of free and total carnitine. The overall mortality rate was 48% within 30 days of the investigation in study patients with the highest mortality in liver disease (90%). The hospitalization range was 14 to 129 days in study patients. Most study patients had lost weight (4% to 19%) and had abnormal body composition. Patients with liver disease, septicemia, renal insufficiency, and those on long-term glucose feeding had significantly higher than predicted metabolic rate (+25% +/- 3%), while patients with severe malnutrition had decreased metabolic rate compared with controls. Patients with liver disease had increased plasma concentrations of free (96 +/- 16 mumol/L) and total (144 +/- 27 mumol/L) carnitine compared with controls (45 +/- 3, 58 +/- 7 mumol/L, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Co-variation between walking ability and circulatory alterations in patients with intermittent claudication.

Unselected patients (n = 183) with subjective symptoms of intermittent claudication were examined clinically and by various circulatory tests (calf blood-flow, ankle, toe pressures). The aims of the present study were to evaluate to what extent the central or peripheral circulation is limiting in unselected patients with subjective symptoms of intermittent claudication, to determine the co-variation between the maximum walking capacity and traditional haemodynamical measures mentioned above and to evaluate to what extent a traditional bicycle ergometer exercise test and treadmill walking test give similar information regarding maximum performance. Eighty-five per cent of all patients were or had been smokers and 16% were diabetics. The mean ankle/brachial blood pressure index was 0.58 +/- 0.02 and the average post-ischemic maximum calf bloodflow was 13.3 +/- 0.6 ml/min/100 ml tissue. Leg arterial insufficiency was the limiting factor of walking capacity in 90% of all patients at 87 +/- 2 W corresponding to a walking distance of 282 +/- 13 m, while leg exhaustion was the limiting factor in 80% of the patients during test on the bicycle ergometer at maximum 84 +/- 2W. The mean maximum walking capacity for all patients was 86 +/- 3W and the mean maximum capacity on the bicycle ergometer was 87 +/- 2W. The ankle/brachial index showed only a weak correlation (r = 0.30, p < 0.002) to walking capacity. Our results demonstrate that the maximum walking capacity on a treadmill agrees with mean values of maximum exercise capacity on a bicycle ergometer.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Cardiac effects of caloric restriction-mechanisms and potential hazards.

The heart is not spared from the catabolic effects of undernutrition, but is subject to the same degree of weight loss as skeletal muscle. Pumping performance, however, is not reduced in proportion to myocardial wasting and thus functional protection prevents failure of the hypotrophic heart. In animal experiments, no major qualitative changes in myocardial composition apart from reduced myosin ATPase activity have been found. This reduction in ATPase activity might be associated with down-regulation of thyroid hormones and the development of insulin resistance and serve as an energy saving adaptation. Increased cardiac sensitivity to adrenergic stimulation may also constitute a means to increase heart performance in situations with augmented circulatory demands. On the other hand, increased sensitivity and maximum response to adrenergic stimulation might render the heart more susceptible to arrhythmia, and thus explain sudden unexpected death following rapid weight loss.

Animals↗
PubMed1991

Effects of indomethacin, cytokines, and cyclosporin A on tumor growth and the subsequent development of cancer cachexia.

C57BL/6J mice bearing a low or undifferentiated rapidly growing tumor were treated daily with either i.p. injections of the recombinant cytokines interleukin(IL)-1 alpha, IL-1 beta (21 ng/g), and tumor necrosis factor alpha (21 ng/g) or s.c. injections of cyclosporin A (60 micrograms/g) or indomethacin (1 micrograms/g). In some experiments, indomethacin was administered in the drinking water corresponding to the amount of s.c. injections. Survival and the time course of tumor growth and food and water intake were measured. The nutritional state (body composition) of the animals was registered at spontaneous death in the course of tumor disease. Indomethacin prolonged survival from 14 +/- 1 to 22 +/- 1 days in tumor-bearing mice when administered either in the drinking water or as s.c. injections. This effect, which was due to tumor growth inhibition, was equally effective irrespective of whether indomethacin was instituted on Day 1, 5, 7, or 9 following tumor implantation. Indomethacin did not inhibit tumor cell growth in vitro. Indomethacin-treated tumor-bearing mice were also less anorectic than untreated tumor-bearing mice, and their nutritional state, particularly lean body mass, was significantly improved by indomethacin at doses (1 micrograms/g) that did not influence the food intake or body composition in non-tumor-bearing mice. At spontaneous death, indomethacin-treated tumor-bearing mice had a significantly larger tumor burden when accounting for their degree of malnutrition as compared with untreated tumor bearers. Indomethacin did not decrease the elevation in hepatic concentrations of RNA seen in response to tumor progression. Adherent peritoneal macrophages from tumor-bearing mice had a lower prostaglandin E2 synthesis compared with macrophages from non-tumor-bearing controls in the basal state (1100 +/- 150 pg/10(6) cells versus 3700 +/- 922 pg/10(6) cells). Lipopolysaccharide stimulated macrophages from tumor-bearing mice to produce significantly more prostaglandin E2 in vitro compared with control macrophages (39,500 +/- 4208 pg/10(6) cells versus 12,500 +/- 4330 pg/10(6) cells).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Role of endogenous tumor necrosis factor alpha and interleukin 1 for experimental tumor growth and the development of cancer cachexia.

The aim of this study was to evaluate to what extent tumor necrosis factor alpha (TNF-alpha) and interleukin 1 may explain the development of experimental cancer cachexia. For this purpose, C57BL/6J mice bearing a transplantable low differentiated rapidly growing tumor were passively immunized every other day with rabbit or rat neutralizing immunoglobulins against either TNF-alpha (anti-TNF) or against an interleukin 1 receptor (anti-IL-1r). Anti-IL-1r in itself had no agonistic effect to the type I, T-cell/fibroblast IL-receptor. Tumor-bearing mice receiving either preimmune antiserum or nonimmune rat hybridoma IgG served as controls. Anti-TNF and anti-IL-1r inhibited tumor growth significantly, as measured by a lower wet and dry tumor weight at the end of 11 days of antiserum treatment (P less than 0.05). The acute phase response in tumor-bearing animals, measured as an increase in liver weight, hepatic RNA content, and increases in plasma concentrations of circulating IL-6, serum amyloid P, transferrin, complement (C3), and a decrease in plasma albumin, were unaffected by the specific antiserum treatments. Food intake, which declined significantly in pre/nonimmune injected tumor-bearing controls, was significantly improved in tumor-bearing animals immunized against TNF-alpha or the IL-1r. Whole body lipid content showed a trend to improvement in specifically immunized animals (P less than 0.07). The effects on whole body fat-free dry weight were insignificant, although numerically higher in specifically immunized tumor-bearing animals. The combination of anti-TNF and anti-IL-1r antiserum had no additive effects compared to single antiserum treatment suggesting that the two antibody treatments acted through a common mechanism. Cultured tumor cells, established from growing tumors, were sensitive to anti-TNF and anti-IL-1r, which both reduced tumor growth in vitro. This inhibitory effect by the antiserum could in part be reversed by the addition of recombinant IL-1 alpha and TNF alpha. We conclude that both TNF and IL-1 are involved in tumor growth and thus the progression of cancer cachexia. It seems as if the role of TNF and IL-1 was to promote tumor growth rather than restrict tumor growth in the present model. In this sense both TNF and IL-1 may act as tumor growth factors.

Acute-Phase Proteins↗
PubMed1991

Tumor cytokinetic effects of acute starvation versus polyamine depletion in tumor-bearing mice.

Previous investigations in our laboratory have demonstrated that both acute host starvation and polyamine depletion by means of the irreversible ODC-inhibitor (ODC = ornithine-decarboxylase) fluoro-methylornithine (DFMO) lead to pronounced growth retardation of rapidly proliferating tumors. The aim of this investigation was to elucidate how these different interventions affect cell kinetics and cell cycle phases in vivo. Adult nongrowing mice (C57Bl/J) bearing a poorly differentiated rapidly growing methylcholanthrene induced sarcoma were used. Combined measurements of bromodeoxyuridine incorporation into DNA and flow cytometric techniques were used. Starvation and DFMO treatment resulted in a prolonged cell cycle transit compared to freely fed animals. Tumor cells from DFMO-treated mice demonstrated an increased time for DNA synthesis and a relatively larger accumulation of cells in the G2M phase, whereas tumor cells from starved animals were accumulated in the G0G1 phase. The fractional cell loss of tumor cell during proliferation was calculated to be around 18% higher in DFMO-treated animals compared to starved and freely fed tumor-bearing mice. This study demonstrates that different mechanisms are involved in tumor growth suppression from substrate deficiency (starvation) and from inhibition of polyamine synthesis.

Animals↗
PubMed1991

Evaluation of ornithine decarboxylase activity as a marker for tumor growth rate in malignant tumors.

Ornithine decarboxylase (ODC) is a rate-limiting enzyme in the synthesis of polyamines. Polyamines regulate DNA synthesis by a mechanism that is not fully understood. High levels of polyamines and ODC activity are associated with rapid cell growth, particularly in tumor tissues. The aim of this study was to determine whether ODC activity as a marker for rapid alterations in tumor growth could be used to investigate whether nutritional support in cancer patients stimulates tumor cell proliferation. Weight-losing head and neck cancer patients and tumor-bearing mice (MCG 101, C57/BL) were studied during different feeding regimens. The ODC activity in tumor tissue was investigated in relation to the following variables: (1) histopathologic differentiation; (2) DNA content; and (3) bromodeoxyuridine (BrdUrd) incorporation into DNA. After the animals were starved for 24 hours, a significant reduction of tumor growth was demonstrated in the experimental tumor along with a reduction of ODC activity, an accumulation of cells in the G0G1 phase, and a reduction of cells incorporating BrdUrd into DNA. Refeeding after 24 hours generated a response by all variables. Tumor biopsy specimens from patients with head and neck cancer malignancies demonstrated aneuploidy in the cells of 70% of the patients. High ODC activity in tumor tissue was demonstrated mainly among poorly differentiated tumors, and ODC activity was correlated with the compartment size of aneuploidic cells in the tumor. High ODC activity indicated a poor short-term survival (1 year). It was concluded that experimental tumor growth is highly dependent on host feeding. However, there was no evidence supporting the claim that nutritional support to cancer patients stimulates tumor cell proliferation. Determination of ODC activity may be used to monitor rapid changes in DNA synthesis and may have prognostic significance for survival.

Aged↗
PubMed1991

Identification of tissue sites for increased albumin degradation in sarcoma-bearing mice.

Plasma albumin concentration declines in both experimental and clinical cancer. Previous investigations have demonstrated that this is partly explained by increased breakdown of albumin. The present study has identified the tissue sites for increased albumin degradation in a nonmetastasizing sarcoma mouse (C57/BL6J) model. Results have been compared to nontumor-bearing animals either freely fed or food restricted (pair-weighed) so that their body composition was similar to tumor-bearing animals. Tumor-bearing mice had increased albumin degradation (0.13 +/- 0.02 mg/hr/g bw) compared to both freely fed (0.09 +/- 0.007) and pair-weighed control animals (0.05 +/- 0.008). Radioactivity from circulating [3H]raffine aldehyde labeled albumin appeared with maximum peak values in lysosomes isolated from both tumor and nontumor tissues at 48 hr following iv injection. The intralysosomal accumulation of radioactivity was two- to threefold higher in tumor tissue compared to liver tissue, although the specific activity of protease(s) for albumin degradation measured in vitro was not higher in tumor tissue (30.4 +/- 3.6 mg/hr/g tissue) compared to normal liver tissue (36.9 +/- 1.7). Accounting for the entire tumor the proteolytic capacity for albumin breakdown was however much larger in the tumor (161.6 +/- 32.6 mg/organ) compared to both normal liver (37.5 +/- 2.3) and tumor-host liver (56.4 +/- 2.8). Pepstatin inhibited 78 +/- 6% of the proteolytic activity in the tumor measured by 125I-labeled undenatured mouse albumin as the substrate. Leupeptin inhibited 49 +/- 6%. There was a significantly decreased breakdown of albumin in both skeletal muscles and the gastrointestinal tract from tumor-bearing animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Elevated energy expenditure in cancer patients with solid tumours.

Cancer patients (n = 106) and non-cancer subjects (n = 96) were classified as weight stable (n = 70) or weight-losing (n = 132). Cancer patients had elevated resting energy expenditure (REE) compared with either weight-losing (23.6 [0.4] vs. 20.5 [0.5] kcal/kg per day, P less than 0.001) or weight-stable controls (22.0 [0.6] vs. 17.9 [0.4], P less than 0.001). Cancer patients had increased fat oxidation irrespective of weight loss (1.24 [0.07] vs. 0.87 [0.04] mg/kg per min; 1.07 [0.04] vs. 0.78 [0.04], P less than 0.001). Elevated energy expenditure was counter-regulated by a decrease in thyroid hormones. Abnormal liver function had no impact on REE in either group. Heart rate was the most powerful factor for prediction of high energy expenditure in both patients and controls. Elevated energy expenditure was related to the increased heart rate in cancer patients in a significantly higher proportion than that in controls. Increased metabolic rate is a significant component behind weight loss in cancer disease, independent of malnutrition and an elevated adrenergic state may be a likely explanation.

Analysis of Variance↗
PubMed1991

Effect on whole-body protein synthesis after institution of intravenous nutrition in cancer and non-cancer patients who lose weight.

Cancer and non-cancer patients received total parenteral nutrition (TPN) corresponding to either 120% or 200% non-protein energy resting energy expenditure. Whole-body tyrosine flux and leg exchange of various metabolites were measured in the fasted and fed state. Feeding with the moderate TPN rate did not stimulate whole-body protein synthesis in either group, but the high rate did. Both TPN rates switched an efflux of branched-chain aminoacids from the leg to an uptake in both groups, but this did not apply to tyrosine or phenylalanine. Only the high TPN rate stimulated glucose uptake across the leg in both groups. The leg exchanges of lactate, glycerol and free fatty acids were not significantly influenced by moderate or high TPN rates in either group, although changes in arterial concentrations indicated significant exchanges in compartments other than leg tissues. Thus standard TPN is insufficient to stimulate overall protein synthesis in both malnourished cancer and non-cancer patients, which may explain why previous studies have demonstrated insignificant functional effects with nutritional support to cancer patients.

Aged↗
PubMed1991

Ornithine decarboxylase activity in mouse tumour tissue in response to refeeding and diet components.

Ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase activity (SAMD) were measured in tumour tissue in mice during periods of starvation (24 h) and refeeding. Starvation led to a 60% reduction in tumour ODC activity. Refeeding normalised the activity within 4 h. Restitution in ODC activity, representing de novo enzyme synthesis, preceded DNA resynthesis. SAMD activity continued to fall along the increase in ODC activity during refeeding, while difluoro-methyl-ornithine (DFMO) caused a compensatory increase in SAMD activity as expected. A fall and regain in ODC activity was associated with inhibition and regrowth of the tumour. Starvation-refeeding was not related to any decrease in tumour polyamine concentrations, while systemic DFMO blockade was. Glucose stimulated ODC when refed orally, but not when given systemically. Tumour ODC activity was not decreased in refed mice by anti-insulin, a procedure that antagonised insulin's bioactivity. Exogenous insulin did not stimulate tumour ODC activity. Our results suggest that gastrointestinal metabolism of carbohydrates stimulates the release of a factor, which initiates both ODC activity and DNA synthesis in tumour cells. This factor was not insulin.

Adenosylmethionine Decarboxylase↗
PubMed1991

Chronic lower limb ischaemia. A prospective randomised controlled study comparing the 1-year results of vascular surgery and percutaneous transluminal angioplasty (PTA).

In a prospective randomised study, performed over a 6-year period, 102 patients with severe lower limb ischaemia or claudication resistant to exercise training were randomised either to percutaneous transluminal angioplasty (PTA) or vascular surgery. Only patients who could be treated by both methods were included, constituting only 5% of the total number of patients treated during this period. The two groups were similar regarding age, severity of symptoms and diabetes. The immediate and 1-year results showed similar success and complication rates. There was, however, a significantly shorter hospital stay for patients treated with PTA. Due to early complications and initial failures PTA should, however, only be used in institutions where vascular surgical facilities are available since PTA demands access to such treatment.

Adult↗
PubMed1991

Tumor cytokinetic response to total parenteral nutrition in patients with head and neck cancers.

Refeeding of patients with malignant tumors may induce tumor-cell DNA synthesis. The present study was aimed at evaluating whether induction of altered cell-cycle kinetics could be induced by intravenous total parenteral nutrition (TPN) in tumor biopsies from head and neck cancers. Nine malnourished patients with squamous cell carcinoma in the head-and-neck area were investigated before and after 5-7 d of continuous TPN. Tumor biopsies were taken in both fasted and fed states for determination of 1) ornithine decarboxylase (ODC) activity, which is rate limiting for polyamine synthesis; 2) flow-cytometric-DNA-distribution measurements; and 3) the fraction of proliferating cells expressed as immunohistochemical reactivity with the monoclonal antibody Ki-67. The histopathological differentiation, the fraction of aneuploidic cells, ODC activity, and Ki-67 reactivity were not significantly related to each other, although the number of aneuploidic cells in replicative phases correlated with the number of cells expressing the Ki-67 antigen (r = 0.86, P less than 0.01). Tumor cytokinetics showed no evidence of being changed by TPN administration.

Aged↗
PubMed1991

Effects of intravenous nutrition on lipoprotein metabolism, body composition, weight gain and uremic state in experimental uremia in rats.

The effect on serum lipids, lipoprotein fractions, body composition, weight gain and uremic state of including fat in intravenous nutrition was evaluated in rats with chronic uremia. Uremic rats were given high energy (1385 kJ.kg body weight-1.day-1), low nitrogen (0.6 g N.kg body weight-1.day-1) total parenteral nutrition (TPN) for 12 d with either glucose or glucose plus 30% lipids (Intralipid) as the energy source. Additional uremic and nonuremic groups were fed a standard diet orally. During TPN, serum triglyceride and cholesterol levels were slightly higher in rats fed lipid-based TPN compared to those administered glucose-based TPN or fed the oral diet; but there were no differences 8 h after feeding. The serum lipoprotein fractions showed accumulation of lipids in LDL resulting from the lipid-based TPN but no differences in VLDL. In orally fed uremic rats, more lipids were found in HDL than in the TPN-treated rats. The fractional clearance of the fat emulsion was normal and independent of the nutrition composition. Uremic rats administered lipid-based TPN for 21 d had the same weight gain as orally fed, nonuremic control rats (23 +/- 3 vs. 22 +/- 2%); glucose-based TPN did not support normal growth (10 +/- 1%). Uremic rats fed orally did not grow and retained significantly more body water than TPN-fed uremic rats. In uremic animals, lipid-based TPN also was associated with normal body composition despite significantly lower levels of carnitine in plasma, skeletal muscle and heart tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗