Ingvar Karlberg

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.

Glucose turnover, gluconeogenesis from glycerol, and estimation of net glucose cycling in cancer patients

A double isotope method was used in patients with progressive malignancy and in control patients to measure: glucose turnover, conversion rate of carbon skeleton of glycerol into glucose, and the interorgan cycling of glucose carbons (Cori‐cycle plus alanine‐glucose cycle). [U‐14Clglycerol and [6‐3H]glucose were given intravenously as a single dose injection. The time course of the specific radioactivities of [6‐3H] and [U‐14C]glucose was followed in blood. The pool size and the turnover rate of glucose were increased in the cancer group as compared with the control patients. The net recycling of glucose carbons was not increased in the cancer group, despite the increased turnover of glucose. The alterations in the metabolism of glucose did not correlate with the plasma levels of insulin or thyroid hormones (T4, T3, rT3) neither in the entire cancer group nor in those cancer patients who were repeatedly investigated at different intervals of time. The turnover rate of glucose in the cancer patients correlated inversely to their body weight index. The gluconeogenesis rate, given as the fractional conversion rate of the injected radioactive dose of [14C]glycerol, or as mol glucose · kg body weight−1 · day−1, was increased in the cancer group, but still contributed only 3% of the glucose turnover rate in both cancer and control patients. We conclude that an increased gluconeogenesis from glycerol is not significant in terms of energy expenditure in patients with progressive malignancy, as has previously been concluded for the gluconeogenesis from alanine.15 It seems that increased turnover of glucose may contribute to inappropriately high energy expenditure in cancer patients.

A comparative study of the influence of malignant tumor on host metabolism in mice and man. Evaluation of an experimental model.

Metabolic alterations in skeletal muscles and liver tissue from cancer patients were compared with corresponding alterations in mice (C‐57) with sarcoma (MCG‐101). In tumor‐bearing man and mice similar changes in enzyme activities and in protein turnover were found. Glycolytic and oxidative enzyme activities were decreased in skeletal muscle tissue. Tumor‐associated increase in lysosomal enzyme activities was found in both species. Leucine was incorporated into skeletal muscle proteins at a lower rate and into hepatic proteins at a higher rate in both species with malignant tumor. In tumor‐bearing mice ribosome profiles from skeletal muscle, heart muscle and liver showed a preponderance of slowly sedimenting units of polyribosomes suggesting that initiation of protein synthesis may be a rate limiting step. The metabolic host reactions in tumor‐bearing mice were similar to those in cancer patients implying that experimental tumors are relevant to use for analysis of mechanisms behind the development of cancer cachexia in man.

Why are people without medical needs transported by ambulance? A study of indications for pre-hospital care.

Objective The purpose of this report was to describe the characteristics of patients transported by ambulance, in spite of being evaluated by the ambulance staff at the scene as not requiring prehospital care. A second aim was to compare these patients with those judged as being in need of this care. Methods Three ambulance service districts located in different rural and metropolitan geographical areas were included in the study and all three were covered by a single emergency dispatch centre. Following the dispatch of ambulances, the staff assessed and recorded the medical needs of the patients at the scene, according to a questionnaire developed for the study. In addition to the questionnaire, data were extracted from the ambulance medical records database for each patient. If the patients were just transported by ambulance without receiving any other prehospital intervention, they were assessed as not being in need of the emergency service. The evaluation included events at the scene and during transportation. The ambulance staff making the needs assessments were emergency medical technicians and registered nurses. In this report, 604 patients who did not require prehospital care are described and compared with the remaining group of patients who required this care (1373). For analysis, descriptive statistics were used to analyse the data. Results The ambulance staff assessed that, among patients reported by the emergency medical dispatch centre as having abdominal or urinary problems, 42% did not need the ambulance service. Even among intrahospital transports (patients for whom medical personnel made the request for an ambulance), 45% did not require ambulance transport, as judged by the ambulance staff. Among patients reported by the emergency medical dispatch centre as having chest pain or other heart symptoms or trauma/accidents, respectively, only small percentages (18%) and (17%) did not require the ambulance service, as assessed by the ambulance staff. Most of the patients without obvious medical needs had been allocated an ambulance response for nonurgent conditions, that is priority level 2 or 3, but patients without medical needs were even found at the highest priority level 1. Of the patients who did not require an ambulance, more than half (55%) would have been able to get to a hospital in their own car or by taxi, whereas the remainder of the patients needed a transport vehicle in which they could lie down, but which was not equipped and staffed like an ambulance. Conclusion Among the patients transported by the emergency medical service system in the study areas, a significant percentage were judged by the ambulance staff as not being in need of prehospital interventions. The majority were transported by a fully equipped emergency medical ambulance to an emergency medical department at a hospital, without requiring any prehospital interventions either at the scene or during transportation. The emergency medical service organization has to develop clear criteria for the utilization of ambulance services that can be accepted and implemented by the dispatch centres and by healthcare personnel. These criteria need to include safety margins and at the same time enable the appropriate use of resources.

Economic burden of stroke in a large county in Sweden.

BackgroundStroke remains to be a major burden of disease, often causing death or physical impairment or disability. This paper estimates the economic burden of stroke in a large county of 1.5 million inhabitants in western Sweden.MethodsThe economic burden of stroke was estimated from a societal perspective with an incidence approach. Data were collected from clinical registries and 3,074 patients were included. In the cost calculations, both direct and indirect costs were estimated and were based on costs for 12 months after a first-ever stroke.ResultsThe total excess costs in the first 12 months after the first-ever stroke for a population of 1.5 million was 629 million SEK (€69 million). Men consumed more acute care in hospitals, whereas women consumed more rehabilitation and long-term care provided by the municipalities. Younger patients brought a significantly higher burden on society compared with older patients due to the loss of productivity and the increased use of resources in health care.ConclusionsThe results of this cost-of-illness study were based on an improved calculation process in a number of fields and are consistent with previous studies. In essence, 50% of costs for stroke care fall on acute care hospital, 40% on rehabilitation and long-time care and informal care and productivity loss explains 10% of total cost for the stroke disease. The result of this study can be used for further development of the methods for economic analyses as well as for analysis of improvements and investments in health care.

Validity and utilization of epidemiological data: A study of ischaemic heart disease and coronary risk factors in a local population

OBJECTIVES To calculate the burden of ischaemic heart disease (IHD) and coronary risk factors in a defined population using data from all public providers of health care, i.e. inpatient and outpatient care in all settings. STUDY DESIGN Cross-sectional, 1-year retrospective study. METHODS The main outcome measures were the number of individuals by diagnosis and by care setting, and gender- and age-specific event rates by diagnosis. RESULTS Less than half of the individuals who visited any care provider for IHD or coronary risk factors were identified in the hospital discharge register. Calculation of the actual burden of disease in the population showed that when hospital discharge data were combined with outpatient data, there were no or slight differences in the age-specific rates of acute myocardial infarction (AMI), while the rates of angina were between two-fold and four-fold higher, and unspecified IHD was between three-fold and ten-fold higher in individuals aged > or =50 years compared with using hospital discharge data alone. The rates of hypertension, diabetes and lipid disorders increased in all age groups when outpatient data were added to hospital discharge data. The differences in the rates were more pronounced in women aged 50-79 years. However, the age-specific rates were higher in men except for hypertension which was higher in older women. CONCLUSION Data for epidemiological analyses of diseases are often based on hospital discharge data. This study found that hospital discharge data provide limited information on patients treated for IHD and coronary risk factors, except for AMI. These findings suggest that hospital discharge data should be combined with outpatient care data to provide a more comprehensive estimate of the burden of IHD and its risk factors.

Does ambulance use differ between geographic areas? A survey of ambulance use in sparsely and densely populated areas

AIM The aim of this study was to analyze possible differences in the use of ambulance service between densely and sparsely populated areas. METHODS This study was designed as a 2-step consecutive study that included the ambulance service in 4 different areas with different geographical characteristics. A specific questionnaire was distributed to the enrolled ambulance services. Completion of one questionnaire was required for each ambulance mission, that is, 1 per patient, during the study periods. For calculations of P values, geographic area was treated as a 4-graded ordered variable, from the most densely populated to the most sparsely populated (ie, urban-suburban-rural-remote rural area). Statistical tests used were Mann-Whitney U test and Spearman rank statistic, when appropriate. All P values are 2 tailed and considered significant if below .01. RESULTS The medical status of the patients in the prehospital care situation was more often severe in the sparsely populated areas. In addition, drugs were more often used in the ambulances in these areas. In the sparsely populated areas, ambulance use was more frequently judged as the appropriate mode of transportation compared with the more densely populated areas. CONCLUSIONS Our study suggests that the appropriateness of the use of ambulance is not optimal. Furthermore, our data suggest that geographical factors, that is, population density, is related to inappropriate use. Thus, strategies to improve the appropriateness of ambulance use should probably take geographical aspects into consideration.

Insulin sensitivity, hormonal levels and skeletal muscle protein metabolism in tumour-bearing exercising rats

We have previously shown that spontaneous physical exercise can delay onset of experimental anorexia and cachexia, and retard tumour growth; we now report the effects on insulin sensitivity, hormonal levels and skeletal muscle protein metabolism. Insulin sensitivity determined with a euglycaemic hyperinsulinaemic clamp revealed a normalised glucose disposal rate in tumour-bearing exercising (TBE) versus sedentary (TBS) animals (TBE 15.55 +/- 2.71 versus TBS 2.47 +/- 2.12 mg/kg/min; P < 0.05). Both TBE and TBS animals had decreased levels of corticosterone during the clamp. Serum levels of insulin during tumour progression were unaffected by exercise, but the insulin: glucagon ratio increased and the progressive decrease in rT3 was attenuated. The concentration of glucagon decreased in both tumour-bearing groups during the experiment, while TBE animals showed a relative reduction in corticosterone. Capacity for skeletal muscle protein synthesis, expressed as RNA: protein ratio, was normalised in TBE animals in two tumour protocols (TBE 5.9 +/- 0.6 versus TBS 4.7 +/- 0.3; TBE 2.9 +/- 0.4 versus TBS 1.8 +/- 0.2; P < 0.05, respectively). Incorporation rate of 14C-phenylalanine into skeletal muscle protein was increased in the TBE group in vitro and in vivo. In the postexercise period, protein degradation evaluated by tyrosine release in vitro was increased, but decreased over time. This study has confirmed a positive skeletal muscle protein balance in exercising tumour-bearing animals, partly explained by the increased insulin sensitivity. This conclusion was further supported by the less catabolic pattern indicated by hormonal levels.

Albumin and hepatic protein synthesis in patients with early cancer

The synthesis capacity of albumin and hepatic proteins was studied in vitro in hepatic tissue from 21 patients with early‐stage cancer and without liver metastasis and from 26 control subjects. Hepatic tissue was obtained intraoperatively and incubated under protein synthesizing conditions. Albumin was isolated with monospecific antiserum. Cancer patients showed an increased capacity for hepatic protein synthesis and an unchanged capacity for synthesis and intracellular transport of albumin. The ratio between the synthesis of hepatic protein and albumin was statistically significantly increased in cancer patients. The albumin synthesis was inversely correlated to a body weight index in cancer patients (r = −0.62), suggesting the presence of a compensatory mechanism for enhanced albumin synthesis in patients who are unable to ingest sufficient quantities of nutrients to supply the demands of the host and the tumor. Cancer 46:71–76, 1980.

Ultrastructural changes and enzyme activities for energy production in hearts concomitant with tumor-associated malnutrition

Morphometric data on left ventricular papillary muscle structures have been determined in tumor-induced malnutrition and related to the maximum activities of key enzymes for energy production in the whole myocardium. Adult, nongrowing mice with a syngeneic sarcoma were used to represent a condition of cancer associated host tissue wasting. Hearts from mice 11 days after tumor implantation showed atrophy and a significantly reduced amount of myofibrillar, soluble, and collagen proteins than hearts from control animals. The cross-sectional area of myocardial cells was 33% smaller in tumor-bearing mice (p less than 0.025), but the total number of capillaries and the residual interstitial volume were similar in the two groups. The total number of subcellular structures per cell, such as mitochondria, myofibrils, and myosin filaments per myofiber, were significantly lower in the tumor-bearing animals (p less than 0.025). Conversely, the proportion of myofibrils was higher (p less than 0.05) in tumor-bearing animals while the proportion of mitochondria was lower. Maximum activities (Vmax) of selected regulatory key enzymes for energy production (glycogenolytic, glycolytic, and mitochondrial) were not significantly altered in hearts from tumor-bearing mice. The results support the conclusion that myocardial functional capacity is better preserved than overall structural components would imply in tumor-host associated malnutrition, which is probably secondary to deprived food intake. Teleologically, this may be a means by which functional deterioration of the heart is minimized during the induction of malnutrition.