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Biomedical subjects

E Lindholm

Publications and source records attributed to E Lindholm.

At least 19 recordsLinked to original sources

Protection of metabolic and exercise capacity in unselected weight-losing cancer patients following treatment with recombinant erythropoietin: a randomized prospective study.

This study was aimed at evaluating whether anemia could be prevented in unselected weight-losing cancer patients on anti-inflammatory treatment by early and prophylactic treatment with recombinant human erythropoietin (rhEPO) and whether such a benefit could be translated into improved physical function and metabolic efficiency. One hundred eight cancer patients who experienced progressive cachexia due to solid, mainly gastrointestinal tumors were randomized to receive twice daily a cyclo-oxygenase inhibitor (controls; indomethacin, 50 mg twice a day) or indomethacin and erythropoietin, provided on individual basis to prevent development of progressive anemia (study patients; indomethacin, 50 mg twice a day plus rhEPO; range, 12,000-30,000 units per week). All patients were treated and followed up until death or to preterminal stage. Biochemical tests (blood, liver, kidney, and thyroid), nutritional state assessment (food intake and body composition), and exercise testing with simultaneous measurements of respiratory gas exchanges before and during exercise were performed before institution of treatments and then at regular intervals during the treatment period (2-30 months after start). Study and control patients did not differ in survival. rhEPO prevented development of anemia during the entire observation period. This was associated with a significantly more preserved maximum exercise capacity in study patients compared to control patients during the follow-up period (101 +/- 10 versus 66 +/- 6 W; P < 0.0001), based on more effective ventilation and whole-body respiratory gas exchanges. These improvements were also evident when exercise performance was normalized to lean body mass, an indirect measure of the skeletal muscle mass. The metabolic efficiency, expressed as oxygen uptake per watt produced, was also significantly preserved in rhEPO-treated patients compared to controls (14.1 +/- 1.1 versus 16.3 +/- 0.9 ml O2/W, P < 0.05). Our results demonstrate that institution of early and prophylactic rhEPO treatment to patients with progressive cancer prevents development of tumor-induced anemia. This achievement was associated with a better preserved exercise capacity, which is explained in part by improved whole-body metabolic and energy efficiency during work load.

Aged

Screening for colorectal neoplasia with faecal occult blood testing compared with flexible sigmoidoscopy directly in a 55-56 years' old population.

Reduced mortality from colorectal cancer may be achieved by screening with faecal occult blood testing. Screening for neoplasia in the rectum and sigmoid colon with flexible sigmoidoscopy is suggested to be more effective, particular among persons between 50 and 60 years of age. A cohort of 6367 persons 55-56 years of age were randomised to screening with rehydrated Hemoccult II tests (HII group) or with flexible videosigmoidoscopy directly (FS group). In the HII group 59% (1893/3183) attended, compared to 49% (1353/3184) in the FS group. Of the 1893 persons who attended in the HII group, 4% had a positive HII test and in 13% (10/78) of them a neoplasm > or = 1 cm in the rectum or sigmoid colon was diagnosed by endoscopy. The corresponding rate in the FS group was 2.3%. Overall the number of persons with a neoplasm > or = 1 cm diagnosed in the HII group was 10 and in the FS group 31. A subgroup in the flexible sigmoidoscopy group, who also performed rehydrated HII tests, showed a sensitivity of the HII test for neoplasia > or = 1 cm of 26% and a specificity of 95.6%. To find a neoplasm > or = 1 cm in the rectum or sigmoid colon, 44 examinations were needed when using flexible sigmoidoscopy directly and 7 examinations when only those with positive HII tests were examined. In mass screening for neoplasia in the rectum and sigmoid colon, the relatively low prevalence of colorectal neoplasia at 55-56 years of age makes primary selection with rehydrated Hemoccult testing an alternative to the resource-consuming endoscopy of all invited persons.

Adenoma

Worry associated with screening for colorectal carcinomas.

BACKGROUND: We wanted to assess the worry created by a screening program for colorectal cancer with fecal occult blood testing. METHODS: Six thousand three hundred and sixty-six individuals (47% men; 53% women) were asked to what extent they were worried when they received an invitation letter including a Hemoccult II test (HII). The questionnaire was supplemented by a structured telephone interview of a selected number of individuals with different outcome of the HII. RESULTS: Three thousand four hundred and eighty-six subjects performed the HII test, and 3548 (56%) answered the questionnaire. Eighty-four per cent (n = 2932) of the participants and 21% (n = 616) of the non-participants completed the questionnaire. Half of the participants (54%) were not worried at all, but 16%, more women than men, felt severe worry, which lasted less than 1 week in 59%. In 4.7% of the participants daily life was negatively influenced by the invitation letter. In the telephone interview 19% reported severe worry before they received the result of the first test, and in 5.8% daily life was negatively affected. The worry rate increased to 60% in the groups with an initial positive HII test, and in 15% daily life was negatively influenced. After the examination the worry decreased in most but was still pronounced in 10%. One year after the work-up 96% declared that they appreciated the study. Subjects with only elementary school education expressed more worry than those with a higher level of education (P < 0.05). CONCLUSIONS: Severe worry in connection with the invitation was reported by a minority of the invited participants, more women than men. The worry increased among those who had a positive test but decreased after the examination. One year after the work-up most appreciated the study.

Anxiety

Chromosome-specific panels of tri- and tetranucleotide microsatellite markers for multiplex fluorescent detection and automated genotyping: evaluation of their utility in pathology and forensics.

A set of 391 microsatellite markers (Weber set 6), 85% of which consist of tri- and tetranucleotide repeat markers, were used to design chromosome-specific panels that allowed for a high degree of multiplexing with respect to the fragment size range and fluorophore (FAM, HEX, TET). This marker set has an average coverage of 10.5 cM, with the largest gap being 28.1 cM. The markers were divided into 49 panels, with a maximum degree of multiplexing of 15 markers per panel. The utility of the markers for analysis of DNA from blood, hair, and formalin-fixed archival tissue biopsies was evaluated with respect to amplification efficiency, product yield, and degree of preferential amplification of the shorter allele in heterozygotes. The amplification efficiency was inversely related to repeat length and amplicon length. Based on the analysis of DNA from formalin-fixed biopsies, 51 markers suitable for loss of heterozygosity (LOH) studies were identified. The utility of the marker set for genome scanning, LOH, and forensic analyses is discussed.

Chromosomes

The effect of recombinant human IGF-I on protein metabolism in post-operative patients without nutrition compared to effects in experimental animals.

This study has evaluated the effects of recombinant human insulin-like growth factor I (rhIGF-I) to moderately stressed post-operative patients provided with dextrose as the only exogeneous substrate. Thirty patients who underwent elective colorectal surgery were randomized to receive either rhIGF-I (80 micrograms kg-1 bw) subcutaneously twice daily or placebo injections in a double-blind parallel group design. Nitrogen balance, urinary 3-methyl-histidine excretion plasma growth hormone (GH), serum cortisol, IGF-I binding proteins (IGFBP-1,3), glomerular filtration rate, plasma amino acid concentrations and whole-body energy expenditures were measured as effector variables during days 1-5 post-operatively. Animal and isolated tissue experiments were performed as additional control experiments to confirm cellular effectiveness of the recombinant material. rhIGF-I increased significantly the glomerular filtration rate and prevented the adaptive decrease in whole-body energy expenditure in response to partial starvation in the postoperative period. Serum and plasma concentrations of IGFBP-1,3 cortisol, blood glucose and amino acids were not significantly influenced by rhIGF-I administration, while plasma GH levels decreased significantly as expected. rhIGF-I had no effect on either nitrogen balance or protein breakdown (3-methylhistidine excretion) in post-operative patients on dextrose supplementation only, although plasma concentrations of IGF-I increased from 130-140 ng mL-1 to a range of 300-450 ng mL-1. In contrast, IGF-I stimulated the synthesis of both globular and myofibrillar proteins (+50%, P < 0.01), when given as a single dose (100 micrograms kg-1) 2 h before measurements of protein synthesis in skeletal muscles of overnight fasted adult mice. This stimulatory effect by IGF-I (1 microgram mL-1) was also confirmed by measurements of skeletal muscle protein synthesis in vitro (+40%, P < 0.05). Orally re-fed mice had a normal transcription of IGF-I mRNA in skeletal muscle cells, while overnight fasted mice showed a trend to down-regulated transcription. Our results demonstrate that rhIGF-I has several significant physiological effects, without major side-effects, when supplied to partially starved patients in the post-operative phase. The lack of a whole-body nitrogen sparing effect by rhIGF-I alone to post-operative patients is not clear, but was most likely explained by subnormal plasma concentrations of amino acids.

Aged

Factors associated with participation in screening for colorectal cancer with faecal occult blood testing.

BACKGROUND: Factors associated with attending screening for colorectal cancer with faecal occult blood testing was studied. METHODS: Sixty-eight per cent of 34,144 subjects participated in the primary screening and/or rescreening in a randomized screening study. The mortality and causes of death in the two groups were studied. A sample of the subjects received a questionnaire, in which they were asked about their reaction to the invitation. A statistical sample was called for a telephone interview. RESULTS: The mortality among the non-attenders was higher than among the attenders (p < 0.001), which might reflect a higher morbidity among the non-attenders. The mortality was equal in the test and control groups. There was no difference among the attenders and non-attenders who had a full or 50% pension. Among immigrants the attitude to screening was less positive among those born in 1918 but was the same as that of the whole group among those born in 1929. Significantly fewer persons among the non-attenders than among the attenders could be reached for a telephone interview (p < 0.001). CONCLUSION: There is a possibility that the compliance can be increased. The non-attenders' attitude to screening was more negative than that of the attenders.

Aged

Evaluation of a Swedish version of the Ostomy Adjustment Scale.

The main aim of the present study was to adapt an instrument measuring patients' adjustment to life with an ostomy to Swedish conditions and to test reliability and validity of the adapted instrument. The Ostomy Adjustment Scale (OAS), which is focused on three domains: physical function, psychologic state, and social interaction, was selected as suitable. After translation into Swedish, equivalence and internal consistency of the scale were calculated. Subjects with various types of urine or faeces diversions were recruited for self-rating with the OAS and a visual analogue scale estimating total quality of life (QOL). The instruments were tested in 48 patients with five different diagnoses, 36 with and 12 without ostomy, and re-tests were carried out in 25 of the patients. Reliability (Cronbach's alpha) was 0.95. A positive correlation was found between the OAS and QOL (r = 0.67), indicating that the instrument has some validity.

Adaptation, Psychological

Urinary diversion to the augmented and valved rectum. An experimental study in dogs.

A new model for diverting urine to the rectum was tried in dogs. An intussusception valve was constructed at the junction of the sigmoid colon and the rectum allowing passage only in aboral direction. The rectum was augmented by patching it with an opened and folded ileal segment. The ureters were implanted into the rectum by a new anti-reflux method. All three dogs survived the operation. The volume of the augmented rectum increased from 80-150 ml at operation to a maximum of 750 ml six months after the operation. The pressure in the rectum did not exceed 18 cm of water during maximal filling. No reflux to the bowel proximal to the intussusception valve or to the ureters could be observed even during maximal filling of the augmented rectum. No signs of obstruction of the fecal stream by the intussusception valve were seen. In three out of five implanted renal units strictures developed at the implantation sites and resulted in impaired renal function. In the two renal units without strictures, no impairment of kidney function was found. Involuntary leak from the anus was not observed and no masceration was found around the anus. These experiments are regarded as very encouraging an a clinical trial is now under way.

Animals

Cardiopulmonary function as related to thromboxane A2 synthesis in experimental septic shock.

The aim of the present study was to explore the possible involvement of thromboxane A2(TxA2) in the development of cardiopulmonary dysfunction in experimental septic shock. Sepsis was induced in anesthetized cats by intravenous (i.v.) infusion of live Escherichia coli. One series (No. = 12) was pretreated with a specific TxA2 synthetase inhibitor, dazmegrel; another (No. = 8) served as a septic control series. In both series a systemic arterial hypotension developed after 2 hr; no differences in cardiac function were detected. After 2 hr bacteremia cardiac preload was increased by a rapid infusion of dextran. This showed that cardiac function was significantly more preserved in dazmegrel-pretreated cats compared with septic controls. Pretreatment with dazmegrel totally prevented the pulmonary vascular response to bacterial infusion. The pulmonary compliance decreased to 40% in controls but to only 75% in the dazmegrel series, and airway resistance increased to 300% and 140%, respectively. The ventilation-perfusion ratio was less impaired in the pretreated series. Pretreatment with dazmegrel abolished the increase in thromboxane B2 (TxB2), the stable metabolite of TxA2, seen in the untreated series. The rise in 6-keto-prostaglandin F1a (6-keto-PGF1a), the stable metabolite of prostaglandin I2PGI2, was evident in both series. We concluded that TxA2 is important for the impaired cardiac performance in septic shock. Furthermore, TxA2 is involved, but not as the only factor, in the development of pulmonary dysfunction.

Airway Resistance

Cardiac-related cortical activity during variations in mean heart rate.

Koriath and Lindholm (Int. J. Psychophysiol., 1986; 4: 183-195) reported cardiac-related cortical inhibition and speculated that cardiovascular events could modulate electrocortical activity by setting constraints on cortical excitability during diastole based on levels of blood pressure during systole. One dimension of this proposal could be supported if the extent of cardiac-related cortical activity (CRCA) varies with changes in heart rate and blood pressure. The current study investigated this dimension of cardio-cortical relationship by having each subject perform a fixed-foreperiod reaction time task while pedalling a bicycle ergometer under three conditions of workload: No Pedal (0 kpm/min), Lo Pedal (150 kpm/min), and Hi Pedal (450 kpm/min). Mean HR increased significantly from No Pedal to Lo Pedal to Hi Pedal. Results confirmed the presence of CRCA during variations in mean HR and indicated that the extent of CRCA increases with increases in mean HR. This investigation reinforces the importance of the extrahomeostatic effects of cardiovascular afferent fibers and supports the importance of psychophysiological measures which integrate the activity of cardiovascular, autonomic, and central nervous systems.

Adolescent

Expansion of various types of ileal reservoirs in situ. An experimental study in rats.

In experiments on rats four types of ileal reservoirs were constructed and left to expand in situ. After 3 months the volumes and tissue weights of the various reservoirs were compared. The reservoir types were: two loops, isoperistaltic (type I), two loops, antiperistaltic (type II), three loops, S-shaped (type III) and "four loops', double-folded U loop (Kock pouch) (type IV). There was a considerable volume increase in all types of reservoir as well as a marked increase in their tissue weight. The expansion of the reservoirs in groups III and IV was significantly greater than that in groups I and II. The difference in expansion could possibly be explained by the greater radius in three- and four-loop reservoirs compared with two-loop reservoirs if Laplace's law is applied to this process. According to this law the tension in the wall of a tube increases with increasing radius.

Anal Canal

Cardiac-related cortical inhibition during a fixed foreperiod reaction time task.

Lacey and Lacey hypothesize the presence of cortical inhibitory influences which result from the cardiac events which initiate baroreceptor discharge. The current study provides evidence of cardiac-related cortical inhibitory influences when normal humans are required to attend to environmental input and respond to the information they perceive (fixed foreperiod reaction time task). Averaged EEG waveforms time locked to pulse transit time (PTT) were comprised of slower frequencies than averaged EEG waveforms randomly selected from the same cardiac cycles, and pre-PTT EEG was comprised of slower frequencies than post-PTT EEG in the averaged waveforms. Results of this experiment raise the speculation that cardiovascular events may modulate brain activity with variations in baroreceptor discharge setting constraints on cortical excitability on a beat-to-beat basis.

Animals

Analysis of multiple event related potential components in a tone discrimination task.

Subjects performed in a tone discrimination task at two levels of difficulty, and a reaction time response was required on half of the trials. Four prominent components of the event-related potential waveform (N1, P2, N2, and P3) were analyzed. The results suggested that P2 represents the beginning of a central process responsible for stimulus identification and the initiation of decision making, while N2 and possibly P3 represent the end of this process. The notion that the P3 component is an unusually important sign of central processing is questioned, and the notion that P3 represents a central process of memorial update is also questioned. It seems more likely that N2 or p3 represent the end of a central process started at the time of P2.

Adult

Autonomic activity and workload during learning of a simulated aircraft carrier landing task.

Heart rate, heart rate variability, and skin conductance responses were continuously recorded from six naive males during learning of a simulated aircraft carrier landing task. There were 30 learning trials spanning more than 1 h. Over trials, heart rate decreased while flight performance increased, indicating that heart rate is sensitive to practice effects. Independent of practice, heart rate and skin conductance amplitude always increased during the last minute of final approach to landing. The results supported the following conclusions: (a) heart rate and skin conductance amplitude are reliable indicators of short-term workload increases as typified by final approach; (b) heart rate is a reliable indicator of longer term workload decreases resulting from practice and increased mastery of the task. Results are discussed within the framework of autonomic activation theory.

Aerospace Medicine

Physiological and morphological changes in the gastrointestinal tract induced by hypothalamic intervention: an overview.

Neural control and modulation of gastric secretion is well established. The role of the parasympathetic vagal system as a final motor pathway in gastric acid secretion is clearer than the involvement of the sympathetic nervous system. Both portions of the autonomic nervous system, however, appear to play an important role in the pathogenesis of at least experimentally induced gastric erosions. With respect to higher neural control there are numerous reports of hypothalamic effects on gastric secretion, motility, and morphology, yet the results of many of these reports appear equivocal. This ambiguity can be attributed in part to species differences, time course of observations, and differences in stimulation and lesion parameters. However, a mcal description of the sites of central lesions and stimulation. Implications of several of the studies concerning hypothalamic involvement in gastric functions are reviewed and recent methodological advances including neural fiber transection, relatively specific neural cell damage with neurotoxins (e.g., 6-OHDA, kainic acid), histochemistry and intracerebral infusions of gut hormones are suggested as alternative approaches to studying brain-gut relationships.

Animals