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Biomedical subjects

E Holm

Publications and source records attributed to E Holm.

At least 37 records · Page 2Linked to original sources

In situ sorption of technetium using activated carbon

The sorption of technetium in pertechnetate form on carbon has been investigated. The sorption is pH dependent with maximal distribution coefficients, Kd, in the order of 10(6) at pH 2-4 for activated carbon with a grain size < or = 100 microm. The equilibrium time to reach such distribution coefficient was about 5 h at room temperature. The exact mechanisms for the sorption are not fully understood but reduction of Tc by the carbon might be an important process. Technetium can effectively and rapidly (5 l min(-1)) be sorbed from very large volumes (several hundred liters) of environmental waters on commercial cartridge filters impregnated with activated carbon. After incineration, the filters can be analyzed for 99Tc by conventional methods.

Journal Article↗

Ipsilateral local recurrence in relation to therapy and morphological characteristics in patients with ductal carcinoma in situ of the breast.

METHOD AND RESULTS: A standardized histopathological protocol has been designed, in which different histological characteristics of ductal carcinoma in situ (DCIS) are reported: nuclear grade (ng), growth pattern according to Andersen et al., necrosis, size of the lesion, resection margins and focality. Using this protocol a re-evaluation of a population-based consecutive series of 306 cases of DCIS has been done as well as a thorough clinical follow-up. After a median follow-up of 63 months, 13% have developed ipsilateral local recurrences, invasive and/or in situ. Ipsilateral local recurrence-free survival (IL-RFS) was significantly better for patients operated with mastectomy (ME) or breast conserving therapy (BCT) with radiotherapy (RT) than for patients operated with BCT without RT (5-year IL-RFS 96% vs 94% vs 79%, P<0.001). In the subgroup of BCT without RT there were significant differences in IL-RFS between histopathological subgroups: ng 1 + 2 (non-high grade) vs ng 3 (high grade; P=0.014), non-high-grade without comedo-type necrosis vs non-high-grade with comedo-type necrosis vs high-grade (the Van Nuys classification system; P=0.025). Growth pattern (not diffuse vs diffuse) and margins (free vs involved or not evaluated) showed a tendency (P=0.07 and 0.05, respectively) to be associated to IL-RFS. In contrast, no significant differences in IL-RFS were found in subgroups based on mode of detection, focality or size. Ninety-four per cent of the local recurrences after BCT appeared at the previous operation site. CONCLUSIONS: In the BCT without RT group, combinations of either non-high grade and not a diffuse growth pattern or non-high grade and free margins identified groups (constituting approximately 30% of the patients) were at low risk of developing ipsilateral recurrences (6-10%), compared to a 31-37% recurrence risk in the remaining groups during the observed follow-up time. The beneficial effect of post-operative RT for these low-risk groups can be questioned, and should be studied further.

Adult↗

Effect of carnitine on muscular glutamate uptake and intramuscular glutathione in malignant diseases.

Abnormally low intramuscular glutamate and glutathione (GSH) levels and/or a decreased muscular uptake of glutamate by the skeletal muscle tissue have previously been found in malignant diseases and simian immunodeficiency virus (SIV) infection and may contribute to the development of cachexia. We tested the hypothesis that an impaired mitochondrial energy metabolism may compromise the Na+-dependent glutamate transport. A randomized double-blind clinical trial was designed to study the effects of L-carnitine, i.e. an agent known to enhance mitochondrial integrity and function, on the glutamate transport and plasma glutamate level of cancer patients. The effect of carnitine on the intramuscular glutamate and GSH levels was examined in complementary experiments with tumour-bearing mice. In the mice, L-carnitine treatment ameliorated indeed the tumour-induced decrease in muscular glutamate and GSH levels and the increase in plasma glutamate levels. The carnitine-treated group in the randomized clinical study showed also a significant decrease in the plasma glutamate levels but only a moderate and statistically not significant increase in the relative glutamate uptake in the lower extremities. Further studies may be warranted to determine the effect of L-carnitine on the intramuscular GSH levels in cancer patients.

Adult↗

Histologic grading in breast cancer--reproducibility between seven pathologic departments. South Sweden Breast Cancer Group.

Histologic grade, including tubular formations, nuclear grade, and mitotic activity, is a well-documented prognostic factor in breast cancer. In comparison with other prognostic parameters, the evaluation of histologic grade is cheap and can be performed, in principle, in all cases of breast cancer. One possible disadvantage is that the evaluation may vary between different pathological departments. The aim of the present work was therefore to study the reproducibility of the histologic grading system by distributing haematoxylin-erythrosin-stained slides from 93 invasive breast cancers to the seven pathology departments within the southern healthcare region of Sweden. The evaluation was performed blindly and without any knowledge of other clinical parameters. In 31% of the cases the same histologic grade was obtained for all departments. The overall mean kappa was 0.54, indicating a moderate reproducibility. Of the three factors included in histologic grade, the agreement was best for tubular formations and poorest for nuclear grade and mitotic activity. The overall moderate reproducibility should be considered when the clinical usefulness of histologic grading is compared with other prognostic instruments.

Adult↗

Serum-ionised magnesium in patients with acute myocardial infarction. Relation to cardiac arrhythmias, left ventricular function and mortality.

Measurement of serum-ionised magnesium has recently become available, and we report the first study of the relation of this parameter to arrhythmias, left ventricular function and mortality in patients with an acute myocardial infarction. Serum-ionised magnesium was determined in 217 consecutive patients admitted to hospital with an enzyme confirmed AMI. 70 healthy subjects acted as a control group. The main study parameters were occurrence of arrhythmias, left ventricular function estimated by echocardiography, and mortality after 10 months for the AMI patients. AMI patients had significantly lower serum-ionised magnesium compared to healthy controls but the level of serum-ionised magnesium in the acute phase of a MI was neither related to arrhythmias, left ventricular function nor mortality.

Adult↗

Radioactive contamination: state of the science and its application to predictive models.

Information on environmental levels and transport processes of natural and anthropogenic radioactivity, although plentiful, is widely scattered, and relatively few attempts have been made to summarize and synthesize this information. Furthermore, most experimental observations and experiments on environmental radioactivity have been designed for documentation or testing of specific hypotheses, rather than for providing key information for transport simulation models or on fundamental processes which such models seek to represent. This paper examines three basic questions, namely (1) what is the current state of the science of radioecology?; (2) how well is this science being incorporated into predictive models?; and (3) how well are the models being used to guide and improve the science? These discussions will be preceded by a brief description of the field of radioecology, and comments on its relevance to other sciences as well as to major societal problems stemming from environmental releases of radioactivity. In addition to assessing the current state of the science and its use in predictive models, specific ideas for improving both the science and its associated models will be advanced. These ideas fall under the categories of (1) environmental transport processes and model parameters, (2) estimating exposure and dose to human and ecological receptors, and (3) dose-effect relationships for plants and animals.

Journal Article↗

Amino acid metabolism in liver disease.

The impairment of transsulphuration during methionine degradation in hepatic failure can be counteracted by treatment with S-adenosylmethionine. Regarding the pathogenesis of hepatic encephalopathy, no convincing evidence exists for tryptophan, glutamine or glutamate being involved. Portal-systemic shunting-induced hyperammonaemia may reduce plasma branched-chain amino acids. The glucose effect on urea synthesis does not exist in cirrhosis.

Amino Acids↗

Fatal liver failure associated with valproate therapy in a patient with Friedreich's disease: review of valproate hepatotoxicity in adults.

PURPOSE: Valproate (VPA)-associated hepatotoxicity is usually considered a problem of young children with polytherapy, mental retardation, and underlying metabolic defects. METHODS: An adult patient with fatal liver failure during treatment with VPA is presented, and a review of the literature on other adult patients is given. RESULTS: A 29-year-old female patient with Friedreich's ataxia and partial seizures with acute liver failure during VPA treatment is reported. The first symptoms of liver failure (i.e., apathy during febrile upper airway infection) occurred 2 months after starting VPA therapy. VPA was discontinued 10 days later on hospital admission, when she had hepatic encephalopathy and severe bleeding diathesis. The patient died of severe liver failure and bronchopneumonia after 4 weeks of supportive treatment. CONCLUSIONS: Twenty-six adult patients (>17 years) with VPA-associated fatal hepatotoxicity have been reported in the literature. Of the 26 adult patients, three were receiving VPA monotherapy. The age ranged between 17 and 62 years. The duration of VPA treatment before the first symptom varied between 7 days and 6 years. Twelve of the 26 affected adults had no underlying disease or a clearly nonmetabolic and non-hepatic disease. Therefore VPA-associated severe side effects also must be considered in adult patients without any evidence of a metabolic defect or underlying neurologic disease.

Adolescent↗

A survey of present levels of radiocesium in Swedish pulp mill liquors and the implications for wood radiocesium transfer factors.

Assessments of the impact from radioactive fallout on the pulp industry and the accumulation processes for radionuclides in such industries, using wood and water as primary raw materials, have been conducted in previous studies. Hitherto, there is a general lack of data on present levels of radioactivity in pulp mill liquors apart from the few mills studied by Nilsson (1992); Ravila and Holm (1992); Manjón et al. (1996); Krosshavn et al. (1997). A survey was therefore initiated to describe and compare the present activity levels in pulp mill liquors from various mill locations in Sweden. The 137Cs activity in pulp mill liquors were compared with the mill location and the deposition pattern of the Chernobyl fallout and nuclear weapons fallout. The large input of wood (approx. 2500 m3 day-1) to an average Nordic Kraft mill and the relatively long-term retention time for radiocesium in the Kraft mill recovery cycle enables representative sampling of substances directly related to the activity concentration in wood.

Cesium Radioisotopes↗

Role of cysteine and glutathione in signal transduction, immunopathology and cachexia.

Abnormally low plasma cystine levels have been found in the late asymptomatic stage of HIV infection and several other diseases associated with progressive loss of skeletal muscle mass. The phenomenon is commonly associated with a low NK cell activity, skeletal muscle wasting or muscle fatigue and increased rates of urea production. In its extreme form, the negative nitrogen balance leads to overt cachexia and is associated with severe debilitation and psychological stress. The low NK cell activity is in most cases not life-threatening but may be disasterous in HIV infection, because it may compromise the initially stable balance between immune system and virus and trigger disease progression. This review summarizes briefly (i) the role of cysteine in the physiological regulation of body cell mass and the development of skeletal muscle wasting, and (ii) the role of glutathione in the immune system.

Animals↗

The prognostic value of the QT interval and QT interval dispersion in all-cause and cardiac mortality and morbidity in a population of Danish citizens.

AIMS: To evaluate the prognostic value of the QT interval and QT interval dispersion in total and in cardiovascular mortality, as well as in cardiac morbidity, in a general population. METHODS AND RESULTS: The QT interval was measured in all leads from a standard 12-lead ECG in a random sample of 1658 women and 1797 men aged 30-60 years. QT interval dispersion was calculated from the maximal difference between QT intervals in any two leads. All cause mortality over 13 years, and cardiovascular mortality as well as cardiac morbidity over 11 years, were the main outcome parameters. Subjects with a prolonged QT interval (430 ms or more) or prolonged QT interval dispersion (80 ms or more) were at higher risk of cardiovascular death and cardiac morbidity than subjects whose QT interval was less than 360 ms, or whose QT interval dispersion was less than 30 ms. Cardiovascular death relative risk ratios, adjusted for age, gender, myocardial infarct, angina pectoris, diabetes mellitus, arterial hypertension, smoking habits, serum cholesterol level, and heart rate were 2.9 for the QT interval (95% confidence interval 1.1-7.8) and 4.4 for QT interval dispersion (95% confidence interval 1.0-19-1). Fatal and non-fatal cardiac morbidity relative risk ratios were similar, at 2.7 (95% confidence interval 1.4-5.5) for the QT interval and 2.2 (95% confidence interval 1.1-4.0) for QT interval dispersion. CONCLUSION: Prolongation of the QT interval and QT interval dispersion independently affected the prognosis of cardiovascular mortality and cardiac fatal and non-fatal morbidity in a general population over 11 years.

Adult↗

Linkage between postabsorptive amino acid release and glutamate uptake in skeletal muscle tissue of healthy young subjects, cancer patients, and the elderly.

Several diseases of varying etiology that are commonly associated with the loss of skeletal muscle mass were found to be associated with a decrease in muscular glutamate and glutathione levels and in glutamate uptake in the postabsorptive state. In view of the Na+ dependency and insulin responsiveness of glutamate transport we studied the postabsorptive glutamate exchange in more detail. Our study demonstrates a linkage between glutamate uptake and the export of other amino acids, suggesting that protein catabolism and the resulting coexport of amino acids plus Na+ substitute for insulin as a driving force for the Na+ gradient in the postabsorptive state. The regression function of the correlation between relative glutamate exchange and cumulative amino acid exchange in cancer patients was lower than that in non-tumor-bearing subjects, suggesting that cancer patients must release more amino acids to achieve the same glutamate uptake. In addition, cancer patients had a lower average cumulative amino acid exchange rate than non-tumor-bearing subjects, suggesting that the abnormally low relative glutamate exchange capacity of cancer patients results mainly from inadequate postabsorptive protein catabolism in the skeletal muscle tissue. Both cancer patients and non-tumor-bearing elderly subjects had higher arterial glutamate levels and alanine release than young subjects, indicative of a substantial glycolytic activity in the skeletal muscle. However, elderly non-tumor-bearing subjects showed, in contrast to cancer patients, in the postabsorptive state a stronger cumulative amino acid release and postabsorptive glutamate uptake than healthy young subjects. These changes are discussed in view of the age-related loss of skeletal muscle mass.

Adult↗

Cystine levels, cystine flux, and protein catabolism in cancer cachexia, HIV/SIV infection, and senescence.

Patients with skeletal muscle catabolism (cachexia) fail to conserve the skeletal muscle protein and release large amounts of nitrogen as urea. Previous studies suggest that the threshold for the conversion of amino acids into other forms of chemical energy and the concomitant production of urea are regulated by the plasma cystine level and hepatic cysteine catabolism. Studies of plasma amino acid exchange rates in the lower extremities now show that healthy young subjects regulate their plasma cystine level in a process that may be described as controlled constructive catabolism. The term controlled describes the fact that the release of cystine and other amino acids from the peripheral tissue is negatively correlated with (certain) plasma amino acid levels. The term constructive describes the fact that the release of cystine is correlated with an increase of the plasma cystine level. The regulation of the plasma cystine level is disturbed in conditions with progressive skeletal muscle catabolism including cancer, HIV infection, and old age. These conditions show also a low plasma glutamine:cystine ratio indicative of an impaired hepatic cystine catabolism. In HIV+ patients and SIV-infected macaques, a decrease of the plasma cystine level was found to coincide with the decrease of CD4+ T cells.

Adipose Tissue↗

Role of cysteine and glutathione in HIV infection and other diseases associated with muscle wasting and immunological dysfunction.

The combination of abnormally low plasma cystine and glutamine levels, low natural killer (NK) cell activity, skeletal muscle wasting or muscle fatigue, and increased rates of urea production defines a complex of abnormalities that is tentatively called "low CG syndrome." These symptoms are found in patients with HIV infection, cancer, major injuries, sepsis, Crohn's disease, ulcerative colitis, chronic fatigue syndrome, and to some extent in overtrained athletes. The coincidence of these symptoms in diseases of different etiological origin suggests a causal relationship. The low NK cell activity in most cases is not life-threatening, but may be disastrous in HIV infection because it may compromise the initially stable balance between the immune system and virus, and trigger disease progression. This hypothesis is supported by the coincidence observed between the decrease of CD4+ T cells and a decrease in the plasma cystine level. In addition, recent studies revealed important clues about the role of cysteine and glutathione in the development of skeletal muscle wasting. Evidence suggests that 1) the cystine level is regulated primarily by the normal postabsorptive skeletal muscle protein catabolism, 2) the cystine level itself is a physiological regulator of nitrogen balance and body cell mass, 3) the cyst(e)ine-mediated regulatory circuit is compromised in various catabolic conditions, including old age, and 4) cysteine supplementation may be a useful therapy if combined with disease-specific treatments such as antiviral therapy in HIV infection.

Animals↗

Diagnostic studies of abortion in Danish dairy herds.

Diagnostic findings in 218 aborted bovine foetuses are reported. The materials were examined in a matched case-control study of 69 Danish dairy herds with a sudden increase in the number of abortions and a corresponding 69 control herds. Foetuses aborted during the subsequent 6-month period were examined to identify the cause of abortion if possible. A total of 186 specimens were submitted from case herds and 32 from control herds. A likely cause of abortion was diagnosed in 73 foetuses. The most common cause was bovine viral diarrhoea virus (BVDV: 13%) followed by Neospora caninum infection (10%), mycosis (5%) and Bacillus licheniformis infection (4%). Foetal and/or placental lesions were found in a further 27 cases. Only BVDV infection and neosporosis were diagnosed in more than one foetus per herd and only protozoal associated abortions occurred significantly more frequently in the case, rather than in the control, herds.

Abortion, Septic↗

[Transjugular intrahepatic portasystemic shunt. A new therapeutic method in portal hypertension].

Over the last three years, 53 patients underwent transjugular portosystemic shunting (TIPS). 49 patients were treated successfully (92.5%). Procedure-related morbidity (intention to treat) was seen in 11 patients (20.8%): encephalopathy (n = 5), sepsis (n = 3), right heart failure (n = 2) and progressive liver failure (n = 1). 30-day mortality rate was 13.2% (7/53); five of these patients were in stage Child-Pugh C, one patient in stage B, and one patient had a known coronary heart disease. 30-day rebleeding rate was 6.1% (3/49), but all these patients could be retreated successfully by radiological methods (PTA, embolisation, thrombolysis). Angiographic follow-up (mean six months) of 35 patients detected 30 (85.7%) haemodynamic relevant obstructions (stenosis of stent: n = 4, stenosis of hepatic vein: n = 15, stenosis of stent and hepatic vein: n = 5, occlusion of TIPS-shunt: n = 6). Secondary patency rate following percutaneous reintervention was 91.3%. All rebleedings in the follow-up (n = 7) were treated successfully by TIPS-revision. Five out of 12 patients (41.7%) with refractory ascites were treated successfully by TIPS (complete resolution of ascites after three months: n = 4, significant reduction of ascites: n = 1). We conclude that transjugular portosystemic shunt is an effective way of treating portal hypertension, but there is a need to develop methods to prevent the high incidence of shunt stenosis.

Adult↗

Elevated venous glutamate levels in (pre)catabolic conditions result at least partly from a decreased glutamate transport activity.

Abnormally high postabsorptive venous plasma glutamate levels have been reported for several diseases that are associated with a loss of body cell mass including cancer, human/simian immunodeficiency virus infection, and amyotrophic lateral sclerosis. Studies on exchange rates in well-nourished cancer patients now show that high venous plasma glutamate levels may serve as a bona fide indicator for a decreased uptake of glutamate by the peripheral muscle tissue in the postabsorptive period and may be indicative for a precachectic state. High glutamate levels are also moderately correlated with a decreased uptake of glucose and ketone bodies. Relatively high venous glutamate levels have also been found in non-insulin-dependent diabetes mellitus and to some extent also in the cubital vein of normal elderly subjects, i.e., in conditions commonly associated with a decreased glucose tolerance and progressive loss of body cell mass.

ATP-Binding Cassette Transporters↗