Biomedical subjects

A Danielsson

Publications and source records attributed to A Danielsson.

At least 37 records · Page 2Linked to original sources

PubMed2000

Muscle and tendon stiffness in patients with upper motor neuron lesion following a stroke.

The objective of this study was to investigate muscle and tendon stiffness in the triceps surae muscles in patients who had previously had a stroke. The participants were 12 men showing slight to moderate degrees of muscle tonus in the affected leg. All patients showed minimal or no overt clinical motor symptoms, and all walked without mechanical aid. Muscle strengths in isometric and isokinetic activities were measured, as was passive resistance during plantarflexion in each leg. Walking speed was also measured. Evaluations of physical performance and muscle tone were made. Muscle and tendon stiffness was calculated from measurements whilst passively stretching during electrical stimulation, separately for each leg. Muscle strength was significantly higher in the non-affected than in the affected leg. Muscle stiffness was significantly higher in the affected leg than in the non-affected leg. Tendon stiffness was significantly higher in the non-affected than in the affected leg. The higher muscle stiffness in the affected leg might enhance the possibility for storing elastic energy during preactivation. Lower tendon stiffness in the affected leg might reduce the development of fatigue in movements at low velocities.

Adult↗

PubMed2000

Allopurinol in addition to 5-aminosalicylic acid based drugs for the maintenance treatment of ulcerative colitis.

BACKGROUND: To investigate the value of combined treatment with allopurinol and 5-aminosalicylic (5-ASA) based drugs as maintenance treatment for ulcerative colitis (UC). METHODS: 199 patients with UC in remission but with active disease during the preceding 3 years were included. Allopurinol 100 mg twice daily or placebo was added to the 5-ASA based maintenance treatment. Clinical and endoscopic follow up was performed after 1, 6 and 12 months. RESULTS: Intention-to-treat analysis after 6 and 12 months showed similar results in both groups. A log-rank test showed that 77% in the allopurinol compared to 59% in the placebo group were still in remission after 6 months (P=0.0083) and 62% and 53% after 12 months, respectively (P=0.0936). This was mainly due to a higher than expected number of relapses during the first 3 months in the placebo group. After the first 3 months, the rate of relapse in each group was similar. CONCLUSIONS: It appears possible that allopurinol in combination with 5-ASA is better than 5-ASA alone for a 6-month, but not a 12-month period. This has to be verified in further dose-ranging studies.

Adult↗

PubMed2000

Neuroendocrine changes in colon of mice with a disrupted IL-2 gene.

Neuroendocrine peptides have a variety of physiological functions in the gastrointestinal tract. This study was carried out to investigate the impact of IL-2 deficiency on the neuroendocrine system in normal colon, and the neuroendocrine changes during colonic inflammation. Mice with homozygous disrupted IL-2 gene (IL-2-/-) spontaneously developed a bowel disease with similarities to human ulcerative colitis. Different types of colonic endocrine cells and myenteric nerves were analysed in the IL-2-/- mice using immunomorphometry. The neuropeptide contents in the colonic tissues were determined by radioimmunoassay. Age-matched healthy IL-2+/- and IL-2+/+ mice served as controls and the colonic IL-2 levels were compared between these two groups of mice by ELISA. Our data showed that less than half the amount of IL-2 was synthesized in the colon of IL-2+/- mice compared with the IL-2+/+ wild-type mice. Two major differences in the neuroendocrine colon were found between the mice with an intact and disrupted IL-2 gene. One was age-related. The frequencies of various endocrine cells and myenteric nerves increased with age in the IL-2+/+ mice. However, no such increases were seen in the mice with a disrupted IL-2 gene. Instead, the volume densities of enteroglucagon, serotonin cells and substance P (SP), vasoactive intestinal polypeptide (VIP) and total myenteric nerves were lower in the older IL-2+/- and IL-2-/- mice compared with the wild type. The other was disease-related. Polypeptide YY (PYY) cells and tissue levels of PYY, SP and VIP were significantly decreased in the IL-2-/- mice during the course of bowel inflammation compared with the healthy IL-2+/- and IL-2+/+ controls. These findings indicate that colonic neuroendocrine alterations did occur in the mice with a disrupted IL-2 gene and diminished local IL-2 level, suggesting a role of IL-2 in the regulation of the neuroendocrine system and a prevalent interaction between the immune and neuroendocrine systems in normal colon. On the other hand, there were some changes that seemed to correlate with the bowel inflammatory process. They might be associated with the impaired function in inflamed gut and contribute to the development and/or prolongation of disease.

Animals↗

PubMed2000

Primary biliary cirrhosis: survival of a cohort followed for 10 years.

OBJECTIVES: To study the natural course of primary biliary cirrhosis (PBC) in order to be able to design accurate clinical pharmacological studies and evaluate the need for liver transplantation. DESIGN: A cohort of 86 patients with PBC living in northern Sweden was followed for a 10-year period during 1983-93. No patients received therapy with ursodeoxy cholic acid or other drugs during the follow-up period. METHOD: At start all patients were investigated personally by the authors. At follow-up medical notes were scrutinized and special questionnaires to the current responsible physician were applied. Endpoints were the time of dropout, liver transplantation, death or end of the study period. RESULTS: At follow-up data were available for 84 patients (97%). During the study period 34 patients died, of whom 28 were symptomatic; 15 deaths had no direct connection to PBC. Nineteen deaths were related to PBC of whom two were asymptomatic, the most common cause being end-stage liver disease with liver coma. During the study period in all eight patients were subjected to liver transplantation. CONCLUSIONS: The survival rate of the 32 asymptomatic PBC patients at the start of the study was the same as a sex- and age-matched standard background population. Those patients with symptomatic PBC from the beginning of study had a survival rate at 10 years of 50%, and the most ominous sign was a bilirubin greater than 35 micromol L(-1) . Liver transplantation was performed in almost 10% in this cohort until 1993. Since then, the indications and referral practice for liver transplantation has changed and is now higher.

Adult↗

PubMed2000

Oxygen consumption during treadmill walking with and without body weight support in patients with hemiparesis after stroke and in healthy subjects.

OBJECTIVE: To compare oxygen consumption during walking with body weight support (BWS) with oxygen consumption during unsupported treadmill walking. DESIGN: Patient and reference group. Comparisons between two walking conditions within each group. SETTING: Research laboratory of a university hospital. PARTICIPANTS: Nonrandom convenience sample of 9 hemiparetic and 9 healthy subjects, mean age of 56 and 57 years, respectively. INTERVENTIONS: The subjects walked on a treadmill with 0% and 30% BWS at their self-selected and maximum walking speeds. The trials were performed twice. MAIN OUTCOME MEASURES: Ventilatory oxygen uptake (VO2) and heart rate were measured by computerized breath-by-breath analysis and electrocardiography. RESULTS: VO2 was lower during walking with 30% BWS than during unsupported walking. At self-selected speed the Wilcoxon's signed rank p values were <.01 for both patients and reference group; at maximum velocity, p values were p < .02 for the patients and p < .05 for the reference group. Patients' heart rates were lower when they walked with 30% BWS than at 0% BWS, at both self-selected and maximum walking speeds (p < .05 and p < .02, respectively). CONCLUSIONS: The 30% body weight supported condition requires less oxygen consumption than full weight bearing. Treadmill training with BWS can be tolerated by patients with cardiovascular problems.

Body Weight↗

PubMed2000

Outcome of gastrointestinal complications after liver transplantation for familial amyloidotic polyneuropathy.

BACKGROUND: Gastrointestinal disturbances are important prognostic factors for mortality and morbidity after liver transplantation for familial amyloidotic polyneuropathy (FAP). However, the impact of liver transplantation on malabsorption and bacterial small-bowel contamination has not been evaluated. METHODS: Twenty-three FAP patients were available for the study. They were examined for gastrointestinal disturbances as a part of the evaluation for liver transplantation for FAP. Bile acid malabsorption was diagnosed with the [75Se]-homocholic acid taurate (SeHCAT) test; fat malabsorption by measuring faecal fat excretion; and bacterial small-bowel contamination with the hydrogen breath test (HBT). RESULTS: No significant improvement of malabsorption test results were noted from the pre-transplant evaluation 8 months (range, 2-20 months) before transplantation to the post-transplant evaluation performed a median of 20 months (range, 9-62 months) after the procedure. The SeHCAT test result became abnormal in two patients and normal in one, and changes in the test correlated with the time the patients were waiting for transplantation. Faecal fat excretion after transplantation correlated with duration of the disease and with fat excretion before transplantation. A significantly increased fat excretion was noted at the post-transplant evaluation. A change in HBT result was noted in only one patient, in whom the test result became normal; pre-transplant values correlated with those obtained after transplantation. CONCLUSION: For most FAP patients no improvement in gastrointestinal function was found after transplantation. The finding underlines the importance of an early transplantation before the patients have developed gastrointestinal dysfunction.

Adult↗

PubMed2000

Characterisation of mucosal lymphoid aggregates in ulcerative colitis: immune cell phenotype and TcR-gammadelta expression.

BACKGROUND AND AIMS: A histopathological feature considered indicative of ulcerative colitis (UC) is the so-called basal lymphoid aggregates. Their relevance in the pathogenesis of UC is, however, unknown. We have performed a comprehensive analysis of the immune cells in these aggregates most likely corresponding to the lymphoid follicular hyperplasia also described in other colitides. METHODS: Resection specimens of UC and normal colon were analysed by immunomorphometry, immunoflow cytometry, and immunoelectron microscopy, using a large panel of monoclonal antibodies. RESULTS: (1) In all cases of UC, colonic lamina propria contained numerous basal aggregates composed of lymphocytes, follicular dendritic cells, and CD80/B7.1 positive dendritic cells. (2) CD4(+)CD28(-) alphabeta T cells and B cells were the dominant cell types in the aggregates. (3) The aggregates contained a large fraction of cells that are normally associated with the epithelium: that is, gammadelta T cells (11 (7)%) and alpha(E)beta(7)(+) cells (26 (13)%). The gammadelta T cells used Vdelta1 and were CD4(-)CD8(-). Immunoelectron microscopy analysis demonstrated TcR-gammadelta internalisation and surface downregulation, indicating that the gammadelta T cells were activated and engaged in the disease process. (4) One third of cells in the aggregates expressed the antiapoptotic protein bcl-2. CONCLUSIONS: Basal lymphoid aggregates in UC colon are a consequence of anomalous lymphoid follicular hyperplasia, characterised by abnormal follicular architecture and unusual cell immunophenotypes. The aggregates increase in size with severity of disease, and contain large numbers of apoptosis resistant cells and activated mucosal gammadelta T cells. The latter probably colonise the aggregates as an immunoregulatory response to stressed lymphocytes or as a substitute for defective T helper cells in B cell activation. gammadelta T cells in the aggregates may be characteristic of UC.

Adult↗

PubMed1999

Studies on the active site of deacetoxycephalosporin C synthase.

The Fe(II) and 2-oxoglutarate-dependent dioxygenase deacetoxycephalosporin C synthase (DAOCS) from Streptomyces clavuligerus was expressed at ca 25 % of total soluble protein in Escherichia coli and purified by an efficient large-scale procedure. Purified protein catalysed the conversions of penicillins N and G to deacetoxycephems. Gel filtration and light scattering studies showed that in solution monomeric apo-DAOCS is in equilibrium with a trimeric form from which it crystallizes. DAOCS was crystallized +/-Fe(II) and/or 2-oxoglutarate using the hanging drop method. Crystals diffracted to beyond 1.3 A resolution and belonged to the R3 space group (unit cell dimensions: a=b=106.4 A, c=71.2 A; alpha=beta=90 degrees, gamma=120 degrees (in the hexagonal setting)). Despite the structure revealing that Met180 is located close to the reactive oxidizing centre of DAOCS, there was no functional difference between the wild-type and selenomethionine derivatives. X-ray absorption spectroscopic studies in solution generally supported the iron co-ordination chemistry defined by the crystal structures. The Fe K-edge positions of 7121.2 and 7121.4 eV for DAOCS alone and with 2-oxoglutarate were both consistent with the presence of Fe(II). For Fe(II) in DAOCS the best fit to the Extended X-ray Absorption Fine Structure (EXAFS) associated with the Fe K-edge was found with two His imidazolate groups at 1.96 A, three nitrogen or oxygen atoms at 2.11 A and one other light atom at 2.04 A. For the Fe(II) in the DAOCS-2-oxoglutarate complex the EXAFS spectrum was successfully interpreted by backscattering from two His residues (Fe-N at 1.99 A), a bidentate O,O-co-ordinated 2-oxoglutarate with Fe-O distances of 2.08 A, another O atom at 2.08 A and one at 2.03 A. Analysis of the X-ray crystal structural data suggests a binding mode for the penicillin N substrate and possible roles for the C terminus in stabilising the enzyme and ordering the reaction mechanism.

Binding Sites↗

PubMed1999

A 3-year prospective study on serum tumor markers used for detecting cholangiocarcinoma in patients with primary sclerosing cholangitis.

BACKGROUND/AIMS: Patients with primary sclerosing cholangitis (PSC) have an increased risk of developing cholangiocarcinoma (CC), which is notoriously difficult to diagnose since these patients may have increased levels of bilirubin due to benign strictures. To evaluate the validity of different tumor markers as an aid to diagnosing CC, we have carried out serial serum tumor marker analyses in patients with PSC who have been followed for several years. METHODS: Seventy-five patients with PSC, without any clinical signs of CC were included in the study. They were investigated every 6th months for 3 years, with extensive liver function tests and four tumor serum markers CEA, CA 19-9, CA 50 and CA 242. The patients were then followed for 5 years to exclude the possibility that CC remained unrecognized. RESULTS: Of the 75 patients, two (3%) developed CC during the 3-year period. One of these had normal levels, and one had significantly increased levels of the tumor markers. In the follow-up part of the study two further patients died from CC and one from hepatocellular carcinoma, 3 and 4 years after the 3-year study, respectively. Twenty-one patients had an increase of one of the markers on at least one occasion. Five patients had a transient increase of more than double the upper normal limit of the tumor markers on more than one occasion. There was a good correlation between CA 19-9, CA 50 and CA 242, but not with CEA. Fourteen of the 75 patients had periods of increased bilirubin levels, but none of these showed increased tumor markers. CONCLUSIONS: The serum tumor markers CEA, CA 19-9, CA 50 and CA 242 are of limited value for the detection of CC in patients with PSC because of low specificity. However, we found no falsely increased values in patients with hyperbilirubinemia.

Adult↗

PubMed1999

Changes in intestinal endocrine cells in the mouse after unilateral cervical vagotomy.

The effect of right or left unilateral cervical vagotomy on the intestinal endocrine cells was studied in 23 mice at 2 and 8 weeks after operation, respectively. The results were compared with that from 10 sham operated mice. Various types of endocrine cells in duodenum and proximal colon were detected by immunohistochemistry and quantified by computerized image analysis. In mouse duodenum, chromogranin-, CCK/gastrin-, GIP- and somatostatin-cells were significantly decreased at 2 weeks after right vagotomy, but returned to the control levels at 8 weeks. Serotonin-cells were reduced at both 2 and 8 weeks after right vagotomy. The amount of the duodenal endocrine cells did not change after left vagotomy with the exception of secretin-cells, which were diminished at 8 weeks after both right and left vagotomy. In the proximal colon, chromogranin-cells were also decreased at 2 weeks after right vagotomy. Serotonin-cells were reduced at 8 weeks after left vagotomy but not right vagotomy. There was no significant difference between the unilaterally vagotomized and the sham operated mice with regard to PYY- and glucagon-cells. It was concluded that vagotomy affected the intestinal endocrine cells in mouse. The influence was more pronounced in the small intestine than the proximal colon. The right vagus nerves seemed to exert more effect on the intestinal endocrine cells than the left ones.

Animals↗

PubMed1999

Effects of unilateral cervical vagotomy on antral endocrine cells in mouse.

The present study was carried out to investigate the effect of unilateral cervical vagotomy on the antral endocrine cells in mouse. Fifty-four mice were randomly divided into three groups, 18 in each, for left or right cervical vagotomy, or sham operation as controls. The animals were sacrificed 2, 4, and 8 weeks after the operation, respectively. Chromogranin-, gastrin/CCK-, serotonin-, and somatostatin-cells were detected by immunohistochemistry and quantitated by computerised image analysis. The results showed that the number of chromogranin-cells was decreased in both left and right vagotomized mice after 4 weeks and remained at the same level after 8 weeks. The numbers of gastrin-, serotonin- and somatostatin-cells did not change after right vagotomy. However, the numbers of gastrin- and somatostatin-cells were decreased after left vagotomy, whereas no change was found in serotonin-cells. Endocrine cells with vacuolated cytoplasm and pyknotic nuclei were also observed during the course of time. The alteration in the antral endocrine cells observed in this study seemed to be dynamic and depended on the observation time after the operation as well as the denervated branches of the vagus nerve. This may explain, at least partially the contradictory results obtained earlier by different investigators.

Animals↗

PubMed1999

Toxicity of hepatotoxins: new insights into mechanisms and therapy.

Liver injury caused by hepatotoxins, such as carbon tetrachloride (CCl4), ethanol, and acetaminophen (APAP), is characterised by varying degrees of hepatocyte degeneration and cell death via either apoptosis or necrosis. The generation of reactive intermediate metabolites from the metabolism of hepatotoxins, and the occurrence of reactive oxygen species (ROS) during the inflammatory reaction account for a variety of pathophysiologic pathways leading to cell death, such as covalent binding, disordered cytosolic calcium homeostasis, glutathione (GSH) depletion, onset of mitochondrial permeability transition (MPT) and associated lipid peroxidation. The metabolism of hepatotoxins by cytochrome P-450 enzyme subtypes is a key step of the intoxication; therefore, enzyme inhibitors are shown to minimise the hepatotoxin-associated liver damage. Understanding the function of transcription factors, such as nuclear factor kappaB (NF-kappaB) in acute liver injury, may provide some answers as to the molecular mechanisms of toxic insults. Moreover, substantial evidence exists that MPT is involved in ROS-associated hepatocellular injury and new findings offer a novel therapeutic approach to attenuate cell damage by blocking the onset of MPT. Thus, oxidant stress and lipid peroxidation are crucial elements leading to hepatotoxin-associated liver injury. In addition to specific treatment for a given hepatotoxin, the general strategy for prevention and treatment of the damage includes reducing the production of reactive metabolites of the hepatotoxins, using anti-oxidative agents, and selectively targeting therapeutics to Kupffer cells or hepatocytes for on-going processes, which play a role in mediating a second phase of the injury.

Journal Article↗

PubMed1999

Intestinal endocrine cells in myotonic dystrophy: an immunocytochemical and computed image analytical study.

OBJECTIVES: To study intestinal endocrine cell types in patients suffering from myotonic dystrophy (MD) and diarrhoea. DESIGN: Comparative study between MD patients and matched controls. SETTING: Departments of Medicine, Central Hospital, Boden, and University Hospital, Umeå, Sweden. SUBJECTS: Ten patients with MD (four males and six females) and suffering from diarrhoea. Ten healthy volunteers served as controls for the duodenal study and 13 patients under investigation for rectal bleeding and with endoscopically normal mucosa were controls for the rectal study. MEASUREMENTS: The duodenal and rectal endocrine cell types were identified by immunohistochemical investigation and quantified by computed image analysis. RESULTS: The total endocrine cell area in the duodenum as demonstrated by chromogranin A-immunoreactivity was significantly increased in MD as compared with the controls (126 +/- 58 vs. 48 +/- 22 x 10(3) microns 2 mm-2 in crypts and 230 +/- 183 vs. 28 +/- 22 in villi, respectively, P < 0.01). The increase included all types of endocrine cells studied, namely those positive for serotonin, cholecystokinin (CCK)/gastrin, secretin, gastric inhibitory peptide (GIP) and somatostatin. In the rectum, the total endocrine cell area as determined by chromogranin A-immunoreactivity was also significantly increased, but there was no statistical difference between the controls and patients with respect to the area of serotonin-, peptide YY (PYY)-, pancreatic polypeptide (PP)- or somatostatin-immunoreactive cells. CONCLUSIONS: The increase in endocrine cell area indicates a disturbed endocrine regulation of the gastrointestinal tract that may contribute to the development of gastrointestinal symptoms encountered in MD patients.

Adult↗

PubMed1999

Intestinal endocrine cells in myotonic dystrophy: an immunocytochemical and computed image analytical study.

OBJECTIVES: To study intestinal endocrine cell types in patients suffering from myotonic dystrophy (MD) and diarrhoea. DESIGN: Comparative study between MD patients and matched controls. SETTING: Departments of Medicine, Central Hospital, Boden, and University Hospital, Umeå, Sweden. SUBJECTS: Ten patients with MD (four males and six females) and suffering from diarrhoea. Ten healthy volunteers served as controls for the duodenal study and 13 patients under investigation for rectal bleeding and with endoscopically normal mucosa were controls for the rectal study. MEASUREMENTS: The duodenal and rectal endocrine cell types were identified by immunohistochemical investigation and quantified by computed image analysis. RESULTS: The total endocrine cell area in the duodenum as demonstrated by chromogranin A-immunoreactivity was significantly increased in MD as compared with the controls (126 +/- 58 vs. 48 +/- 22 x 10(3) micron 2 mm-2 in crypts and 230 +/- 183 vs. 28 +/- 22 in villi, respectively, P < 0.01). The increase included all types of endocrine cells studied, namely those positive for serotonin, cholecystokinin (CCK)/gastrin, secretin, gastric inhibitory peptide (GIP) and somatostatin. In the rectum, the total endocrine cell area as determined by chromogranin A-immunoreactivity was also significantly increased, but there was no statistical difference between the controls and patients with respect to the area of serotonin-, peptide YY (PYY)-, pancreatic polypeptide (PP)- or somatostatin-immunoreactive cells. CONCLUSIONS: The increase in endocrine cell area indicates a disturbed endocrine regulation of the gastrointestinal tract that may contribute to the development of gastrointestinal symptoms encountered in MD patients.

Adult↗

PubMed1998

S-phase fraction related to prognosis in localised prostate cancer. No specific significance of chromosome 7 gain or deletion of 7q31.1.

A flow-cytometric (FCM) and fluorescence in situ hybridization (FISH) study was performed in 153 patients with clinically localised prostate cancer (PC) to evaluate retrospectively the prognostic significance of DNA ploidy, S-phase fraction (SPF) and chromosome 7 copy number. Deletions in 7q31.1 were analysed in a subset of 26 tumours. The mean follow-up time was 6 years (range 4-16 years). Twelve cases of benign prostatic hyperplasia (BPH) were studied as a control. Chromosome 7 enumeration and deletion studies were conducted using the alpha-satellite D7Z1 probe and a cosmid probe specific for the marker D7S522 on 7q31.1. Higher SPF was associated with shorter overall survival and shorter time to local progression and metastasis. Near diploid (DNA index 1.05-1.20) cases had a lower frequency of metastases and lower Gleason scores than aneuploid cases. Increased absolute chromosome 7 copy number (centromere count) was associated with higher Gleason score, higher SPF and shorter local progression-free and prostate cancer survival. Absolute chromosome 7 copy number was concordant with FCM DNA ploidy in the majority (75%) of cases. Relative gain or loss of chromosome 7 (centromere counts compared to ploidy) was infrequent, and no correlation was found with clinical parameters. Deletions in 7q31.1 were infrequent. Our results indicate that in localised PC (i) SPF is a prognostic factor, (ii) absolute chromosome 7 copy number is concordant with the ploidy status of the tumour (relative gain or loss of chromosome 7 is infrequent and has no independent prognostic value) and (iii) the frequency of deletions in 7q31.1 is low and not correlated with clinical outcome.

Adenocarcinoma↗

PubMed1998

[Treatment response in chronic hepatitis C. Content of virus in serum is decisive for the outcome].

The article consists in a brief review of pre-treatment evaluation and antiviral treatment of chronic hepatitis C (HCV) infection. Patients with viraemia (i.e. HCV RNA seropositive with the PCR technique) should be evaluated historically if they lack contraindications for interferon alpha (IFN-alpha) treatment. Patients with depression, autoimmune and thyroid disorders, decompensated cirrhosis, or solid organ transplants, are ineligible for-IFN-alpha treatment. If the histological evaluation shows moderate to severe chronic hepatitis, and the HCV RNA level is < 3 million Eq/mL serum as measured by bDNA, naive (i.e. formerly untreated) patients should be given an initial 12-week course of IFN-alpha to evaluate treatment response. Those who become HCV-negative should continue the treatment for 48 weeks to increase the likelihood of sustained virological response after treatment cessation. Treatment should be discontinued in the case of patients still HCV-positive at 12 weeks, as the chances of obtaining sustained response are remote. Patients with higher pre-treatment HCV RNA levels (> or = 3 million Eq/mL) and patients manifesting unsustained response to earlier IFN treatment should receive combination treatment with ribavirin and IFN-alpha, as treatment with IFN alone is associated with poor chances of sustained response. This treatment approach is associated with an estimated sustained response rate in naive patients of 40-50 per cent.

Antiviral Agents↗

PubMed1998

Low leptin gene expression and hyperleptinemia in chronic renal failure.

BACKGROUND: The ob gene product leptin is thought to be a key regulator of food intake and body weight. Patients having advanced chronic renal failure (CRF) have markedly higher serum leptin levels. It is not known whether the increase in leptin levels in CRF is caused by a decreased plasma clearance and/or increased production. METHODS: In the present study serum leptin levels and glomerular filtration rate (GFR) were measured in 219 patients having various degrees of renal failure. In addition, serum leptin levels, C-reactive protein (CRP), body composition (by dual-energy x-ray absorptiometry) and ob gene expression (by in situ hybridization histochemistry) were determined in 15 patients with advanced CRF. Seven of the patients were re-evaluated following 12 months of peritoneal dialysis (PD) treatment. RESULTS: Serum leptin levels correlated negatively to GFR (r = -0.26; P < 0.0001). The ob gene expression was significantly lower in patients with CRF than in healthy controls. A negative correlation between serum leptin levels and ob gene expression (r = -0.66; P < 0.05) was found in patients with CRP < 25 mg/liter. The ob gene expression (20.0 +/- 1.8 vs. 15.0 +/- 1.0 nCi/g; P < 0.05) was significantly higher in 5 patients with CRP > 25 mg/liter than in 10 patients with CRP < 25 mg/liter. Following 12 months of PD, the amount of body fat increased by 30% while the ob gene expression remained unchanged. CONCLUSION: The present study shows a correlation between serum leptin levels and GFR, and our results suggest that elevated leptin levels, due to a decreased plasma clearance, down-regulate the expression of the ob gene. We also found that an ongoing inflammation stimulates ob gene expression in patients with CRF. Therefore, it is suggested that the hyperleptinemia induced feedback inhibition of ob gene expression is overcome by inflammatory cytokines.

Adipose Tissue↗

PubMed1998

Factors predicting malnutrition in hemodialysis patients: a cross-sectional study.

Signs of protein-energy malnutrition are common in maintenance hemodialysis (HD) patients and are associated with increased morbidity and mortality. To evaluate the nutritional status and relationship between various parameters used for assessing malnutrition, we performed a cross-sectional study in 128 unselected patients treated with hemodialysis (HD) thrice weekly for at least two weeks. Global nutritional status was evaluated by the subjective global nutritional assessment (SGNA). Body weight, skinfold thicknesses converted into % body fat mass (BFM), mid-arm muscle circumference, hand-grip strength and several laboratory values, including serum albumin (SA1b), plasma insulin-like growth factor I (p-IGF-I), serum C-reactive protein (SCRP) and plasma free amino acids, were recorded. Dose of dialysis and protein equivalence of nitrogen appearance (nPNA) were evaluated by urea kinetic modeling. The patients were subdivided into three groups based on SGNA: group I, normal nutritional status (36%); group II, mild malnutrition (51%); and group III, moderate or (in 2 cases) severe malnutrition (13%). Clinical factors associated with malnutrition were: high age, presence of cardiovascular disease and diabetes mellitus. nPNA and Kt/V(urea) were similar in the three groups. However, when normalized to desirable body wt, both were lower in groups II and III than in group I. Anthropometric factors associated with malnutrition were low body wt, skinfold thickness, mid-arm muscle circumference (MAMC), and handgrip strength. Biochemical factors associated with malnutrition were low serum levels of albumin and creatinine and low plasma levels of insulin-like growth factor 1 (IGF-1) and branched-chain amino acids (isoleucine, leucine and valine). The serum albumin (SAlb) level was not only a predictor of nutritional status, but was independently influenced by age, sex and SCRP. Plasma IGF-1 levels also reflected the presence and severity of malnutrition and appeared to be more closely associated than SAlb with anthropometric and biochemical indices of somatic protein mass. Elevated SCRP (> 20 mg/liter), which mainly reflected the presence of infection/inflammation and was associated with hypoalbuminemia, was more common in malnourished patients than in patients with normal nutritional status, and also more common in elderly than in younger patients. Plasma amino acid levels, with the possible exception of the branched-chain amino acids (isoleucine, leucine, valine), seem to be poor predictors of nutritional status in hemodialysis patients.

Adult↗