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1.
Endoscopy ; 45(5): 357-61, 2013.
Article in English | MEDLINE | ID: mdl-23468194

ABSTRACT

BACKGROUND AND STUDY AIMS: The aim of this study was to investigate whether telemedicine can help to ensure high-quality endoscopic retrograde cholangiopancreatography (ERCP) in patients living in rural areas. The study was conducted by investigators from two centers: the Karolinska University Hospital, a high-volume center which provided the teleguided support, and the Visby District Hospital, a low-volume center. PATIENTS AND METHODS: From September 2010 to August 2011, 26 ERCP procedures performed at a district hospital were teleguided by an experienced endoscopist at the Karolinska University Hospital. To ensure patient data protection, all communication went through a network (Sjunet) that was separate from the Internet and open only to accredited users. The indications for ERCP were common bile duct stones (n = 12), malignant strictures (n = 12), and benign biliary strictures (n = 2). In 15 cases, this was the patient's first ERCP procedure. RESULTS: The common bile duct was successfully cannulated in all 26 teleguided procedures. The local endoscopist scored the teleguided support as crucial for the successful outcome in 8 /26 cases, as an important factor in 8, and as being of less importance in the remaining 10. In the eight cases where the teleguided support was judged to be crucial, six subsequent percutaneous transhepatic cholangiography procedures and two repeat ERCPs were avoided. The overall cannulation rate at the district hospital improved from 85 % to 99 % after teleguided support was introduced. No procedure-related complications occurred. CONCLUSION: Distant guidance of advanced ERCP procedures in a low-volume center, through teleguided support from a high-volume center, has the potential to improve the quality of care, as reflected in high cannulation rates and the ability to complete the scheduled interventions.


Subject(s)
Biliary Tract Diseases/surgery , Cholangiopancreatography, Endoscopic Retrograde/standards , Digestive System Neoplasms/complications , Hospitals, Low-Volume/standards , Rural Health Services/standards , Telemedicine , Adult , Aged , Aged, 80 and over , Ampulla of Vater , Attitude of Health Personnel , Biliary Tract Diseases/diagnostic imaging , Biliary Tract Diseases/etiology , Catheterization , Cholestasis/diagnostic imaging , Cholestasis/etiology , Cholestasis/surgery , Constriction, Pathologic/diagnostic imaging , Constriction, Pathologic/etiology , Constriction, Pathologic/surgery , Female , Gallstones/diagnostic imaging , Gallstones/surgery , Humans , Male , Middle Aged , Operative Time
2.
Eur Surg Res ; 45(3-4): 134-7, 2010.
Article in English | MEDLINE | ID: mdl-20924188

ABSTRACT

We investigated whether cells expressing hypoxia-inducible factor-1α (HIF-1α) are specially related to blood vessels in human pancreatic tumors. HIF-1α and blood vessels were stained in 7 pancreatic ductal adenocarcinomas (PDAC) and 3 nonmalignant tumors. HIF-1α(+) cells accounted for 37 ± 5% of the total PDAC cells and increased to 52 ± 4% in perivascular PDAC cells and to 67 ± 4% in PDAC cells found in intratumoral blood vessels. In nonmalignant tumors, 12 ± 3% of the total tumoral cells examined were HIF-1α(+), and HIF-1α(+) cells decreased to 2 ± 0.3% in perivascular cells examined in the tumors. In conclusion, HIF-1α(+) cells in PDAC and nonmalignant pancreatic tumors differ not only in their amounts but also in their relation to intratumoral blood vessels. HIF-1α(+) cells usually are adjacent to intratumoral blood vessels in PDAC tumors, but are farther away from the vessels in nonmalignant pancreatic tumors.


Subject(s)
Carcinoma, Pancreatic Ductal/blood supply , Carcinoma, Pancreatic Ductal/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Pancreatic Neoplasms/blood supply , Pancreatic Neoplasms/metabolism , Aged , Blood Vessels/metabolism , Blood Vessels/pathology , Carcinoma, Pancreatic Ductal/pathology , Female , Humans , Immunohistochemistry , Male , Middle Aged , Pancreatic Neoplasms/pathology
3.
Br J Cancer ; 102(10): 1541-8, 2010 May 11.
Article in English | MEDLINE | ID: mdl-20407445

ABSTRACT

BACKGROUND: The regulatory gene pathways that accompany loss of adipose tissue in cancer cachexia are unknown and were explored using pangenomic transcriptome profiling. METHODS: Global gene expression profiles of abdominal subcutaneous adipose tissue were studied in gastrointestinal cancer patients with (n=13) or without (n=14) cachexia. RESULTS: Cachexia was accompanied by preferential loss of adipose tissue and decreased fat cell volume, but not number. Adipose tissue pathways regulating energy turnover were upregulated, whereas genes in pathways related to cell and tissue structure (cellular adhesion, extracellular matrix and actin cytoskeleton) were downregulated in cachectic patients. Transcriptional response elements for hepatic nuclear factor-4 (HNF4) were overrepresented in the promoters of extracellular matrix and adhesion molecule genes, and adipose HNF4 mRNA was downregulated in cachexia. CONCLUSIONS: Cancer cachexia is characterised by preferential loss of adipose tissue; muscle mass is less affected. Loss of adipose tissue is secondary to a decrease in adipocyte lipid content and associates with changes in the expression of genes that regulate energy turnover, cytoskeleton and extracellular matrix, which suggest high tissue remodelling. Changes in gene expression in cachexia are reciprocal to those observed in obesity, suggesting that regulation of fat mass at least partly corresponds to two sides of the same coin.


Subject(s)
Adipose Tissue/metabolism , Cachexia/genetics , Neoplasms/genetics , Signal Transduction/genetics , Weight Loss/genetics , Aged , Cachexia/etiology , Female , Gene Expression , Gene Expression Profiling , Gene Expression Regulation/genetics , Humans , Male , Neoplasms/complications , Neoplasms/metabolism , Obesity/genetics , Obesity/metabolism , Oligonucleotide Array Sequence Analysis , Reverse Transcriptase Polymerase Chain Reaction
4.
Palliat Med ; 23(6): 556-64, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19477887

ABSTRACT

In this study, patients' views and experiences of using home artificial nutrition, and factors associated with use of home parenteral nutrition (HPN) were investigated. Structured telephone interviews with 620 cancer patients enrolled in 21 palliative home care services were analysed. HPN was more common (11%) than home enteral tube feeding (HETF, 3%). Home artificial nutrition (including HPN and HETF) was usually introduced more than four months before death. Three of four HPN recipients also had oral food intake. HPN use was associated with eating difficulties, nausea/vomiting, and fatigue rather than gastrointestinal problems per se. HETF was generally used for patients with problems related to oesophagus and head and neck tumours. In conclusion the results suggest that, contrary to existing guidelines, HPN is used to supplement oral intake, and not only for patients with a non-functioning gastrointestinal tract.


Subject(s)
Home Care Services/organization & administration , Neoplasms/therapy , Palliative Care/organization & administration , Parenteral Nutrition, Home/standards , Adult , Aged , Aged, 80 and over , Enteral Nutrition/standards , Female , Home Care Services/standards , Humans , Logistic Models , Male , Middle Aged , Palliative Care/standards
5.
Support Care Cancer ; 17(2): 153-61, 2009 Feb.
Article in English | MEDLINE | ID: mdl-18528714

ABSTRACT

GOAL OF WORK: The aim of this study was to investigate the nutritional risk status and use of nutritional support among cancer patients enrolled in palliative home care services. Differences in the use of nutritional support in relation to nutritional, social and clinical factors, as well as survival were also investigated. PATIENTS AND METHODS: Structured telephone interviews were conducted with cancer patients enrolled in all 21 palliative home care services in the Stockholm region. An interview guide was designed to investigate topics related to the patient's nutritional situation. MAIN RESULTS: Interviews with 621 patients were analysed. Sixty-eight percent of the patients were scored as at nutritional risk according on a modified version of NRS-2002. Nutritional support was used by 55% of the patients, with oral nutritional supplements most common and 14% using artificial nutrition. Use of nutritional support was related to low BMI and severe weight loss and was more common in patients with shorter survival times. CONCLUSIONS: These findings demonstrate that nutritional support is used to treat already malnourished patients with shorter survival time, rather than to prevent malnutrition. A more structured approach to nutritional issues for patients in palliative phases, which considers life expectancy and psycho-social aspects of nutritional issues, could help identify potential candidates for nutritional support.


Subject(s)
Home Care Agencies , Nutrition Therapy , Palliative Care , Aged , Female , Humans , Interviews as Topic , Male , Middle Aged , Neoplasms , Nutrition Assessment , Risk Assessment
6.
Am J Transplant ; 8(2): 458-62, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18093267

ABSTRACT

A 7-year-old girl with severe hereditary pancreatitis underwent total pancreatectomy. A total of 160,000 islet equivalents (6400 islet/kg) were transplanted to the brachioradialis muscle of the right forearm. Her plasma C-peptide level was undetectable after pancreatectomy but increased to 1.37 ng/mL after 17 days; at this time point, her insulin requirement was 0.75 units of insulin/kg/day. At 5- and 27-months, her hemoglobin A1c (HbA1c) and insulin requirements were 4.5 and 5.3% and 0.3 and 0.18 units/kg/day, respectively. Basal and stimulated C-peptide levels were 0.67 +/- 0.07 and 3.36 +/- 1.37 ng/mL, respectively. Stimulated insulin levels were 30% higher in the islet-bearing arm compared to the contralateral arm after glucagon stimulation. After surgery and islet transplantation, the quality of life improved dramatically and she gained 8 kg of weight. In summary, a normal HbA1c, a low insulin requirement and the absence of recurrent hypoglycemia and the gradient of insulin between the arms indicate that the intramuscularly transplanted islets contribute to a long-term clinically significant metabolic control.


Subject(s)
Islets of Langerhans Transplantation/methods , Pancreatectomy , Pancreatitis/surgery , Transplantation, Autologous/methods , Child , Follow-Up Studies , Glycated Hemoglobin/analysis , Humans , Muscle, Skeletal , Pancreatitis/genetics , Time Factors , Treatment Outcome
7.
Diabetologia ; 51(2): 227-32, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18040664

ABSTRACT

Clinical islet transplantation is currently being explored as a treatment for persons with type 1 diabetes and hypoglycaemia unawareness. Although 'proof-of-principle' has been established in recent clinical studies, the procedure suffers from low efficacy. At the time of transplantation, the isolated islets are allowed to embolise the liver after injection in the portal vein, a procedure that is unique in the area of transplantation. A novel view on the engraftment of intraportally transplanted islets is presented that could explain the low efficacy of the procedure.


Subject(s)
Diabetes Mellitus, Type 1/surgery , Islets of Langerhans Transplantation/methods , Animals , Diabetes Mellitus, Type 1/immunology , Diabetes Mellitus, Type 1/pathology , Graft Survival/immunology , Humans , Immunity, Innate/immunology , Islets of Langerhans/immunology , Models, Biological
8.
Pancreatology ; 7(1): 37-44, 2007.
Article in English | MEDLINE | ID: mdl-17449964

ABSTRACT

BACKGROUND/AIMS: After pancreaticoduodenectomy (PD) patients may be deficient in essential micronutrients. This study was designed to determine if this is a consequence of surgery. METHODS: Long-term survivors (>6 months) of PD for peri-ampullary neoplasia and healthy controls (patients' spouse/partner) were enrolled in the study. Specific clinical parameters were recorded, serum micronutrient levels were measured and subjects completed 7-day food diaries. RESULTS: Thirty-seven patients were studied, 25 with paired controls. All were well nourished, as defined by body mass index and food diary analysis. Patients with paired controls were representative of all patients studied. Patients had raised transferrin (median 2.60 vs. 2.16 g/l, p = 0.001) and low ferritin levels (34.9 vs. 119.0 g/l, p < 0.001) indicating relative iron deficiency. Patients also demonstrated lower levels of the anti-oxidants selenium (0.77 vs. 0.93 micromol/l, p < 0.001) and vitamin E (23.2 vs. 35.7 micromol/l, p < 0.001) with 57% of patients having frank selenium deficiencies. Patients had lower levels of vitamin D than controls (15.7 vs. 19.6 micromol/l, p = 0.001) and 30% of patients had a raised parathyroid hormone level, suggesting compensatory mechanisms operate to maintain normocalcaemia. CONCLUSIONS: Long-term survivors of PD are relatively deficient in several micronutrients compared to non-operated controls taking the same diet. We recommend that micronutrient status should be regularly checked in these patients and treated where necessary.


Subject(s)
Micronutrients/deficiency , Pancreatic Neoplasms/surgery , Pancreaticoduodenectomy/adverse effects , Aged , Aged, 80 and over , Avitaminosis/etiology , Female , Humans , Male , Micronutrients/blood , Middle Aged , Survivors , Trace Elements/blood , Trace Elements/deficiency , Vitamins/blood
9.
Br J Cancer ; 93(11): 1310-5, 2005 Nov 28.
Article in English | MEDLINE | ID: mdl-16288300

ABSTRACT

We examined the associations of body mass index (BMI), waist circumference, a history of diabetes, and cigarette smoking with risk of pancreatic cancer among 37,147 women and 45,906 men followed up during 560,666 person-years in the Swedish Mammography Cohort and the Cohort of Swedish Men; 136 incident cases of pancreatic cancer were diagnosed. The multivariate rate ratio (RR) of pancreatic cancer for obese women and men (BMI > or =30 kg/m(2)) was 1.81 (95% CI: 1.04-3.15) compared to those with a BMI of 20-25 kg/m(2). For a difference of 20 cm (about two standard deviations) in waist circumference, the multivariate RRs were 1.32 (95% CI: 0.73-2.37) among women and 1.74 (95% CI: 1.00-3.01) among men. Pancreatic cancer risk was associated with history of diabetes (multivariate RR: 1.88; 95% CI: 1.09-3.26) and cigarette smoking (multivariate RR for current compared with never smokers: 3.06; 95% CI: 1.99-4.72). Current smokers of > or =40 pack-years had a five-fold elevated risk compared with never smokers. Risk among past smokers approached the RR for never smokers within 5-10 years following smoking cessation. Findings from this prospective study support positive relationships of overall obesity, abdominal adiposity, diabetes and smoking with risk of pancreatic cancer.


Subject(s)
Diabetes Complications , Obesity/complications , Pancreatic Neoplasms/epidemiology , Pancreatic Neoplasms/etiology , Smoking/adverse effects , Abdominal Fat , Adult , Aged , Aged, 80 and over , Body Mass Index , Cohort Studies , Female , Humans , Male , Middle Aged , Risk Factors , Sex Factors , Sweden/epidemiology
10.
Br J Surg ; 92(12): 1559-64, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16231283

ABSTRACT

BACKGROUND: The aim of this study was to investigate the occurrence of postoperative delirium (POD) in elderly patients undergoing major abdominal surgery and to identify factors associated with delirium in this population. METHODS: Data were collected prospectively from 51 patients aged 65 years or more. Delirium was diagnosed by the Confusion Assessment Method and from the medical records. The Mini Mental State Examination (MMSE) was used to identify cognitive impairment. RESULTS: POD occurred in 26 of 51 patients. Delirium lasted for 1-2 days in 14 patients (short POD group) and 3 days or more in 12 patients (long POD group). The latter patients had significantly greater intraoperative blood loss and intravenous fluid infusion, a higher rate of postoperative complications, a lower MMSE score on postoperative day 4 and a longer hospital stay than patients without POD. Patients in the short POD group were significantly older than those in the long POD group and those who did not develop delirium. CONCLUSION: Approximately half of the elderly patients in this study developed POD. Bleeding was found to be an important risk factor for delirium.


Subject(s)
Abdomen/surgery , Delirium/etiology , Postoperative Complications/etiology , Aged , Cognition Disorders/diagnosis , Cognition Disorders/etiology , Female , Humans , Male , Prospective Studies
12.
Pancreatology ; 5(1): 29-36, 2005.
Article in English | MEDLINE | ID: mdl-15775697

ABSTRACT

AIMS/HYPOTHESIS: Islet amyloid polypeptide (IAPP) reduces food intake and body weight in laboratory animals. In addition, IAPP appears to regulate nutrient metabolism. In the present studies, we investigated the effect of chronic IAPP treatment on different aspects of energy homeostasis. METHODS: IAPP was infused (25 pmol/kg/min) from subcutaneous osmotic pumps for 2-7 days. Rats in 2 saline-infused control groups were fed ad libitum (AF) or pair-fed (PF) against the IAPP-treated rats. RESULTS: As expected, the IAPP infusion reduced food intake and body weight gain. In addition, the IAPP treatment decreased the epididymal fat pad (vs. PF rats, p < 0.05) and lowered circulating levels of triglycerides (vs. PF rats, p < 0.05), free fatty acids (vs. PF rats, p < 0.05), leptin (vs. both AF and PF rats, p < 0.05) and insulin (vs. AF rats, p < 0.05). In contrast, glucose and protein metabolism in the IAPP-treated rats was largely unchanged, as shown in results regarding serum glucose, glucose transport in skeletal muscle, blood urea nitrogen, and glycogen and protein content in the liver and in skeletal muscle. CONCLUSION/INTERPRETATION: In summary, chronic IAPP exposure led to a changed lipid metabolism, which was characterized by decreased adiposity, hypolipidemia and hypoleptinemia, and to unchanged glucose and protein homeostasis. These results were similar to those seen in rodents during chronic exposure to another satiety/adiposity regulator, leptin. In conclusion, chronically administered IAPP plays a role as a satiety and adiposity signal in rats, and helps regulate energy homeostasis.


Subject(s)
Adipose Tissue/growth & development , Amyloid/physiology , Feeding Behavior/physiology , Adipose Tissue/drug effects , Amyloid/administration & dosage , Amyloid/pharmacology , Animals , Feeding Behavior/drug effects , Gene Expression/drug effects , Homeostasis/drug effects , Homeostasis/physiology , Insulin/blood , Ion Channels , Islet Amyloid Polypeptide , Leptin/blood , Membrane Transport Proteins/metabolism , Mitochondrial Proteins/metabolism , Muscle, Skeletal/metabolism , Rats , Rats, Sprague-Dawley , Rats, Wistar , Uncoupling Protein 2 , Weight Gain/drug effects , Weight Gain/physiology
13.
Scand J Immunol ; 61(1): 72-81, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15644125

ABSTRACT

The objective of this study was to investigate B-lymphocyte reconstitution in patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT) after myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC) regimens. B-lymphocyte reconstitution was studied by monitoring the CDR3 repertoire with spectratyping. We demonstrate a delay in the recovery of the B-lymphocyte repertoire, measured by variation in size distribution of the immunoglobulin H CDR3 in patients conditioned with RIC compared to MAC. We found no general explanation for this finding, but when clinical data for each patient were studied in detail, we could identify a cause for the oligoclonality of the B-lymphocyte repertoire after HSCT with RIC for each of the patients. Older patients and donors, low cell dose at transplantation, relapse, graft-versus-host disease (GVHD) and its treatment as well as cytomegalovirus infection and its treatment are all possible causes for the restriction of the B-lymphocyte repertoire observed in this study. Taken together, reconstitution of the B-lymphocyte repertoire after HSCT is a process dependent on multiple factors and differs between patients. The conditioning regimen may be of importance, but data from this study suggest that individual factors and the various complications occurring after HSCT are more likely to determine the development of the B-lymphocyte repertoire.


Subject(s)
Complementarity Determining Regions/genetics , Hematopoietic Stem Cell Transplantation , Acute Disease , Adult , B-Lymphocytes/immunology , Chimera/immunology , Chronic Disease , Female , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Immunoglobulin Allotypes/blood , Immunoglobulin G/blood , Lymphocyte Subsets/immunology , Male , Middle Aged , Time Factors , Transplantation Conditioning/methods , Transplantation, Homologous
14.
Exp Neurol ; 190(2): 535-43, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15530892

ABSTRACT

This experiment investigated the influence of age on prefrontal acetylcholine (ACh) release and Fos response in the hypothalamic paraventricular nucleus and the nucleus tractus solitarius (NTS) of rats following isoflurane anesthesia. It is known that isoflurane decreases acetylcholine release in most brain regions. In the present study, we found that the level of prefrontal acetylcholine was significantly lower in 28-month-old rats (14% of baseline) than in 3-month-old rats (38% of baseline) during 2 h of isoflurane anesthesia (P < 0.05). The old rat group showed significantly greater Fos induction in the paraventricular nucleus compared to the young adult rat group (P < 0.05), indicating that the old rats were subjected to stress. No difference in Fos response was noted in the nucleus tractus solitarius. The old rats displayed a significant increase in feeding behavior during the 3-h recovery period (P < 0.05), but there was no difference in overall acetylcholine levels. Taken together, these findings suggest that isoflurane anesthesia influences old rats more profoundly than young adult rats with regard to reductions in acetylcholine release and stress responses. This may have implications for understanding the development of postoperative delirium in aged patients.


Subject(s)
Acetylcholine/metabolism , Anesthetics, Inhalation/pharmacology , Hypothalamus/drug effects , Isoflurane/pharmacology , Oncogene Proteins v-fos/drug effects , Prefrontal Cortex/drug effects , Acetylcholine/analysis , Age Factors , Animals , Hypothalamus/metabolism , Immunohistochemistry , Male , Microdialysis , Oncogene Proteins v-fos/metabolism , Prefrontal Cortex/metabolism , Rats , Rats, Wistar
15.
Scand J Gastroenterol ; 39(1): 74-80, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14992565

ABSTRACT

BACKGROUND: Obesity is associated with increased severity in patients with acute pancreatitis (AP). The underlying mechanisms are unknown. Genetically obese rats exhibit decreased survival rate in experimental AP, but the clinical relevance of this model of obesity may be questioned. It is proposed that development of organ failure in AP occurs in two stages: initial priming of leucocytes followed by a second inflammatory attack. The aim was to evaluate the impact of diet-induced obesity on outcome in a 'two-hit' model of AP. METHODS: Lipopolysaccharide (LPS) was injected i.p. 3 h after retrograde bile duct infusion of sodium taurocholate in rats. Three experiments were done: 1) an LPS dose-response experiment, 2) chronic high-fat feeding (HF) for 16 weeks, and 3) acute HF for 10 days. Control rats received normal chow. Obesity, morphology and survival rate were assessed. RESULTS: LPS dose-dependently decreased survival rate and increased morphological severity. HF increased weight, intra-abdominal and liver fat. Only acute HF induced hyperlipidaemia. In AP, acute obese rats exhibited less pancreatic inflammation, but total histological severity between groups was not different. In the chronic experiment only obese animals succumbed before 24 h of pancreatitis, but 72-h survival rate was not statistically different in either high-fat experiment. CONCLUSION: An addition of LPS to AP decreases survival rate and intensifies the peri-pancreatic processes. Despite significant obesity, neither hyperlipidaemia nor increased intra-abdominal or hepatic fat influenced local pancreatic injury or survival negatively. The amount of fat per se seems not to be responsible for the deleterious influence of obesity on acute pancreatitis.


Subject(s)
Diet , Dietary Fats/administration & dosage , Lipopolysaccharides/administration & dosage , Obesity/complications , Pancreatitis, Acute Necrotizing/complications , Pancreatitis, Acute Necrotizing/pathology , Animals , Dose-Response Relationship, Drug , Male , Models, Animal , Obesity/pathology , Rats , Rats, Zucker
16.
Clin Exp Immunol ; 134(1): 159-66, 2003 Oct.
Article in English | MEDLINE | ID: mdl-12974769

ABSTRACT

The objective of this study was to investigate if oligoclonality of the Ig repertoire post-haematopoietic stem cell transplantation (HSCT) is restricted to memory B lymphocytes or if it is a general property among B lymphocytes. As a measure of B lymphocyte repertoire diversity, we have analysed size distribution of polymerase chain reaction (PCR) amplified Ig H complementarity determining region 3 (CDR3) in naive and memory B lymphocytes isolated from patients before HSCT and at 3, 6 and 12 months after HSCT as well as from healthy controls. We demonstrate a limited variation of the IgH CDR3 repertoire in the memory B lymphocyte population compared to the naive B cell population. This difference was significant at 3 and 6 months post-HSCT. Compared to healthy controls there is a significant restriction of the memory B lymphocyte repertoire at 3 months after HSCT, but not of the naive B lymphocyte repertoire. Twelve months after HSCT, the IgH CDR3 repertoire in both memory and naive B lymphocytes are as diverse as in healthy controls. Thus, our findings suggest a role for memory B cells in the restriction of the oligoclonal B cell repertoire observed early after HSCT, which may be of importance when considering reimmunization of transplanted patients.


Subject(s)
B-Lymphocyte Subsets/immunology , Complementarity Determining Regions/genetics , Genes, Immunoglobulin , Hematopoietic Stem Cell Transplantation , Immunologic Memory , Adult , Antibody Diversity , Case-Control Studies , Clone Cells , Female , Flow Cytometry , Follow-Up Studies , Graft vs Host Disease/prevention & control , Humans , Male , Middle Aged , Polymerase Chain Reaction/methods , Postoperative Period , Statistics, Nonparametric , Transplantation Conditioning , Transplantation, Autologous , Tumor Necrosis Factor Receptor Superfamily, Member 7/immunology
17.
Cell Mol Life Sci ; 60(5): 991-8, 2003 May.
Article in English | MEDLINE | ID: mdl-12827286

ABSTRACT

In mature human skeletal muscle, insulin-stimulated glucose transport is mediated primarily via the GLUT4 glucose transporter. However, in contrast to mature skeletal muscle, cultured muscle expresses significant levels of the GLUT1 glucose transporter. To assess the relative contribution of these two glucose transporters, we used a novel photolabelling techniques to assess the cell surface abundance of GLUT1 and GLUT4 specifically in primary cultures of human skeletal muscle. We demonstrate that insulin-stimulated glucose transport in cultured human skeletal muscle is mediated by GLUT4, as no effect on GLUT1 appearance at the plasma membrane was noted. Furthermore, GLUT4 mRNA and protein increased twofold (p < 0.05), after differentiation, whereas GLUT1 mRNA and protein decreased 55% (p < 0.005). Incubation of differentiated human skeletal muscle cells with a non-peptide insulin mimetic significantly (p < 0.05) increased glucose uptake and glycogen synthesis. Thus, cultured myotubes are a useful tool to facilitate biological and molecular validation of novel pharmacological agents aimed to improve glucose metabolism in skeletal muscle.


Subject(s)
Insulin/pharmacology , Monosaccharide Transport Proteins/analysis , Muscle Proteins , Muscle, Skeletal/drug effects , Adult , Aged , Cell Differentiation/drug effects , Cells, Cultured , Female , Glucose/metabolism , Glucose Transporter Type 1 , Glucose Transporter Type 4 , Humans , Male , Middle Aged , Muscle, Skeletal/cytology , Muscle, Skeletal/metabolism
18.
Scand J Gastroenterol ; 37(1): 104-11, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11843026

ABSTRACT

BACKGROUND: A majority of patients with pancreatic cancer have obstructive jaundice and diabetes with skeletal muscle insulin resistance. Surgery for these patients is associated with significant morbidity. Uncoupling protein 2 (UCP2) has been proposed to regulate energy expenditure and promote liver vulnerability. The effects of obstructive jaundice on muscle glucose metabolism and expression of UCP2 in liver and muscle are unknown. METHODS: Rats were operated with bile duct ligation (BDL). After 7 days, UCP2 mRNA levels were determined in liver and muscle. Simultaneously, insulin-stimulated glucose transport and glycogen synthesis in skeletal muscle were analyzed in vitro. RESULTS: The jaundiced rats lost more weight than pair-fed controls. UCP2 mRNA levels were increased 5-fold in liver but not in muscle in jaundiced rats compared to pair-fed controls. The jaundiced rats were hypoglycemic and hypoinsulinemic but demonstrated intact or enhanced insulin action on skeletal muscle glucose transport and glycogen synthesis in vitro. Muscle glycogen content was increased in the jaundiced rats. CONCLUSIONS: Experimental obstructive jaundice in the rat is associated with increased liver expression of UCP2, rapid weight loss, and intact insulin action on skeletal muscle glucose metabolism. Obstructive jaundice, by upregulated liver UCP2, may contribute to the cachexia and high surgical morbidity observed in these patients, but not to skeletal muscle insulin resistance in pancreatic cancer patients.


Subject(s)
Cholestasis/genetics , Cholestasis/metabolism , Glucose/genetics , Glucose/metabolism , Liver/metabolism , Membrane Transport Proteins , Mitochondrial Proteins , Muscle, Skeletal/metabolism , Proteins/genetics , Proteins/metabolism , Uncoupling Agents/metabolism , Animals , Disease Models, Animal , Gene Expression/genetics , Gene Expression/physiology , Insulin Resistance/genetics , Insulin Resistance/physiology , Ion Channels , Male , Rats , Rats, Sprague-Dawley , Uncoupling Protein 2 , Weight Loss/genetics , Weight Loss/physiology
19.
Bone Marrow Transplant ; 27(11): 1163-71, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11551027

ABSTRACT

Treatment with neuroendocrine hormones has been suggested to promote reconstitution of the immune system after hematopoietic stem cell transplantation (HSCT). We investigated the expression of genes encoding receptors for growth hormone (GH), insulin-like growth factor-I (IGF-I) and triiodothyronine (T3), at various time points after HSCT in 16 patients and 15 healthy controls. Peripheral blood mononuclear cells were isolated and RNA for GH receptor (GHR), IGF-I receptor (IGF-IR) and thyroid hormone receptor (TRalpha1) was amplified by RT-PCR. The expression of the genes was compared with the expression of beta-actin. We demonstrate increased expression of TRalpha1 RNA in patients at 1.5 months post HSCT, compared to a group of healthy controls, and decreased expression of IGF-IR RNA at 2 and 3 months post HSCT, compared to the controls. Serum from three of the patients was also analyzed for levels of T3, T4, TSH and IGF-I at several time points after HSCT. Serum levels for T3, thyroxine (T4), thyroid stimulating hormone (TSH) and IGF-I were within the normal range in all samples. Our results on the molecular level indicate a role for thyroid hormones and IGF-I in immune reconstitution after HSCT, even though the serum levels of T3, T4, TSH and IGF-I are normal.


Subject(s)
Graft Survival/genetics , Hematopoietic Stem Cell Transplantation , Receptor, IGF Type 1/metabolism , Receptors, Thyroid Hormone/metabolism , Adult , Case-Control Studies , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Female , Hematologic Neoplasms/complications , Hematologic Neoplasms/therapy , Hematopoiesis/genetics , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/methods , Humans , Leukocytes, Mononuclear/chemistry , Male , Middle Aged , RNA, Messenger/analysis , Receptor, IGF Type 1/genetics , Receptors, Cytoplasmic and Nuclear/genetics , Receptors, Cytoplasmic and Nuclear/metabolism , Receptors, Thyroid Hormone/genetics , Reverse Transcriptase Polymerase Chain Reaction , Time Factors , Transplantation, Homologous/adverse effects , Transplantation, Homologous/methods
20.
Acta Oncol ; 40(2-3): 135-54, 2001.
Article in English | MEDLINE | ID: mdl-11441927

ABSTRACT

This report by The Swedish Council on Technology Assessment in Health Care (SBU) reviews, classifies, and grades the scientific literature on cancer chemotherapy in some major tumour types, describes the practice of chemotherapy in Sweden, compares practice with scientific knowledge, and analyses the costs and cost-effectiveness of chemotherapy. The report is intended primarily for decision-makers at various levels, both practitioners and administrators. It is also of interest for the medical profession. The extensive body of scientific literature was reviewed according to strict criteria that reflected the scientific weight of the literature. Sixteen experts representing different disciplines (oncology, surgery, internal medicine, health economy and quality of life research) participated in the literature review. Each section was discussed within the project group and was reviewed by at least one, but usually two international researchers. Additional input was provided by national experts representing different scientific disciplines. For the final evaluation to be as close to the objective truth as possible, a concerted effort was made to guarantee objectivity and thorough assessment of current knowledge about the effects of chemotherapy on the selected cancers. The tumour types selected for this assessment include firstly those types where three investigations had shown an increased use of chemotherapy in Sweden during the latest decade. These were non-small cell lung cancer (NSCLC), gastric cancer, pancreatic cancer, colorectal cancer and urinary bladder cancer. Secondly, the two tumour types comprising the greatest number of patients treated with chemotherapy in Sweden, breast cancer and haematological malignancies, were included. Among the haematological malignancies, the most prevalent ones, acute myeloid leukaemia (AML), chronic lymphocytic leukaemia (CLL), Hodgkin's disease (HD), aggressive non-Hodgkin's lymphoma (NHL) of the large B-cell type and indolent NHL of follicular type were evaluated. These constitute about 75%, of all haematological malignancies. Thirdly, ovarian cancer was included since chemotherapy has been extensively used and since, at the time of the planning of this overview, a group of very expensive drugs, the taxanes, had preliminarily shown promising results. A wealth of scientific literature has been published on cancer therapy. The review presented in this report is limited to scientific studies judged to be important for evaluating chemotherapy efficacy. Assessments of the content and quality of these studies, and a critical summary of the results in all stages of the selected tumours, have never before been attempted in this way. However, similar comprehensive overviews of certain stages of the tumours have previously been made. These overviews were also critically evaluated. Totally 1,496 studies involving 558,743 patients were reviewed. The survey of practice of chemotherapy use involved all departments of surgery, urology, gynaecology, internal medicine including haematologic units, pulmonary medicine and general and gynaecologic oncology at 16 hospitals in two health care regions in Sweden, covering 39% of the Swedish population. During the 4 weeks of the survey, all patients with the diagnoses concerned who received chemotherapy were registered. The study included 1,590 patients. The working group's general conclusions are summarised in the following points: The literature on the effects of chemotherapy is extensive. Chemotherapy has a well-documented role in the curative and palliative treatment of patients with several types of cancer. The use of chemotherapy is of utmost importance for the possibility of cure in certain tumour types. In other tumours, chemotherapy increases the possibility of cure when added to local and regional treatments, particularly surgery. In the instances of no possibility of cure, chemotherapy may to a variable extent improve both patient survival and well-being. In Sweden chemotherapy is largely used in accordance with that documented in the scientific literature. The extent of both over- and under-treatment seems to be limited but cannot be excluded at the individual patient level. The literature-based knowledge is scientifically of lower quality in the most chemotherapy sensitive tumours than in tumours showing more limited sensitivity. In the more sensitive tumours, positive effects on a symptomatic stage and survival were seen several decades ago. In those days, clinical treatment studies did not fulfil the current high quality requirements. Small life-prolonging effects of chemotherapy are sometimes very well documented in large, high quality scientific studies. Some of these s


Subject(s)
Antineoplastic Agents/therapeutic use , Neoplasms/drug therapy , Technology Assessment, Biomedical , Antineoplastic Agents/economics , Cost-Benefit Analysis , Decision Making , Drug Costs , Evidence-Based Medicine , Humans , Sweden
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