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Biomedical subjects

A Waage

Publications and source records attributed to A Waage.

At least 19 recordsLinked to original sources
PubMed2005

Myocardial ischaemia and the inflammatory response: release of heat shock protein 70 after myocardial infarction.

OBJECTIVES: To test the hypothesis that heat shock protein (Hsp) 70 may be released into the circulation after acute myocardial infarction (AMI) by exploring the kinetics of Hsp70 release and the relations between Hsp70 and markers of inflammation and myocardial damage in AMI. DESIGN: Blood samples from 24 patients were prospectively collected through to the first day after AMI. Hsp70, interleukin (IL) 6, IL-8, and IL-10 in serum were measured by enzyme linked immunosorbent assay (ELISA). RESULTS: Median Hsp70 concentrations in AMI patients measured at arrival, six hours thereafter, and the following morning were 686, 868, and 607 pg/ml, respectively. These concentrations were all significantly different from those of the control patients with angina with a median serum Hsp70 concentration of 306 pg/ml. Peak Hsp70 correlated with creatine kinase (CK) MB (r = 0.62, p < 0.01) and cardiac troponin T (r = 0.58, p < 0.01). Furthermore, serum Hsp70 correlated with IL-6 and IL-8 at six hours (r = 0.60, p < 0.01 and r = 0.59, p < 0.01, respectively). CONCLUSIONS: In this study, Hsp70 was rapidly released into the circulation after AMI. Circulating Hsp70 is suggested as a marker of myocardial damage. In addition, Hsp70 may have a role in the inflammatory response after AMI.

Biomarkers↗
PubMed2005

Identification of new targets for therapy of osteolytic bone disease in multiple myeloma.

One of the most characteristic features of multiple myeloma is the development of osteolytic bone lesions. Myeloma-associated bone disease is caused by an increase in osteoclastic bone resorption and a decrease in osteoblastic new bone formation. Insight into the molecular mechanisms of osteoclastogenesis has been provided by the detection of receptor activator of NF-kappaB ligand (RANKL), its specific receptor (RANK) and its decoy receptor antagonist osteoprotegerin (OPG). The RANK signaling system is abnormally regulated in multiple myeloma and targeting this system may ameliorate myeloma bone disease. Less is known about the development of osteoblastic dysfunction, and further knowledge about the interaction between myeloma cells and osteoblasts is required. The aim of this review is to focus on the principles of bone biology for a better understanding of the development of myeloma bone disease and to identify possible therapeutic targets.

Bone Remodeling↗
PubMed2004

Laparoscopic hand-assisted spleen autotransplantation.

BACKGROUND: Only recently has the spleen been perceived as an organ with a major immune function. This raised an interest in spleen salvage after spleen trauma and pancreatic tail resection, for the treatment of hematologic disorders and inducement tolerance for allogenic transplants. The purpose of this study was to evaluate the feasibility of a new technique for spleen transplantation: laparoscopic spleen autotransplantation in a large animal model. METHODS: Ten 35-kg pigs were used for this study. A laparoscopic hand-assisted splenectomy was first performed. The spleen was extracted through the handport to be flushed with a 4 degrees C saline solution and prepared extracorporeally. The graft was then reintroduced into the same animal's abdominal cavity, and a splenic-to-common iliac artery and vein bypass was performed laparoscopically using a 7-0 polytetrafluoroethylene running suture. The animal was killed 1 week postoperatively for histologic examination. RESULTS: All 10 animals tolerated the procedure well. No conversion to open surgery was required. The mean operative time was 253 +/- 45 min. The mean time needed to create the artery and vein anastomoses was 116 +/- 165 min, and the mean blood loss was 190 +/- 120 ml. There was no intra- or postoperative death. Intraoperative complications included two stenosed vascular anastomoses, which were taken down and revised. Seven of the 10 spleens were histologically viable 1 week after surgery. The nonviable transplantations were attributable to a thrombosis of the common iliac artery (n = 1) or the transplant artery (n = 2). CONCLUSIONS: Hand-assisted laparoscopic spleen autotransplantation is feasible in an animal model. This procedure could constitute an option when spleen resection is necessary for pancreatic tail resection, or when spleen preservation is important to the maintenance or restoration of an immune function.

Animals↗
PubMed2004

Dual endoscopic-assisted endoluminal colostomy reversal: a feasibility study.

BACKGROUND: Emergent colostomies are associated with increased morbidity related to second closure operations. The purpose of this canine pilot study was to create a minimally invasive procedure that would reduce the time interval and morbidity involved with colostomy reversals after left colon end colostomies. METHODS: Six mongrel dogs underwent modified laparoscopic Hartmann's procedures in which the stapled end of the rectal stump was approximated to the left colon proximal to the stoma. After 1 week, they underwent an endoluminal colostomy reversal with a computer-mediated, circular stapling device and varying anvil insertion methods. Variables recorded included anvil insertion technique and feasibility, OR time, complications, and number of days to first meal and bowel movement. A contrast enema performed 1 week post colostomy reversal ruled out anastomosis leaks and stenosis. The dogs were euthanized and subjected to necropsy. RESULTS: Of four anvil insertion techniques tested, the most feasible employed a large-bore needle to perforate through the stapled end of the Hartmann pouch into the lumen of the left colon. Simultaneous endoluminal views of the rectal stump with a sigmoidoscope and the left colon lumen with an endoscope permitted a controlled and safe needle puncture. Through the needle, a guide wire was inserted to withdraw the anvil via the colostomy into place. A transanally inserted stapler was then married to the anvil under fluoroscopic guidance, thus completing the anastomosis. The colostomy was then taken down and transected at the level of the colocolostomy. Average operating time was 126 min (range 90-180), diet was tolerated within 1.5 days, and average number of days to first bowel movement was 2.5. The absence of stenosis, leaks, and inadvertent visceral injuries confirmed feasibility. CONCLUSIONS: In this canine model, a dual endoscopic-assisted colostomy reversal with a computer-mediated, circular stapling device is feasible. Using this technique, colostomy reversals can possibly be performed 1 week post-colostomy without entering the peritoneal cavity, thus reducing the number of invasive operations and subsequent morbidity required to manage emergent colon perforations.

Anastomosis, Surgical↗
PubMed2003

Long-term results from laparoscopic common bile duct exploration.

BACKGROUND: The aim of this study was to evaluate the long-term results after laparoscopic common bile duct exploration (LCBDE). METHODS: A retrospective review of 175 consecutive patients who underwent attempted LCBDE between 1992 and 1999 was conducted. Laparoscopic transcystic exploration was accomplished in 110 patients and laparoscopic choledochotomy in 52 patients. Conversion to an open common bile duct exploration was required for 13 patients (7.4%). Retained common bile duct stones occurred in eight patients (4.6%). The 30-day postoperative morbidity was 6.9%, and there was no 30-day mortality. All the patients (alive and localized) received a questionnaire evaluating long-term results. RESULTS: Of the 175 patients, 169 (4 unrelated deaths and 2 patients lost to follow-up evaluation) received and 152 (90%) returned the questionnaire. The follow-up period ranged from 6 to 72 months (median, 36 months). One patient developed recurrent common bile duct stones. There were no signs or evidence of common bile duct stricture in any patient. CONCLUSION: The LCBDE procedure can be performed without increased risk of late bile duct complications.

Abscess↗
PubMed2003

Pharmacokinetics of thalidomide in patients with impaired renal function and while on and off dialysis.

There is a renewed interest in thalidomide for use in malignancies and systemic inflammatory diseases. Reduced renal function is not uncommon among patients with these disease states but the pharmacokinetics has not been fully investigated. The aim of this study was to investigate the pharmacokinetics of thalidomide in haemodialysis patients while on and off dialysis and in myeloma patients with varying degrees of renal function. Two studies were performed. To establish the pharmacokinetics of thalidomide in patients with mild to moderate renal failure, blood samples were taken over 12 weeks from 40 patients with multiple myeloma. A second study was performed in six patients with end-stage renal disease both on a non-dialysis day and before and during a haemodialysis session. Thalidomide concentration was determined by HPLC. A one-compartment open model with first-order absorption and elimination was used to fit total thalidomide concentration to population pharmacokinetics and statistical models using the NONMEM program. Clearance and volumes were slightly below 10 L h-1 and 1 L kg-1, respectively, in both patient groups. The inter- and intra-patient variability was low. Clearance was doubled during dialysis. There was no correlation between thalidomide clearance and renal function. In conclusion, the pharmacokinetics of thalidomide in patients with renal failure are very similar to values reported by others for patients with normal renal function. Although clearance during dialysis is doubled, thalidomide dose need not be changed for patients with decreased kidney function. There is also no need for a supplementary dose due to haemodialysis.

Adult↗
PubMed2002

[Laparoscopic hepatectomy].

AIM: To report the current indications and techniques of laparoscopic liver resections, and assess the results of this technique by reviewing international literature. REVIEW OF THE LITERATURE: About 200 laparoscopic hepatectomies have been reported from 1991 to 2001. 102 resections were performed for malignant tumours, and 84 for benign tumours. Global conversion rate was 7% (13/186). Morbidity rate was 16.1% with two cases of possible gas embolisms (1.1%). Mortality rate was 0.54% (1/186 patients). Mean hospital stay was 7.7 days. CONCLUSION: Laparoscopic hepatectomy is feasible, with a morbidity and mortality rate comparable to open procedures according to a careful selection of patients. However, prospective randomized trials are still needed to confirm those results, especially for resection of metastasis or malignant tumors. Evolution of laparoscopic hepatectomies will probably depend on the development of new techniques and instrumentations.

Hepatectomy↗
PubMed2002

Hereditary haemochromatosis in two cousins with cluster headache.

A 60-year-old woman with secondary chronic cluster headache had increased serum ferritin and serum transferrin saturation and was homozygous for the C282Y mutation in the HFE gene, which is indicative of hereditary haemochromatosis. Treatment with venesection that normalized her iron stores led to a radical improvement of her headache complaints that had been daily for several years. Later, the headache returned to some degree in spite of normal serum ferritin levels. Her cousin, a 33-year-old man who had had episodic cluster headache for several years, also had increased transferrin saturation and was compound heterozygous for two mutations, a genotype known to be associated with a slightly increased frequency of haemochromatosis. This is the first report of a headache disorder in a patient with hereditary haemochromatosis. The coexistence of the two disorders may be a mere coincidence, but the temporary improvement of headache from depletion of iron stores may indicate a causal relation, possibly mediated by iron deposits in pain-modulating centres in the brainstem.

Adult↗
PubMed2001

[Thalidomide--a dreaded drug with new indications].

BACKGROUND: Thalidomide was introduced as a non-toxic sleeping pill in 1957 and was prescribed in more than 20 countries. In 1961 the link between congenital limb defects and thalidomide use in pregnancy was proven, resulting in withdrawal of the drug. MATERIAL AND METHODS: On the basis of literature searches and personal experience we review the effects and use of thalidomide today. RESULTS: In vitro, thalidomide has immunoregulatory properties. This has lead to the administration of thalidomide in many immunological diseases. In 1964 it was discovered that thalidomide was effective against erythema nodosum leprosum. Thalidomide also has effect on aphthous stomatitis and Behçet's disease. The effect is more uncertain in graft-versus-host-disease, rheumatoid arthritis and Crohn's disease. Thalidomide reduces angiogenesis in experimental animals, and this has led to several studies of thalidomide as a possible anticancer drug. Advanced or resistant multiple myeloma may be a new target for thalidomide; at least 30% of these patients obtain response during treatment. Results indicate that patients with breast cancer and glioma do not benefit from treatment with thalidomide. INTERPRETATION: Thalidomide has proven to be effective in the treatment of erythema nodosum leprosum and aphthous stomatitis. It is also effective in advanced multiple myeloma, but not in other cancers.

Abnormalities, Drug-Induced↗
PubMed2001

Serum osteoprotegerin levels are reduced in patients with multiple myeloma with lytic bone disease.

Osteoprotegerin (OPG), the neutralizing decoy receptor for the osteoclast activator RANK ligand, was measured in serum taken from patients with multiple myeloma at the time of diagnosis. Median OPG was lower in the patients with myeloma (7.4 ng/mL; range, 2.6-80; n = 225) than in healthy age- and sex-matched controls (9.0 ng/mL; range 5.1-130; n = 40; P =.02). Importantly, OPG levels were associated with degree of radiographically assessed skeletal destruction (P =.01). The median OPG level in patients lacking osteolytic lesions was 9.1 ng/mL, as compared with 7.6 ng/mL and 7.0 ng/mL, respectively, in patients with minor or advanced osteolytic disease. Furthermore, OPG levels were associated with World Health Organization performance status (P =.003) and correlated to serum levels of carboxy-terminal propeptide of type I procollagen (PICP; P <.001) but not with clinical stage or survival. These findings suggest impaired OPG function in myeloma and give a rationale for OPG as a therapeutic agent against myeloma bone disease.

Adult↗
PubMed2001

[High dose therapy with autologous stem cell support--finally a progress in myelomatosis].

BACKGROUND: Since the introduction of the simple cyclic oral treatment with melphalan and prednisone in the late 1960s, there has been no substantial improvement in the therapy of multiple myeloma. In 1994, the Nordic Myeloma Study Group initiated a population-based, prospective study to evaluate the impact on survival of high dose chemotherapy in newly diagnosed, symptomatic patients under 60 years of age, compared to a conventionally treated control group. MATERIAL AND METHODS: 274 patients were treated according to a specified high dose protocol and compared to 274 patients from previous population-based trials fulfilling the same eligibility criteria. RESULTS: Median survival was 44 months in the control group and 62 months in the intensive treatment group (risk ratio 1.65; 95% CI = 1.28-2.14, P = 0.0001). A study of health-related quality of life (HRQoL) which was integrated in the trial showed a moderately reduced HRQoL associated with the intensive treatment phase, but no statistically significant difference beyond the first year of follow-up. In a cost-utility analysis of the trial, the cost per (quality-adjusted life years) was estimated at USD 26,000. INTERPRETATION: The incremental cost of the treatment is within what is usually thought to be acceptable limits. Further improvement of the results and reduction of stay in hospital would give an even more favourable cost-utility ratio.

Adult↗
PubMed2001

[Thalassemia and sickle-cell disease in Norway].

BACKGROUND: Thalassemia is common in the Mediterranean countries, the Middle East, parts of India and South East Asia, with the prevalence of mutations reported to be 2.5-15%. Sickle-cell anaemia is endemic primarily in central parts of Africa, but it also appears in the thalassaemia areas. The purpose of this study was to establish the prevalence of beta-thalassaemia, alfa-thalassaemia and sickle-cell anaemia in Norway. MATERIAL AND METHODS: A questionnaire was sent to 149 departments of paediatrics, gynaecology and medicine in Norway. We asked for numbers registered in 1996 and 1997 of beta-thalassaemia and alfa-thalassaemia with subgroups, and sickle-cell anaemia. RESULTS: The number of patients with thalassaemia was 44 (0.001%) in 1996 and 48 in 1997. In 1996 there were 28 patients with beta-thalassaemia minor, three with intermediary and five major, and six patients with alfa-thalassaemia minor and one with major. In 1996, ten patients were registered with sickle-cell anaemia; in 1997, fifteen patients. INTERPRETATION: The numbers of patients with thalassaemia major or sickle-cell anaemia probably reflect the true prevalence of these diseases. However, for thalassaemia minor and sickle-cell anaemia trait the numbers appear to be too low, as most of these patients do not contact a hospital. The appearance of these diseases in Norway is closely related to immigration from endemic areas.

Anemia, Sickle Cell↗
PubMed2001

Bone morphogenetic protein-4 inhibits proliferation and induces apoptosis of multiple myeloma cells.

Bone morphogenetic proteins (BMPs) can be isolated from organic bone matrix and are able to initiate de novo cartilage and bone formation. Here it is shown that BMP-4 inhibited DNA synthesis in a dose-dependent manner in 3 IL-6-dependent multiple myeloma (MM) cell lines (OH-2, IH-1, and ANBL-6). In contrast, no effect on DNA synthesis was observed in 3 IL-6-independent MM cell lines (JJN-3, U266, and RPMI 8226). BMP-4 induced cell cycle growth arrest in the G(0)/G(1) phase in OH-2 and ANBL-6 cells but not in IH-1 cells. BMP-4 induced apoptosis in OH-2 and IH-1 cells, but not significantly in ANBL-6 cells. Furthermore, BMP-4 induced apoptosis in freshly isolated MM cells from 4 of 13 patients. In the OH-2 and ANBL-6 cell lines and in a patient sample, immunoblotting showed that BMP-4 down-regulated IL-6-induced tyrosine phosphorylation of Stat3, suggesting a mechanism for the apparent antagonism between IL-6 and BMP-4. BMP-4 or analogues may be attractive therapeutic agents in MM because of possible beneficial effects on both tumor burden and bone disease.

Aged↗
PubMed2000

High levels of soluble syndecan-1 in myeloma-derived bone marrow: modulation of hepatocyte growth factor activity.

Syndecan-1 is a heparan sulfate proteoglycan expressed on the surface of, and actively shed by, myeloma cells. Hepatocyte growth factor (HGF) is a cytokine produced by myeloma cells. Previous studies have demonstrated elevated levels of syndecan-1 and HGF in the serum of patients with myeloma, both of negative prognostic value for the disease. Here we show that the median concentrations of syndecan-1 (900 ng/mL) and HGF (6 ng/mL) in the marrow compartment of patients with myeloma are highly elevated compared with healthy controls and controls with other diseases. We show that syndecan-1 isolated from the marrow of patients with myeloma seems to exist in an intact form, with glucosaminoglycan chains. Because HGF is a heparan-sulfate binding cytokine, we examined whether it interacted with soluble syndecan-1. In supernatants from myeloma cells in culture as well as in pleural effusions from patients with myeloma, HGF existed in a complex with soluble syndecan-1. Washing myeloma cells with purified soluble syndecan-1 could effectively displace HGF from the cell surface, suggesting that soluble syndecan-1 can act as a carrier for HGF in vivo. Finally, using a sensitive HGF bioassay (interleukin-11 production from the osteosarcoma cell line Saos-2) and intact syndecan-1 isolated from the U-266 myeloma cell line, we found that the presence of high concentrations of syndecan-1 (more than 3 microg/mL) inhibited the HGF effect, whereas lower concentrations potentiated it. HGF is only one of several heparin-binding cytokines associated with myeloma. These data indicate that soluble syndecan-1 may participate in the pathology of myeloma by modulating cytokine activity within the bone marrow.

Biopsy, Needle↗
PubMed2000

Serum syndecan-1: a new independent prognostic marker in multiple myeloma.

Serum samples drawn at diagnosis from 174 myeloma patients were analyzed for the presence of the heparan [corrected] sulfate proteoglycan, syndecan-1. Syndecan-1 was elevated in 79% of patients (median, 643 units/mL) compared with 40 healthy controls (median, 128 units/mL), P <.0001. Serum syndecan-1 correlated with the following: serum creatinine, secretion of urine M-component over the course of 24 hours, soluble interleukin-6 (IL-6) receptor, C-terminal telopeptide of type I collagen, beta(2)-microglobulin, percentage of plasma cells in the bone marrow, disease stage, and serum M-component concentration. In order to evaluate syndecan-1 as a prognostic marker in multiple myeloma, it was entered into a multivariate Cox regression model. Data from 138 patients were available for this analysis. As a continuous variable, syndecan-1 was an independent prognostic parameter in addition to serum beta(2)-microglobulin and World Health Organization performance status. When syndecan-1 was dichotomized by the best cutoff (66th percentile, 1170 units/mL), the survival difference between the groups was highly significant: "high" syndecan-1 group had a median survival of 20 months, and the "low" syndecan-1 group had a median of 44 months (P <.0001). We conclude that syndecan-1 is a new independent prognostic parameter in multiple myeloma, and its role in prognostic classification systems should be further investigated. (Blood. 2000;95:388-392)

Biomarkers↗
PubMed2000

Perfusion magnetic resonance imaging of the lung: characterization of pneumonia and chronic obstructive pulmonary disease. A feasibility study.

Perfusion magnetic resonance (MR) imaging is a promising new method for detection of perfusion defects in the diagnosis of pulmonary embolism. In the present study we evaluated the first-pass characteristics of perfusion MR imaging in patients with pneumonia or chronic obstructive pulmonary disease (COPD), frequent differential diagnoses to pulmonary embolism. Dynamic contrast-enhanced MR images of 12 patients with acute pneumonia and 13 patients with exacerbation of COPD were acquired in both the coronal and transaxial planes (an inversion recovery prepared gradient-echo sequence using 0.05 mmol/kg gadodiamide/injection). The MR images and the signal intensity (SI) versus time curves were characterized for each disease entity and compared with normal lung and the findings in pulmonary embolism from our previous study. The perfusion MR images of pneumonia showed distinct regions of increased contrast enhancement; in COPD with signs of emphysema (11 of the 13 COPD patients), the images showed a coarse pattern of reduced contrast enhancement. The SI versus time curves of pneumonia, COPD with signs of emphysema, and normal lung were statistically different, the respective pooled SI values (+/-95% CI) being as follows: mean baseline SI, 20.7 (1.1), 7.4 (0.4), and 8.5 (0.3); mean peak SI, no peak, 12.9 (1.5), and 27 (4.6); and mean max change of SI in percent, 110 (27), 79 (22), and 205 (52). Perfusion MR imaging of pneumonia and COPD with signs of emphysema showed first-pass that were characteristics promising for diagnostic use. Both the MR images and the SI versus time curves were different from the perfusion characteristics in normal lung and pulmonary embolism shown previously.

Contrast Media↗