Long-term quality of life in pouch patients compared with stoma patients following rectal cancer surgery.

AIM: Low and ultralow anterior resection for rectal cancer with colorectal or coloanal anastomosis does not compromise oncological results compared with abdominoperineal excision. Although avoidance of a permanent colostomy is regarded as beneficial for a patient's quality of life (QoL), patients undergoing sphincter-sparing surgery may develop a number of functional problems. A colonic pouch significantly improves functional outcome after rectal resection and low anastomosis and may positively influence QoL. The aim of this study was to compare QoL in long-term survivors who underwent ultralow anterior resection with total mesorectal excision and colonic J-pouch anastomosis (CPA) with patients treated with abdominoperineal excision (APE) and end colostomy for rectal cancer. METHOD: The medical records from our institution's prospectively maintained rectal cancer database of 151 patients who underwent surgery for ultralow rectal cancer from 2001 to 2007 were analysed. QoL in 59 eligible patients was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 core and Colorectal Cancer 29. Results were compared for patients with CPA and APE. RESULTS: The median follow-up in the 59 patients was 74 (37-119) months. QoL was good in all patients, but it was better in CPA than in APE patients. Global health status (P = 0.009), physical functioning (P = 0.0002), role functioning (P = 0.03), cognitive functioning (P = 0.046), social functioning (P = 0.002), body image (P = 0.053), embarrassment (P = 0.002) and urinary frequency (P = 0.003) were significantly improved for patients with CPA. CONCLUSION: QoL after rectal resection and CPA was better than after APE in several respects. However, QoL should not be regarded as an isolated concept but rather as one of several possible clinical outcomes of interest.

Re-transfusion of salvaged washed red cells improves clot formation in pigs as measured by rotational thrombelastometry (ROTEM).

BACKGROUND AND OBJECTIVE: Patients exhibiting considerable blood loss are prone to develop dilutional coagulopathy following volume supply. In such patients, in addition to transfusing stored blood components, cell saver systems are used to minimize allogeneic transfusion. Since red cell transfusion might influence the haemostatic system by further dilution, we investigated the effects of re-transfusion of salvaged washed red blood cells on the haemostatic process in an animal model of controlled haemorrhage using rotational thrombelastometry (ROTEM; Pentapharm Co., Munich, Germany). METHODS: Anaesthetized pigs (n = 20) developed coagulopathy following haemorrhagic shock (withdrawal of 66% of estimated blood volume) and volume resuscitation with 6% hydroxyethyl starch 130/0.4. The shed blood was processed in a Cellsaver device (CATS; Fresenius AG, Bad Homburg, Germany), and the resulting salvaged red blood cells were re-transfused. ROTEM assays were performed at baseline, after blood loss, after volume resuscitation and following re-transfusion of salvaged red blood cells. RESULTS: As compared with baseline, blood loss and subsequent volume resuscitation resulted in significantly increased median values of clotting time (CT: 47.0, 5 .3 and 103.5 s), and clot formation time (CFT: 36.0, 40.0 and 186.0 s), whiggle maximum clot firmness decreased (MCF: 72.0, 68.5 and 39.5 mm). After re-transfusion of salvaged red blood cells (805 +/- 175 mL) all these parameters improved (CT: 80.5 s; P = 0.05, CFT: 144.0 s; P = 0.0008, MCF: 42.0 mm; P = 0.0019) although baseline values were not reached. CONCLUSION: In the case of extreme isovolaemic haemodilution, increasing the circulating red cell mass by re-transfusing salvaged red blood cells did not worsen the findings of dilutional coagulopathy but interestingly, at least partially, improves the clot formation process.

Recurrence and complications after laparoscopic versus open inguinal hernia repair: results of a prospective randomized multicenter trial.

BACKGROUND: The aim of this prospective randomized multicenter trial was to evaluate the recurrence rates and complications of open versus laparoscopic repairs of inguinal hernias. METHODS: Patients with primary unilateral inguinal hernias were randomized to Shouldice repair, Bassini operation, tension-free hernioplasty (Lichtenstein repair), laparoscopic transabdominal extraperitoneal hernioplasty (TEP), or laparoscopic transabdominal preperitoneal hernioplasty (TAPP). The primary outcome parameter was the rate of recurrence at 3 years. The secondary outcome was the rate of intraoperative, perioperative, and long-term complications. Follow-up comprised of clinical examination after 1, 2, and 3 years. RESULTS: Three hundred and sixty-five patients were randomly assigned to one of the five procedures. The intention-to-treat analysis showed that the cumulative 3-year recurrence rate was 3.4% in the Bassini group, 4.7% in the Shouldice group, 0% in the Lichtenstein group, 4.7% in the TAPP group, and 5.9% in the TEP group (p = 0.48). Comparing open (Bassini, Shouldice, Lichtenstein) versus laparoscopic (TAPP, TEP) techniques (p = 0.29) and comparing the use of mesh prostheses (Lichtenstein, TAPP, TEP) versus suturing techniques (Bassini, Shouldice) (p = 0.74) showed no significance in the rate of recurrence. The rates of intraoperative (p = 0.15), perioperative (p = 0.09), and long-term complications (p = 0.13) were without significance between the five groups. Comparing mesh techniques (Lichtenstein, TAPP, TEP) versus suturing techniques (Bassini, Shouldice) showed no significance in the rate of complications. The per-protocol analysis for the comparison of mesh (Lichtenstein, TAPP, TEP) versus suturing (Bassini, Shouldice) techniques revealed that recurrences (p = 0.74), intraoperative (p = 0.64), perioperative (p = 0.27), and long-term complications (p = 0.91) were evenly distributed. CONCLUSIONS: In this multicenter study, no significant difference in the recurrence rate and complications between laparoscopic and open methods of hernia repair was revealed.

Effects of colloid and crystalloid solutions on endogenous activation of fibrinolysis and resistance of polymerized fibrin to recombinant tissue plasminogen activator added ex vivo.

BACKGROUND: The study was conducted to explore the effects of colloid and crystalloid solutions on activation of fibrinolysis during orthopaedic surgery and to determine whether fluids facilitate clot dissolution at a particular fibrinolytic activity. METHODS: Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) were measured in plasma samples of 66 orthopaedic patients randomly receiving gelatin solution, hydroxyethyl starch (HES) (130/0.4), or exclusively Ringer's lactate solution. Plasma obtained before induction of anaesthesia (undiluted) and at the end of surgery (diluted) was exposed to recombinant tissue plasminogen activator (r-tPA) in vitro and analysed by modified thrombelastography (ROTEM). RESULTS: There were similar changes in t-PA and PAI-1 concentrations in the gelatin, HES, and Ringer's lactate groups. When compared with the effect of r-tPA on undiluted plasma samples, the presence of colloids prompted faster clot dissolution than did Ringer's lactate solution. Lysis index at 30 min decreased significantly [median (min/max); P vs Ringer's lactate solution] to 43 (1/82)% (P=0.007), 14 (3/70)% (P<0.001), and 91 (34/97)%, lysis onset time decreased to 1269 (1054/1743) s (P=0.007), 972 (490/1565) s (P<0.001), and 1970 (1260/2165) s, and lysis time to 2469 (1586/3303) s (P=0.019), 2002 (1569/3600) s (P=0.006), and 3012 (2017/3600) s in the gelatin, HES, and Ringer's lactate groups, respectively. CONCLUSIONS: The type of i.v. fluid used does not influence endogenously occurring fibrinolytic activity in patients undergoing major orthopaedic surgery. However, during hyperfibrinolysis, the presence of HES or gelatin solution facilitates clot disintegration to a greater extent than Ringer's lactate solution, because the weaker clots formed with colloids dissolve faster.

Increased serum levels of cartilage oligomeric matrix protein in patients with psoriasis vulgaris: a marker for unknown peripheral joint involvement?

OBJECTIVE: Cartilage oligomeric matrix protein (COMP) is a parameter for the current extent of cartilage destruction. It has been shown that the release pattern of cartilage oligomeric matrix protein in serum reflects cartilage turnover. The aim of our study was to explore the utility of sCOMP as a marker for disease activity in patients with active psoriatic arthritis (PsA) in comparison to a control group only with psoriasis vulgaris (PV). METHODS: Serum levels of COMP were measured in 64 patients with PsA and psoriasis vulgaris. The control group consisted of a population with PV from a dermatological outpatient clinic. ELISA-tests were used to detect sCOMP levels according to the manufacturer instructions. RESULTS: In our 64 patients with PsA, we found increased sCOMP levels, which correlated significantly with inflammatory parameters and the number of swollen joints. Patients with active PsA had significantly higher sCOMP levels (p<0.0001) than the 39 patients with a low inflammatory status. In our control group with PV we also found elevated sCOMP levels, which correlated significantly with the increased C-reactive protein (CRP) levels in this group. The difference between the PsA and the PV group was not significant (p=0.092). CONCLUSION: In our study, sCOMP has been demonstrated to be an indicator for disease activity in patients with PsA. Patients with active PsA showed significantly elevated sCOMP levels compared to the patients with low clinical and laboratory disease activity. The increased sCOMP levels in our control group with PV indicate that all patients with psoriatic lesions should be screened for additional joint involvement and should lead to an exact joint examination.

Safety and immunogenicity of a Vero-cell-derived, inactivated Japanese encephalitis vaccine: a non-inferiority, phase III, randomised controlled trial.

BACKGROUND: Japanese encephalitis virus (JEV) is the leading cause of viral encephalitis in southeast Asia. Although no treatment is currently available, vaccination effectively prevents the disease. In a non-inferiority study, we aimed to compare the safety and immunogenicity of a novel, second-generation, inactivated candidate vaccine for JEV with a licensed, mouse-brain-derived vaccine. METHODS: We included 867 adults in a multicentre, multinational, observer-blinded, randomised controlled phase III trial. Study sites were located in the USA, Germany, and Austria. Volunteers received either the JEV test vaccine intramuscularly on a two-dose schedule (on days 0 and 28; n=430) or the licensed vaccine subcutaneously according to its recommended three-dose schedule (on days 0, 7, and 28; n=437). The primary endpoint was immunogenicity, with respect to neutralising JEV-specific antibodies assessed by a plaque-reduction neutralisation test, which was assessable in 725 patients in the per-protocol population. This trial is registered as a clinical trial, EudraCT number 2004-002474-36. FINDINGS: The safety profile of the test vaccine was good, and its local tolerability profile was more favourable than that of the licensed vaccine. Frequency of adverse events was similar between treatment groups, and vaccine-related adverse events were generally mild. The seroconversion rate of the test vaccine was 98% compared with 95% for the licensed vaccine on day 56 (95% CI for the difference -1.33 to 3.43). Geometric mean titre for recipients of the test vaccine was 244 (range 5-19 783), compared with 102 (5-1864) for the licensed vaccine (ratio 2.3 [95% CI 1.967-2.75]). INTERPRETATION: The test JEV vaccine has a promising immunogenicity and safety profile.

The effect of fibrinogen concentrate on thrombocytopenia.

OBJECTIVES: The hypothesis that the administration of fibrinogen concentrate enables restoration of impaired clot formation and increased bleeding in severe thrombocytopenia was tested. METHODS: Thirty pigs were anesthetized, instrumented for blood sampling (routine coagulation tests, modified thrombelastography ROTEM, hemodynamic monitoring and platelet apheresis to a target below 30 x 10(9) L(-1) after splenectomy. Thereafter 10 each of the animals randomly received two apheresis platelet concentrates, 250 mg kg(-1) fibrinogen concentrate or normal saline solution. A standardized liver injury was subsequently inflicted to induce uncontrolled hemorrhage. RESULTS: Median (Q1, Q3) clot firmness increased significantly more in thrombocytopenic pigs after fibrinogen administration (42 mm (41, 43) to 60 mm (57, 63)) than following platelet transfusion (40 mm (37, 45) to 52 mm (48, 55), P = 0.0004) or placebo (45 mm (41, 48) to 45 mm (43, 46), P = 0.0002). Median blood loss velocity after liver injury was significantly less with fibrinogen (33 mL min(-1), P = 0.005) than with platelets (62 mL min(-1), P = 0.037) or saline (84 mL min(-1), P = 0.005), and median survival time after liver injury was 55 min in the fibrinogen, 26 min in the platelet (P = 0.035) and 19 min in the saline group (P = < 0.0001). CONCLUSIONS: These data show for the first time that impaired clot formation during thrombocytopenia improves with administration of fibrinogen concentrate, which results in a slowdown of blood loss and prolonged survival.

Efficacy of fibrinogen and prothrombin complex concentrate used to reverse dilutional coagulopathy--a porcine model.

BACKGROUND: This study was conducted to assess whether the combined administration of fibrinogen and prothrombin complex concentrate (PCC) enables the reversal of dilutional coagulopathy resulting from intended blood loss and fluid replacement, and whether this treatment reduces further blood loss and mortality. METHODS: In 20 anaesthetized pigs, approximately 65% of the estimated blood volume was withdrawn and replaced with the same amount of hydroxyethyl starch (6% HES 130/0.4) to mimic blood loss and to develop a dilutional coagulopathy. Pigs (randomized) received either fibrinogen (200 mg kg(-1)) and PCC (35 IU kg(-1)) (n=10), or placebo (n=10). Thereafter, a standard liver laceration was performed to induce uncontrolled haemorrhage. The subsequent blood loss and survival time were determined as primary outcome variables. Throughout the experiment serial blood samples were obtained to assess the competence of the haemostatic system using standard coagulation tests, modified Thrombelastograph measurements (ROTEM) and electron microscopy clot imaging. RESULTS: As compared with baseline, after haemodilution both groups showed statistically significant impairment of haemostasis as measured with standard coagulation tests and thrombelastography. These parameters significantly improved after administration of the study drugs while aPPT measurements remained unchanged. Blood loss after liver injury was significantly less in the treatment group as compared with placebo: 240 ml (50-830) vs 1800 ml (1500-2500) (P<0.0001). All treated animals survived, whereas 80% of the placebo group died (P<0.0001). CONCLUSION: During haemodilution, substitution of fibrinogen and PCC causes an enhancement of coagulation and final clot strength. This reversal of dilutional coagulopathy may reduce blood loss and mortality when large amounts of colloids are needed to maintain normovolaemia during huge blood losses.

Postoperative pain and quality of life after laparoscopic and open inguinal hernia repair: results of a prospective randomized trial.

BACKGROUND: As part of a large prospective randomized Austrian multicenter trial evaluating recurrence rates and complications of open and laparoscopic unilateral inguinal hernia repairs we assessed postoperative pain and quality of life. METHODS: Approximately 151 patients were randomized to Shouldice repair, Bassini operation, or laparoscopic transabdominal preperitoneal hernioplasty (TAPP). Pain was recorded preoperatively and on the first four postoperative days. Quality of life was recorded preoperatively and 1 month postoperatively. RESULTS: Patients having Shouldice repairs had significantly higher visual analog-scale scores for pain on the fourth postoperative day (P=0.048) and significantly higher scores in McGill pain questionnaires on the first four postoperative days (P=0.046) compared with the other groups. Apart from a significantly lower score in postoperative bodily pain in the Shouldice group (P=0.039), no significant differences in quality of life were apparent among the three methods. CONCLUSIONS: The TAPP and Bassini repairs result in less short-term postoperative pain.

Improvement of metabolic syndrome markers through altitude specific hiking vacations.

To study the influence of a 3-week hiking vacation at moderate (1700 m) and low altitude (LA) (200 m) on key-markers of the metabolic syndrome, 71 male volunteers (age 36-66 yr old) with the metabolic syndrome [according to the National Cholesterol Education Program's Adult Treatment Panel III (NCEP-ATP III) - or World Health Organization (WHO) - definition] participated in the study and were randomly assigned into a moderate altitude (MA) group (1700 m, no. 36) and a low altitude (LA) group (200 m, no. 35). The 3-week vacation program included 12 moderate- intensity guided hiking tours [4 times/week, 55-65% heart rate maximum (HRmax)] with a total exercise time of 29 h plus moderate recreational activities. Both study groups had a comparable and balanced nutrition with no specific dietary restrictions. Anthropometric, metabolic and cardiovascular parameters were measured 10-14 days before vacation, several times during the 3-week vacation, 7-10 days and 6-8 weeks after return. All participants tolerated the vacation without any adverse effects. Body weight, body fat, waist-circumference, fasting glucose, total cholesterol, LDL-cholesterol (LDL-C), plasma fibrinogen, resting systolic and diastolic blood pressure were significantly decreased over time in both study groups. In the LA group, fasting insulin and homeostasis model assessment (HOMA)-index were significantly decreased one week after return. Relative cycle ergometry performance was significantly increased after return compared to baseline. In both study groups, waist-to-hip ratio (WHR), 2-h oral glucose tolerance test (OGTT), HDL-cholesterol (HDL-C), and triglycerides remained unchanged. The 3-week vacation intervention at moderate and LA had a positive influence on all key-markers of the metabolic syndrome. No clinically relevant differences could be detected between the study groups. A hiking vacation at moderate and LA can be recommended for people with stable, controlled metabolic and cardiovascular risk factors.

Austrian experiences with redo antireflux surgery.

BACKGROUND: From 1996, the entire number of fundoplications performed in Austria increased dramatically, favoring the laparoscopic technique. Despite good results, some patients experience failure of antireflux surgery and therefore require redo surgery if medical therapy fails to control symptoms. The aim of the study was to describe the refundoplication policy in Austria with evaluation of the postoperative results. METHODS: A questionnaire was sent to all Austrian surgical departments at the beginning of 2003 with questions about redo fundoplications (number, techniques, intraoperative complications, history, migration of patients, preoperative workup, mortality, and postoperative long-term complaints). It also included questions about primary fundoplications (number, technique, postoperative symptoms). RESULTS: Out of 4,504 primary fundoplications performed in Austria since 1990, 3,952 have been carried out laparoscopically. In a median of 31 months after the primary operation, 225 refundoplications have been performed, laparoscopically in the majority of patients. The Nissen and the partial posterior fundoplication were the preferred techniques. The conversion rate in these was 10.8%, mainly because of adhesions and lacerations of the spleen, the stomach, and the esophagus. The mortality rate after primary fundoplications was 0.04%, whereas the rate after refundoplications was 0.4%, all resulting from an open approach. CONCLUSION: Laparoscopic refundoplications are widely accepted as a treatment option after failed primary antireflux surgery in Austria. However, the conversion rate is 6 times higher and the mortality rate is 10 times higher than for primary antireflux surgery. Therefore, redo fundoplications should be performed only in departments with large experience.

Effects of protamine and heparin can be detected and easily differentiated by modified thrombelastography (Rotem): an in vitro study.

BACKGROUND: Precise coagulation monitoring might help prevent heparin-protamine mismatch and thus decrease postoperative blood loss. We therefore measured coagulation time (CT) by modified thrombelastography (Rotem) as a possible differential monitor of the effects of heparin and protamine. METHODS: Undiluted and diluted blood samples from 26 healthy volunteers were spiked with increasing concentrations of heparin (0.1, 0.2, 0.4, 0.8 and 1 U ml(-1)). In addition, undiluted blood was spiked with protamine hydrochloride (0.1, 0.2, 0.4, 0.8 and 1.6 U ml(-1)), and we tested the effect of protamine on the reversal of heparin 0.4 U ml(-1). Heparin-containing samples were analysed using the heparin-sensitive INTEM test and the heparinase-containing HEPTEM test; protamine series were also analysed with the EXTEM test (tissue factor activation). RESULTS: CT by the INTEM test [CT-INTEM; median (min/max)] increased significantly and dose-dependently with increasing concentrations of heparin [control, 175 s (146/226); heparin, 1.0 U ml(-1) 1320 s (559/2100); P<0.001] and protamine [control, 172 s (150/255); protamine, 1.6 U ml(-1) 527 s (300/1345); P<0.0001]. Up to heparin concentrations of 0.4 U ml(-1), results were similar in undiluted and diluted blood samples. As expected, CT-HEPTEM remained within the normal range for all tested heparin concentrations (median 180-183 s), but increased similarly to CT-INTEM for increasing protamine concentrations. CONCLUSION: CT measurement using the Rotem technique appears to be a valuable tool for heparin-protamine management. For detection of heparin alone, protamine alone and the two combined, the ratio of CT-INTEM:CT-HEPTEM can be used to distinguish the effects of heparin excess (CT-INTEM:CT-HEPTEM>1) from those of protamine excess (CT-INTEM:CT-HEPTEM=1).

Totally extraperitoneal inguinal hernioplasty with titanium-coated lightweight polypropylene mesh: early results.

BACKGROUND: This prospective study of a new titanium-coated low-weight polypropylene (PP) mesh (16 g PP/m2) was designed to investigate the clinical efficacy and safety of totally extraperitoneal endoscopic hernioplasty (TEP). METHODS: In this study, 400 patients (average age, 53.5 years; range, 19-80 years) with a total of 588 inguinal hernias underwent surgery with the TEP technique between September 2002 and October 2003. Of these patients, 12.4% had experienced recurrent hernias after open suture herniotomy. In 92% of the cases (368 patients with 540 hernias), a lightweight (16 g PP/m2) titanium-coated polypropylene mesh was implanted without fixation, and in 8% (32 patients with 48 hernias) an identical medium-weight (35 g PP/m2) mesh was implanted. The first follow-up examination was scheduled for postoperative week 6. RESULTS: In the lightweight mesh group, the mean group, operating time per patient was 61 min, corresponding to a calculated time per hernia of 41 min. Two intraoperative major complications occurred: an injury to the cecum and an injury to the bladder. In 12 cases (2%), bleeding from epigastric, testicular, or pubic bone vessels was observed. No injuries to pelvic vessels were seen. One patient was underwent an endoscopic revision to deal with an anticoagulation-related bleed. The mortality rate was 0%. In 12 patients, postoperative hematomas developed. One preperitoneal lipoma had to be extirpated. No infections of the mesh occurred. The median follow-up period for 371 patients (92.3%) was 7.2 weeks (range, 4-14 weeks). These 343 patients (with 504 hernias) had been provided with a lightweight titanium-coated polypropylene mesh (16 g PP/m2) (follow-up rate, 93.2%). Of these patients, 3.5% reported persistent ingunial pain, 1.7% described a sensation of rigidity in the region of the groin, and 3.2% reported dysesthesia. The early recurrence rate was 0.2%. CONCLUSIONS: The TEP procedure can be performed safely and effectively with the appreciably material-reduced and titanium-coated polypropylene mesh without the need for fixation of the implant. The low early recurrence rate of 0.2% is evidence that the posterior wall of the inguinal canal is adequately augmented. The question whether the material reduction and the titanium coating of the mesh may bring about a reduction in postoperative chronic pain and the sensation of rigidity in the inguinal area via an improvement in biocompatibility must await the results of the scheduled follow-up examination 1 year after the surgical procedure.

Effect of fibrinogen on reversal of dilutional coagulopathy: a porcine model.

BACKGROUND: This study was conducted to determine whether replacement of fibrinogen is useful in reversing dilutional coagulopathy following severe haemorrhage and administration of colloids. METHODS: In 14 anaesthetized pigs, approximately 65% of the estimated blood volume was withdrawn and replaced with the same amount of gelatin solution to achieve dilutional coagulopathy. Animals were randomized to receive either 250 mg kg(-1) fibrinogen (n=7) or normal saline (n=7). A standardized liver injury was then inflicted to induce uncontrolled haemorrhage. Modified thrombelastography and standard coagulation tests were performed at baseline, after blood withdrawal, after dilution, after injection of the study drugs, and on conclusion of the protocol. Further, electron microscopy imaging of the blood clots was performed and blood loss after liver injury was determined. RESULTS: Severely impaired haemostasis was observed after haemodilution with gelatin substitution. With administration of fibrinogen, clot firmness and dynamics of clot formation reached baseline values. Median blood loss following liver injury was significantly less (P=0.018) in the fibrinogen-treated animals (1100 ml; 800-1400 ml) than in the placebo group (2010 ml; 1800-2200 ml). CONCLUSIONS: Replacing 65% of the estimated blood volume with gelatin in swine resulted in dilutional coagulopathy; subsequent fibrinogen administration improved clot formation and reduced blood loss significantly.

Osteoprotegerin and the receptor activator of NF-kappa B ligand in the serum and synovial fluid. A comparison of patients with longstanding rheumatoid arthritis and osteoarthritis.

We examined OPG and soluble RANKL in the serum (sOPG, sRANKL) and synovial fluid (synOPG, synRANKL) in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). OPG and RANKL were measured in 85 patients (44 with RA, 41 patients with OA) in serum and synovial fluid as well. For measuring of OPG and RANKL ELISA tests were used. The results of OPG and RANKL were compared with clinical and radiological scores. We found a negative correlation for OPG and RANKL in synovial fluids: not only for the whole group of patients (P < 0.003, r = -0.32), but also for the subgroups (RA: P < 0.04, r = -0.28, OA: P < 0.002, r = -0.54). SRANKL and synRANKL were positively correlated in the whole group (P < 0.01, r = 0.25) and in the OA group (P < 0.02, r = 0.35); the RA group was showing a trend (P < 0.063, r = 0.24), however. Serum OPG was lower in RA, synOPG higher in OA. The difference between the two patient groups was only significant for synOPG (P < 0.03, r = 0.056), but not for sOPG (P < 0.09, r = 0.19), sRANKL (P < 0.43, r = 0.85) or synRANKL (P < 0.11, r = 0.22). The synOPG:synRANKL ratio was significantly correlated with the Larsen score (P < 0.004, r = 0.38). Synovial OPG is significantly decreased in rheumatoid joints, whereby synovial RANKL is increased. Lower synOPG could reflect a lower protective effect on bone, thus leading to an earlier and more pronounced bone destruction in RA. However, the effect of different mediators for joint destruction in RA and OA seems not to be important to the pathophysiological changes in the joints. The upregulation of serum OPG might be the result of the inflammation; in contrast, an upregulation of RANKL could not be found in the serum of patients with RA and OA.

Serum levels of cartilage oligomeric matrix protein. A predicting factor and a valuable parameter for disease management in rheumatoid arthritis.

OBJECTIVE: To examine whether cartilage oligomeric matrix protein (COMP) correlates with inflammation and/or joint destruction of patients with rheumatoid arthritis (RA) and to test COMP as predicting factor for the outcome of patients with established RA. METHODS: Serum levels of COMP were measured in sera of 62 patients, suffering from RA according to the ACR criteria and treated in intervals in our department, over a period of 5 years. A commercially available sandwich--type ELISA-kit developed by AnaMar Medical AB, Sweden, was used. The results of serum COMP were compared with the Disease Activity Score (DAS), the Larsen Score, and clinical and laboratory parameters. RESULTS: We found a positive correlation between serum levels of COMP at baseline and deterioration of Larsen score even after 5 years (p < 0.007; r = 0.34). To confirm serum COMP as an independent predicting factor for patients with RA we looked at a subgroup of patients (n = 17) with elevated serum levels of COMP (mean 11,7 U/l) and low clinical prognostic factors. In this subgroup we also found a significant correlation with delta Larsen score (p < 0.01; r = 0.59) after 5 years. CONCLUSION: Serum levels of COMP is known to reflect increased cartilage turnover. The results indicate that serum COMP may be used as a prognostic marker of cartilage degradation in a patient group with established RA.

Plasma amine oxidase: a postulated cardiovascular risk factor in nondiabetic obese patients.

Increased activity of semicarbazide-sensitive plasma amine oxidase (SSAO), an enzyme converting various amines, has been implicated in the generation of endothelial damage through formation of cytotoxic reaction products. We investigated if SSAO activity is elevated in morbidly obese patients, which might contribute to the increased cardiovascular risk associated with obesity. SSAO activity was determined in 74 nondiabetic, obese patients (median body mass index [BMI]: 42.9 kg/m(2)) and in 32 healthy, non-obese controls (median BMI: 23.3 kg/m(2)) using a radiometric assay based on the conversion of [(14)C]benzylamine. SSAO and parameters of glucose and lipid metabolism were compared for subgroups of obese patients with normal (n = 49) and impaired (n = 25) glucose tolerance using nonparametric statistical tests. Median SSAO activity was 434 microU/mL in obese patients, which was significantly higher than in healthy, non-obese controls (median SSAO activity: 361 microU/mL). Median SSAO activity in patients with normal and impaired glucose tolerance was 423 and 464 microU/mL, respectively. SSAO activity was not correlated with any other clinical or laboratory parameters characteristic of the metabolic alterations associated with obesity. Elevated SSAO activity is found in nondiabetic, morbidly obese patients and might be an interesting independent risk factor for obesity-related cardiovascular morbidity. Long-term follow-up of SSAO and its possible role in pathogenic events is warranted since intervention with specific SSAO inhibitors is available.

Prospective multicentre trial comparing the efficacy of, and compliance with, glimepiride or acarbose treatment in patients with type 2 diabetes not controlled with diet alone.

AIM: To determine the efficacy of, and compliance with, glimepiride or acarbose in patients with Type 2 diabetes. METHODS: Two hundred and nineteen patients with Type 2 diabetes uncontrolled by diet alone were randomized to receive either glimepiride (1, 2, 3, 4 or 6 mg once daily, n = 111) or acarbose (50, 100, 150 or 200 mg 3 times daily, n = 108). Both drugs were titrated in a 6-week dose-finding phase to achieve a fasting blood glucose (FBG) concentration < or = 7.8 mmol/ (140 mg/dl). Patients achieving this target entered a 20-week treatment period. Efficacy was assessed by responder rate, number of patients achieving a FBG of < or = 7.8 mmol/l, HbA1c, blood glucose concentrations in response to a standard breakfast, body weight and compliance. RESULTS: Glimepiride was associated with a significantly greater responder rate than acarbose (61 vs 34%, p < 0.001), significantly greater decreases in HbA1c (2.5 +/- 2.2% vs 1.8 +/- 2.2%, p = 0.014) and FBG (2.6 +/- 2.6 mmol/l vs 1.4 +/- 2.8 mmo/l, p = 0.004), a decreased glucose response to breakfast compared with acarbose [area under curve (AUC) end: 8.9 +/- 2.7 mmol/l vs 11.3 +/- 3.9 mmol/l, p = 0.0001], and was accompanied by significantly greater compliance (91 < or = 12% vs 66 +/- 26%, p = 0.0001). Weight loss during the study was observed in both the acarbose group (1.9 +/- 3.9 kg, p = 0.001) and glimepiride group [0.4 +/- 5.2 kg, p = 0.8 (NS)]. CONCLUSIONS: Improved efficacy and greater compliance were observed in response to treatment with glimepiride compared with acarbose, in patients with Type 2 diabetes.