Magnetic resonance imaging of the fifth metatarsophalangeal joint compared with conventional radiography in patients with early rheumatoid arthritis

OBJECTIVE: To evaluate if magnetic resonance imaging (MRI) is superior to conventional radiography for detection of erosions in the fifth metatarsophalangeal (MTP5) joint. METHODS: Within one year from the onset of rheumatoid arthritis (RA) (baseline), one and three years thereafter MRI and conventional radiographs of the MTP5 joint were performed in 23 patients. RESULTS: MRI revealed erosions in 10 patients at baseline, in 15 after one year and in 15 patients after 3 years. On conventional radiography, there were erosions in 10 patients at baseline, 16 after one year as well as after 3 years. The agreement between the two imaging methods was fair to good at baseline and after one and three years (kappa 0,65, 0,51 and 0,51 respectively). The number of patients with clinical evidence of synovitis decreased considerably over time although the number of patients with MRI-synovitis was unchanged and the number of patients with erosions increased. CONCLUSIONS: MRI was not superior to conventional radiography in detecting erosions in MTP5 joints in patients with early RA. Most erosions developed during the first year of observation. Synovitis on MRI may be a marker of future development of erosions in the MTP5 joint.     

Progress in allogenic bone marrow and peripheral blood stem cell transplantation for multiple myeloma: a comparison between transplants performed 1983--93 and 1994--8 at European Group for Blood and Marrow Transplantation centres

Out of 690 allogeneic matched sibling donor transplants for multiple myeloma reported to the European Group for Blood and Marrow Transplantation (EBMT) registry, 334 were performed during the period 1983-93 (all with bone marrow) and 356 during 1994-98 [223 with bone marrow and 133 with peripheral blood stem cells (PBSCs)]. The median overall survival was 10 months for patients transplanted during the earlier time period and 50 months for patients transplanted with hone marrow during the later period. The use of PBSCs was associated with earlier engraftment but no significant survival benefit compared to bone marrow transplants during the same time period. The improvement in survival since 1994 with the result of a significant reduction in transplant-related mortality, which was 38%, 21% and 25% at 6 months and 46%, 30% and 37% at 2 years during the earlier period, and the later period with bone marrow and PBSCs respectively. Reasons for the reduced transplant-related mortality appeared to be fewer deaths owing to bacterial and fungal infections and interstitial pneumonitis, in turn a result of earlier transplantation and less prior chemotherapy. Better supportive treatment and more frequent use of cytokines may also play a role. The improvement in survival was not directly related to the increased use of PBSCs.     

Conversion of alpha-lactalbumin to a protein inducing apoptosis

In this study alpha-lactalbumin was converted from the regular, native state to a folding variant with altered biological function. The folding variant was shown to induce apoptosis in tumor cells and immature cells, but healthy cells were resistant to this effect. Conversion to HAMLET (human alpha-lactalbumin made lethal to tumor cells) required partial unfolding of the protein and a specific fatty acid, C18:1, as a necessary cofactor. Conversion was achieved with alpha-lactalbumin derived from human milk whey and with recombinant protein expressed in Escherichia coli. We thus have identified the folding change and the fatty acid as two key elements that define HAMLET, the apoptosis-inducing functional state of alpha-lactalbumin. Although the environment in the mammary gland favors the native conformation of alpha-lactalbumin that serves as a specifier in the lactose synthase complex, the conditions under which HAMLET was formed resemble those in the stomach of the nursing child. Low pH is known to release Ca(2+) from the high-affinity Ca(2+)-binding site and to activate lipases that hydrolyze free fatty acids from milk triglycerides. We propose that this single amino acid polypeptide chain may perform vastly different biological functions depending on its folding state and the in vivo environment. It may be speculated that molecules like HAMLET can aid in lowering the incidence of cancer in breast-fed children by purging of tumor cells from the gut of the neonate.     

Conditioned pain modulation in temporomandibular disorders (TMD) pain patients

The aims were to investigate (1) if temporomandibular disorders (TMD) patients with temporomandibular joint (TMJ) pain had different conditioned pain modulation (CPM) compared with healthy subjects and, (2) if clinical pain characteristics influenced CPM. Sixteen TMD pain patients and 16 age-matched healthy subjects were participated. A mechanical conditioning stimulus (CS) was applied to pericranial muscles provoking a pain intensity of 5/10 on a visual analogue scale. Pressure pain thresholds (PPT) and pressure pain tolerance thresholds (PPTol) were assessed at masseter, forearm and painful TMJ (only PPT) before, during, and 20 min after CS. Data were analyzed with ANOVAs. The correlations between CPM effect and ratings of TMD pain intensity on a numerical rating scale (NRS) or the pain duration were calculated (correlation coefficient; R). The relative PPT and PPTol increases (mean for the three assessment sites) during CS were significantly higher than baseline in healthy subjects (43.0 ± 3.6, 33.0 ± 4.0 %; P < 0.001, P < 0.001) but not in the TMD pain patients (4.9 ± 2.7, ?1.4 ± 4.1 %; P = 0.492, P = 1.000) with significant differences between groups (P < 0.001). In the patients, the relative PPT changes during CS were not significantly higher than baseline at TMJ (5.3 ± 3.8 %, P = 0.981) and masseter (?2.8 ± 4.8 %, P = 1.000) but significantly higher at forearm (12.3 ± 4.7 %, P = 0.039). No correlation was detected between TMD pain intensity and CPM effect (R = ?0.261; P = 0.337) or between pain duration and CPM effect (R = ?0.423; P = 0.103) at painful TMJ. These findings indicate that CPM is impaired in TMD pain patients especially at sites with chronic pain but not at pain-free sites and that the clinical pain characteristics do not influence CPM.     

Platelet Activation by Streptococcus pyogenes Leads to Entrapment in Platelet Aggregates,from Which Bacteria Subsequently Escape

Platelet activation and aggregation have been reported to occur in response to a number of Gram-positive pathogens. Here, we show that platelet aggregates induced by Streptococcus pyogenes were unstable and that viable bacteria escaped from the aggregates over time. This was not due to differential activation in response to the bacteria compared with physiological activators. All the bacterial isolates induced significant platelet activation, including integrin activation and alpha and dense-granule release, at levels equivalent to those induced by potent physiological platelet activators that induced stable aggregates. The ability to escape the aggregates and to resist the antibacterial effects of platelets was dependent on active protein synthesis by the bacteria within the aggregate. We conclude that S. pyogenes bacteria can temporarily cover themselves with activated platelets, and we propose that this may facilitate survival of the bacteria in the presence of platelets.     

Mechanical sensitivity and psychological factors in patients with burning mouth syndrome

Clinical Oral Investigations - The aim of this study was to compare mechanical sensitivity on the tongue using quantitative sensory testing (QST) and psychological factors using the General Health...     

Superior beta cell proliferation, function and gene expression in a subpopulation of rat islets identified by high blood perfusion

Aims/hypothesis  

The blood perfusion of individual pancreatic islets is highly variable, with a subgroup of islets having high perfusion and blood vessels responsive to further blood flow increase induced by glucose. This study tested the hypothesis that there is heterogeneity between islets with regard to beta cell proliferation, function and gene expression based on differences in their blood perfusion.     

Long-term mortality in patients with type 2 diabetes undergoing coronary angiography: the impact of glucose-lowering treatment

Aims/hypothesis  

The aim of this study was to analyse whether the increased mortality rates observed in insulin-treated patients with type 2 diabetes and coronary artery disease are explained by comorbidities and complications.     

Effects of hyperinsulinemia on lipoprotein lipase, angiopoietin-like protein 4, and glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 in subjects with and without type 2 diabetes mellitus

Our aims were to compare the systemic effects of insulin on lipoprotein lipase (LPL) in tissues from subjects with different degrees of insulin sensitivity. The effects of insulin on LPL during a 4-hour hyperinsulinemic, euglycemic clamp were studied in skeletal muscle, adipose tissue, and postheparin plasma from young healthy subjects (YS), older subjects with type 2 diabetes mellitus (DS), and older control subjects (CS). In addition, we studied the effects of insulin on the expression of 2 recently recognized candidate genes for control of LPL activity: angiopoietin-like protein 4 (ANGPTL4) and glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1. As an effect of insulin, LPL activity decreased by 20% to 25% in postheparin plasma and increased by 20% to 30% in adipose tissue in all groups. In YS, the levels of ANGPTL4 messenger RNA in adipose tissue decreased 3-fold during the clamp. In contrast, there was no significant change in DS or CS. Regression analysis showed that the ability of insulin to reduce the expression of ANGPTL4 was positively correlated with M-values and inversely correlated with factors linked to the metabolic syndrome. Expression of glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 tended to be higher in YS than in DS or CS, but the expression was not affected by insulin in any of the groups. Our data imply that the insulin-mediated regulation of LPL is not directly linked to the control of glucose turnover by insulin or to ANGPTL4 expression in adipose tissue or plasma. Interestingly, the response of ANGPTL4 expression in adipose tissue to insulin was severely blunted in both DS and CS.