A new biodegradable braided self-expandable PLGA prostatic stent: an experimental study in the rabbit

PURPOSE: The biodegradable PLGA (a copolymer of L-lactide and glycolide) urethral stent with a spiral configuration has been used clinically for the prevention of postoperative urinary retention after different types of thermal therapy for benign prostatic hyperplasia. A new braiding pattern for this stent has recently been developed by our group. The aim here was to investigate the in situ degradation and biocompatibility of the new braided stent in the rabbit urethra. MATERIALS AND METHODS: PLGA stents with a one-over-one braiding pattern and steel stents served as controls that were inserted into the posterior urethras of 24 male rabbits using a special delivery instrument. The animals were sacrificed after 1 week, 1 month, 2 months, or 4 months, and light microscopy and histologic analyses were performed. RESULTS: The delivery instrument worked well and cystoscopy was not needed in the insertion process. The braided PLGA stents degraded smoothly in 1 to 2 months. The metallic stents induced more epithelial hyperplasia and epithelial changes than the biodegradable stents at all time points analyzed. These differences increased during follow-up. CONCLUSION: The degradation process was well controlled and the biodegradable stents were more biocompatible than the metallic stents. The new stent can be inserted into the posterior urethra without cystoscopic aid.     

MMP-1 (collagenase-1) expression in primary colorectal cancer and its metastases

OBJECTIVE: The role of MMP-1 (collagenase-1) in the development of a metastatic phenotype in colorectal cancer (CRC) has not been fully studied. The aim of this study was to investigate the mechanisms involved in the dissemination of CRC by examining the expression of MMP-1 in the primary tumours and their metastases, with special reference to standard clinicopathological features and disease outcome. MATERIAL AND METHODS: Surgical specimens from the primary tumours (P) and their metastatic (M) lesions were available from 30 patients with Stage II, III and IV CRC, and were subjected to immunohistochemical (IHC) staining for MMP-1. Both cytoplasmic expression in cancer cells (CC) and stromal (ST) expression were related to pertinent clinical and follow-up data. RESULTS: In a pairwise comparison of P-M pairs, CC expression (but not ST expression) in P and M was significantly different (Wilcoxon rank test, p=0.037). Strong CC expression in P was significantly related to the presence of lymph node involvement at diagnosis (p=0.008). CC expression in M was intense only in metachronous metastases (Stage II/III disease) but never in synchronous metastases (Stage IV) (p=0.034). There was a significant down-regulation of CC (p=0.004) in liver metastasis (n=9) in comparison with all other metastatic sites (n=21). ST expression in P (but not in M) showed a linear decrease in parallel with increasing stage (p=0.028 for linear trend). MMP-1 expression was not significantly associated with any other clinicopathological variables, including age, gender, carcinoembryonic antigen (CEA) or patients' disease-free or overall survival. CONCLUSIONS: These data suggest that MMP-1 may play an important role in tumour invasion and metastasis of CRC.     

Underlying factors in the association between depressed mood and mobility limitation in older people

BACKGROUND: Depressed mood may either precede mobility limitation or follow from mobility limitation. OBJECTIVE: To compare mood status among people with manifest mobility limitation, those with preclinical mobility limitation and those without mobility limitation and investigate factors explaining the association between depressed mood and mobility limitation. DESIGN: Cross-sectional. Subjects: 645 community-living 75- to 81-year-old people. METHODS: Depressed mood was assessed using the Centre for Epidemiologic Studies Depression Scale (CES-D, cut-off score 16); difficulty walking 500 m was assessed by self-report. Those reporting difficulty were categorised as having manifest mobility limitation. Those with no difficulty but reporting task modifications, such as reduced frequency of walking, were categorised as having preclinical mobility limitation. The association between depressed mood and mobility limitation was analysed using logistic regression analysis with gender, age, economic situation, the availability of a confidant, chronic conditions, and widespread pain as covariates. RESULTS: Depressed mood was found in 34% of subjects with manifest mobility limitation, in 26% of those with preclinical mobility limitation, and in 13% of those without mobility limitation. The unadjusted odds ratio for depressed mood was 3.43 (95% CI 2.04-5.76) among subjects with manifest mobility limitation and 2.38 (95% CI 1.52-3.73) among those with preclinical mobility limitation, compared to those without mobility limitation.Adjustment for covariates reduced the risks to 2.10 (95% CI 1.15-3.82) and 1.99 (95% CI 1.24-3.20), respectively. Widespread pain explained 28% of the increased risk of depressed mood among those with manifest mobility limitation. CONCLUSION: The dose-response relationship between depressed mood and mobility limitation suggests that both conditions may progress simultaneously and may share aetiology, at least in part. Pain may be an underlying factor in both depressed mood and mobility limitation.     

Cardiac arrest and left ventricular fibrosis in a Finnish family with the lamin A/C mutation

Introduction: We screened the candidate genes from a Finnish family in which the mother was resuscitated from ventricular fibrillation and the daughter died suddenly without any prior cardiac symptoms.
Methods and Results: In addition to screening of potential structural gene mutations, phenotyping of the proband and medico-legal autopsy of the victim of the sudden death, including histopathological examinations, were performed. Genetic screening revealed an R541C mutation in the lamin A/C gene both in the proband and her daughter. None of the 16 first- or second-degree relatives, or 96 unrelated healthy subjects, carried the same mutation. In the proband, the size and the global function of the left ventricle (LV) were normal, but a local hypokinesia and thinning of inferoposterior area of the LV were seen in 2D echocardiography and magnetic resonance imaging. Coronary angiogram and the results of the electrophysiological study were normal. Autopsy of the victim of sudden death showed localized thinning and fibrosis in the inferoposterior area of the LV, with only minimal fibrosis in the right ventricle and no abnormalities in the interventricular septum.
Conclusion: These observations indicate that a fatal or near-fatal cardiac arrhythmia can be the first clinical manifestation of a "de novo" mutation R541C of the lamin A/C gene. Replacement of cardiac myocytes by fibrosis seems to be the predominant pathologic-anatomic finding.     

A novel mutation, Ser143Pro, in the lamin A/C gene is common in finnish patients with familial dilated cardiomyopathy.

AIMS: The mutations most frequently associated with dilated cardiomyopathy (DCM) have been reported in the lamin A/C gene. The role of variants of the lamin A/C gene was investigated in patients with DCM from eastern and southern Finland. METHODS AND RESULTS: All 12 exons of the lamin A/C gene were screened in 18 well-characterised familial DCM patients from eastern and southern Finland and in 72 sporadic DCM patients from eastern Finland using the PCR-SSCP method. A novel mutation, Ser143Pro (S143P), was detected in the lamin A/C gene in 24 subjects from 5 unrelated families and in one sporadic case of DCM. Sinus or atrioventricular nodal dysfunction occurred in the majority of the affected subjects, many of which required pacemaker implantation. Seven patients (28%) with the S143P mutation died suddenly or from progressive heart failure, or underwent heart transplantation. The haplotypes 5-5-5-3, 5-5-5-2, and 5-5-5-1 co-segregated with the Ser143Pro mutation, suggesting a founder effect of this mutation. CONCLUSIONS: A novel mutation S143P in the lamin A/C gene was found to be common among Finnish DCM patients. Haplotype analysis strongly suggests a founder effect of this mutation. The phenotype is characterised by severe heart failure, progressive atrioventricular conduction defects, and sudden death. Screening for the lamin A/C gene and, particularly, the S143P mutation seems warranted when patients with DCM have conduction system disturbances.     

Bone oedema predicts erosive progression on wrist MRI in early RA--a 2-yr observational MRI and NC scintigraphy study

OBJECTIVES: To investigate if disease assessment by contrast-enhanced dynamic and static magnetic resonance imaging (MRI) and quantitative nanocolloid (NC) scintigraphy gives useful additional information in early rheumatoid arthritis (RA). METHODS: Twenty-seven patients with early RA (disease duration < or =12 months) were followed up for 1 yr and 24 of them for 2 yrs with contrast-enhanced MRI and NC scintigraphy of the wrist joint. Synovial inflammation was assessed by measuring time-dependent enhancement rates (E-rate) from dynamic MRI scans and technetium(99m)-labelled nanocolloid ((99m)Tc-NC) uptake from scintigraphy scans. Synovial membrane hypertrophy, bone oedema and erosions were semiquantitatively scored according to the Outcome Measures in Rheumatology Clinical Trials RA-MRI scoring system from static MR images. Response to the treatment was evaluated based on whether or not > or = 50% improvement was achieved in the tender and swollen joint scores and the Health Assessment Questionnaire score, with normal C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) levels. Progression of the erosion score on wrist MRI was evaluated as the outcome. RESULTS: The baseline MRI bone oedema score (rho= 0.67), MRI synovitis score (rho= 0.57), ESR (rho= 0.56), CRP (rho= 0.48), E-rate (rho= 0.47) and (99m)Tc-NC uptake (rho= 0.45) were related with the change in the MRI erosion score from baseline to 2 yrs (rho= Spearman's correlation). In the multivariate logistic regression model, the bone marrow oedema score was the only baseline variable that predicted erosive progression at 2 yrs' follow-up (OR 4.2, 95% CI 1.3-13.8). The median (interquartile range) change in the erosion score from baseline to 2 yrs was 0 (0, 0) and 4 (2, 5) in the patients with (n= 9) and without (n= 15) a persistent clinical response over the 2 yrs, respectively (P= 0.001). The non-responders who presented with erosive progression from 1 yr to 2 yrs had higher MRI synovitis scores, bone oedema scores, E-rate and (99m)Tc-NC uptake at 1-yr follow-up than the non-responders without progressive bone damage. CONCLUSION: The degree of local synovial inflammation at baseline, evaluated by dynamic and static MRI and quantitative NC scintigraphy, is closely related to the progression of wrist joint erosions during the first 2 yrs of the disease. Furthermore, at follow-up, if no persistent clinical response is achieved, these imaging methods may help to predict future erosiveness and help in clinical therapeutic decision making.     

No variants in the cardiac actin gene in Finnish patients with dilated or hypertrophic cardiomyopathy

Background Dilated and hypertrophic cardiomyopathies are primary myocardial diseases that cause considerable morbidity and mortality. Although these cardiomyopathies are clinically heterogeneous, genetic factors play an important role in their etiology and pathogenesis. The defects in the cardiac actin (ACTC) gene can cause both cardiomyopathies. The aim of our study was to screen for variants in the ACTC gene in patients with dilated or hypertrophic cardiomyopathy from Eastern Finland. Materials and Methods Altogether, 32 patients with dilated and 40 patients with hypertrophic cardiomyopathy were included in the study. Commonly approved diagnostic criteria were applied, and secondary cardiomyopathies were carefully excluded. All 6 exons of the ACTC gene were amplified with polymerase chain reaction and screened for variants with single-strand conformation polymorphism analysis. Results and Conclusion We did not find any new or previously reported variants. Our results indicate that defects in the ACTC gene do not explain dilated cardiomyopathy or hypertrophic cardiomyopathy in subjects from Eastern Finland and confirm earlier results that the ACTC gene does not play an important role in the genetics of dilated or hypertrophic cardiomyopathies. (Am Heart J 2002;143:11-4.)     

All known human rhinovirus species are present in sputum specimens of military recruits during respiratory infection

Human rhinoviruses (HRV) are known to cause common cold as well as more complicated respiratory infections. HRV species -A, -B and -C have all been associated with lower respiratory infections and exacerbations of asthma. However, the type distribution of strains connected to different kinds of lower respiratory conditions is not clearly known. We have analysed the presence of HRV in sputum specimens derived from military recruits with and without pre-diagnosed asthma at times of acute respiratory infection (CIAS Study, 2004-2005). The analysis was performed with HRV and HEV real-time RT-PCR assays. Subsequently we studied type distribution of HRV strains by genetic typing in the VP4/VP2 genomic region. In total 146 (38.8%) specimens were HRV-positive and 36 (9.3%) HEV-positive. No difference was found in HRV detection between the asthmatic vs. non-asthmatic patients. Most of the genetically typed strains, 18 (62.1%), belonged to HRV-A, while HRV-B strains constituted five (17.2%) of the HRV-positive strains. HRV-C strain was typed four times from the HRV-positive cases and a HEV-D strain twice. We further typed six HEV positive strains in the partial VP1 region. Three of these belonged to HRV-A and three to HEV-D. HRV-A strains were discovered throughout the study period, while HRV-C strains originated from winter and spring specimens. Interestingly, four out of five typed HRV-B strains originated from the summer season specimens.