Alterations in the pattern of collagen deposition may contribute to the deterioration of systolic function in hypertensive patients with heart failure.

OBJECTIVES: We sought to assess the distribution of collagen deposits and collagen degradation in hypertensive patients with either systolic heart failure (SHF) or diastolic heart failure (DHF). BACKGROUND: Increased collagen synthesis and deposition have been described in the myocardium of heart failure (HF) hypertensive patients. METHODS: We studied 39 HF hypertensive patients subdivided into two groups: 16 with SHF and 23 with DHF. Endomyocardial biopsies were performed to quantify mysial (i.e., perimysial plus endomysial) and perivascular and scar-related collagen volume fraction (CVF). Matrix metalloproteinase (MMP)-1 and its tissue inhibitor matrix metalloproteinase (TIMP)-1 were analyzed in cardiac samples by Western blot and immunohistochemistry, and in blood samples by enzyme-linked immunosorbent assay. RESULTS: Mysial CVF was lower in SHF hypertensive patients than in normotensive (p < 0.05) and DHF hypertensive patients (p < 0.01). Perivascular and scar-related CVF was higher (p < 0.05) in the two groups of hypertensive patients than in normotensive subjects, and in SHF hypertensive compared with DHF hypertensive patients. The MMP-1:TIMP-1 ratio was increased (p < 0.05) in tissue and serum samples from the SHF hypertensive group compared with the other two groups of subjects. The MMP-1 expression was increased (p < 0.01) in the interstitium and cardiomyocytes of SHF hypertensive patients compared with DHF hypertensive and normotensive subjects. The serum MMP-1:TIMP-1 ratio was inversely correlated with ejection fraction (r = -0.510, p < 0.001) and directly correlated with left ventricular end-diastolic diameter (r = 0.549, p < 0.001) in all subjects. CONCLUSIONS: These findings show that the pattern of collagen deposits and the balance of the MMP-1/TIMP-1 system are different in the myocardium of SHF and DHF hypertensive patients. It is proposed that excessive degradation of mysial collagen may be related to the compromise of systolic function in HF hypertensive patients.     

SEOM clinical guidelines for the treatment of follicular non-Hodgkin’s lymphoma

Follicular lymphoma (FL) is the second most common subtype of non-Hodgkin’s lymphoma (NHL) in the Western world. FL constitutes the most frequent indolent lymphoma, well characterized by its clinical presentation related to nodal involvement and its morphologic and biologic features. It is often managed as an incurable disease. However, several active therapeutic approaches from the ‘wait and watch” strategy to the allogeneic transplantation are available for management of patients with FL and clearly have changed the natural history of this disease, achieving a long-term disease-free survival. Therapeutic decision is mostly conditioned by patient’s characteristics, stage, histological grade, tumor burden, and risk-predicting factors. This article try to summarizes the diagnosis and treatment of this heterogeneous group of patients.     

ANP in the prevention of acute renal failure after transplantation

Transplant International -     

A comparative study of etanercept plus methotrexate and methotrexate alone in Taiwanese patients with active rheumatoid arthritis: a 12-week, double-blind, randomized, placebo-controlled study.

BACKGROUND AND PURPOSE: Etanercept (Enbrel), a recombinant tumor necrosis factor receptor fusion protein, has been shown to be effective in the treatment of patients with rheumatoid arthritis (RA). The purpose of this study was to compare the efficacy and safety of etanercept in combination with methotrexate (MTX) and MTX alone in Taiwanese patients with active RA. METHODS: In this double-blind study, 58 patients with active RA who were maintained on MTX therapy at a stable dose of 12.5 to 20 mg per week for 4 weeks were randomized to receive either etanercept 25 mg (n = 29) or placebo (n = 29) by subcutaneous injection twice weekly over a period of 12 weeks. The primary endpoint was the reduction of tender and swollen joint counts by 20% (ACR 20), 50% (ACR 50), and 70% (ACR 70) as determined by the American College of Rheumatology criteria at the 12th week. RESULTS: The addition of etanercept to MTX resulted in a greater reduction in the number of tender (7.00 vs 2.45, p = 0.012) and swollen joints (8.55 vs 3.86, p = 0.017), and in serum levels of C-reactive protein (1.26 mg/dL vs 0.45 mg/dL, p = 0.014) compared to MTX alone after 12 weeks of therapy. In addition, the global assessment of disease activity by both physicians and patients, duration of morning stiffness, pain visual analog scale score, and Health Assessment Questionnaire were all improved by etanercept plus MTX therapy. Results for the overall improvement in disease activity assessed by ACR 20 (90% vs 34%), ACR 50 (66% vs 10%) and ACR 70 (24% vs 0%) all favored the etanercept plus MTX group. However, the adverse events were comparable between the 2 treatment groups. CONCLUSION: Etanercept in combination with MTX was well tolerated and provided significantly more clinical benefit than MTX alone in Taiwanese patients with active RA.     

A double cryptic chromosome imbalance is an important factor to explain phenotypic variability in Wolf-Hirschhorn syndrome

A total of five Wolf-Hirschhorn syndrome (WHS) patient with a 4p16.3 de novo microdeletion was referred because of genotype-phenotype inconsistencies, first explained as phenotypic variability of the WHS. The actual deletion size was found to be about 12 Mb in three patients, 5 Mb in another one and 20 Mb in the last one, leading us to hypothesize the presence of an extrachromosome segment on the deleted 4p. A der(4)(4qter --> p16.1::8p23 --> pter) chromosome, resulting from an unbalanced de novo translocation was, in fact, detected in four patients and a der(4)(4qter --> q32::4p15.3 --> qter) in the last. Unbalanced t(4;8) translocations were maternal in origin, the rec(4p;4q) was paternal. With the purpose of verifying frequency and specificity of this phenomenon, we investigated yet another group of 20 WHS patients with de novo large deletions (n = 13) or microdeletions (n = 7) and with apparently straightforward genotype-phenotype correlations. The rearrangement was paternal in origin, and occurred as a single anomaly in 19 out of 20 patients. In the remaining patient, the deleted chromosome 4 was maternally derived and consisted of a der(4)(4qter --> 4p16.3::8p23 --> 8pter). In conclusions, we observed that 20% (5/25) of de novo WHS-associated rearrangements were maternal in origin and 80% (20/25) were paternal. All the maternally derived rearrangements were de novo unbalanced t(4;8) translocations and showed specific clinical phenotypes. Paternally derived rearrangements were usually isolated deletions. It can be inferred that a double, cryptic chromosome imbalance is an important factor for phenotypic variability in WHS. It acts either by masking the actual deletion size or by doubling a quantitative change of the genome.     

Characterization of chimpanzee-hamster hybrids by chromosome painting

A panel of chimpanzee-human somatic cell hybrids was characterized by dual Alu-PCR of the chimpanzee DNA in the hybrid and subsequent hybridization of the labeled PCR products to human and chimpanzee chromosomes. In addition to the identification of the intact chimpanzee chromosomes retained in each hybrid, chromosome fragments were identified that will be useful in regional mapping. This technique also revealed the presence of centric inversions.     

Molecular cytogenetic characterization of a complex rearrangement involving chromosomes 9 and 22 in a case of Ph-negative chronic myeloid leukemia

The "golden path", produced by the Human Genome Project effort, is composed of a collection of overlapping and fully sequenced BAC/PAC clones covering almost completely the human genome. These clones can be advantageously exploited as fluorescence in situ hybridization (FISH) probes for the characterization of rearrangements frequently found in tumors. Breakpoint characterization can be further refined by generating additional smaller FISH probes through LONG-PCR amplification of specific DNA segments, 5-10 kb in size, using appropriate BAC/PAC probes as template. We report here an example of this approach that has been used to characterize a complex Ph-negative chronic myeloid leukemia (CML Ph-) case in which the BCR/ABL fusion gene was found located on chromosome 9.     

Reactive Compatibilization of PA6/LDPE Blends with Glycidyl Methacrylate Functionalized Polyolefins

Summary: Blends of polyamide‐6 (PA6) and low density polyethylene (LDPE) were compatibilized by melt mixing with various polyolefins functionalized with glycidyl methacrylate (GMA), i.e., GMA grafted LDPE (LDPE‐g‐GMA), GMA grafted styrene‐ethylene/butylene‐styrene block copolymer (SEBS‐g‐GMA) and ethylene‐co‐glycidyl methacrylate copolymer (E‐GMA). Blends with PA6/LDPE composition ratios of 25/75 and 75/25 wt.‐%/wt.‐% were prepared in a Brabender internal mixer and their properties were evaluated by SEM, rheological measurements and DSC. Morphological investigation by SEM showed a neat improvement of phase dispersion and interfacial adhesion in all compatibilized blends when compared to PA6/LDPE binary blends. The variation of the dispersed phase size was analyzed as a function of blend composition, compatibilizer concentration and GMA content. The emulsification curves of compatibilized blends showed that the equilibrium size of dispersed particles at the saturation concentration of copolymer was lower when PA6 was the major component. The finest dispersion of the LDPE phase (<0.25 μm) was observed in the presence of SEBS‐g‐GMA copolymer. LDPE‐g‐GMA and E‐GMA displayed a similar compatibilizing efficiency. In all cases, the blends with a polyamide matrix presented a marked rise in torque and melt viscosity with increasing compatibilizer content. These effects were accounted for by a reaction between the epoxide groups of LDPE‐g‐GMA and the carboxyl/amine end‐groups of PA6, leading to the formation of an interchain graft copolymer. The phase transition processes of PA6 in the blends were influenced by the compatibilizer content and the interfacial interactions between the polymer components, suggesting a different role for the compatibilizer at the PA6/LDPE interface.

SEM micrograph of PA6/LDPE 25/75 blend compatibilized with 2.5 phr SEBS‐g‐GMA.