Abnormal left ventricular relaxation and symptoms of heart failure

Objectives

The purpose of our study was to assess the echocardiographic and angiographic parameters in patients with symptomatic heart failure (HF) and mild diastolic dysfunction (grade I).

Background

It remains uncertain why some patients with mild diastolic dysfunction exhibit HF symptoms and others are asymptomatic.

Methods

The study enrolled 80 hospitalized patients with impaired left ventricular (LV) relaxation. Patients were divided into two groups; one group had chronic functional class II to III dyspnea and the other group had no symptoms of HF. After admission, echocardiography and coronary angiography were performed for all patients and LV systolic and diastolic parameters were compared between the two groups.

Results

More patients in the asymptomatic group were hypertensive (p-value: 0.012). However, coronary artery disease was more prevalent in symptomatic patients (p-value: 0.022). The LV ejection fraction (EF) was significantly lower in symptomatic patients [median 54.33 %, 95 % confidence interval (53.76–54.87 %) in asymptomatic patients and median 49.43, 95 % confidence interval (47.23–50.91 %) in symptomatic patients, p-value <0.001]. Furthermore, the systolic LV internal dimension was significantly larger in this group (p-value: 0.037). The results of logistic regression identified that only the absolute level of the LVEF was the negative determinant of the occurrence of HF in patients with impaired LV relaxation.

Conclusion

Our study showed that LV systolic performance has an important role in occurrence of HF symptoms in patients with grade I diastolic dysfunction.

     

Drug-induced bone loss: a major safety concern in Europe

Introduction: Drug-induced bone loss remains the major cause of vertebral and hip fractures and significantly associated to morbidity and mortality. This article will review the common drugs identified as the causes of bone loss and the risk factors and management in European countries.

Areas covered: Beyond glucorticoid – the most cause of osteoporosis, many different drugs could cause harmful skeletal disorders. The antiepileptics, hormonal therapy, GnRH antagonists, aromatase inhibitors are well-known cause of bone loss. Osteoporosis and fractures risk also increased with calcineurin inhibitors, antiretroviral drugs, selective inhibitors of serotonin reuptake, loop diuretics, heparins, oral anticoagulants, high doses of thyroxine and proton pump inhibitors.

Expert opinion: Drugs are an important secondary cause of osteoporosis. Healthcare professionals should reassess the requirement for drugs and use the lowest dosage and shortest duration. Lifestyle changes, adequate calcium, vitamin D supplement, appropriate monitoring of bone status and initiating osteoporosis treatment if indicated are recommended when drugs having potential deleterious effects on bone are used, particularly in high risk patients. The update and further studies would provide concluded evidences of controversial drugs induced bone loss and determine the best prevention and treatment strategies.     

Surface characteristics of aesthetic restorative materials - an SEM study

To determine the degree of surface roughness of glass-ionomer cements (GICs) and polyacid-modified resin composite (PAMRC) after polishing and immersion in various foodstuffs. Three tooth-coloured restorative materials were used: a PAMRC (F2000), a conventional glass-ionomer cement (CGIC) (Fuji IX) and a resin-modified glass-ionomer cements (RM-GIC) (Fuji II LC). Disk-shaped specimens were prepared and tested with either a plastics matrix finish or after polishing with wet silicon carbide papers up to 2000-grit. All specimens were immersed in 37 degrees C-distilled water for 1 week, followed by three different foodstuffs (red wine, coffee or tea) for a further 2 weeks. Replicas of specimens were prepared by taking polyvinyl siloxane impressions, casting in epoxy resin, gold sputter-coating and examining using a Field-Emission Scanning Electron Microscope. The polished and matrix finish specimens of F2000 showed many microcracks at low magnification, and eroded surfaces with missing and protruding particles at high magnification in the polished specimens. The surface-polished specimens of Fuji II LC were considerably rougher than the matrix-finish specimens, with large voids and protruding filler particles. The effects of foodstuffs on Fuji II LC and F2000 were not noticeable. The CGIC became noticeably rougher after exposure to coffee and tea. All specimens had the smoothest surface when they were cured against a plastics matrix strip, and all materials had a rougher surface after polishing. None of the foodstuffs produced a perceptible increase in roughness on RM-GIC and PAMRC surfaces, whereas coffee and tea markedly increased the surface roughness of Fuji IX.     

Successful renal transplantation in a family with a novel mutation in COL4A3 gene and autosomal recessive Alport syndrome

Alport syndrome (AS) is an inherited disorder of basement membranes caused by mutations affecting specific proteins of the type IV collagen family, presenting with nephropathy and extrarenal manifestations such as sensorineural deafness and ocular anomalies. Ten percentage to 15% of the patients with AS have autosomal recessive (ARAS) due to mutation in either COL4A3 or COL4A4 gene. We report a novel mutation in the COL4A3 gene in an Indian family with ARAS. The above‐mentioned genetic anomaly was a missense variation in exon 26 of the COL4A3 gene (chr2:228137797G>A; c.1891G>A) that resulted in the amino acid substitution of Arginine for Glycine at codon 631 (p.Gly631Arg) that was present in the heterozygous state in the asymptomatic parents and homozygous state in the male offspring who presented with early‐onset end‐stage renal disease, lenticonus and hearing loss. The patient (male offspring) underwent successful renal transplantation with his mother as a donor.     

Accuracy of sentinel node biopsy in esophageal carcinoma: a systematic review and meta-analysis of the pertinent literature

The use of sentinel node surgery for esophageal carcinoma is still under investigation. We evaluated the data available in the literature on this topic, and herein present the results in a systematic review format. PUBMED, SCOPUS, the ISI web of knowledge and the information from the annual meetings of the Japan Esophageal Society were searched using the search terms: “(esophagus OR esophageal) AND sentinel”. The outcomes of interest were the detection rate and sensitivity. Overall, 18 studies were included. The pooled detection rate was 89.2 % [82.6–93.5]. Patients with T1 and two tumors had a 17 % higher detection rate compared to those with T3 and four tumors. The pooled sensitivity was 84 % [78–88 %]. The sensitivity was higher for adenocarcinoma compared to squamous cell carcinoma (SCC) (91 vs. 81 %). In the SCC patients, there was a trend toward decreased sensitivity associated with an increasing tumor depth (T1:88 %, T2:76 %, T3:50 %). Our analysis indicated that sentinel node biopsy is useful in adenocarcinoma patients. For SCC patients, including only cN0 patients (preferably T1 and 2) would increase the detection rate and sensitivity. Due to the limited number of high-quality studies, drawing any more definite conclusions is impossible. Large cohort studies with a standardized and consistent design will be needed in the future.     

Analysis of platelet adhesion to a collagen-coated surface under flow conditions: the involvement of glycoprotein VI in the platelet adhesion

Platelet adhesion to the exposed surface of the extracellular matrix in flowing blood is the first and critical reaction for in vivo thrombus formation. However, the mechanism of this in vivo platelet adhesion has yet to be studied extensively. One of the reasons for this is the lack of a practical assay method for assessing platelet adhesion under flow conditions. We have devised an assay method (the fluorescent adhesion assay) that is based on the technique originally reported by Hubbell and McIntire (Biomaterials 7:354, 1986) with some modifications to make it more amenable for assaying small samples and have developed an analysis method to quantify the extent of platelet adhesion and aggregation from fluorescence images by using a computer-assisted image analysis system. In our assay, platelet adhesion, expressed as the percentage of the area covered by adhered platelets, was found to increase biphasically as a function of time. In the first phase, platelets interacted with the coated collagen, transiently stopping on the surface; we called this reaction the temporary arrest. In the second phase, platelets adhered much more rapidly and permanently on the surface, and this adhesion was dependent on the shear rate; platelets formed aggregates in this phase. We used our assay to analyze the effects of platelet aggregation inhibitors on platelet adhesion. All three examined inhibitors, EDTA (10 mmol/L), antiglycoprotein (GP) IIb/IIIa, and GRGDS peptide (1 mmol/L), inhibited the second phase adhesion in flowing blood. Furthermore, GPVI-deficient platelets also showed defective second-phase adhesion under the same conditions. These results suggested that GPIIb/IIIa activation and GPVI contribute to the reaction inducing the second phase. The second-phase adhesion has been extensively investigated, and the consensus is that this reaction is mainly attributable to the platelet-platelet interaction. In this report, we were able to detect an earlier reaction, the temporary arrest. This temporary arrest would reflect the fast and weak interaction between platelet GPIb/IX and collagen-von Willebrand factor complexes on the collagen-coated surface.     

Hematopoietic growth factors for graft failure after bone marrow transplantation: a randomized trial of granulocyte-macrophage colony- stimulating factor (GM-CSF) versus sequential GM-CSF plus granulocyte- CSF

Delay in hematologic recovery after bone marrow transplantation (BMT) can extend and amplify the risks of infection and hemorrhage, compromise patients' survival, and increase the duration and cost of hospitalization. Because current studies suggest that granulocyte- macrophage (GM) colony-stimulating factor (CSF) may potentiate the sensitivity of hematopoietic progenitor cells to G-CSF, we performed a prospective, randomized trial comparing GM-CSF (250 micrograms/m2/d x 14 days) versus sequential GM-CSF x 7 days followed by G-CSF (5 micrograms/kg/d x 7 days) as treatment for primary or secondary graft failure after BMT. Eligibility criteria included failure to achieve a white blood cell (WBC) count > or = 100/microL by day +21 or > or = 300/microL by day +28, no absolute neutrophil count (ANC) > or = 200/microL by day +28, or secondary sustained neutropenia after initial engraftment. Forty-seven patients were enrolled: 23 received GM-CSF (10 unrelated, 8 related allogeneic, and 5 autologous), and 24 received GM- CSF followed by G-CSF (12 unrelated, 7 related allogeneic, and 5 autologous). For patients receiving GM-CSF alone, neutrophil recovery (ANC > or = 500/microL) occurred between 2 and 61 days (median, 8 days) after therapy, while those receiving GM-CSF+G-CSF recovered at a similar rate of 1 to 36 days (median, 6 days; P = .39). Recovery to red blood cell (RBC) transfusion independence was slow, occurring 6 to 250 days (median, 35 days) after enrollment with no significant difference between the two treatment groups (GM-CSF: median, 30 days; GM-CSF+G- CSF; median, 42 days; P = .24). Similarly, platelet transfusion independence was delayed until 4 to 249 days (median, 32 days) after enrollment, with no difference between the two treatment groups (GM- CSF: median, 28 days; GM-CSF+G-CSF: median, 42 days; P = .38). Recovery times were not different between patients with unrelated donors and those with related donors or autologous transplant recipients. Survival at 100 days after enrollment was superior after treatment with GM-CSF alone. Only 1 of 23 patients treated with GM-CSF died versus 7 of 24 treated with GM-CSF+G-CSF who died 16 to 84 days (median, 38 days) after enrollment, yielding Kaplan-Meier 100-day survival estimates of 96% +/- 8% for GM-CSF versus 71% +/- 18% for GM-CSF+G-CSF (P = .026). These data suggest that sequential growth factor therapy with GM-CSF followed by G-CSF offers no advantage over GM-CSF alone in accelerating trilineage hematopoiesis or preventing lethal complications in patients with poor graft function after BMT.(ABSTRACT TRUNCATED AT 400 WORDS)