Traditional and novel approaches to management of heart failure: successes and failures

Although considerable progress has been made in the pharmacologic and device management of chronic heart failure in recent decades, heart failure patients continue to remain symptomatic, with high hospitalization and mortality rates. A number of novel agents, including endothelin antagonists and tumor-necrosis factor blockers, have recently failed to improve the clinical outcomes of patients with heart failure. Have we reached a ceiling in preventing the progression of the disease? This article reviews successes and late-stage clinical trial disappointments in the treatment of patients with heart failure. Furthermore, the article discusses how agents that have beneficial effects in heart failure also generally attenuate or reverse ventricular remodeling, whereas the newer agents that have failed to improve clinical outcomes either had no effect on remodeling or have been associated with adverse remodeling.     

Variations of the renal function parameters in rectal cancer patients with a defunctioning loop ileostomy

Purpose

The objective of this study is to investigate the impact of the temporary loop ileostomy on renal function and also to assess the factors associated with the change in renal function observed between the index surgery (the moment of the radical surgical procedure) and the closure of the ileostomy (the moment of the secondary surgical act of suppression of the ileostomy).

Methods

A total of 69 rectal cancer patients from a single referral surgical unit who had a loop ileostomy during low anterior resection of the rectum were included in this study. Serum creatinine levels were evaluated, and estimated glomerular filtration rate (eGFR) was calculated prior to index surgery and closure of the ileostomy.

Results

During this time interval, there was a significant decrease in eGFR levels (mean difference ??4.5 mL/min/1.73 m², 95% CI ??7.8 to ??1.3 mL/min/1.73 m²), and also a significant increase in the serum creatinine values (mean difference 0.07, 95% CI 0.02–0.12 mg/dL). The eGFR decrease was more pronounced in diabetic patients, in those with a baseline Charlson Comorbidity Index score?≥?1 or in those that received chemotherapy. In a multivariable regression analysis, the use of neoadjuvant chemotherapy was the only variable significantly associated with the change in eGFR levels between the two surgical interventions.

Conclusion

Renal function impairment is an important event that the surgeon has to take into consideration when deciding upon opting for a loop ileostomy to temporarily defunction a colorectal anastomosis.

     

A novel proteolytic processing of prolysyl oxidase

Lysyl oxidase (LOX) is an amine oxidase that is critical for the stability of connective tissues. The secreted proLOX is enzymatically quiescent and is activated through proteolytic cleavage between residues Gly(162) and Asp(163) (residue numbers according to the mouse LOX) by bone morphogenetic protein (BMP)-1 gene products. Here we report a novel processing of proLOX identified in vitro and in vivo. Two forms of mature LOX were identified and characterized by their immunoreactivity to specific antibodies, amine oxidase activity, and mass spectrometry. One form was identified as a well-characterized BMP-1 processed LOX protein. Another was found to be a truncated form of LOX resulting from the cleavage at the carboxy terminus of Arg(192). The truncated form of LOX still appeared to retain amine oxidase activity. The results from the proLOX gene deletion and mutation experiments indicated that the processing occurs independent of the cleavage of proLOX by BMP-1 gene products and likely requires the presence of LOX propeptide. These results indicate that proLOX could be processed by two different mechanisms producing two forms of active LOX.     

A comparative ultrastructural study of a new type of autoschizis versus a survival cellular mechanism that involves cell membranes of cerebral arteries in humans

The authors analyzed by transmission electron microscopy the modifications of plasmalemma and nuclear envelope in the cerebral arterial wall in humans. Their ultrastructural observations are performed on the tunica media and endothelium. During autoschizis, some smooth muscle cells showed deep invaginations of the nuclear envelope with multiple craters that disintegrate the nucleus, whereas in the endothelium repetitive invaginations of plasmalemma lead to cell demise by cytoplasmic self-excisions. During survival mechanism, a perinuclear constriction of plasmalemma occurs, which conserves nucleus and cytoskeleton, and only a segregated cytoplasmic area, without organelles, is removed in lumen.     

Increasing tuberculosis case detection: lessons from the Republic of Moldova

The Republic of Moldova undertook reforms in tuberculosis (TB) control and health care consistent with international recommendations and advanced towards the global target for case detection. The number of TB cases notified increased overall by 50% during 2001-2005. Expansion of the DOTS strategy and full coverage coincided with a greater role for primary health care (PHC) in TB control and the advent of national insurance for TB diagnosis and treatment. These developments and improvements in laboratories, surveillance, medical personnel skills, and public awareness contributed to increased case detection. The Republic of Moldova addressed both demand and supply sides in these efforts. It increased effective demand for TB services by dispersing diagnostic capability, instituting financing mechanisms and saturating the public with information on symptoms, transmission and treatment. It increased the supply of TB services by upgrading the laboratory network, revamping surveillance and training practitioners. The Republic of Moldova's experience offers lessons for other countries: TB-PHC integration allowed more suspect cases to be diagnosed at nearby PHC clinics, contributing to more cases being notified. Innovative TB communications reached the general public, vulnerable groups, practitioners and the media. TB control projects built on each other and national coordination mechanisms served to identify funding for the most pressing needs. There are challenges remaining for TB control in the Republic of Moldova, not least the stable treatment success rate, but the country can list valuable lessons and achievements.     

Rational emotive behavior therapy, cognitive therapy, and medication in the treatment of major depressive disorder: a randomized clinical trial, posttreatment outcomes, and six-month follow-up

A randomized clinical trial was undertaken to investigate the relative efficacy of rational-emotive behavior therapy (REBT), cognitive therapy (CT), and pharmacotherapy in the treatment of 170 outpatients with nonpsychotic major depressive disorder. The patients were randomly assigned to one of the following: 14 weeks of REBT, 14 weeks of CT, or 14 weeks of pharmacotherapy (fluoxetine). The outcome measures used were the Hamilton Rating Scale for Depression and the Beck Depression Inventory. No differences among treatment conditions at posttest were observed. A larger effect of REBT (significant) and CT (nonsignificant) over pharmacotherapy at 6 months follow-up was noted on the Hamilton Rating Scale for Depression only.     

Ternary Nanocomposites Based on Oxidized Carbon Nanohorns as Sensing Layers for Room Temperature Resistive Humidity Sensing

This paper presents the relative humidity (RH) sensing response of a resistive sensor employing sensing layers based on a ternary nanocomposite comprising graphene oxide-oxidized carbon nanohorns-polyvinylpyrrolidone (GO-CNHox–PVP), at 1/1/1, 1/2/1, and 1/3/1 w/w/w mass ratios. The sensing structure is composed of a silicon substrate, a SiO₂ layer, and interdigitated transducers (IDT) electrodes, on which the sensing layer is deposited via the drop-casting method. The morphology and the composition of the sensing layers are investigated through scanning electron microscopy (SEM) and RAMAN spectroscopy. The RH sensing capability of each carbonaceous nanocomposite-based thin film was analyzed by applying a current between the two electrodes and by measuring the voltage difference when varying the RH from 0% to 100% in humid nitrogen. The sensors have a room temperature response comparable to that of a commercial humidity sensor and are characterized by a rapid response, excellent linearity, good sensitivity, and recovery time. The manufactured sensing devices’ transfer functions were established, and we extracted the response and recovery times. While the structures with GO/CNHox/PVP at 1/1/1 ratio (w/w/w) had the best performance in terms of relative sensibility, response time, and recovery time, the sensors employing the GO/CNHox/PVP nanocomposite at the 1/2/1 ratio (w/w/w) had the best linearity. Moreover, the ternary mixture proved to have much better sensing properties compared to CNHox and CNHox-PVP-based sensing layers in terms of sensitivity and linearity. Each component of the ternary nanocomposites’ functional role is explained based on their physical and chemical properties. We analyzed the potential mechanism associated with the sensors’ response; among these, the effect of the p-type semiconductor behavior of CNHox and GO, correlated with swelling of the PVP, was dominant and led to increased resistance of the sensing layer.     

Comprehensive preclinical evaluation of a multi-physics model of liver tumor radiofrequency ablation

Purpose

We aim at developing a framework for the validation of a subject-specific multi-physics model of liver tumor radiofrequency ablation (RFA).

Methods

The RFA computation becomes subject specific after several levels of personalization: geometrical and biophysical (hemodynamics, heat transfer and an extended cellular necrosis model). We present a comprehensive experimental setup combining multimodal, pre- and postoperative anatomical and functional images, as well as the interventional monitoring of intra-operative signals: the temperature and delivered power.

Results

To exploit this dataset, an efficient processing pipeline is introduced, which copes with image noise, variable resolution and anisotropy. The validation study includes twelve ablations from five healthy pig livers: a mean point-to-mesh error between predicted and actual ablation extent of 5.3 ± 3.6 mm is achieved.

Conclusion

This enables an end-to-end preclinical validation framework that considers the available dataset.

     

Malignant peritoneal mesothelioma

Mesothelioma is a neoplasm originating from the mesothelial surface lining cells of the serous human cavities. It may involve the pleura, less frequently the peritoneum rarely, the pericardium, the tunica vaginalis testis and ovarian epithelium. Asbestos has been widely used in industry. A causal relationship between asbestos exposure and pleural, peritoneal and pericardial malign mesothelioma was suggested, the risk of cancer being correlated to cumulate exposure. Studies from National Cancer Institute, USA, show that the malignant mesothelioma is a rare and aggressive asbestos related malignancy. The symptomatology is insidious and poses difficult problems in diagnosis and treatment. This paper presents the case of a 59 year old patient with malignant peritoneal mesothelioma who worked almost 40 years as an electrician, exposed to asbestos fibers. He was hospitalized for important weight loss, abdominal pain and tiredness being diagnosed after imaging tests with a giant tumor, localized at the abdominal upper level, which seems to originate from the spleen's superior pole. During surgery we discovered a tumor with cystic parts, intense vascularized, which turn to be adherent in the upper side to the lower face of the left midriff cupola, to the spleen superior pole and 1/3 middle level of the great gastric curve. It was performed surgical ablation of the tumor, splenectomy with favorable postoperative evolution, the patient being now under chemotherapy treatment.     

The co-infection with hepatitis virus B and D--cases admitted in the infectious diseases hospital from Iaşi, Romania (2003-2005)

Despite the major medical advance, over 350 million people worldwide still have chronic infection with hepatitis B virus and HBV-associated liver disease remains a major cause of morbidity and mortality. 15-50% of patient VHB infected have serological markers for VHD co-infection. We retrospectively studied 252 cases of acute hepatitis B (AHB) admitted in our hospital between 2003-2005; 12 of them (4.76%) had a co-infection with hepatitis D virus. Most of the patients were young males with an urban origin. The route of transmission was unknown in 8/12 cases. Abdominal pain was more frequent during the onset of the disease than in AHB (p < 0.05). A cholestatic pattern was noted in 9 cases. The frequency of severe/ fulminant cases was greater then in AHB. The HBsAg was absent in 3 patients, and the HBV-DNA was present at low levels in 3/12 patients tested. Two patients had HBsAg present 6 month later.