Manganese superoxide dismutase activity and incidence of hepatocellular carcinoma in patients with Child-Pugh class A liver cirrhosis: a 7-year follow-up study.

AIMS: To evaluate possible modifications in the manganese superoxide dismutase (MnSOD) activity during neoplastic transformation of a cirrhotic liver and to find out whether its assessment may have predictive value to identify cirrhotic patients at a higher risk of hepatocellular carcinoma (HCC). METHODS: Seventy-one consecutive subjects with Child-Pugh class A liver cirrhosis were recruited. At the time of enrolment, HCC was diagnosed in 20 cirrhotic patients. The 51 cirrhotic patients without HCC were followed up for the occurrence of tumour by 6-monthly screening for 7 years. During follow-up, 16 patients developed HCC. Seventy healthy subjects formed the control group. MnSOD activity was assayed spectrophotometrically. RESULTS: Serum MnSOD activity was significantly lower in 70 healthy subjects compared with 51 cirrhotic patients and 20 cirrhotic patients with HCC. Cirrhotic patients who developed HCC during follow-up showed significantly higher values of MnSOD activity than HCC-free patients. The best cut-off of MnSOD activity was 0.40 U/ml. At this cut-off, chi2 analysis revealed that MnSOD activity was significantly different between the HCC-free cirrhotic patients and cirrhotic patients who developed HCC. CONCLUSION: The present findings suggest that during neoplastic transformation of cirrhotic liver, an increase in MnSOD activity may occur already during the precancerous phase, making this enzyme a probable malignancy-associated parameter.     

Selective depression of interferon-gamma and granulysin production with increase of proliferative response by Vgamma9/Vdelta2 T cells in children with tuberculosis

Vgamma9/Vdelta2 T cells can contribute to protective immune response against Mycobacterium tuberculosis, although the extent to which and mechanisms by which they could actually protect against human tuberculosis remain unclear. We have previously reported that Vgamma9/Vdelta2 T cells from tuberculin purified protein derivative (PPD)-positive children, either healthy or affected by different clinical forms of tuberculosis, strongly proliferate to different phosphoantigens in vitro, whereas Vgamma9/Vdelta2 T cells from PPD-negative healthy subjects proliferate very poorly. We report here that Vgamma9/Vdelta2 T cells from tuberculous children have an increased proliferative activity, but decreased interferon (IFN)-gamma production and granulysin expression. After successful chemotherapy, the Vgamma9/Vdelta2 T cell proliferative response strongly decreased, whereas IFN-gamma and granulysin production consistently increased. Disease-associated changes in Vgamma9/Vdelta2 T cell effector functions in patients with tuberculosis are consistent with the possibility that these T cells may play a protective role in immune response against M. tuberculosis infection.     

Fine-needle liver biopsy in patients with severely impaired coagulation

ABSTRACT— Severe coagulation defects, as reflected by platelet count and prothrombin time, have always been considered a contraindication to needle biopsy of the liver, but there are very limited data on the actual rate of bleeding in patients with such severe alterations and none whatsoever on the bleeding risk associated with newer, fine-gauge needles that produce less trauma to the liver tissue. In addition, there has never been any evidence that platelet count and/or prothrombin time are the most sensitive indices of bleeding risk. This retrospective study of 85 patients, with platelet counts less than 50 000/mm³ and/or prothrombin times less than 50% of controls, subjected to ultrasound-guided fine-needle liver punctures for diagnostic or therapeutic (percutaneous ethanol injection) purposes showed no bleeding episodes after any of the 229 punctures performed. No type of replacement therapy was administered to correct clotting defects prior to the procedure. Correct pathologic diagnoses were obtained in 81.2% of all patients. Ultrasound-guided fine needle puncture appears to be safer than currently believed in patients with severe clotting defects and deserves further evaluation as an alternative to surgical procedures to diagnose and treat liver lesions, even when severe coagulation impairment is present.     

Triplet structure of von Willebrand factor reflects proteolytic degradation of high molecular weight multimers.

High molecular weight (HMW) and low molecular weight (LMW) forms of von Willebrand factor (vWF) were isolated from normal human plasma in the presence of protease inhibitors. HMW and LMW vWF preparations were subjected to reduction of interdimeric disulfide bridges under mild reducing conditions. Following sodium dodecyl sulfate electrophoresis in 3% agarose, the vWF bands were detected by immunoblotting with a polyclonal rabbit anti-vWF antiserum as well as with two monoclonal antibodies directed against epitopes located in the NH2-terminal (MAb 418) or in the COOH-terminal (MAb 9) region of the vWF subunit. Our results suggest that the slowest migrating band of the dimeric triplet set of LMW vWF represents an asymmetric structure composed of an intact subunit to which one NH2-terminal and one COOH-terminal fragment are linked by disulfide bridges. The intermediate band of the first triplet of LMW vWF strongly reacted with MAb 9 but not with MAb 418, indicating that it represents a dimer of COOH-terminal fragments. The fastest migrating band of the same triplet is apparently a dimer of the NH2-terminal fragments because it reacted with MAb 418 but not with MAb 9. Each next higher family of triplets seems to contain one more asymmetric fragment of dimeric size. These results are compatible with a model according to which LMW forms of vWF are derived from HMW vWF by proteolytic cleavage in the circulating blood.     

Can cardiorespiratory polygraphy replace portable polysomnography in the assessment of sleep-disordered breathing in heart failure patients?

Purpose

Portable polysomnography (PSG) and cardiorespiratory polygraphy are increasingly being used in the assessment of sleep-disordered breathing (SDB) in heart failure patients. Scoring of SDB from cardiorespiratory polygraphy recordings is based only on respiratory signals, while electroencephalographic, electrooculographic and electromyographic channels are taken into account when using PSG recordings. The aim of this study was to assess the agreement between these two scoring methods.

Methods

An overnight sleep study was performed in 67 heart failure patients using a standard portable polysomnograph. Each recording was scored twice, once using all acquired signals (PSG mode) and, after a median of 64 days, using only respiratory signals (cardiorespiratory mode). Agreement was assessed by Bland–Altman analysis and Cohen’s kappa.

Results

We found that (1) more respiratory events were detected using cardiorespiratory analysis [median (25th percentile, 75th percentile), 75 (39, 200) events] compared to analysis of portable PSG [69 (29, 173) events, p?<?0.0001], the extra events being, for the vast majority, central in origin; (2) the apnea/hypopnea index (AHI) estimated by cardiorespiratory polygraphy [11.9 (5.7, 30.8)/h] showed a negligible negative bias relative to portable PSG [15.1 (5.7, 33.6)/h; bias, ?0.8 (?2.9, 0.4)/h, p?=?0.0002]; (3) limits of agreement between the two systems (?6.2/h, 1.7/h) were much smaller than those previously observed between two nights using the same scoring modality; and (4) the kappa coefficient using categorised AHI was 0.89 (95 % confidence interval (CI) 0.82, 0.96).

Conclusions

We found a high degree of agreement between the AHIs obtained from the two scoring methods, thus suggesting that cardiorespiratory polygraphy may be used as an alternative to portable PSG in the assessment of SDB in heart failure patients.

     

Prefrontal Cortex Activated Bilaterally by a Tilt Board Balance Task: A Functional Near-Infrared Spectroscopy Study in a Semi-Immersive Virtual Reality Environment

The aim of this study was to assess the prefrontal cortex (PFC) oxygenation response to a 5-min incremental tilt board balance task (ITBBT) in a semi-immersive virtual reality (VR) environment driven by a depth-sensing camera. It was hypothesized that the PFC would be bilaterally activated in response to the increase of the ITBBT difficulty, given the PFC involvement in the allocation of the attentional resources to maintain postural control. Twenty-two healthy male subjects were asked to use medial–lateral postural sways to maintain their equilibrium on a virtual tilt board (VTB) balancing over a pivot. When the subject was unable to maintain the VTB angle within ±35° the VTB became red (error). An eight-channel fNIRS system was employed for measuring changes in PFC oxygenated-deoxygenated hemoglobin (O₂Hb-HHb, respectively). Results revealed that the number of the performed board sways and errors augmented with the increasing of the ITBBT difficulty. A PFC activation was observed with a tendency to plateau for both O₂Hb-HHb changes within the last 2 min of the task. A significant main effect of the level of difficulty was found in O₂Hb and HHb (p < 0.001). The study has demonstrated that the oxygenation increased over the PFC while the subject was performing an ITBBT in a semi-immersive VR environment. This increase was modulated by the task difficulty, suggesting that the PFC is bilaterally involved in attention-demanding tasks. This task could be considered useful for diagnostic testing and functional neurorehabilitation given its adaptability in elderly and in patients with movement disorders.