Role of hepatic vein catheterisation and transient elastography in the diagnosis of idiopathic portal hypertension

Background

Idiopathic portal hypertension is a rare cause of portal hypertension, frequently misdiagnosed as cryptogenic cirrhosis. This study evaluates specific findings at hepatic vein catheterisation or liver stiffness in idiopathic portal hypertension.

Methods

39 cases of idiopathic portal hypertension patients were retrospectively reviewed. Hepatic vein catheterisation and liver stiffness measurements were compared to matched patients with cirrhosis and portal hypertension, and non-cirrhotic portal vein thrombosis, included as controls.

Results

Hepatic vein-to-vein communications were found in 49% idiopathic portal hypertension patients precluding adequate hepatic venous pressure gradient measurements in 12. In the remaining 27 patients, mean hepatic venous pressure gradient (HVPG) was 7.1 ± 3.1 mmHg. Only 5 patients had HVPG ≥ 10 mmHg. HVPG was markedly lower than in cirrhosis (17 ± 3 mmHg, p < 0.001). Mean liver stiffness in idiopathic portal hypertension was 8.4 ± 3.3 kPa; significantly higher than in non-cirrhotic portal vein thrombosis (6.4 ± 2.2 kPa, p = 0.009), but lower than in cirrhosis (40.9 ± 20.5 kPa, p = 0.005). Only 2 idiopathic portal hypertension patients had liver stiffness >13.6 kPa.

Conclusions

Patients with idiopathic portal hypertension frequently have hepatic vein-to-vein communications and, despite unequivocal signs of portal hypertension, HVPG and liver stiffness values much lower than the cut-off for clinical significant portal hypertension in cirrhosis. These findings oblige to formally rule-out idiopathic portal hypertension in the presence of signs of portal hypertension.     

Effectiveness of systemic amoxicillin/metronidazole as an adjunctive therapy to full-mouth scaling and root planing in the treatment of aggressive periodontitis: a systematic review and meta-analysis

Background: The systemic use of combined amoxicillin and metronidazole (AMX/MET) as an adjunctive treatment to full‐mouth scaling and root planing (FMSRP) has been proposed for the treatment of generalized aggressive periodontitis; however, its effectiveness and clinical safety remain to be defined. The purpose of the present meta‐analysis is to assess the effectiveness of FMSRP + AMX/MET compared to FMSRP alone. Methods: An electronic search of eight databases and a hand‐search of 10 international dental journals were conducted through September 11, 2011. Gain in clinical attachment level (CAL), reduction in probing depth (PD), secondary outcomes, and adverse events were analyzed. A random‐effect model was used to pool the extracted data. The weighted mean difference (MD) with 95% confidence interval (CI) was calculated for continuous outcomes, whereas risk difference (RD) with 95% CI was used for dichotomous data; heterogeneity was assessed with the χ²‐based Cochran Q test and I² statistic. The level of significance was set at P <0.05. Results: After the selection process, six randomized clinical trials were included. Results of the meta‐analysis showed significant CAL gain (MD, 0.42; 95% CI, 0.23 to 0.61; P <0.05) and PD reduction (MD, 0.58; 95% CI, 0.39 to 0.77; P <0.05) in favor of FMSRP + AMX/MET; moreover, no significant RD was found in the occurrence of adverse events (RD, 0.01; 95% CI, ?0.02 to 0.04; P >0.05). Conclusion: The findings of the meta‐analysis seem to support the effectiveness and the clinical safety of FMSRP + AMX/MET; however, future studies are needed to confirm these results.     

MPTP‐induced dopamine neuron degeneration and glia activation is potentiated in MDMA‐pretreated mice

Clinical observations report a greater propensity to develop Parkinson's disease (PD) in amphetamine users. 3,4‐Methylenedioxymethamphetamine (MDMA; “ecstasy”) is an amphetamine‐related drug that is largely consumed by adolescents and young adults, which may have neuroinflammatory and neurotoxic effects. Here, the objective was to evaluate in mice whether consumption of MDMA during adolescence might influence the neuroinflammatory and neurotoxic effects of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP), a toxin known to induce PD in humans. The activation of astroglia and microglia by glial fibrillary acidic protein (GFAP) and complement receptor type 3 (CD11b) immunohistochemistry and the degeneration of dopaminergic neurons by tyrosine hydroxylase (TH) immunohistochemistry were evaluated. MPTP (20 mg/kg × 4) was administered to mice treated from ages 8 weeks to 17 weeks with MDMA (10 mg/kg twice daily, two times a week). In mice that were chronically treated with MDMA, administration of MPTP induced a higher microglial and astroglial response in both the striatum and the substantia nigra pars compacta (SNc) compared with vehicle‐treated or vehicle + MPTP‐treated mice. Inflammatory changes were associated with a decrease in TH immunoreactivity in the SNc of MDMA‐treated mice and with a further decrease in the striatum and the SNc of MDMA + MPTP‐treated mice compared with vehicle‐treated, MDMA‐treated, and MPTP‐treated mice. The results demonstrate that chronic administration of MDMA during late adolescence in mice exacerbates the neurodegeneration and neuroinflammation caused by MPTP, suggesting that MDMA may constitute a risk factor for dopaminergic neuron degeneration. © 2013 International Parkinson and Movement Disorder Society     

Electron microscopic findings in skin biopsies from patients with infantile osteopetrosis and neuronal storage disease

Infantile osteopetrosis with neuronal storage disease is a rare lysosomal storage disorder. It is an autosomal recessive disease that is associated with mutations in the OSTM1 and chloride channel ClCN-7genes. So far mutations in the OSTM1 gene have been identified in only 8 patients. To date, the clinical and morphological features of nine patients with infantile osteopetrosis with neuronal storage have been reported, but no ultrastructural findings of skin have been described in these patients. Skin biopsy is a cost-effective tool for the diagnosis of lysosomal storage disease. The purpose of this report is to define the ultrastructure of affected cells seen in skin biopsies of 2 boys whose mutation of OSTM1 has been characterized. The children presented in infancy with severe osteopetrosis and neurological deficiencies whose predominant symptoms were marked cerebral atrophy, decreased myelinization, and severe central nervous system involvement. Because of the difficulties in distinguishing this disorder from some lysosomal storage diseases such as mucopolysaccharidosis that have both neurological and skeletal abnormalities, the authors elected to examine skin biopsies from these children. Ultrastructural examination revealed the presence of swollen unmyelinated axons containing spheroids, reduced numbers of myelinated axons, and the presence of secondary lysosomes in Schwann cells containing lipofuscin. This study demonstrates that electron microscopy of skin biopsy is a useful diagnostic method to identify patients with clinical features of osteopetrosis with neuronal storage disease.     

Increased susceptibility to amyloid toxicity in familial Alzheimer's fibroblasts

Much experimental evidence suggests that an imbalance in cellular redox status is a major factor in the pathogenesis of Alzheimer's disease (AD). Our previous data showed a marked increase in membrane lipoperoxidation in primary fibroblasts from familial AD (FAD) patients. In the present study, we demonstrate that when oligomeric structures of Abeta 1-40 and Abeta 1-42 are added to the culture media, they accumulate quicker near the plasma membrane, and are internalized faster and mostly in APPV717I fibroblasts than in age-matched healthy cells; this results in an earlier and sharper increase in the production of reactive oxygen species (ROS). Higher ROS production leads in turn to an increase in membrane oxidative-injury and significant impairment of cellular antioxidant capacity, giving rise to apoptotic cascade activation and finally to a necrotic outcome. In contrast, healthy fibroblasts appear more resistant to amyloid oxidative-attack, possibly as a result of their plasma membrane integrity and powerful antioxidant capacity. Our data are consistent with increasing evidence that prefibrillar aggregates, compared to mature fibrils, are likely the more toxic species of the peptides. These findings provide compelling evidence that cells bearing increased membrane lipoperoxidation are more susceptible to aggregate toxicity as a result of their reduced ability to counteract amyloid oligomeric attack.     

Monitoring HCV RNA viral load by locked nucleic acid molecular beacons real time PCR

Locked nucleic acids (LNA) based real time PCR was used in particular situations where there are difficulties in primer design due to sequence complexity. In this study a new real time RT-PCR assay was developed using LNA modified primers and LNA molecular beacon probes to monitor hepatitis C virus (HCV) viral load in plasma and serum samples. The technique did not suffer from an heterogeneity of the HCV genome and, in addition, an internal RNA control was amplified in the same reaction tube with different short primers and beacon probe. Due to the short consensus LNA primers length, the PCR efficiency was close to 100% with no formation of hairpin loop structures. In summary a new LNA molecular beacon based real time RT-PCR assay was used successfully to measure quantitatively the total level of HCV RNA in both experimental and clinical specimens. The high sensitivity (50 IU/ml), the wide range of genotype detection, increased specificity and robustness obtained with this test are particularly useful for screening large number of specimens and measuring viral loads to monitor the progress of the disease.     

Sexual and psychological symptoms in the climacteric years

OBJECTIVES: To provide epidemiological data about psychological and sexual functioning during menopausal transition in a large Italian non-clinical sample, and to investigate their correlation with life events. METHODS: The study design was a cross-sectional postal survey of a menopausal sample of women recruited from the General Registry Office in Ferrara's province. The sample was composed of four thousand and seventy-three women; they were sent a questionnaire designed on the basis of the Women's Health Questionnaire (WHQ). Together with the WHQ, the subjects filled out a personal file to define social status, cultural level, family's characteristics, recent menstrual cycles, gynaecological history and operations, drug assumption, life events in the last year, and lifetime depression. RESULTS: One thousand three hundred and forty-five women provided usable questionnaires. Factor analysis resulted in eight clusters: somatic symptoms, depressive symptoms, depressed mood with anxiety symptoms, cognitive difficulties, anxiety, sexual functioning, vasomotor symptoms and sleep problems. Mood and sexual function were impaired through the menopausal transition, with depressive and sexual symptoms being higher in the post-menopausal group compared to the pre-menopausal one. Therefore, the correlation between the two was greater in the pre- and peri-menopausal period. CONCLUSION: Depressive and sexual symptoms presented greater severity in the post-menopausal group. Both clusters of symptoms were strongly associated with life events. The parallel course of the two clusters could be related with a common pathoplastic action of life events, both on sexual symptoms and on depressive symptoms, occurring right at the time that a woman has to face the transition into menopause.