Bacillus clausii therapy to reduce side-effects of anti-Helicobacter pylori treatment: randomized, double-blind, placebo controlled trial

BACKGROUND: Helicobacter pylori eradication fails in about 10% of patients, particularly because of the occurrence of resistance to antibiotics and side-effects. During anti-H. pylori therapy, probiotics have been successfully used to reduce the incidence of side-effects. AIM: To evaluate the effect of Bacillus clausii, a probiotic, on incidence (primary variable) and severity of antibiotic-associated side-effects during anti-H. pylori therapy. METHODS: One hundred and twenty H. pylori-positive patients were randomly screened to receive: (i) a standard 7 days triple therapy with rabeprazole 20 mg b.d., clarithromycin 500 mg b.d. and amoxicillin 1 g b.d. and B. clausii t.d.s. (each preparation containing 2 x 10(9) spores) for 14 days starting from the first day of treatment. (ii) The same 7 days triple therapy and placebo t.d.s. for 14 days starting from the first day of treatment. Side-effects were assessed using a validated questionnaire and were recorded for 4 weeks from the start of therapy. RESULTS: The incidences of nausea, diarrhoea and epigastric pain in patients treated with B. clausii were significantly lower than in placebo group, in both PP and ITT analysis. Equally, intensity of nausea and diarrhoea in patients treated with B. clausii was significantly lower than in placebo group. There were no differences in adherence to treatment and H. pylori eradication rates between groups. Conclusion : In symptom-free, H. pylori-positive subjects B. clausii bacteriotherapy reduces the incidence of the most common side-effects related to anti-H. pylori antibiotic therapy compared with placebo.     

13C-breath tests in the study of mitochondrial liver function

Breath tests for "dynamic" liver function evaluation have been proposed several years ago. A variety of carbon-labelled breath tests for the assessment of mitochondrial, microsomal and cytosolic liver function have been described with the aim to increase data on liver disease staging, prognosis, and response to therapy. In the last years a great interest is developed about the use of breath test for liver mitochondrial function evaluation since it results impaired in a wide range of liver diseases either of genetic or acquired origin. In these cases mitochondrial oxidative metabolism of some substrates, as far as recovery of the hepatic energy state after a metabolic insult, results impaired because of the disfunction of the electron transport chain and/or ATP synthesis. Ketoisocaproic acid and methionine are the best studied carbon-labelled substrates for the investigation of mitochondrial functional damages related to structural alterations that occur in many liver diseases. Although these tests are simple, cost-effective and safe, to date there is still not general approval for their usefulness in clinical settings since they should fulfill several requirements to overcome the drawbacks of traditional quantitative tests. On the other hand, this field is relatively young and further studies are needed in order to assess the suitable substrate for the evaluation of the complex mitochondrial metabolism both in healthy subjects and in patients with liver disease.     

Gabapentin for the treatment of behavioural alterations in dementia: preliminary 15-month investigation

BACKGROUND: Although the core feature of dementia is progressive cognitive disruption, non-cognitive behavioural problems are expressed in most patients with dementia during the course of their illness. While psychotropic drugs are frequently used to control behavioural symptoms, comorbidities, which are very common in the geriatric population, could often limit their use. Gabapentin may be a potential treatment in such situations. METHODS: In this open, baseline comparison study 20 patients with probable Alzheimer's disease with behavioural alterations and serious comorbidities (paralytic ileus, open-angle glaucoma, ischaemic cardiopathy, hepatic failure or severe prostatic hyperplasia) received gabapentin for 15 months. Patients were allowed to continue any previous therapy for concurrent diseases. However, concomitant antipsychotic or benzodiazepine intake was not permitted. RESULTS: Gabapentin appeared to be efficacious and well tolerated in this patient population, and did not appear to interact with other drugs. General benefit is reflected by a reduction of caregiver stress. No patients withdrew before the end of the study and no serious adverse events were reported. CONCLUSION: The results of this study in patients with probable Alzheimer's disease with behavioural alterations and serious comorbidities indicate that gabapentin provides significant and sustained efficacy in terms of behaviour, with associated reductions in caregiver burden. The results of an ongoing larger, randomised, double-blind study of gabapentin are keenly awaited and may help to provide a safer and more efficacious treatment option for this group of patients.     

Levofloxacin-based triple therapy vs. quadruple therapy in second-line Helicobacter pylori treatment: a randomized trial

BACKGROUND: Levofloxacin has been shown to be effective in Helicobacter pylori eradication. Two 10-day levofloxacin-based triple therapies were compared with standard 7- and 14-day quadruple regimens in second-line treatment. METHODS: Two hundred and eighty consecutive patients who failed to respond to standard triple therapy (clarithromycin, amoxicillin, rabeprazole) were randomly assigned to four groups: (1) levofloxacin 500 mg o.d., amoxicillin 1 g b.d., rabeprazole 20 mg b.d. for 10 days (LAR, n = 70); (2) levofloxacin 500 mg o.d., tinidazole 500 mg b.d., rabeprazole 20 mg b.d. for 10 days (LTR, n = 70); (3) tetracycline 500 mg q.d.s., metronidazole 500 mg t.d.s., bismuth salt 120 mg q.d.s., rabeprazole 20 mg b.d. for 7 days (7TMBR, n = 70); and (4) for 14 days (14TMBR, n = 70). Helicobacter pylori status and side-effects were assessed 6 weeks after treatment. RESULTS: The eradication rate was 94% in the LAR group and 90% in the LTR group in both intention-to-treat and per protocol analyses. Helicobacter pylori eradication was achieved in 63 and 69% of the 7TMBR group and in 69 and 80% of the 14TMBR group in intention-to-treat and per protocol analysis, respectively. Side-effects were significantly lower in the LAR and LTR groups than in the 14TMBR group. CONCLUSION: Ten-day levofloxacin-based therapies are better than standard quadruple regimens as second-line option for H. pylori eradication.     

Neuropsychological changes after subthalamic nucleus stimulation: a 12 month follow-up in nine patients with Parkinson's disease

Deep brain stimulation of the subthalamic nucleus has been recognized as one of the most promising techniques to decrease 'off' motor symptoms and motor fluctuations, allowing a reduction of drug therapy and limiting side effects of drug therapy. However, there is still open debate on the possible consequences of chronic subthalamic stimulation on general cognitive performance. A general amelioration of cognitive performance, in particular of executive functions has been reported but results are not homogeneous. We studied nine patients with Parkinson's Disease for 12 months following surgery for deep stimulation, studying their cognitive performances, paying particular attention to linguistic tests and selective alternating words production. Our results may be consistent with a slowing of cognitive activity, with a reduction of quantitative production, but with an increase in control of linguistic production, which is more precise and definite. We discuss the possible significance of these results, fully aware that only nine patients were involved, and that the potential for generalization is seriously limited, with a particular overview on the frontal-subthalamic pathway, which in our opinion is responsible for the results we observed.     

HLA genotypes and disease severity assessed by magnetic resonance imaging findings in patients with multiple sclerosis

The objective of the study was to examine the relationship between HLA genotypes and disease severity as measured by brain MRI quantitative markers of demyelinating and destructive pathology in patients with multiple sclerosis (MS). We studied 100 patients with MS and 122 age, sex-, ethnic- and residence-matched controls. The DNA extraction and the genomic typing (A, B, DRB1 and DQB1 loci) were obtained with sequence-specific oligonucleotide method, using a commercially available reversible line blot assay (INNO-LIPA). All patients underwent a 1.5 tesla MRI examination of the brain. Disease severity was assessed by clinical (Expanded Disability Status Scale (EDSS)) and MRI (T2- and T1-lesion load (LL) and brain parenchymal fraction (BPF)) outcome measures. HLA-DQB1* 02 (OR 19.9, 95% C. I. 16.2–24.3, uncorrected (uncorr)- p<0.00001, corr-p<0.0006), -DQB1*03 (OR 16.8, 95% C. I. 13.6–20.5, uncorr-p<0.00001, corrp< 0.0006), -DRB1*15 (OR 4.6, 95% C. I. 3.7–5.6, uncorrp= 0.0001, corr-p=0.006), and -DRB1*03 (OR 3.9, 95% C. I. 3.2–4.8, uncorr-p=0.0001, corrp= 0.006) alleles were associated with MS. T2-, T1-LL, BPF and EDSS were not significantly different according to the carrier status of these HLA alleles. No differences were found in the ratios of disease severity/disease duration according to the HLA car rier status. Multiple regression analysis showed that a higher T2-LL was associated with the presence of DRB1*04 (uncorr- R2=0.15, p=0.006 and corr- R2=0.11, p=0.025) and B7 alleles (uncorr-R2=0.08, p=0.02 and corr-R2=0.07, p=0.018), T1-LL was associated with B7 (uncorr- R2=0.30, p<0.0001 and corr- R2=0.27, p=0.0001) and DRB1*12 (uncorr-R2=0.25, p<0.0001 and corr-R2=0.21, p=0.0002) alleles, whereas the BPF was predicted only by the presence of DRB1*12 allele (uncorr-R2=0.24, p=0.002 and corr-R2=0.20, p=0.004). The study findings suggest that some HLA alleles may predict the destructive pathological processes visible on MRI. Since the size of the sample studied is relatively small, further studies are needed to draw any firm conclusion about genotype/phenotype correlation in patients with MS.     

Excretory urography with iohexol: evaluation in children

A multicenter clinical study was conducted using iohexol, a second-generation nonionic contrast medium, for excretory urography performed in 130 children. Doses of iohexol (300 mg iodine/ml) ranged between 150 and 660 mgI/kg (0.5 and 2.2 ml/kg). Iohexol was tolerated well, and no significant adverse reactions occurred. Sixty-five iohexol urograms were evaluated to determine the minimum dose for adequate visualization of the kidneys and collecting systems. A dose greater than 300 mgI/kg (1.0 ml/kg) always resulted in a urogram of diagnostic quality, while visualization was insufficient for diagnosis in 10% of studies done with doses of 150-300 mgI/kg (0.5-1.0 ml/kg). Another 65 iohexol urograms were compared in a blinded manner with a similar number of studies performed using iothalamate meglumine at comparable iodine concentration and dose. Visualization of calyces and pelvoinfundibular structures achieved with iohexol was rated better with statistical significance, but there was no difference in visualization of the renal parenchyma or ureters. Use of iohexol in excretory urography may be advantageous in children who are at greatest risk for an adverse reaction to contrast media or in those most likely to benefit from use of a low osmolality contrast agent.     

Primary retroperitoneal myxoid/round cell liposarcoma is a nonexisting disease: an immunohistochemical and molecular biological analysis

Almost all primary retroperitoneal liposarcomas can be classified as well-/dedifferentiated liposarcoma. Rarely, however, primary retroperitoneal liposarcoma is classified as myxoid/round cell liposarcoma, based on the presence of myxoid areas and vascular crow's feet pattern, which has resulted in a debate on the classification of liposarcoma in the retroperitoneum. Genetically, myxoid/round cell liposarcoma and well-/dedifferentiated liposarcoma are different diseases. Myxoid/round cell liposarcoma is characterized by a translocation causing FUS-CHOP or EWSR1-CHOP fusion, whereas well-/dedifferentiated liposarcoma is characterized by an amplification of the 12q13-15 region, including MDM2 and CDK4 genes. As myxoid/round cell liposarcoma is highly radio- and chemosensitive, differentiation between subtypes is important to optimize treatment. We studied whether primary retroperitoneal liposarcomas diagnosed as myxoid/round cell liposarcoma represent molecularly true myxoid/round cell liposarcoma or are histopathological mimics and represent well-/dedifferentiated liposarcoma. Primary retroperitoneal myxoid/round cell liposarcoma (n=16) were compared to primary extremity myxoid/round cell liposarcoma (n=20). Histopathological and immunohistochemical features were studied. Amplification status of the 12q13-15 region was studied using a multiplex ligation-dependent probe amplification analysis, and FUS-CHOP or EWS-CHOP translocations were studied using RT-PCR. In primary retroperitoneal myxoid/round cell liposarcoma, MDM2 and CDK4 staining was both positive in 12 of 15 cases. In primary extremity myxoid/round cell liposarcoma, MDM2 was negative in 18/20 and CDK4 was negative in all cases. Multiplex ligation-dependent probe amplification showed the amplification of 12q13-15 region in 16/16 primary retroperitoneal myxoid/round cell liposarcomas and in 1/20 primary extremity myxoid/round cell liposarcomas. Translocation was present in all (18/18) primary extremity myxoid/round cell liposarcomas, but absent in all primary retroperitoneal myxoid/round cell liposarcomas. On the basis of immunohistochemical and molecular characteristics, apparent primary retroperitoneal myxoid/round cell liposarcoma can be recognized as well-/dedifferentiated liposarcoma with morphological features mimicking myxoid/round cell liposarcoma. In these cases, treatment should probably be specifically designed as for well-/dedifferentiated liposarcoma. Moreover, finding of myxoid/round cell liposarcoma translocations in a retroperitoneal localization is highly suggestive of metastasis and should prompt search for a primary localization outside the retroperitoneum.