Significance of haemorrhagic lacunes on MRI in patients with hypertensive cerebrovascular disease and intracerebral haemorrhage

Our purpose was to determine the frequency and signifcance of haemorrhagic lacunes (HL) on MRI in patients with a history of, or at risk for intracerebral haemorrhage. We examined 72 patients with old spontaneous intracerebral haemorrhage (ICH) using T1-and T2-weighted spin-echo sequences. MRI studies of 137 consecutive patients with cerebrovascular disease but no known ICH were also reviewed. Both groups showed about the same degree of age-related white matter change and nonhaemorrhagic lacunar infarcts, whereas the ICH group had a higher frequency of HL (12/72 patients) than the non-ICH group (6/131 patients,p<0.01). These results correlate well with reported pathological findings. We conclude that haemorrhagic lacunes found on MRI studies of patients with cerebrovascular disease may suggest a higher risk of intracerebral haemorrhage.     

Detection of circulating anticellular antibodies by indirect immunofluorescence on HEp-2 cell substrates: study of the clinical value of rare fluorescence patterns

We detected anticellular antibodies (Ab) in 867 sera from patients with inflammatory rheumatic disorders by indirect immunofluorescence technique on HEp-2 cells and searched for clinically relevance of the rare fluorescence staining pattern (n = 133). We could find associations of 1. spekled nuclear pattern and Ab to U1-nRNP and La, 2. nucleolar pattern and scleroderma, 3. peripheral nuclear membrane pattern, Ab to dsDNA and SLE, 4. centromere staining and CRST syndrome, 5. intermedi?r filament pattern and permanent cellular destructions in erosive arthritis, 6. mitochondrial staining and inflammatory hepatic disorders. The anticellular Ab staining patterns on HEp-2 cells might be precious additionally markers for diagnosis and prognosis of inflammatory rheumatic diseases.     

Two novel mutations at exon 8 of the Sequestosome 1 (SQSTM1) gene in an Italian series of patients affected by Paget's disease of bone (PDB).

PDB is genetically heterogeneous. Mutations of the sequestosome1 gene have been reported in sporadic and familial forms of Paget's in patients of French Canadian and British descent. Mutational analyses in different ethnic groups are needed to accurately investigate hereditary diseases. We describe two novel mutations of sequestosome1 in 62 Italian sporadic patients, confirming the role of the encoded protein in this disorder. INTRODUCTION: Paget's disease of bone (PDB) is a relatively common disease of bone metabolism reported to affect up to 3% of whites over 55 years of age. The disorder is genetically heterogeneous, and at present, there is scientific evidence that at least eight different human chromosomal loci are correlated with its pathogenesis. Mutations of the sequestosome1 (SQSTM1) gene were identified as responsible for most of the sporadic and familial forms of Paget in patients of French Canadian and British descent. Such mutations were located at exon 7 and 8 levels, encoding for the ubiquitin protein-binding domain (UBA) and representing a mutational hot spot area. MATERIALS AND METHODS: To verify the involvement of this gene in Italian subjects affected by PDB, we performed mutational analysis in 62 sporadic PDB cases. RESULTS: We described three different mutations at exon 8 level: P392L, already described in the French Canadian population and families predominantly of British descendent, and two novel mutations consisting of the amino acid substitutions M404V and G425R. No significant differences in the clinical history of PDB have been observed in patients with SQSTM1 mutations in respect to those without. CONCLUSIONS: Even though our findings suggest a minor involvement of the SQSTM1 gene in the pathogenesis of sporadic Italian Paget's cases, the identification of different significant mutations within the SQSTM1 gene in unrelated, but clinically similar individuals, offers extremely convincing evidence for a causal relationship between this gene and PDB. Longitudinal studies are needed to assess the penetrance of genotype/phenotype correlations. Our findings confirm the evidence of a clustered mutation area at this level in this disorder.     

HISTOPATHOLOGIC STUDY OF CONJUNC-TIVA IN PATIENTS WITH HYPEREMIA DURING BIMATOPROST THERAPY

Purpose: Conjunctival hyperemia has been reported as a frequent side effect of bimatoprost, a prostamide with efficacious ocular hypotensive action. To investigate the possible inflammatory basis of the hyperemia, we analysed, by means of light microscopy, the conjunctival specimens of patients who developed ocular hyperemia during bimatoprost therapy and who underwent cataract surgery. Methods: Patients were divided in two groups;     

Monitoring motor function during resection of tumours in the lower brain stem and fourth ventricle

Objectives Even in the days of modern microsurgery, the removal of a brain stem lesion remains a surgical challenge. Especially when operating on children, the prognosis is directly related to the radicality of the resection; however, a radical resection is often associated with surgical morbidity. Intraoperative neuromonitoring could help to minimise the surgical morbidity, but few studies have been performed to clarify the value of this monitoring. We investigated a prospective series of 21 patients with lesions involving the brain stem for the prognostic value and benefits of neuromonitoring.Methods We performed intraoperative neuromonitoring of cranial nerve function by electromyography (EMG) and motor evoked potential (MEP). The results were correlated with postoperative neurological deficits.Conclusions There is a good correlation between intraoperative neurophysiological events and postoperative neurological deficits in patients with lesions of the brain stem. In general, transient, prolonged, spontaneous activity in EMG is associated with a transient paresis of the respective muscle, whereas a permanent spontaneous activity is associated with a permanent deficit. Intraoperative neuromonitoring reliably predicts postoperative neurological function in patients with tumours of the lower brain stem and fourth ventricle. This neuromonitoring guides the neurosurgeon in the operation and may decrease surgical morbidity. We recommend using monitoring of MEP and EMG of the lower cranial nerves in surgery on all patients with lesions involving the lower brain stem and fourth ventricle.     

Epilepsie und Hormone

Ohne Zusammenfassung     

The Parkinson-Control study: a 1-year randomized, double-blind trial comparing piribedil (150 mg/day) with bromocriptine (25 mg/day) in early combination with levodopa in Parkinson's disease.

Dopamine agonists have been recommended as early treatment for Parkinson's disease (PD), alone or combined with levodopa. Piribedil is a non-ergot selective D(2)/D(3) agonist with alpha(2) antagonist properties shown to be effective in the treatment of PD. This 12-month international, randomized, double-blind trial aimed to assess the efficacy of piribedil 150 mg versus bromocriptine 25 mg, in early combination with levodopa in Stage I to III PD patients. Motor efficacy was assessed using the Unified Parkinson's Disease Rating Scale (UPDRS III, Items 18-31) as improvement from baseline. Response rate was defined as a 30% improvement. Among the 425 randomly assigned patients, 178 were also included in a substudy on cognitive follow-up evaluated by a dysexecutive syndrome oriented battery. A relevant improvement in UPDRS III over the 12-month study duration was observed both in the piribedil and bromocriptine groups (-7.9 +/- 9.7 points from baseline versus -8.0 +/- 9.5; not significant [n.s.]) with a response rate of 58.4% and 55.3% (n.s.), respectively. Piribedil and bromocriptine resulted in similar improvement on all UPDRS III subscores. Piribedil patients required less levodopa dose increase than those on bromocriptine. Cognitive performance remained generally unchanged in both groups, with a significant effect of piribedil limited to the Wisconsin Card Sorting Test. An overall good tolerability of piribedil was observed. Early combination of piribedil 150 mg with levodopa resulted in significant long-term improvement of all motor symptoms in PD patients insufficiently controlled by levodopa alone. Taking into account both efficacy and acceptability in the long-term, piribedil proved in this bromocriptine controlled study to be an effective and safe treatment for PD.     

Does Fluid Flow Across the Intestinal Mucosa Affect Quantitative Oral Drug Absorption? Is It Time for a Reevaluation?

Purpose. Hydrophilic and charged solutes have a lower membrane permeability which is due to a lower partition into the lipid membrane (low solubility in the membrane phase) and/or a slower transcellular diffusion coefficient. They are therefore anticipated to be absorbed through the paracellular route, which is a consequence of diffusion and a convective volume flow through the water-filled intercellular space. Methods. Two approaches have been used to investigate the mechanisms underlying the paracellular drug transport across the intestinal mucosa: (a) including water transport by exposing the apical side of the epithelium with a hypotonic solution, and (b) stimulated paracellular transport by widening of tight junction and increased water absorption as a consequence of the sodium-coupled transport of nutrients. Results. Among the first studies that recognized this fluid flux dependent transmucosal transport of drugs, was one published by Oschenfahrt & Winne in 1973 and the one by Kitazawa et al. in 1975. During the last two decades the importance of this paracellular route for drug delivery have been explored in vitro and in situ. Conclusions. The limits concerning molecular weight, shape, ionization and the effect of physiological stimulants, such as luminal concentrations of nutrients, osmolality and motility, are currently under investigation. However, recently published in vivo human data by ourselves and others indicate that the promising results obtained in vitro and in situ for various hydrophilic compounds might not be valid in quantitative aspects in humans, especially not for drugs with a molecular weight over 200.