Functional polymorphisms of interleukin 4 and interleukin 10 may predict evolution and functional outcome of an ischaemic stroke.

BACKGROUND AND PURPOSE: Inflammatory cytokines are involved in the systemic inflammation, which precedes an ischaemic stroke (IS), and also participate into brain ischaemia-reperfusion injury. We sought to investigate whether functional polymorphisms of two anti-inflammatory molecules, interleukin (IL)4-589C>T and IL10-1082G>A, might be associated with the occurrence, clinical course and functional outcome of an acute IS. METHODS: We genotyped 290 subjects (145 consecutive IS cases and 145 age- and sex-matched controls) using a real-time PCR technology, prototypically designed for these mutations. Patients were evaluated with the Scandinavian Stroke Scale, and definitions of severity grouping and stroke progression were applied based on international agreements. Follow-up on months 1, 3, and 6 included registration of disease relapses, deaths and functional outcome measured by the Barthel Index. RESULTS: IL4-589 and IL10-1082 genotypes did not significantly differ between cases and controls. The presence of IL4-589 T allele was associated with total IS recurrences [OR (95% CI) = 3.34 (1.18-9.45)], adjusted for age, sex and conventional risk factors. IL10-1082 GG genotype was found to significantly predict early stroke progression [OR (95% CI) = 3.72 (1.28-10.76)] and functional outcome by months 1 and 3 [OR (95% CI) = 5.03 (1.15-21.94) and 5.84 (1.07-31.85), respectively], after further corrections for stroke severity and TOAST categories. CONCLUSIONS: The functional IL4-589C>T and IL10-1082G>A polymorphisms seem not to be associated with occurrence of an IS, but may predict IS relapses, progressing strokes and functional outcome, independently of conventional risk factors. Our results merit further confirmation in future studies.

Serum adiponectin acutely after an ischemic stroke: implications for a long-lasting, suppressed anti-inflammatory role.

OBJECTIVE: Past ischemic stroke (IS) patients display suppressed adiponectin (ADPN) levels a few months after disease onset. It is still unclear whether hypoadiponectinemia is already present by the early stages of stroke or occurs as a delayed effect of the acute ischemic reaction. In the present study we investigated ADPN levels acutely after an IS. MATERIALS AND METHODS: Serum ADPN was measured in 82 consecutive acute IS patients, and 30 stroke-free subjects of similar age and sex distributions. RESULTS: Patients had significantly lower ADPN levels than controls. Higher ADPN was significantly associated with reduced odds for IS accounting for age, sex and high-density lipoproteins. This association was strengthened after further adjustments for potential confounders. ADPN levels remained suppressed even 6 months after stroke. CONCLUSIONS: ADPN is significantly suppressed already by the early phases of stroke, and remains unchanged 6 months later. We propose a stable-over-time anti-inflammatory role of ADPN in IS, unrelated to the acute ischemic reaction.

Does motor subtype influence neurocognitive performance in Parkinson's disease without dementia?

The postural instability and gait difficulty (PIGD) motor subtype has been shown to represent a risk factor for development of dementia in Parkinson's disease. Whether this relationship extends to a more subtle cognitive dysfunction in patients is less clear. Therefore, we administered a battery of selected neuropsychological tests to two groups of non-demented patients with mild to moderate disease classified either as PIGD or as non-PIGD subtype and to a group of healthy controls. Groups were matched on potential confounders of neuropsychological performance. No significant differences were revealed between the two groups of patients in the performance of any of the administered neuropsychological tests. However, relative to controls there was a tendency towards a differential pattern of cognitive dysfunction. The PIGD group had slower performance in a test of psychomotor speed and cognitive flexibility, whilst the non-PIGD group performed worse in measures of verbal learning and visuo-spatial perception. In conclusion, the PIGD subtype was not associated with more severe cognitive deficits and may to a certain extent share common mechanisms of cognitive dysfunction with non-PIGD subtypes. Diverse pathological processes however may develop to account for unequal rates of dementia amongst different motor subtypes.

Disclosing the diagnosis of multiple sclerosis.

CONTEXT: The question of how best to disclose to patients the diagnosis of serious and/or incurable neurological diseases has been much explored, but that of when has received little rigorous study. The present study investigates this question in relation to multiple sclerosis (MS), a disease marked by its incurability, unpredictability and predilection for young adults. OBJECTIVES: We aimed to ascertain the preferences of Greek MS sufferers concerning when they should ideally be informed they have the disease, and their preferences and reactions regarding disclosure of the diagnosis. Design, setting and patients 1,200 Greek MS patients,members of the MS Society, were asked to complete a questionnaire regarding their experience of and attitudes towards receiving the diagnosis. DESIGN, SETTING AND PATIENTS: 1,200 Greek MS patients,members of the MS Society, were asked to complete a questionnaire regarding their experience of and attitudes towards receiving the diagnosis. RESULTS: 657 patients (55 %) responded. 91% favoured learning the diagnosis immediately, but only 44% had had this experience: 29% had been informed within 1-3 years, and 27% later. Interestingly, however, a significant minority (9 %) suggested a possible preference for delayed delivery of diagnosis and 23.2% stated that concealing the diagnosis would not lead to loss of confidence in their doctor. CONCLUSION: This study-the largest of its kind-provides objective data supporting prompt disclosure of diagnosis as the clearly-expressed preference amongst most patients. Interestingly, however, the results also re-emphasise the importance of a difficult medical art: attempting to judge whether an individual patient is one (of the 91%) preferring immediate disclosure-or of the nearly 1-in-10 (9%) who may not.

Gabapentin in the management of the recurrent, refractory, idiopathic priapism.

Recurrent idiopathic priapism is a difficult problem to treat and a true emergency for the physicians, and often even invasive therapeutic interventions fail. We recently managed three men with refractory idiopathic priapism with oral gabapentin. They responded to treatment within 48 h. Two men continue not to experience prolonged erections while treated with lower doses of gabapentin for 16 and 24 months, respectively. The third, after a successful treatment for 6 months, stopped gabapentin and priapism recurred. He responded to treatment again and continues to be free of episodes for 9 months. Gabapentin may be a safe alternative for the management of refractory idiopathic priapism.

A programmable digital video pattern generator controlled by microprocessor for basic research and clinical applications.

A programmable digital video pattern generator controlled by a microprocessor is described as a part of any commercial or specific visual evoked potential analysis system. The generator handles all kinds of patterns (uniform, orthogonal and radial) with all known presentation modes (onset, offset and reversal) and resolution 640 x 200 square pixels. The frame rate of the generator is adjusted to be compatible to either low cost 50 Hz video monitor or expensive ones of higher frame rate. The operation parameters defined by software are: pattern selection, trigger mode, field selection and stimulation rate. The development of software applications for special research demands is desirable because of the control of the generator by a microprocessor.

Spontaneous esophageal rupture in adult dermatomyositis.

Dermatomyositis is a chronic inflammatory myopathy with severe prognosis. A 57-year-old woman suffering from dermatomyositis is presented who, in the course of the disease, developed acute spontaneous esophageal rupture due to dermatomyositis involvement of the esophagus. She was successfully treated with total esophagectomy and stomach interposition. This is the first report of spontaneous rupture of esophagus in dermatomyositis.

Pattern reversal visual evoked potentials in retinitis pigmentosa.

Pattern reversal visual evoked potentials (PR-VEPs) of 31 patients with retinitis pigmentosa (RP) and 20 normal control subjects were recorded and compared. Recordings were taken from Oz referred to Fz, by stimulating with squares subtending 60 min, presented at a visual field of 30 degrees and 98% contrast. The mean latency of the main positive component P100 of the PR-VEP of the RP patients was 116.1 msec (SD 12.71) and 114.84 after stimulation of the left and right eye respectively. These values are significantly different (p < 0.001) from the equivalent values of the normal controls (102.5 ms (SD 5.1) and 100.6 ms (SD 4.6) for the left and right eye, respectively). Fourteen patients had a P100 latency more than 3 SDs from the normal mean value. Subsequently the patients were classified into three groups (for each eye separately) according to visual acuity (VA) and comparison for PR-VEP amplitude and latency was performed. In group A patients with VA 6/6, in B with 6/9 and in G with 6/12 or more were included. Decrease of VA was significantly associated with increased latency. The amplitude was not significantly affected except for group C. All 3 groups were not significantly different in age. The P100 in group A was consistently prolonged, compared to normals. It seems that RP can introduce significant increase in the PR-VEP latency associated with decreased VA. This may have diagnostic and prognostic implications.

Sarcoidosis in a patient with myasthenia gravis. Case report and review of the literature.

The case of a 38-year-old white female, with a long history of myasthenia gravis, who developed sarcoidosis is presented. The diagnosis of myasthenia gravis had been established on the basis of typical clinical symptoms with severe myastenic crises necessitating respiratory support, characteristic electromyographic findings, positive anti-acetylcholine receptor antibodies and response to appropriate medications. After 9 years of disease and while in apparent remission, she presented with ankle arthritis and bilateral hilar adenopathy. A transbronchial lung biopsy showed noncaseating granuloma, typical of sarcoidosis. To our knowledge, the combination of myasthenia gravis and sarcoidosis is extremely rare and emphasizes the intriguing tendency of some immunologic disorders to appear together in certain individuals.

Phonological fluency strategy of switching differentiates relapsing-remitting and secondary progressive multiple sclerosis patients.

The strategies used to perform a verbal fluency task appear to be reflective of cognitive abilities necessary for successful daily functioning. In the present study, we explored potential differences in verbal fluency strategies (switching and clustering) used to maximize word production by patients with relapsing-remitting multiple sclerosis (RRMS) versus patients with secondary progressive multiple sclerosis (SPMS). We further assessed impairment rates and potential differences in the sensitivity and specificity of phonological versus semantic verbal fluency tasks in discriminating between those with a diagnosis of MS and healthy adults. We found that the overall rate of impaired verbal fluency in our MS sample was consistent with that in other studies. However, we found no differences between types of MS (SPMS, RRMS), on semantic or phonological fluency word production, or the strategies used to maximize semantic fluency. In contrast, we found that the number of switches differed significantly in the phonological fluency task between the SPMS and RRMS subtypes. The clinical utility of semantic versus phonological fluency in discriminating MS patients from healthy controls did not indicate any significant differences. Further, the strategies used to maximize performance did not differentiate MS subgroups or MS patients from healthy controls.

Cerebellar hemorrhage after supratentorial burr hole drainage of a chronic subdural hematoma.

Cerebellar hemorrhage is an unusual, but increasingly recognized complication after supratentorial surgery. Even rarer are the cases of cerebellar hemorrhage after supratentorial burr-hole drainage of a chronic subdural hematoma (CSDH). The pathophysiology of this rare complication still remains unclear. Hypertension and overdrainage of cerebrospinal fluid seem to be causative factors of postoperative cerebellar hemorrhage. The most important key to minimize this hazardous sequel is to be aware of this potential complication and its pathogenetic mechanisms. We report our case of a 43-year old man who developed cerebellar hemorrhage after burr hole trephination for supratentorial CSDH.

Emerging therapeutic approaches multi-targeting receptor tyrosine kinases and g protein-coupled receptors in cardiovascular disease.

Advances in molecular biology and functional genomics have demonstrated that the "one gene-one phenotype-one drug" paradigm, that has dominated pharmaceutical industry and clinical pharmacology thinking, is too simplistic for management of complex polygenic traits. The traditional highly specific drugs with unique target have proven their clinical usefulness. However, they do not always display the required efficacy versus side-effect profile, in major part because polygenic traits are determined by redundant mechanisms. Simultaneously modulating multiple targets may enhance therapeutic efficacy in the treatment of a range of disorders. Multi-targeting can be achieved by the combination of different drugs having specific single target activity. This approach introduces potential problems with pharmacokinetic interactions, toxicity and patient compliance. High efficacy can be achieved, alternatively, by administering selectively non-selective drugs with complex pharmacological profiles directed towards various molecular targets and affording pleiotropic actions. Dual- or multiple-ligands can be discovered accidentally, but can also be rationally designed according to validated medicinal chemical approaches. The merits of multiple-target versus single-target approaches for cardiovascular disease traits are assessed in the present review. The main aim is to make evident the molecular biological basis of the possibility for targeting multiple sites and the subsequently emerging strategies for interventions with superior clinical value by harnessing receptor tyrosine kinases (RTKs) such as VEGFR, PDGFR, bFGFR, as well as G protein-coupled receptors (GPCRs). The premises for lead discovery in this new area and the challenges of medicinal chemistry behind the rational design of multitasked ligands are also discussed.

Robust moving averages, with Hopfield neural network implementation, for monitoring evoked potential signals.

This technical note describes a robust version of moving averages, that enables reliable monitoring of the evoked potential (EP) signals. A cluster analysis (CA) procedure is introduced to robustify the signal averaging (SA). It is implemented via a Hopfield neural network (HNN), which performs selection of the trials forming a cluster around the current state of the EP signal. The core of this cluster serves as an estimate of the instantaneous EP. The effectiveness of the method, indicated by application to real data, and its computation efficiency, due to the use of simple matrix operations, makes it very promising for clinical observations.

Data dependent weighted averages for recording of evoked potential signals.

Two new filters are proposed to replace conventional on-line artifact rejection routines. They are based on an algorithm that computes a weight for each trial according to its similarity to the rest. The robustness of the two filters and their capacity to reduce recording time significantly were verified experimentally.

Pattern reversal visual evoked potentials in minor head injury.

Pattern reversal visual evoked potentials (PR-VEPs) have been recorded in 50 patients with minor head injury (MHI) on days 1 and 30 after trauma and the data compared to 20 normals. None of the patients had visual complaints. The aim was to investigate a possible visual pathway affection in MHI and test the usefulness of PR-VEPs as an objective noninvasive tool in the detection of a possible subclinical affection of the visual system in MHI. P100 latency and amplitude had no significant difference compared to normals. Comparison of patient data on days 1 and 30 after trauma showed a significant latency decrease and amplitude increase on day 30, compared to day 1. These alterations were not age dependent. Our data suggest affection of the human visual pathway in MHI. PR-VEP recording seems to be a useful, objective, noninvasive tool, helping to identify possible subclinical affections of the visual pathway in MHI.