Ventromedial prefrontal cortex CRF1 receptors modulate the tachycardic activity of baroreflex.

Ventral medial prefrontal cortex (vMPFC) glutamatergic neurotransmission has a facilitatory role on cardiac baroreflex activity which is mediated by NMDA receptors activation. Corticotrophin releasing factor receptors type1 and 2 (CRF1 and CRF2), present in the vMPFC, are colocalized in neurons containing glutamate vesicles, suggesting that such receptors may be involved in glutamate release in this cortical area. Therefore, our hypothesis is that the CRF1 and CRF2 receptors can modulate the baroreflex bradycardic and tachycardic responses. In order to prove this assumption, male Wistar rats had bilateral stainless steel guide cannula implanted into the vMPFC, and baroreflex was activated by intravenous infusion of phenylephrine or sodium nitroprusside through a vein catheter. A second catheter was implanted into the femoral artery for cardiovascular measurements. The CRF1 receptor antagonist administration in either infralimbic cortex (IL) or prelimbic cortex (PL), vMPFC regions, was unable to change the bradycardic responses but increased the slope of the baroreflex tachycardic activity. Microinjection of the CRF2 receptor antagonist into the IL and PL did not alter ether bradycardic nor tachycardic baroreflex responses. The administration of the non-selective CRF receptors agonist, urocortin in these areas, did not modify bradycardic responses but decreased tachycardia slope of the baroreflex. CRF1 receptor antagonist administration prior to non-selective CRF agonist in vMPFC prevented the tachycardic responses reduction. However, CRF2 receptor antagonism could not prevent the effect of CRF receptors agonist. These results suggest that IL and PL CRF1 but not CRF2 receptors have an inhibitory role on the baroreflex tachycardic activity. Furthermore, they have no influence on baroreflex bradycardic activity.

Use of tocilizumab in amyloid a nephropathy associated with Sweet syndrome: a case report and literature review.

Amyloid A nephropathy is a possible complication of chronic inflammatory disease. Proteinuria and kidney failure are the main features of the disease. Tocilizumab (TCZ), an IL6-R antibody approved for rheumatoid arthritis, is a promising choice for histologically demonstrated nephropathy. We describe a case of kidney amyloid associated with Sweet syndrome treated with TCZ. The patient was affected by Sweet syndrome associated with proteinuria. Kidney biopsy showed amyloid deposits. During the follow-up, cutaneous and renal findings were refractory to many immunosuppressive regimen (cyclophosphamide, leflunomide, interferon and steroid). After few years, the patient developed rapidly progressive nephropathy associated with nephrotic syndrome (proteinuria up to 6 g/die). A second kidney biopsy was performed and it showed worsening of amyloid nephropathy. Thus, TCZ was administrated (8 mg/kg once a month) and it stabilized kidney function and induced partial remission of the nephrotic syndrome in the following 2 years.

Proteinuria is a late-onset adverse event in patients treated with cabozantinib.

PURPOSE: The use of tyrosine kinase inhibitors (TKIs) in thyroid cancer patients is often limited by toxicities. Some have a long-term onset and potentially could impact patients' survival. Among them, there is the nephrotoxicity, mainly represented by proteinuria. The aim of the study was to evaluate the prevalence of proteinuria in medullary thyroid cancer patients treated with cabozantinib, to examine whether it could be a marker for treatment monitoring and to evaluate histological kidney alterations. METHODS: We collected data of 31 medullary thyroid cancer patients enrolled in the EXAM trial. Proteinuria was defined and evaluated using the National Cancer Institute's Common Terminology Criteria for Adverse Events. In two symptomatic cases with high-grade proteinuria, a kidney biopsy was performed. RESULTS: Proteinuria was observed in 4/18 patients (22.2%) and occurred after a mean period of 38 months (median: 35.5 months). It was significantly associated with previous chemotherapy (p = 0.005) and/or treatment with other TKIs (p = 0.04), a prolonged use of cabozantinib (p = 0.0004), and a better radiological response at the end of follow-up (p = 0.002). The kidney biopsy showed pathognomonic features of thrombotic microangiopathy in both cases and a focal amyloid deposit in one. CONCLUSION: Proteinuria is a quite frequent adverse event during cabozantinib treatment. It is relatively well manageable with the early detection and correction of risk factors, the temporary discontinuation of cabozantinib and/or its dose reduction, and the use of anti-proteinuric and renoprotective drugs in patient with hypertension. The histological findings confirmed some typical features of the anti-VEGF inhibition injury, already described for other TKIs.

An atypical presentation of diffuse midline pontine glioma in a middle age patient: Case report.

INTRODUCTION: Diffuse midline glioma is a newly WHO defined entity (grade IV) (Louis et al., 2016) which includes diffuse intrinsic pontine glioma (DIPG) reported in pediatric population and, occasionally, in young adults. Here, we present a detailed description of an atypical case of diffuse midline glioma in a 53 years old woman. CASE REPORT: A caucasian woman aged 53 from Ukraine, was referred to another neurological department complaining of 3 months history of progressive postural instability and gait impairment with frequent falling. Magnetic resonance demonstrated two brainstem lesions, hyperintense in FLAIR with "patchy" peripheral enhancement, leptomeningeal and cranial nerves enhancement. CSF was normal. Due to positive antinuclear antibodies test (ANA 1:360), intravenous steroid treatment was administered and reported to initially improve the patient condition. However, the following weeks the lady worsened. Imaging features were unchanged. Because quantiferon test resulted positive, MRI-Spectroscopy showed an inflammatory pattern and MRI perfusion study and brain FDG-PET, were normal, tubercolar granulomatous hypothesis was initially favored. Antitubercular therapy with isoniazid, pyrazinamide, ethambutol and rifampicin was started without any clinical improvement. Hence, the biopsy was proposed. The procedure revealed a diffuse midline pontine glioma. Considering the advanced stage of the disease, radiotherapy was not indicated. Patient died after eight months from the onset of neurological disturbances. CONCLUSION: Our case shows that diffuse midline glioma is a CNS tumor not limited to young population but occurring also in middle aged patients with an insidious pattern. We therefore recommend to perform biopsy at very early stages in patients with atypical brainstem lesions.

Blood pressure phenotype reproducibility in CKD outpatients: a clinical practice report.

Out-of-office blood pressure (BP) measurement is encouraged by recent hypertension guidelines for assessing BP phenotypes. These showed acceptable reproducibility in the short term, but few data exist about long-term reproducibility, particularly for chronic kidney disease (CKD) patients. We evaluated changes of the BP phenotypes at 6 and 12 months in 280 consecutive non-dialysis CKD outpatients (186 males, age 71 ± 12 years, eGFR 38 ± 13 ml/min/1.73), without any change in drug therapy. Elevated BP is defined as office BP > 140/90 and home BP > 135/85 mmHg for defining the following BP phenotypes: sustained uncontrolled hypertension (SUCH); white-coat uncontrolled hypertension (WUCH); masked uncontrolled hypertension (MUCH); and controlled hypertension (CH). At baseline, the prevalence of the phenotypes was SUCH 36.6%, CH 30.1%, WUCH 25.4% and MUCH 7.9%, and it was similar at 6 months and 12 months. On the other hand, individual phenotype reproducibility at 12 months was poor both overall (38.0%) and across the different phenotypes (SUCH 53.9%, WUCH 32.4% and CH 32.1%, MUCH 9.1%). Patients who were not maintaining the same phenotype (non-concordant) were not distinguished by age, sex, BMI, eGFR, presence of diabetes or cardiovascular disease, or pharmacological therapy. When reproducibility of BP phenotypes both at 6 months and at 12 months was assessed, it was very low (19.6%), particularly for MUCH (0%), CH (14%) and WUCH (15.5%), while it was 31% for SUCH. In a CKD cohort, the overall prevalence of the different BP phenotypes defined by office and home BP remains constant over time. However, only 38% of patients maintained the same phenotype at 12 months, suggesting a poor reproducibility over time for the BP phenotypes.

[Nutritional and Functional assessment of peritoneal dialysis patients in the clinical practice: Report from MITO-DP Group]. / Valutazione Nutrizionale e Funzionale dei pazienti in dialisi peritoneale nella pratica clinica: l'esperienza del Gruppo Medico-Infermieristico Toscano di Dialisi Peritoneale (M.I.TO.-DP).

Nutritional abnormalities and physical inactivity are risk factors of increased morbidity and mortality in patients with ESRD. Identify and define malnutrition, in particular protein-energy depletion (PEW), is an important task in the management of renal patients. The aim of this multicenter observational study was to implement the assessment of nutritional status and functional capacity in patients on peritoneal dialysis, including tests and validated methods which are relatively easy to apply in daily clinical practice. The study includes all the 133 prevalent patients (80 m, 53 f, age 65 14 years), in peritoneal dialysis treatment (vintage 26 19 months) in 9 centers in Tuscany. We performed anthropometry, bioimpedance (BIA), clinical biochemistry, evaluation of habitual physical activity (RAPA tests) and performance (Sit-To-Stand test), appetite-evaluation questionnaire, and indices including the Malnutrition Inflammation Score (MIS), Geriatric Nutrition Risk Index (GNRI), Charlson comorbidity index, Barthel and Karnowsky index. The latter showed a condition of dependence in 7.2% and 19.7% of cases, respectively. Poor appetite was recorded in 48.2%. The majority of patients fell within the overweight / obesity range (51%) with waist circumference values associated with increased cardiovascular risk in 51% of males and 60% of females. At the BIA analysis, a BCMI <8 kg/m2 was detected in 39% of patients; an estimated protein intake <1.0 g / kg/d was found in 59% of cases; 34% of patients had serum albumin <3.5 g / dl; control of acidosis was good (bicarbonate 25.4 3.8 mM) but hyperphosphatemia was present in 64.6% of patients. A condition of sedentary or light physical activity was reported by 65.1% of patients, vigorous activity only by 11.9%. The 86.5% of patients able to perform the Sit-to-stand test reported a lower than the reference values for age and sex. A diagnosis of PEW was possible in 8% of our series, while a MIS score> 11, indicative of PEW, took place in 12.7% of cases. The values of the MIS correlated directly with age and the degree of comorbidity and inversely with the sit-to-stand test, RAPA tests and appetite level. The data in this study show that single tests indicative of malnutrition disorders are frequent to be found in our series of peritoneal dialysis patients. However, a diagnosis of PEW is quite infrequent. A large percentage of patients are overweight with increased abdominal adiposity, and reduced cell mass and protein intake below recommended levels; the level of habitual physical activity is low, and the level of physical capability is scarce. Therefore it is conceivable a nutritional counseling intervention to increase the intake of proteins, limiting the phosphorus and (when indicated) energy intake and to stimulating spontaneous physical activity or arranging assisted programs for functional rehabilitation. Close monitoring of the nutritional status and implementation of programs of adapted physical activity should have a prominent role in the clinical management of patients on peritoneal dialysis.

Non-invasive assessment of animal exercise stress: real-time PCR of GLUT4, COX2, SOD1 and HSP70 in avalanche military dog saliva.

Exercise has been shown to increase mRNA expression of a growing number of genes. The aim of this study was to assess if mRNA expression of the metabolism- and oxidative stress-related genes GLUT4 (glucose transporter 4), COX2 (cyclooxygenase 2), SOD1 (superoxide dismutase 1) and HSP70 (heat shock protein 70) in saliva changes following acute exercise stress in dogs. For this purpose, 12 avalanche dogs of the Italian Military Force Guardia di Finanza were monitored during simulation of a search for a buried person in an artificial avalanche area. Rectal temperature (RT) and saliva samples were collected the day before the trial (T0), immediately after the descent from a helicopter at the onset of a simulated avalanche search and rescue operation (T1), after the discovery of the buried person (T2) and 2 h later (T3). Expressions of GLUT4, SOD1, COX2 and HSP70 were measured by real-time PCR. The simulated avalanche search and rescue operation was shown to exert a significant effect on RT, as well as on the expression of all metabolism- and oxidative stress-related genes investigated, which peaked at T2. The observed expression patterns indicate an acute exercise stress-induced upregulation, as confirmed by the reductions in expression at T3. Moreover, our findings indicate that saliva is useful for assessing metabolism- and oxidative stress-related genes without the need for restraint, which could affect working dog performance.

Prevention and management of hyperglycemia after pancreas transplantation.

PURPOSE OF REVIEW: Pancreas transplantation is considered the optimal therapy for patients with insulin-dependent diabetes. Successful pancreas transplantation achieves euglycemia and allows freedom from insulin therapy. Long-term allograft success may be limited by the development of impaired glucose metabolism. The objectives of the present review are to summarize the possible reasons for endocrine pancreatic dysfunction and to focus on its prevention and management and emphasize the role of immunosuppression. RECENT FINDINGS: The diabetogenic effects of current immunosuppressive agents have been well established. Regimens without corticosteroids and calcineurin-inhibitor minimization or avoidance have been promoted. Recent studies have revisited the pathogenesis of type I and type II diabetes and demonstrated common pathways, including apoptosis induction, for the exhaustion and destruction of the pancreatic islets. SUMMARY: The immunosuppressive regimens in pancreatic transplantation should be designed and appropriately modified according to the graft immunological and metabolic conditions. New molecules that are able to preserve islet function and maintain optimal insulin secretion should be considered for pancreas transplant recipients.

Endoscopic treatment of colloid cysts of the third ventricle: long-term results in a series of 6 consecutive cases.

AIM: Colloid cysts of the third ventricle represent 0.5-2% of all intracranial tumors. Several surgical approaches have been proposed for the treatment of these lesions and endoscopy is the most recent one, but the best treatment still remains controversial. We decided to treat colloid cysts with endoscopic approach since 1999. In this paper we present our results in 6 consecutive cases admitted at our institution from 1999 to 2004. METHODS: There were 4 males and 2 females. The mean age was 51.6 (range 29-77). All the cysts were symptomatic. The presenting symptom was headache in 4 patients, gait disturbance in 2, altered vision in 2, mental status change in 2, urinary incontinence in 2, loss of consciousness in 2 and short-term memory loss in 1 patient. All the endoscopic procedures were performed via a right precoronal burr hole, with a rigid endoscope. RESULTS: The removal was radiologically complete in 4 cases and incomplete in 2. Overall outcome was good in all cases, with an improvement of colloid cyst-related hydrocephalus in all the patients. There was no surgical mortality. The mean follow-up period was 52.5 months. No tumor recurrences were observed. Complications occurred in only one patient: a septic ventriculitis, venous thrombosis of the right leg and pulmonary embolism developed, but completely resolved during the hospitalization time. CONCLUSION: The endoscopic approach for the removal of colloid cysts of the third ventricle represents a safe procedure, and can be considered a very good option for the treatment of these lesions.

A survey of Italian cases of dystonia treated by deep brain stimulation.

AIM: The aim of this study was to report on Italian cases of dystonia treated by deep brain stimulation up to the end of 2005. METHODS: Retrospective survey. Presentation of data collection among all Italian neurosurgical institutions. RESULTS: Seven out of 123 Italian neurosurgical centres were enrolled. Sixty-nine patients were operated. According to different classification criteria, cases were grouped as follows: 37 primary and 32 secondary dystonia; 61 generalized and 8 focal dystonia; 16 patients aged at onset <2 years, 22 aged 3-12 years, 14 aged 13-20 years, 17 aged >20 years. Primary dystonia (DYT) mutation 1 was identified in 21% of primary generalized dystonia. Age at surgery was <15 years in 21.7% of cases (N.=15). Mean time between clinical onset and surgery was 17 years. Globus pallidus internus (GPi) was chosen for implantation in all cases. Type of anesthesia, method of target localization, lead and implanted pulse generator (IPG) model differed among centres. Surgical complications occurred in 19% of patients, but at a higher rate (33%) in the pediatric subgroup. Stimulation parameters varied among centres, but the main scheme was 90-120 micros and 130 Hz. Follow-up duration ranged from 3 to 84 months (longer than 24 months in 50% of patients). Mean Burke-Fahn-Marsden scale (BFM) improvement was 42% for both severity and disability score, ranging from 0% to 92%. Improvement of at least 50% in BFM severity score has been reached by 45% of primary and 37% of secondary dystonia. Clinical results were better in the DYT1 subgroup, with 60% of cases improving more than 50%. Among secondary dystonia, the drug-induced group had very good results too. On the contrary delayed surgery and presence of comorbidity were negatively correlated to the outcome. CONCLUSION: In this series, primary generalized dystonia has a better outcome, especially if associated to DYT1 mutation. Among secondary dystonia, the drug-induced group has very good RESULTS: Correlation analysis of time to surgery and associated comorbidity suggests that earlier surgery is advisable.

Gender-related differences in the human subthalamic area: a local field potential study.

The objective of this study was to investigate the possible existence of gender-related neurophysiological differences in the oscillatory activity of the human subthalamic area. To this end, we recorded local field potentials (LFPs) after neurosurgical procedures for deep brain stimulation (DBS) in 24 patients (12 males and 12 females) with Parkinson's disease. LFP recordings at rest before levodopa medication (19 nuclei from 11 female patients and 16 nuclei from ten male patients) showed significantly higher power in the alpha/low-beta band (8-12 Hz, P<0.01; 13-20 Hz, P=0.03) in females than in males. After levodopa medication (ten nuclei from six female patients and 11 nuclei from seven male patients), the power in the high-gamma band (60-90 Hz) and of the 300 Hz rhythm was significantly higher in females than in males (high-gamma, P=0.007; 300 Hz, P=0.002). These findings show that functional gender-related differences in the central nervous system involve the human subthalamic area (STN) and its response to levodopa in Parkinson's disease. Gender-related neurophysiological differences may be important for understanding gender-specific features of neurodegenerative disorders and should be considered when interpreting LFP data from the human basal ganglia.

Clinical utility of histological features of polyomavirus allograft nephropathy.

BACKGROUND: The purpose of this study was to determine if histological features of polyomavirus allograft nephropathy (PVAN) are associated with the clinical presentation and outcomes of PVAN. METHODS: We examined the histological features of initial and follow-up biopsies of 20 kidney and kidney-pancreas transplant recipients with PVAN during a time prior to routine surveillance. The subjects' demographics, clinical characteristics, and outcomes were compared based upon classification of histological features of PVAN on initial biopsy. RESULTS: Diabetes mellitus (45%) and a history of tacrolimus-induced nephrotoxicity (35%) appeared to be prevalent in subjects with PVAN. Although histological severity of PVAN did not predict or correlate with the clinical course of PVAN, subjects with pattern C on initial PVAN biopsy presented later posttransplant, had higher serum creatinine level at presentation, and had significant allograft deterioration at follow-up than subjects with either pattern A or B on initial biopsy. Resolution of PVAN was noted in 60% of follow-up biopsies and occurred more frequently in subjects with pattern B on initial biopsy. Most subjects developed chronic allograft nephropathy after PVAN and viral clearance did not abrogate the progression to chronic allograft nephropathy. CONCLUSIONS: These data indicate that histologic patterns of PVAN may have clinical correlation to disease presentation and prognosis.

Subthalamic oscillatory activities at beta or higher frequency do not change after high-frequency DBS in Parkinson's disease.

This study aimed to assess whether changes in the patterns of local field potential (LFP) oscillations of the subthalamic nucleus (STN) underlie to the clinical improvement within 60 s after turning off subthalamic DBS. We studied by spectral analysis the STN LFPs recorded in 13 nuclei from 7 patients with Parkinson's disease before and immediately after unilateral high-frequency (130 Hz) stimulation of the same nucleus, when the clinical benefit of DBS was unchanged. The results were compared with LFP data previously reported [A. Priori, G. Foffani, A. Pesenti, F. Tamma, A.M. Bianchi, M. Pellegrini et al., Rhythm-specific pharmacological modulation of subthalamic activity in Parkinson's disease. Exp. Neurol. 189 (2004) 369-379]--namely 13 STN from 9 parkinsonian patients recorded before and after levodopa administration--which were used as a control. Before DBS, in the 'off' clinical state after overnight withdrawal of dopaminergic therapy, the STN spectrum did not significantly differ from the control nuclei, showing prominent activity at beta frequencies (13-20 and 20-35 Hz). After DBS (10-15 min) of the STN, the recorded nuclei significantly differed from the control, failing to show significant changes either in the beta bands or at higher frequencies (60-90 and 250-350 Hz). The patterns of subthalamic LFP oscillations after DBS therefore differ from those after dopaminergic medication. These results suggest (1) that subthalamic LFP modulations are not the epiphenomenon of peripheral motor improvement and (2) that the transitory clinical efficacy maintained after discontinuation of subthalamic DBS is not associated with local modulation of LFP activity at beta or higher frequencies within the STN.

Dopamine-dependent non-linear correlation between subthalamic rhythms in Parkinson's disease.

The basic information architecture in the basal ganglia circuit is under debate. Whereas anatomical studies quantify extensive convergence/divergence patterns in the circuit, suggesting an information sharing scheme, neurophysiological studies report an absence of linear correlation between single neurones in normal animals, suggesting a segregated parallel processing scheme. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys and in parkinsonian patients single neurones become linearly correlated, thus leading to a loss of segregation between neurones. Here we propose a possible integrative solution to this debate, by extending the concept of functional segregation from the cellular level to the network level. To this end, we recorded local field potentials (LFPs) from electrodes implanted for deep brain stimulation (DBS) in the subthalamic nucleus (STN) of parkinsonian patients. By applying bispectral analysis, we found that in the absence of dopamine stimulation STN LFP rhythms became non-linearly correlated, thus leading to a loss of segregation between rhythms. Non-linear correlation was particularly consistent between the low-beta rhythm (13-20 Hz) and the high-beta rhythm (20-35 Hz). Levodopa administration significantly decreased these non-linear correlations, therefore increasing segregation between rhythms. These results suggest that the extensive convergence/divergence in the basal ganglia circuit is physiologically necessary to sustain LFP rhythms distributed in large ensembles of neurones, but is not sufficient to induce correlated firing between neurone pairs. Conversely, loss of dopamine generates pathological linear correlation between neurone pairs, alters the patterns within LFP rhythms, and induces non-linear correlation between LFP rhythms operating at different frequencies. The pathophysiology of information processing in the human basal ganglia therefore involves not only activities of individual rhythms, but also interactions between rhythms.

Impact of pyrexia on neurochemistry and cerebral oxygenation after acute brain injury.

BACKGROUND: Postischaemic pyrexia exacerbates neuronal damage. Hyperthermia related cerebral changes have still not been well investigated in humans. OBJECTIVE: To study how pyrexia affects neurochemistry and cerebral oxygenation after acute brain injury. METHODS: 18 acutely brain injured patients were studied at the onset and resolution of febrile episodes (brain temperature > or = 38.7 degrees C). Intracranial pressure (ICP), brain tissue oxygen tension (PbrO2), and brain tissue temperature (Tbr) were recorded continuously; jugular venous blood was sampled intermittently. Microdialysis probes were inserted in the cerebral cortex and in subcutaneous tissue. Glucose, lactate, pyruvate, and glutamate were measured hourly. The lactate to pyruvate ratio was calculated. RESULTS: Mean (SD) Tbr rose from 38 (0.5) to 39.3 (0.3) degrees C. Arteriojugular oxygen content difference (AJD(O2)) fell from 4.2 (0.7) to 3.8 (0.5) vol% (p < 0.05) and PbrO2 rose from 32 (21) to 37 (22) mm Hg (p < 0.05). ICP increased slightly and no significant neurochemical alterations occurred. Opposite changes were recorded when brain temperature returned towards baseline. CONCLUSIONS: As long as substrate and oxygen delivery remain adequate, hyperthermia on its own does not seem to induce any further significant neurochemical alterations. Changes in cerebral blood volume may, however, affect intracranial pressure.

Physiological recordings from electrodes implanted in the basal ganglia for deep brain stimulation in Parkinson's disease. the relevance of fast subthalamic rhythms.

Deep brain stimulation electrodes implanted in the subthalamic nucleus of patients with Parkinson's disease allow electrophysiological recordings from the human basal ganglia. Subthalamic local field potential recordings revealed the presence of multiple rhythms, from the classical EEG frequency range (<50 Hz), to surprisingly high frequencies (70 Hz and 300 Hz). Fast rhythms are particularly attractive because of their likely interaction with the excitatory mechanisms of action of deep brain stimulation. Here we investigated whether the two rhythms at 70 Hz and at 300 Hz represent distinct modes of operation, and therefore different targets, within the subthalamic nucleus. We retrospectively analyzed the dataset we used to describe the 300 Hz rhythm (Foffani, Priori et al., Brain 126: 2153-2163, 2003) searching for significant 70 Hz oscillations after levodopa administration. Whereas (as previously reported) 300 Hz activity was a consistent feature in the dataset, significant 70 Hz activity was observed in only 2 of 11 nuclei. Therefore, 70 Hz oscillations are not a necessary condition for the presence of 300 Hz oscillations. The two rhythms probably arise from different mechanisms, reflecting different functional and/or spatial aspects of subthalamic pathophysiology. Fast subthalamic oscillations could be exploited for intra-operative electrophysiological monitoring of the subthalamic nucleus, post-operative confirmation of electrode placement and patient-specific 'reglage' of the electrical parameters for chronic deep brain stimulation.

Are autoimmune diseases or glomerulonephritis affecting the development of panel-reactive antibodies in candidates for renal transplantation?

Panel-reactive antibodies (PRA) are a major obstacle to kidney transplantation (KTx). It is not completely clear why only some patients develop PRA, whereas others do not. We hypothesized that other factors, such as autoimmune diseases involving the kidney, might be a trigger for PRA development. We reviewed the original diseases that led to renal failure and their possible role in PRA development. Charts of 270 patients on the active waiting list for KTx were reviewed for complete demographics, presence of PRA, peak PRA level, first KTx or retransplantation, original disease, blood transfusions, pregnancy and rejection. Patients were divided into group 1 (PRA >10%) and group 2 (PRA <10%). There was a significantly higher proportion of patients in group 1 with autoimmune diseases than in group 2. The same proportion was found significant for all of the patients as well as for the patients listed for the first KTx (new patients). Previous KTx has significant impact on both class I and II peak PRA levels when compared with new patients who are already sensitized. A subanalysis of retransplantation showed patients with autoimmune disease (54%) have more graft loss due to rejection compared with nonautoimmune disease (43%). There is an association between high PRA level and autoimmune diseases causing renal failure regardless of the previous KTx status. Besides the risk of recurrence, autoimmune disease seems to affect the risk of graft loss due to rejection.

Altered subthalamo-pallidal synchronisation in parkinsonian dyskinesias.

The aim of this work was to study the role of subthalamo-pallidal synchronisation in the pathophysiology of dyskinesias. We recorded local field potentials (LFPs) in a patient with Parkinson's disease and left surgery induced dyskinesias with double, bilateral deep brain stimulation electrode implants in the subthalamic nucleus (STN) and the globus pallidus internus (GPi). Synchronisation was studied through coherence analysis. In the nuclei contralateral to the dyskinetic side of the body there was decreased STN-GPi coherence in the high beta range (20-30 Hz) and an enhanced coherence at low frequencies (<10 Hz). Despite the possible limitations arising from single-case observations, our findings suggest that parkinsonian dyskinesias are related to altered synchronisation between different structures of the basal ganglia. Firing abnormalities within individual basal ganglia nuclei are probably not enough to account for the complex balance between hypokinetic and hyperkinetic symptoms in human parkinsonian dyskinesias and altered interactions between nuclei should also be considered.

Renal pathology and clinical presentations of polyomavirus nephropathy in simultaneous kidney pancreas transplant recipients compared with kidney transplant recipients.

INTRODUCTION: The purpose of this study was to describe and compare the renal histopathology and clinical course of simultaneous kidney-pancreas transplant (SKP) recipients with kidney transplant (KT) recipients with polyomavirus nephropathy (PVN). METHODS: Between 1997 and 2002, 20 patients (7 SKP, 13 KT) were diagnosed with PVN. Clinical characteristics and outcomes of PV-N were correlated with histopathologic examinations of renal allograft biopsy and compared between SKP and KT recipients. RESULTS: There were no differences in demographics between SKP and KT recipients with PV-N. The mean time to PVN was 611 (172 to 1174) days posttransplant in SKP and 343 (83 to 720) days posttransplant in KT (P =.05). The serum creatinine at the time of diagnosis was similar between SKP and KT recipients. All patients were treated with reduction in immunosuppression. After a median follow-up of 2 years, the patient survival was 71% in SKP and 100% in KT. Four grafts (57%) were lost owing to PVN in SKP group and three grafts (23%) were lost owing to PVN in the KT group. More patients (43%) in SKP had a history of acute rejection prior to diagnosis of PVN compared to KT (8%) and biopsy-proven tacrolimus nephrotoxicity prior to PVN was more common in SKPT (86%) than in KT (8%) patients (P <.05). SKP patients with evidence of diffuse fibrosis and high total sum scores at time of presentation all subsequently lost their grafts. CONCLUSIONS: SKP recipients with PVN had a worse clinical course than KT recipients.