Psychosis in epilepsy patients

Summary   Epileptic psychoses reflect a fundamental disruption in the fidelity of mind and occur during seizure freedom or during or after seizures. The psychotic symptoms in epilepsy share some qualities with schizophrenic psychosis, such as positive symptoms of paranoid delusions and hallucinations. Psychotic syndromes in epilepsy are most common but not exclusively associated with temporal lobe epilepsy. De Novo psychosis following epilepsy surgery is rare. Forced normalization—psychosis associated with dramatic reduction of epileptiform activity or seizures is described in small series only. Ictal and postictal psychosis can be prevented with seizure control, but postictal and chronic interictal psychoses require multidisciplinary and psychopharmacologic management.     

Percutaneous transhepatic stenting by wallstents of portal vein and bile duct stenoses caused by immunoblastic sarcoma in a liver transplantation

Posttransplant lymphoproliferative disorders are infrequent tumors related to chronic immunosuppressive therapy. We present a liver transplant recipient who developed such a tumor in the porta hepatis that provoked obstruction of the entire portal triad. Treatment consisted of systemic chemotherapy, percutaneous dilatation, and placement of Wallstent endoprostheses across both biliary and portal vein stenoses. The patient died 3 weeks later of pneumonia and sepsis. At necropsy, the tumor was completely necrosed and the prostheses in both the common bile duct and the portal vein were patent.     

Deficits in spatial coding and feature binding following damage to spatiotopic maps in the human pulvinar.

We report a patient with unilateral damage to the rostral part of the pulvinar who was impaired in localizing stimuli in the inferior visual field contralateral to the lesion and who made errors in the binding of shape and color in that quadrant. The findings demonstrate the importance of the pulvinar in spatial coding and provide support for the function of the thalamus in binding of features. They also provide evidence for a homology between the visual field maps of the inferior and lateral subdivisions of the pulvinar in monkeys and in humans, such that the inferior visual field is represented in the rostral part of the nucleus.     

Neuronal activity in the globus pallidus of multiple system atrophy patients.

The pathophysiological changes in neural activity that characterize multiple system atrophy (MSA) are largely unknown. We recorded the activity of pallidal neurons in 3 patients with clinical and radiological features of MSA who underwent unilateral microelectrode-guided pallidotomy for disabling parkinsonism. Findings in these patients were compared with 4 control patients with a clinical diagnosis of Parkinson's disease (PD). The position, firing rates, and firing patterns of single neurons in the pallidal complex were analyzed in both MSA and PD patients. The mean spontaneous firing rate of neurons in the internal segment of the globus pallidus internus (GPii) was significantly lower in MSA than in PD patients. There were no significant differences between MSA and PD patients, however, in firing rates of neurons in the external globus pallidus (GPe) or in the external segment of GPi (GPie). In addition, no significant differences in firing pattern were found between MSA and PD patients. In conclusion, this study has shown that firing rates of neurons in GPii but not in GPie and GPe are different in MSA patients compared with that in PD patients, a finding that may reflect the poor clinical results of pallidotomy reported in patients with MSA.     

Hydrogen breath test for diagnosis of lactose malabsorption: the importance of timing and the number of breath samples.

BACKGROUND: The hydrogen breath test (H(2)BT) is the most widely used procedure in the diagnostic workup of lactose malabsorption and lactose intolerance. AIM: To establish whether a simplified two- or three-sample test may reduce time, costs and staff resources without reducing the sensitivity of the procedure. PATIENTS AND METHODS: Data from 1,112 patients (292 men, 820 women) with a positive 4 h, nine-sample H(2)BT were retrospectively analyzed. Patients were stratified according to the degree of lactose malabsorption, the occurrence and type of symptoms. Loss of sensitivity in the procedure was evaluated taking into account two-sample tests (0 min and 120 min or 0 min and 210 min) or three-sample tests (0 min, 120 min and 180 min or 0 min, 120 min and 210 min). RESULTS: Using a two-sample test (0 min and 120 min or 0 min and 210 min) the false-negative rate was 33.4% and 22.7%, respectively. With a three-sample test (0 min, 120 min and 180 min or 0 min, 120 min or 210 min), lactose malabsorption was diagnosed in 91.2% (1,014 of 1,112) patients and in 96.1% (1,068 of 1,112) patients, respectively. Of 594 patients with abdominal symptoms, 158 (26.6%) and 73 (12.2%) would have false-negative results with 0 min and 120 min or 0 min and 210 min two-sample tests, respectively. The three-sample tests, 0 min, 120 min and 180 min or 0 min, 120 min and 210 min, have a false-negative rate of 5.9% and 2.1%, respectively. CONCLUSIONS: A three-sample H(2)BT is time- and cost-sparing without significant loss of sensitivity for the diagnosis both of lactose malabsorption and lactose intolerance.     

Antibody Response Against the Glomerular Basement Membrane Protein Agrin in Patients with Transplant Glomerulopathy

Chronic allograft nephropathy (CAN) of renal allografts is still the most important cause of graft loss. A subset of these patients have transplant glomerulopathy (TGP), characterized by glomerular basement membrane (GBM) duplications, but of unknown etiology. Recently, a role for the immune system in the pathogenesis of TGP has been suggested. In 11 of 16 patients with TGP and in 3 of 16 controls with CAN in the absence of TGP we demonstrate circulating antibodies reactive with GBM isolates. The presence of anti-GBM antibodies was associated with the number of rejection episodes prior to diagnosis of TGP. Sera from the TGP patients also reacted with highly purified GBM heparan sulphate proteoglycans (HSPG). Indirect immunofluorescence with patient IgG showed a GBM-like staining pattern and colocalization with the HSPGs perlecan and especially agrin. Using patient IgG, we affinity purified the antigen and identified it as agrin. Reactivity with agrin was found in 7 of 16 (44%) of patients with TGP and in 7 of 11 (64%) patients with anti-GBM reactivity. In conclusion, we have identified a humoral response against the GBM-HSPG agrin in patients with TGP, which may play a role in the pathogenesis of TGP.     

Incorporation of protein-eluting microspheres into biodegradable nerve guidance channels for controlled release.

Nerve guidance channels (NGCs) promote axonal regeneration after transection injury of the peripheral nerve or spinal cord, yet this regeneration is limited. To enhance regeneration further, we hypothesize that localized delivery of therapeutic molecules combined with the NGC is required. In an attempt to achieve such an NGC, we designed and synthesized a novel NGC in which protein-encapsulated microspheres were stably incorporated into the tube wall. Specifically, poly(lactide-co-glycolide) (PLGA 50/50) microspheres were physically entrapped in the annulus between two concentric tubes, consisting of a chitosan inner tube and a chitin outer tube. Taking advantage of the extensive shrinking that the outer chitin tube undergoes with drying, >15 mg of microspheres were loaded within the tube walls. Using BSA-encapsulated microspheres as the model drug delivery system, BSA was released from microsphere loaded tubes (MLTs) for 84 days, and from freely suspended PLGA microspheres for 70 days. An initial burst release was observed for both MLTs and free microspheres, followed by a degradation-controlled release profile that resulted in a higher release rate from MLTs initially, which was then attenuated likely due to the buffering effect of chitin and chitosan tubes. Epidermal growth factor (EGF), co-encapsulated with BSA in PLGA 50/50 microspheres in MLTs, was released for 56 days with a similar profile to that of BSA. Released EGF was found to be bioactive for at least 14 days as assessed by a neurosphere forming bioassay.     

Chronic Inhalation Toxicity and Carcinogenicity Testing of Respirable Fibrous Particles

On May 8–10, 1995, a workshop on chronic inhalation toxicity and carcinogenicity testing of respirable fibrous particles was held in Chapel Hill, North Carolina. The workshop was sponsored by the Office of Pollution Prevention and Toxics, U.S. Environmental Protection Agency (EPA), in collaboration with the National Institute of Environmental Health Sciences (NIEHS), the National Institute for Occupational Safety and Health (NIOSH), and the Occupational Safety and Health Administration (OSHA). The goal of the workshop was to obtain input from the scientific community on a number of issues related to fiber testing. Major issues for discussion were: (i) the optimal design and conduct of studies of the health effects of chronic inhalation exposure of animals to fibers; (ii) preliminary studies which would be useful guides in designing the chronic exposure study; (iii) mechanistic studies which would be important adjuncts to the chronic exposure study to enable better interpretation of study results and extrapolation of potential effects in exposed humans; and (iv) available screening tests which can be used to develop a minimum data set for (a) making decisions about the potential health hazard of the fibers and (b) prioritizing the need for further testing in a chronic inhalation study. After extensive discussion and debate of the workshop issues, the general consensus of the expert panel is that chronic inhalation studies of fibers in the rat are the most appropriate tests for predicting inhalation hazard and risk of fibers to humans. A number of guidances specific for the design and conduct of prechronic and chronic inhalation studies of fibers in rodents were recommended. For instance, it was recommended that along with other information (decrease in body weight, systemic toxicity, etc.), data should be obtained on lung burdens and bronchoalveolar lavage fluid analysis to assist in establishing the chronic exposure levels. Lung burden data are also important for quantifying aspects of risk assessment related to dosimetric adjustments before extrapolation. Although mechanistic studies are not recommended as part of the standard chronic inhalation studies, the expert panel stressed the need for obtaining mechanistic information as far as possible during the course of subchronic or chronic inhalation studies. At present, no single assay and battery of short-term assays can predict the outcome of a chronic inhalation bioassay with respect to carcinogenic effects. Meanwhile, several short-termin vitroandin vivostudies that may be useful to assess the relative potential of fibrous substances to cause lung toxicity/carcinogenicity have been identified.     

What can natural infection of African monkeys with simian immunodeficiency virus tell us about the pathogenesis of AIDS?

The simian immunodeficiency viruses are a diverse group of viruses that naturally infect a wide range of African primates, including chimpanzees, African green monkeys (AGM) and sooty mangabey monkeys (SM). Although natural infection is widespread in feral populations of AGMs and SMs, this infection does not result in immunodeficiency. However, experimental inoculation of Asian macaque species results in an immunodeficiency syndrome that is remarkably similar in pathogenesis to human AIDS. Thus, SIVsm infection of macaques results in AIDS, and similarly experimental inoculation of pigtailed macaques with at least one SIVagm isolate, SIVIhoest or SIVsun, results in AIDS. The extent of plasma viremia in pathogenic infection is an excellent prognostic indicator of clinical course, with higher viral load being predictive of shorter survival and low viremia being predictive of long-term non-progression. Based upon this paradigm, one would have expected naturally infected animals to exhibit low levels of viremia. In reality, AGMs, SMs, mandrills and chimpanzees infected naturally with their own unique viruses display moderate to high levels of plasma viremia. A significant reduction in CD4+ T-cells in infected versus uninfected SMs suggests that the virus may be cytopathic to some degree. These infected animals still maintain adequate CD4+ T-cells over their entire life in captivity. A distinct characteristic of natural infection is the lack of immunopathology as demonstrated by normal lymph node morphology, lower expression of activation and proliferation markers on CD4+ T-cells, and a generally muted immune response to the virus. Naturally infected SMs and AGMs clearly mount antiviral cellular and humoral immune responses. Therefore, models suggesting immune tolerance to SIV are far too simplistic to explain the lack of disease in these animals. It is probable that a unique balance between T-cell renewal and proliferation and loss through activation-induced apoptosis, and virus-induced cell death has been achieved in SMs and AGMs. The study of the dynamics of T-cell production, proliferation and cell death in asymptomatic natural infection should, therefore, yield insights into the pathogenesis of AIDS.