Axonal swellings predict the degeneration of epidermal nerve fibers in painful neuropathies.

OBJECTIVE: To correlate the density of swellings in intraepidermal nerve fibers (IENF) with the longitudinal measurement of the epidermal innervation density in patients with painful neuropathy and to assess the predictive value of IENF swelling to progression of neuropathy. METHODS: Fifteen patients with persistent pain in the feet underwent neurologic examination, nerve conduction studies, quantitative sensory examination, and skin biopsies at proximal thigh and distal leg. In all patients and in 15 healthy subjects, IENF density and swelling ratio (no. swellings/no. IENF) were quantified at distal leg. Follow-up study, including IENF density and swelling ratio quantification, was performed a mean of 19.2 months later. Double staining confocal microscope studies using anti-human protein-gene-product 9.5, anti-tubule, anti-neurofilament, and anti-synaptophysin antibodies were performed to assess specific accumulation within swellings. Ultrastructural investigation of IENF was also carried out. RESULTS: Patients with neuropathy had lower density of IENF and higher swelling ratio than healthy subjects (p < 0.01) at distal leg. At follow-up, patients showed a parallel decrease in both IENF density (p = 0.02) and swelling ratio (p = 0.002). However, swelling ratio remained higher (p = 0.03) than in controls. Progression of neuropathy was confirmed by the decay in sural nerve sensory nerve action potential amplitude. Double immunostaining studies suggest accumulation of tubules and ubiquitin-associated proteins within swellings. Swollen and vacuolated IENF were identified in patients with neuropathy by conventional and immuno-electron microscopy. CONCLUSIONS: Increased swelling ratio predicted the decrease in IENF density in patients with painful neuropathy. Its quantification could support earlier diagnosis of sensory axonopathy.

T-lymphocyte interleukin 6 receptor binding in patients with dementia of Alzheimer type.

OBJECTIVE: To investigate some aspects of T-cell-dependent immune function in patients with dementia of the Alzheimer type (DAT). DESIGN: Assay of interleukin 6 binding on T lymphocytes from patients with DAT, compared with that in healthy controls. SETTING: The study included ambulatory patients in a tertiary care center who were diagnosed as having DAT according to the criteria of the National Institute of Neurologic and Communicative Disorders and Stroke. SUBJECTS: Thirty-five patients with DAT without depression (15 women and 20 men; mean +/- SD age, 68.6 +/- 15.8 years) were selected consecutively. They had not taken any medication for at least 3 weeks and did not smoke. Illness severity was evaluated according to the Clinical Dementia Rating Scale. Thirty-five age- and sex-matched healthy nonsmoking subjects with no family history of neuropsychiatric disorders formed the control group. RESULTS: A significant (P < .001) increase in T-lymphocyte interleukin 6 binding was found in patients with DAT compared with healthy controls (mean +/- SE receptors per cell, 305 +/- 7 vs 276 +/- 6, respectively), whereas the ligand-receptor affinity values were similar in the 2 groups (mean +/- SE, 25.9 +/- 0.9 and 25.3 +/- 0.6 nmol/L). CONCLUSION: These data indicate a derangement of the immune response in patients with DAT since cell-surface interleukin 6 receptors seem to be related to T-lymphocyte immune function.

Platelet and lymphocyte benzodiazepine binding in patients with Alzheimer's disease.

Peripheral blood cells, such as platelets or lymphocytes, have been studied in the investigation of systemic derangements and central nervous system biochemical changes occurring in several neuropsychiatric disorders. In the present work, assaying platelet and lymphocyte peripheral-type benzodiazepine binding in patients with Alzheimer's disease (AD) and healthy controls, we found a significantly reduced number of cell receptors in patients' platelets and lymphocytes. These results are discussed with reference to central nervous system biochemical abnormalities in AD. Moreover, the lymphocyte binding data may represent an impairment of the immune response in AD, since lymphocyte surface peripheral-type benzodiazepine receptors seem to be related to immune function.

T-cell tumour necrosis factor-alpha receptor binding in demented patients.

Dementia of Alzheimer type (DAT) is a neurodegenerative disease of the central nervous system (CNS), in which an unbalanced cytokine network may lead to an altered immunoregulation. Tumour necrosis factor (TNF)-alpha is a cytokine with manifold effects on the neuroimmune system. Specific TNF-alpha receptors have been found on human peripheral blood lymphocytes. The aim of the present study has been to assay TNF-alpha binding on T cells from DAT patients and healthy sex- and age-matched controls. We found that T lymphocytes from demented patients bear significantly more p60 and p80 TNF-alpha receptors than those from controls (Bmax: 705, 29 vs 131, 6 (mean, SEM) receptors/cell). Such TNF-alpha binding sites, of the same type in DAT patients and healthy subjects (Kd: 67.6, 5.0 vs 70.7, 5.6 (mean, SEM) pM), are functional, since they are able to mediate in vitro NF-kappa B activation. These results are discussed in terms of DAT pathogenesis. Since it has been reported that activated T cells have more TNF-alpha receptors than resting cells, an increased number of lymphocyte TNF-alpha receptors might indicate a systemic immune activation in DAT patients as compared with healthy controls.

Platelet monoamine oxidase molecular activity in demented patients.

Blood platelet monoamine oxidase activity, as well as other platelet enzyme activities, have been studied in several neuropsychiatric disorders in an attempt to identify biochemical markers of altered brain function. In this study, we determined both total and molecular monoamine oxidase activity in platelets derived from demented patients, which showed significantly greater enzyme activity than those of the controls. It therefore seems that the high degree of monoamine oxidase activity depends on the increased intrinsic activity of individual enzyme molecules. A significant positive correlation was found between monoamine oxidase activity and the severity of illness, which suggests that monoamine oxidase activity may be a state-dependent marker of neurodegeneration. These findings are discussed with reference to the central nervous system biochemical abnormalities of demented subjects: it may be that Alzheimer-type dementia involves some central biochemical changes that are reflected in certain peripheral tissues (e.g. platelets), or a systemic derangement that also affects the brain.

T-cell interferon gamma binding in patients with dementia of the Alzheimer type.

OBJECTIVE: To study T-cell-dependent immune function in patients with dementia of the Alzheimer type (DAT). DESIGN: Assay interferon gamma binding on T lymphocytes in patients with DAT, as compared with healthy controls. SETTING: The study was performed on ambulatory patients in a tertiary care center, where patients were diagnosed as having DAT according to the National Institute of Neurological Disorders and Stroke criteria. PATIENTS: Thirty-five nondepressed patients with DAT (15 women and 20 men; mean [+/-SD] age, 68.6 +/- 15.8 years) were selected consecutively. They were drug free for at least 3 weeks and did not smoke. Illness severity was evaluated according to the Clinical Dementia Rating Scale. The control group comprised 35 age- and sex-matched, healthy nonsmoking subjects, with no family history of neuropsychiatric disorders. RESULTS: A significant reduction (P < .001) of T-lymphocyte interferon gamma binding was observed in patients with DAT as compared with healthy controls (611 +/- 19 [SE] vs 702 +/- 11 [SE] receptors per cell, respectively), whereas the dissociation constant (ligand-receptor affinity) values were similar in the 2 groups (1.1 +/- 0.06 [SE] and 1.2 +/- 0.06 [SE] nmol/L). CONCLUSION: These data demonstrate a derangement of the immune response in patients with DAT, since cell surface interferon gamma receptors seem to be related with T-lymphocyte immune function.

T lymphocyte benzodiazepine binding is reduced in demented patients.

Blood cells, especially platelets and lymphocytes, are used in neuropsychiatric research as tools for investigating systemic derangements in neuropsychiatric disorders, and as peripheral models for studying central nervous system biochemistry. In the present work, we determined T lymphocyte peripheral-type benzodiazepine binding: a significant reduction of Bmax values was observed in demented patients as compared with healthy controls, whereas Kd values were similar in the two subjects' groups. A significant negative correlation was found between Bmax values and illness severity. These data, which seem to be related to an impairment of immune response and cell energy metabolism in demented patients, may represent a state-dependent marker in monitoring disease course and treatment efficacy.

T-lymphocyte immuno-interferon binding in parkinsonian patients.

Human peripheral blood cells, especially lymphocytes and thrombocytes, are extensively studied in neuropsychiatric research both as tools for investigating systemic derangements in neuropsychiatric disorders, and as peripheral models for getting information on central nervous system biochemistry. Specific interferon (IFN)-gamma receptors have been found on both human lymphocytes and neural cells. The aim of the present study has been to evaluate IFN-gamma binding on peripheral blood T lymphocytes from parkinsonian patients, as compared with that on blood T cells from healthy subjects. We have found that T lymphocytes from parkinsonian patients bear a significantly smaller amount of IFN-gamma receptors than those from controls. Such IFN-gamma binding sites are of the same type in patients and healthy subjects (Kd (mean +/- SEM): 1.4 +/- 0.07 vs. 1.2 +/- 0.06, respectively). These findings, which are not specific for Parkinson's disease, are discussed in terms of its immunopathogenesis, since it has been reported that activated T lymphocytes have decreased amounts of IFN-gamma receptors.

Monoamine oxidase molecular activity in platelets of parkinsonian and demented patients.

Platelet monoamine oxidase activity levels have been evaluated in several neuropsychiatric disorders, to identify biochemical markers for pathological brain functioning. In the present work, we assayed both total and molecular monoamine oxidase activity in platelets of parkinsonian and demented patients: both showed significantly higher enzyme activity values than healthy controls. Thus, high platelet monoamine oxidase activity levels seem to be related to an increased intrinsic activity of single enzyme molecules. A significant positive correlation was found between platelet monoamine oxidase activity and severity of illness in both disorders: monoamine oxidase activity, therefore, may be considered as a state-dependent marker for neuro-degeneration. Such findings are discussed with reference to central nervous system biochemical abnormalities in parkinsonian and demented subjects; it might be that in both Parkinson's Disease and in dementia of Alzheimer type some central biochemical changes are reflected in certain peripheral tissues (thrombocytes, for instance), or that a systemic derangement accompanies the cerebral involvement.

Aplasia cutis congenita: estudio de cuatro casos. / Aplasia cutis congenita: study of 4 cases

Se presentan cuatro casos de aplasia cutis congenita, donde se destacan las caracteristicas clinicas e histopatologicas tipicas de la enfermedad y fundamentalmente el diagnostico diferencial con procesos traumaticos durante el mecanismo del parto. Al examen clinico, los cuatro ninos no revelaron anomalias sistemicas

Aplasia cutis congenita: estudio de cuatro casos. / Aplasia cutis congenita: study of 4 cases

Se presentan cuatro casos de aplasia cutis congenita, donde se destacan las caracteristicas clinicas e histopatologicas tipicas de la enfermedad y fundamentalmente el diagnostico diferencial con procesos traumaticos durante el mecanismo del parto. Al examen clinico, los cuatro ninos no revelaron anomalias sistemicas