[Occupational toxic neuropathies: morphology in peripheral nerve biopsies]. / Neuropatie tossiche occupazionali: quadri morfologici in biopsie del nervo periferico.

Many peripheral neuropathies are caused by the (acute or chronic) toxic action of metals, solvents, pesticides, and other occupational and environmental contaminants. These agents often reproduce the anatomoclinical pictures of hereditary (e.g., Charcot-Marie-Tooth disease), autoimmune (Guillain-Barrè syndrome), or dysmetabolic (thiamine deficiency, diabetic neuropathy) forms. Toxic peripheral neuropathies can be classified on the basis of etiology, clinical features (sensitive, motor, sensitive-motor), or histopathology: neuronopathies (uncommon, mostly secondary to retrograde axonal degeneration; e.g., arsenic, thallium), axonopathies (acrylamide, esacarbons, CS2, organophosphate-induced delayed neuropathy), myelinopathies (trichloroethylene), mixed forms (axonal and demyelinating: lead). For many substances, experimental research has led to the identification of the molecular and cellular targets of neurotoxicity. Several compounds are active by biotransformation (e.g., the esacarbons n-hexane and MnBK are neurotoxic since they are metabolized to 2,5-hexanedione), Genetic, physiological and environmental factors determine the individual metabolic set-up, and they may give origin to differences in the workers' sensitivity. Cessation of exposure is often followed by (microscopically observable) regenerative phenomena and clinical improvement. The morphology of neuropathies can be studied through peripheral nerve biopsy. Samples of sural nerve (or other nervous trunks of the limbs), adequately fixed, sectioned, and stained, allow the observation of alterations in axonal fibres (e.g., giant-axonal neuropathy, dying back neuropathy), myelin (demyelination), Schwann cells, interstitium, and blood vessels; possible inflammatory infiltrates; fibre density; regenerative phenomena (growth cone, remyelination). In occupational medicine, biopsy is indicated when the anamnestic-clinical picture, laboratory tests, and instrumental exams leave doubts about the nature, type, and entity of the neurological damage. In such cases, current optical and electron microscopy techniques can be very useful for injury evaluation, prognosis, and follow-up.

Influence of type 2 diabetes on functional and structural properties of coronary artery bypass conduits.

Recent studies have reported a high incidence of postoperative unfavorable cardiac-related events in patients with diabetes who underwent coronary artery bypass grafting (CABG). Structural and functional characteristics of CABG conduits, which have been shown to play an important role in patient outcome after myocardial revascularization, have not been fully investigated in diabetic subjects. Therefore, we sought to determine the influence of adult-onset diabetes on vasoreactivity and morphological profile of venous and arterial grafts. Of the 160 consecutive patients enrolled in the study, 90 were diagnosed with type 2 diabetes and 70 did not have diabetes (control group). All patients underwent evaluation of glucose control before surgery. Tissue specimens were collected from left internal thoracic artery (LITA) and saphenous vein (SV) grafts harvested during elective CABG. Functional tests were performed to assess contractile and vasodilative responses of bypass conduits. Histological evaluation was carried out to examine vessel wall structure. Univariate and multivariate analyses were performed to correlate the preoperative factors related to the control of the endocrine disorder with histological findings. Patient medical history and demographics did not differ between the groups. Diabetic patients showed significant microalbuminuria and higher plasma levels of C-peptide and GHb as compared with nondiabetic subjects. Functional tests of the LITA segments revealed no difference between groups with regard to contractile and vasodilative responses. In contrast, significant impairment in the endothelium-related vasodilation of the SV grafts was observed in diabetic subjects. Histological studies showed structural preservation of the arterial conduits in both groups. However, marked intimal abnormalities (also atherosclerotic calcified plaques) were detected in SV grafts harvested from diabetic patients. Logistic regression analysis showed that high levels of proteinuria and GHb were independent predictors of advanced structural degeneration of SV conduits. Treatment modality, duration of diabetes, and other demographic or metabolic factors were found to have no influence on the morphological characteristics of SV conduits. In conclusion, biological properties of LITA conduits for CABG were preserved in diabetic patients. However, these patients frequently showed impairment of the endothelium-dependent vasorelaxation and intimal degeneration of SV grafts. The extent of structural abnormalities of SV grafts was inversely correlated with the efficacy of the metabolic control of the endocrine disorder. Further studies are required to conclusively correlate preoperative SV graft abnormalities with postoperative conduit patency rate and the occurrence of adverse cardiac-related events in diabetic subjects.

Ischemia-induced glutamate release in rat frontoparietal cortex after chronic alcohol and withdrawal.

High doses of ethanol increase stroke risk: in this context, a role for excitatory amino acids has been proposed. The present results show that, in frontoparietal cerebral cortex, chronic ethanol treatment (10% v/v in drinking water for 28 days) was able to slightly reduce glutamate release (evaluated through transdialysis coupled with high-pressure liquid chromatography) following focal ischemia as regards non-treated ischemic rats. This reduction was, however, not associated with decreased cerebral damage. In 24-h withdrawing rats, histological and morphometric analyzes showed an exacerbated cerebral damage coupled with higher glutamate and aspartate release compared to controls. These results suggest that adaptive changes following chronic ethanol consumption lead to an increased excitotoxicity that is particularly evident during the withdrawal condition.

Clinico-pathological findings in a patient with progressive cerebellar ataxia, autoimmune polyendocrine syndrome, hepatocellular carcinoma and anti-GAD autoantibodies.

OBJECTIVE: To report clinical and pathological findings of a patient with late onset insulin-dependent diabetes mellitus (IDDM), progressive cerebellar ataxia (PCA) and hepatocellular carcinoma (HCC). PATIENT: A 64-year-old woman, with a long lasting IDDM, progressively developed a severe cerebellar syndrome and died 2 years after the onset of the symptoms for a systemic infection. Autoantibodies to antigastric parietal cell and anti-pancreatic islet cell resulted positive. Autopsy showed a selective loss of Purkinje cells in the cerebellum, with an increase of Bergmann glia and variable microglial proliferation; furthermore, it disclosed an HCC. GAD-Abs were detected both in serum and CSF. CONCLUSIONS: Clinical and experimental reports suggest a possible role of neoplastic cells in producing GAD-Abs. We postulate, in our case, that HCC could have been responsible for an overproduction of GAD-Abs, leading to the onset of PCA. Thus, GAD-Abs could be considered as a paraneoplastic marker in a subgroup of patients with PCA.

In diffuse atrophic gastritis, routine histology underestimates Helicobacter pylori infection.

BACKGROUND: histologic detection of shows high diagnostic accuracy in chronic nonatrophic gastritis. However, when atrophy occurs, the sensitivity of bacterial detection varies. This study assessed the routine histologic sensitivity for current infection in patients with atrophic gastritis, with and without intestinal metaplasia. STUDY: five hundred and ten consecutive patients with diffuse chronic atrophic gastritis, with (174 cases) and without (336 cases) intestinal metaplasia, were investigated following the Sydney System recommendations. In cases with negative tissue staining for Helicobacter-like organisms, serum immunoglobulin G (IgG) antibodies to were assayed. RESULTS: the overall rate of positive staining for Helicobacter-like organisms was 51.8% (264 of 510 cases), 62.8% and 30.4% in cases without and with intestinal metaplasia, respectively. Serum IgG antibody determination was consistent with current infection in 180 (73.2%) of the 246 cases with negative histology. detection rate was significantly lower ( < 0.01) in Grade 3 than in Grade 1 atrophy. When intestinal metaplasia was present, histologic bacterial detection progressively decreased, from 46.3% to 20%, depending on severity. infection was found by histology in 42.2% and in 56.2% of cases with inactive and active disease, respectively. Overall, the diagnostic accuracy of histology was significantly lower ( <0.001) than that of histology combined with serology. CONCLUSIONS: most (87.1%) diffuse chronic atrophic gastritis patients showed serum antibody IgG levels consistent with current infection, although histology was positive in only 59.5% of cases. Gastritis activity and current infection did not ever correlate in the presence of mucosal atrophy and/or intestinal metaplasia. Routine biopsy sampling, hematoxylin and eosin staining, and Giemsa staining therefore underestimated the true prevalence of infection.