Epilepsy in hemiplegic migraine: Genetic mutations and clinical implications.

Objective We performed a systematic review on the comorbidities of familial/sporadic hemiplegic migraine (F/SHM) with seizure/epilepsy in patients with CACNA1A, ATP1A2 or SCN1A mutations, to identify the genotypes associated and investigate for the presence of mutational hot spots. Methods We performed a search in MEDLINE and in the Human Gene Mutation and Leiden Open Variation Databases for mutations in the CACNA1A, ATP1A2 and SCN1A genes. After having examined the clinical characteristics of the patients, we selected those having HM and seizures, febrile seizures or epilepsy. For each gene, we determined both the frequency and the positions at protein levels of these mutations, as well as the penetrance of epilepsy within families. Results Concerning F/SHM-Epilepsy1 (F/SHME1) and F/SHME2 endophenotypes, we observed a prevalent involvement of the transmembrane domains, and a strong correlation in F/SHME1 when the positively charged amino acids were involved. The penetrance of epilepsy within the families was highest for patients carrying mutation in the CACNA1A gene (60%), and lower in those having SCN1A (33.3%) and ATP1A2 (30.9%) mutations. Conclusion Among the HM cases with seizure/epilepsy, we observed mutational hot spots in the transmembrane domains of CACNA1A and ATP1A2 proteins. These findings could lead to a better understanding of the pathological mechanisms underlying migraine and epilepsy, therein guaranteeing the most appropriate therapeutic approach.

Neuropsychiatric adverse events of antiepileptic drugs in brain tumour-related epilepsy: an Italian multicentre prospective observational study.

BACKGROUND AND PURPOSE: We assessed the prevalence and magnitude of neuropsychiatric adverse events (NPAEs) associated with antiepileptic drugs (AEDs) among patients with brain tumour-related epilepsy (BTRE). METHODS: This observational, prospective, multicentre study enrolled 259 patients with BTRE after neurosurgery. All patients received AED monotherapy. Efficacy was assessed through clinical diaries, whereas NPAEs were collected using the Neuropsychiatric Inventory Test-12 questionnaire at baseline and after 5 months. RESULTS: Tumour localization in the frontal lobe was associated with a higher prevalence of NPAEs (odds ratio, 7.73; P < 0.001). Independent of tumour localization, levetiracetam (LVT) treatment was associated with higher prevalence and magnitude of NPAEs (odds ratio, 7.94; P < 0.01) compared with other AEDs. Patients with oligodendroglioma reported more NPAEs than patients with other tumour types. NPAEs were not influenced by chemotherapy, radiotherapy or steroid treatment. Evaluating non-neurobehavioural adverse events of AEDs, no significant differences were found among AEDs, although patients treated with old AEDs had a higher prevalence of adverse events than those treated with new AEDs. CONCLUSIONS: Both tumour localization in the frontal lobe and LVT treatment are associated with a higher risk of NPAEs in patients with BTRE. LVT is regarded as a first-line option in patients with BTRE because of easy titration and few significant drug-to-drug interactions. Thus, as NPAEs lead to poor compliance and a high dropout rate, clinicians need to accurately monitor NPAEs after AED prescription, especially in patients with frontal lobe tumours receiving LVT.

Detection of cytokinins and auxin in plant tissues using histochemistry and immunocytochemistry.

We report a new method for histochemical localization of cytokinins (CKs) in plant tissues based on bromophenol blue/silver nitrate staining. The method was validated by immunohistochemistry using anti-trans-zeatin riboside antibody. Indole-3-acetic acid (auxin, IAA) was localized by anti-IAA antibody in plant tissues as a proof for IAA histolocalization. We used root sections, because they are major sites of CKs synthesis, and insect galls of Piptadenia gonoacantha that accumulate IAA. Immunostaining confirmed the presence of zeatin and sites of accumulation of IAA indicated by histochemistry. The colors developed by histochemical reactions in free-hand sections of plant tissues were similar to those obtained by thin layer chromatography (TLC), which reinforced the reactive sites of zeatin. The histochemical method for detecting CKs is useful for galls and roots, whereas IAA detection is more efficient for gall tissues. Therefore, galls constitute a useful model for validating histochemical techniques due to their rapid cell cycles and relatively high accumulation of plant hormones.

Prevalence of thyroid abnormalities is not increased in Alzheimer's disease.

The aim of this study was to compare the prevalence of pathologically and clinically documented thyroid disorders in patients with Alzheimer's disease (AD) and nondemented individuals. We reviewed the records of 31 patients with a pathological diagnosis of AD and 31 age-matched nondemented patients selected from autopsy files. We examined the pathological findings in the thyroid gland in both groups. Twenty-four cases (77.4%) with AD and 21 patients (67.7%) in the control group showed pathological abnormalities in the thyroid gland. The prevalence of specific types of thyroid gland abnormalities on pathological examination did not differ significantly between the AD and nondemented cases. For the 19 AD and 18 control patients in whom clinical thyroid function had been documented adequately during life, the percentage of patients with abnormal thyroid function was similar in the AD (15.7%) and control (11.1%) groups. These results do not support a relationship between AD and thyroid abnormalities.

Successful small bowel allotransplantation in dogs with cyclosporine and prednisone.

Twelve dogs had transplantation of almost the entire small intestine in the orthotopic location; immunosuppression was with cyclosporine and prednisone. Half the dogs had survival of at least one month, and a third lived for at least four months. Two of the animals are still living after 550 and 555 days. Maintenance of nutrition, and absorption of D-xylose and fat were better than in control animals with an iatrogenic short gut syndrome, but distinctly worse than that of normal dogs.

Immunocytochemical demonstration of cytochrome c oxidase with an immunoperoxidase method: a specific stain for mitochondria in formalin-fixed and paraffin-embedded human tissues.

Cytochrome c oxidase (CO) is the terminal electron carrier of the respiratory chain and is localized exclusively in the inner membrane of the mitochondria. Using a specific rabbit antiserum against bovine heart CO, mitochondria were specifically stained in sections of formalin-fixed paraffin-embedded human tissues by an immunoperoxidase method. The intensity of the immunostaining in different human tissues correlated mainly with the number of mitochondria and abundance of mitochondrial cristae, i.e., surface area of the inner mitochondrial membrane. Mitochondrion-rich cells, such as myocardial and gastric parietal cells, had very strong cytoplasmic staining. This technique was especially useful for the specific identification of oncocytes in normal tissues and in lesions composed of oncocytes. In addition, the immunoperoxidase method for CO makes possible retrospective investigations of lesions composed of oncocytes, since routine paraffin blocks of formalin-fixed tissue are quite suitable for such studies.

Ultrastructural localization of rat Clara cell 10 KD secretory protein by the immunogold technique using polyclonal and monoclonal antibodies.

Using a monoclonal antibody and affinity-purified polyclonal antiserum against a 10 KD protein isolated from rat pulmonary lavage, we have localized the protein within Clara cells by a post-embedment protein A-gold technique. The gold particles were localized over the secretory granules of rat Clara cells. Ultrastructural immunolocalization was abolished when the primary antibodies were previously absorbed with purified 10 KD protein. Other pulmonary cells, including type II pneumocytes and ciliated cells, were negative with this technique. These results demonstrate the presence of the 10 KD protein in the secretory granules of the Clara cell and support the concept that this protein constitutes a specific and unique secretory product of Clara cells.

Oncocytic Schneiderian papilloma: a reappraisal of cylindrical cell papilloma of the sinonasal tract.

Cylindrical cell papilloma (CCP) is the rarest of three morphologically distinct papillomas that occur in the nose and paranasal sinuses. Because it is unfamiliar to many pathologists, it is often mistaken histologically for papillary adenocarcinoma or even rhinosporidiosis. The clinical and pathologic features of six new cases are reported and compared with those of 14 others reported in the literature. The results of the light microscopic, histochemical, immunocytochemical (cytochrome c oxidase), and ultrastructural studies described here provide conclusive evidence that the swollen, granular, eosinophilic epithelial cells that compose CCP are true oncocytes that arise primarily, or perhaps exclusively, from the respiratory (Schneiderian) epithelium of the sinonasal passages rather than from minor salivary glands. Continued designation of the CCP as such should therefore be discouraged in favor of a more precise term reflecting this derivation. The phrase "oncocytic Schneiderian papilloma" is proposed.

Functioning oxyphil cell adenoma of the parathyroid gland: a clinicopathologic study of ten patients with hyperparathyroidism.

Adenomas of the parathyroid gland, the majority of which are of the solitary chief cell type, are the most frequent cause of primary hyperparathyroidism. Parathyroid adenomas composed predominantly or exclusively of oxyphil cells are rare and were previously considered nonfunctioning. Among 160 consecutive patients with primary hyperparathyroidism who were explored surgically, ten (6.25 per cent) had adenomas of the oxyphil cell variety. The eight women and two men in this series ranged in age from 28 to 82 years (average, 58 years). The tumors weighed from 0.2 to 4.0 g (average, 1.2 g). Nine of the adenomas were located in the left neck, while the remaining tumor was in the right neck. Histologically, the tumors were composed almost exclusively of transitional and typical oxyphil cells. A residual "capsular" parathyroid composed of chief cells was identified in each case. Electron microscopy, phosphotungstic acid-hematoxylin staining, and the immunoperoxidase technique for cytochrome c oxidase showed the presence of numerous mitochondria in oxyphil cells. All patients had normal serum calcium levels four months to four years (average, 23 months) after removal of the neoplasms.

Thromboxane generation and pulmonary reactivity to arachidonic acid in heart-lung preparation of guinea-pig: modulation by PCO2.

A dose-related increase of pulmonary vasoconstrictive and bronchoconstrictive effects, as well as of the amounts in the perfusing fluid of TXB2, the stable metabolite of TXA2, was obtained through administration of arachidonic acid (AA) in normocapnic and deeply hypocapnic guinea-pig heart-lung preparations (HLPs) perfused with homologous red blood cells suspended in a modified Tyrode solution. Pulmonary hypertensive effects and the amounts of TXB2 detected in the perfusing fluid were reduced in hypocapnic preparations as compared with the normocapnic ones, while the bronchoconstrictive responses to AA were not affected by CO2 tension. It is concluded that: a) biosynthesis of TXA2 is reduced in hypocapnic group if compared with that observed in normocapnic one, b) the quantitative change of AA metabolism is responsible for hypocapnia reduction of pulmonary vasoconstrictive effects of AA, c) stability of bronchoconstriction due to AA infusions in normocapnic and hypocapnic HLPs might indicate an up regulation for TXA2 bronchial smooth muscle receptors by hypocapnia.

Total pancreaticoduodenal homotransplantation in dogs immunosuppressed with cyclosporine and steroids.

Pancreaticoduodenal transplantation was performed with cyclosporine and steroid immunosuppressive therapy in 10 mongrel dogs that had pancreaticoduodenectomy. There was an average animal survival of 50.6 days and an average duration of normoglycemia of 41.8 days. We suggest that pancreaticoduodenal transplantation, which was abandoned as a clinical procedure 10 years ago, be reconsidered for clinical application.

Löffler's endocarditis. Occurrence with malignant lymphoma with a high content of epithelioid histiocytes ('Lennert's lymphoma').

In a patient who had malignant lymphoma with a high content of epithelioid histiocytes (so-called Lennert's lymphoma), Löffler's endocarditis developed 18 months after her diagnosis of lymphoreticular malignant neoplasm. She died of refractory congestive heart failure, and an autopsy showed the typical gross and microscopic findings of Löffler's endocarditis. To our knowledge, this is the first reported association of these two diseases. We noted nine autopsy cases in the literature of Löffler's endocarditis occurring in patients with lymphoreticular malignant neoplasms (acute lymphoblastic leukemia and lymphoma). Löffler's endocarditis with eosinophilia may be a relatively uncommon but significant complication in patients with malignant lymphoproliferative disorders. The peripheral blood eosinophilia probably represents a reactive response to tumor antigen.

Skeletal myxoid chondrosarcoma with microtubular aggregates within rough endoplasmic reticulum.

A skeletal myxoid chondrosarcoma of the femur was examined by light and electron microscopy. Light microscopic features were characteristic for myxoid chondrosarcoma or "chordoid sarcoma." Electron microscopy disclosed crystalline arrays of microtubules within dilated rough endoplasmic reticulum, a feature previously described in extraskeletal myxoid chondrosarcomas. Tumors with the histologic characteristics of extraskeletal myxoid chondrosarcoma ("chordoid sarcoma") occurring in bone have been rarely reported. We describe herein such a tumor and document the existence of distinct microtubules within the endoplasmic reticulum.

Purification of arachidonic acid metabolites from cell cultures by octadecyl reversed phase cartridges.

The use of rat basophilic leukemia (RBL-1) cell-line as a biosynthetic source of arachidonic acid metabolites has been previously described. We have developed a rapid and effective procedure for the extraction of lipoxygenase and cyclooxygenase products. The cells grown in spinner cultures were harvested and washed in phosphate buffer and stimulated by calcium ionophore A23187. The ethanolic extract of the cells was dried, dissolved in 20% methanol acidified with acetic acid and applied to octadecyl reversed phase cartridge (Backer C18). The cartridge was washed with 50% methanol (4 ml). Prostaglandins were eluted with 75% methanol (4 ml) and leukotrienes and related compounds with 100% methanol (4 ml). The identification of the fractions was carried out with pure standards. The recoveries of radiolabelled compounds ranged from 70% to 90%. This system can therefore accomplish an initial separation of major arachidonate metabolites and be applied in investigating metabolic pathways of arachidonic acid in different experimental conditions.

Primary adenocarcinoma arising at an ileostomy site. An unusual complication after colectomy for ulcerative colitis.

A case is reported of a 45-year-old man who developed a primary adenocarcinoma at the ileostomy site 23 years after proctocolectomy for ulcerative colitis. The patient underwent wide local excision of the tumor and died 13 months later with disseminated adenocarcinoma. Including the present case, a total of seven patients with ileostomy adenocarcinoma have been reported in the literature. Six patients were treated surgically for ulcerative colitis, and the other one for adenomatous polyposis coli. The diagnosis of stomal malignancy was made three to 23 years after the ileostomy (mean interval, 13 years). Of the four patients available for clinical follow-up, two died of disseminated adenocarcinoma ten and 13 months after diagnosis. Awareness of this unusual but important complication of ileostomy should lead to earlier diagnosis and treatment with improvement in prognosis.

Malignant lymphoma with a high content of epithelioid histiocytes (so-called Lennert's lymphoma). Immunocytochemical and ultrastructural observations.

The clinicopathological findings of four cases of an uncommon form of non-Hodgkin's lymphoma called malignant lymphoma with a high content of epithelioid histiocytes (MLHH) are described. In each case the peroxidase antiperoxidase technique was used for detecting cytoplasmic immunoglobulins (CIg) in the diagnostic lymphoid tissue. In one case (patient 1), IgG and IgM heavy chains and kappa light chain were detected in 30 to 40 percent of the atypical lymphoid cells. This result suggests that the proliferating B lymphocytes in this patient with MLHH are neoplastic rather than reactive in nature. We were unable to identify CIg in the proliferating lymphoid cells of the other three patients. Our case when coupled with others reported in the literature suggest that the morphologic features of MLHH (so-called Lennert's lymphoma) can be associated with a neoplastic proliferation of either T or B lymphocytes. The ultrastructural findings of one case are presented.

Teflon felt embolism of coronary arteries after cardiac surgery: a case report.

A case is presented of fatal coronary embolism of Teflon felt used to buttress sutures in the placement of a Björk-Shiley aortic valve prosthesis. The embolism occurred on the tenth postoperative day, lodging in the left anterior descending branch of the left coronary artery 5.5 cm. from the ostium, causing a large anterior myocardial infarct. The patient died in less than 24 hours following the infarct. A review of the literature indicates that this is the first reported case of clinically significant embolism of Teflon felt used in the placement of a Björk-Shiley aortic valve.