Diagnóstico de la enfermedad de CADASIL en pacientes normotensos y no diabéticos con infarto lacunar / Diagnosis of CADASIL disease in normotensive and non-diabetics with lacunar infarct

Introducción: la enfermedad de CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) se caracteriza por isquemias cerebrales recurrentes de tipo lacunar, habitualmente en pacientes sin factores de riesgo vascular. Analizamos la frecuencia de enfermedad de CADASIL en pacientes con infarto lacunar sin factores de riesgo vascular clásicos. Métodos: estudiamos pacientes con un primer infarto lacunar menores de 65 años sin hipertensión, diabetes mellitus u otra causa que justificara la isquemia cerebral. Realizamos estudio inmunohistoquímico de 5μm de espesor sobre biopsia cutánea usando el anticuerpo monoclonal anti-Notch 3 (1E4). Además del estudio inmunohistoquímico se realizó en todos los casos el estudio genético del gen Notch 3 de los exones 3, 4, 5, 6, 11 y 19. Resultados: de 1.519 pacientes con infarto lacunar, sólo 57 (3,7%) cumplieron los criterios de selección, y 30 de ellos aceptaron participar en el estudio. Analizamos 30 pacientes con edad media de 53 años; el 50% fueron hombres y todos presentaron un primer infarto cerebral tipo lacunar. El estudio inmunohistoquímico y genético confirmó la enfermedad de CADASIL en dos pacientes (6,6%) en el exón 4 nt 622C/T (Arg 182 Cys) y 694 T/C (Cys206Arg) respectivamente (AU)

Background: CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is characterized by recurrent cerebral ischemic episodes of the lacunar subtype usually without traditional vascular risk factors. We investigated the frequency of CADASIL among selected patients with cerebral ischemia of the lacunar subtype. Methods: we studied patients under 65 years old who presented cerebral ischemia of the lacunar subtype without hypertension, diabetes mellitus or other causes that explained the cerebral ischemia. On the skin biopsies, we performed immunostaining analysis on 5μm frozen sections with monoclonal antibody anti-Notch 3 (1E4). We also performed a genetic analysis of the Notch 3 gene (exons 3,4,5,6,11 and 19). Results: of 1.519 patients analyzed, only 57 (3.7%) fulfilled the selection criteria, and 30 of them accepted to participated in the study. We studied 30 patients, mean age was 53 years (range 34 to 65), 50% were men and all patients suffered a lacunar stroke. Immunostaining analysis was positive in two patients (6.6%) and the genetic analysis confirmed a mutation characteristic of CADASIL in exon 4 nt 622C/T (Arg 182 Cys) and 694 T/C (Cys206Arg) respectively. Conclusions: CADASIL disease was present in 6.6% of patients younger than 65 years with a lacunar stroke and without hypertension or diabetes mellitus. Screening for CADASIL should be considered in these patients (AU)

Gastric carcinoid tumour. A clinicopathologic and immunohistochemical study of four cases.

Over the last decade a great increase in the frequency of Gastric Carcinoid Tumours has been detected being considered by some authors as the most frequent digestive carcinoid. These have been divided into three types: I) those associated with chronic atrophic gastritis; II) associated with Zollinger-Ellison syndrome, and III) sporadic lesions. We present four cases of gastric carcinoid type I (3 women and 1 man) two of them associated with pernicious anemia and another two with iron deficiency anemia. Three patients were operated upon, and an endoscopy removal was carried out on the fourth patient. The clinical course has been favourable during the follow-up. Multiple lesions were detected in 3 patients, with tumours less than 2 cm in size, except for a 4.5 cm polyp, which invaded the submucous layer. This case presented carcinoid syndrome without evidence of liver metastasis. Argyrophilia. Chromogranin A and Neuronal Specific Enolase tintions were located in the tumor and in the hyperplastic endocrine cells of the mucous.

Testicular function in asymptomatic chronic alcoholics: relation to ethanol intake.

To evaluate the effect of ethanol on testicular function in chronic alcoholics without chronic liver disease, we studied 38 asymptomatic chronic alcoholics and 19 age-matched controls. Detailed clinical history, nutritional status, hormonal analysis, and seminal studies were conducted in each case and control. Alcoholic patients had an average of 39 +/- 2 years old (range: 26 to 60) and reported a daily ethanol consumption from 100 to 350 g (mean: 198 +/- 15) over a period of 18.0 +/- 1.2 years. Alcoholics exhibited a significant increase of the luteinizing hormone (p < 0.001) and a decrease of the Free Androgen Index, compared with controls (p < 0.05) that related significantly with the total lifetime dose of ethanol (p < 0.01, both). Seminal studies indicate that 39.4% of alcoholics had significantly reduced their spermatozoa count (p < 0.01), whereas significant morphological abnormalities were observed in 44.7% of the alcoholics (p < 0.01). Spermatozoa motility from alcoholics was also found to be altered in half of the patients (p < 0.01). A significant increase of serum luteinizing hormone, follicle-stimulating hormone, and sex hormone binding globulin levels, and a decrease of Free Androgen Index were observed in alcoholics with morphology and motility abnormalities (p < 0.05, all). In multivariate analysis, the only independent factor that determined the alterations in sperm (count, morphology abnormalities, and motility alterations) was the total lifetime of ethanol intake (p < 0.001, all). We conclude that alcoholics frequently develop a situation of primary hypogonadism related to a lifetime of ethanol consumption.

Autonomic and peripheral neuropathies in patients with chronic alcoholism. A dose-related toxic effect of alcohol.

OBJECTIVE: To assess autonomic and peripheral nervous system function in patients with chronic alcoholism. DESIGN: A cross-sectional study. PATIENTS: A consecutive sample of 107 alcoholic patients and 61 controls. MAIN OUTCOME MEASURE: For autonomic assessment, heart rate variations during deep breathing and Valsalva maneuver and on standing were measured. Blood pressure response to standing up and to sustained handgrip were also evaluated. For assessment of the peripheral nervous system, an electrophysiologic examination was performed. RESULTS: Alcoholic patients exhibited reduced heart rate variability compared with controls (P < .01, on all parasympathetic tests), whereas no differences in the mean values of the blood pressure responses between both groups were found. Twenty-six patients (24.3%) had criteria of autonomic neuropathy, and 34 (32%) had electrophysiologic criteria of peripheral neuropathy. None of the controls exhibited criteria of autonomic neuropathy, and only one had criteria of peripheral neuropathy. The estimated total lifetime dose of alcohol correlated inversely with the parasympathetic indexes (r = -.48 to -.51; P < .001 on all parasympathetic tests) and the sensory potential amplitudes of upper and lower limbs (r = -.43; P < .001, both limbs). Finally, a significant correlation between autonomic and peripheral neuropathies was observed (P = .01). By contrast, these lesions were not related to age, nutritional status, or other alcohol-related diseases. CONCLUSIONS: Autonomic and peripheral neuropathies are common among hospitalized alcoholic patients. Alcohol appears to be toxic to autonomic and peripheral nerves in a dose-dependent manner.

[Uremic hemolytic syndrome induced by mitomycin C. Presentation of a series of 5 cases and review of the literature]. / Síndrome hemolítico urémico inducido por mitomicina C. Presentación de una serie de cinco casos y revisión de la literatura.

Five new cases of hemolytic uremic syndrome associated mitomycin C treatment in neoplastic patients are presented and clinical, biological, histological therapeutic and the evolution data of 92 other cases from the literature are analyzed. The results point out the high incidence of GI adenocarcinomas (65%), its rare appearance with total mitomycin doses below 50 mg/m2, its frequent clinical presentation with cardiovascular manifestations, the therapeutical difficulties and the possibility of a better prognosis with an early diagnosis.

[Cardiac tamponade as presentation form of lymphoma. Presentation of a case and review of the literature]. / Taponamiento cardíaco como forma de presentación del linfoma. Aportación de un caso y revisión de la literatura.

A case of non-Hodgkin's lymphoma, centrocitic and centroblastic which was presented as cardiac tamponade, is described. The literature is reviewed commenting on other 14 cases with the same presentation. In spite of the rareness, we highlight the importance of its early diagnosis to prevent the hemodynamic alterations, this being after its control with the same prognosis of other patients afflicted by lymphoma.

[Autoimmune hemolytic anemia preceding by 6 years an adenocarcinoma of the gallbladder]. / Anemia hemolítica autoinmune precediendo seis años a un adenocarcinoma de vesícula biliar.

A case of a 59-year-old female suffering from immunohemolytic anemia, coombs negative, is presented. Six years after the diagnosis, this patient developed an adenocarcinoma of the gallbladder, with invasion of lymph nodes, liver and peritoneum; at this moment the coombs, test proving positive. The possible pathogenetic mechanisms are discussed, despite the rareness of this delayed association which is probably the first described in literature.

Immunohistochemical analysis of lymphoid and macrophage cell subsets and their immunologic activation markers in temporal arteritis. Influence of corticosteroid treatment.

To determine the phenotype of infiltrating mononuclear cells in patients with temporal arteritis (TA), we performed immunohistochemical studies on temporal artery biopsy specimens from 24 patients with biopsy-proven TA. Interdigitating reticulum cells (IRC) were observed in 41% of the patients; disease duration was significantly shorter in these patients than in patients lacking IRC (mean 1.5 months versus 3.8 months). Infiltrating cells consisted predominantly of HLA-DR-expressing macrophages and T lymphocytes, especially of the CD4 subset. There were few B cells and no K cells. No relationship between cellular distribution and disease duration or treatment was found. Interleukin-2 receptor expression was observed in 87.5% of biopsy specimens obtained prior to or within the first 4 days of treatment with prednisone, but in only 14% of specimens obtained later. The presence of IRC in patients with TA suggests an autoimmune reaction directed against an antigenic substance that resides in the arterial wall and is presented and processed in situ. DR-expressing macrophages activated by CD4+ T lymphocytes may contribute to arterial damage in TA. Corticosteroids do not modify cellular distribution but induce important functional changes, as demonstrated by the disappearance of interleukin-2 receptor expression in patients treated for more than 4 days.

Vagal neuropathy in chronic alcoholics: relation to ethanol consumption.

Vagal neuropathy in chronic alcoholics seems more common than supposed and its reversibility and relationship with alcohol intake and nutritional status remain obscure. We embarked upon a study of a series of 70 chronic alcoholics in whom reliable alcoholism history, nutritional status evaluation and cardiovascular reflex tests were performed at the beginning of abstinence. Moreover, an electrophysiological study of peripheral nerves was carried out. Five out of 70 patients had symptoms related to autonomic neuropathy. Fourteen alcoholics presented abnormal indices in the deep breathing test (DBT) performed, including the five patients with clinical manifestations. A strong correlation between DBT indices and total lifetime ethanol intake and motor conduction velocity of lower limbs (MCV) was observed. No gross evidence of malnutrition was detected in the alcoholics and the transketolase erythrocyte activity was normal in all but one. Since the MCV also correlated with total lifetime ethanol intake, it appears that ethanol may exercise a dose-related toxic effect on both the autonomic and peripheral nervous systems. Finally, 12 of 14 patients with abnormal DBT index were re-evaluated one year later. Eleven who reported complete ethanol abstinence presented an improvement of this index and nine of them reached the normal range. Three of four patients with clinical manifestations reported an improvement of the symptoms. Thus, vagal neuropathy may reverse in most of the patients who manage to maintain ethanol abstinence.

Polymyalgia rheumatica: a syndrome associated with HLA-DR4 antigen.

HLA class II antigens were determined in 65 patients with biopsy-proven giant cell arteritis (GCA). An increase in DR4 antigen frequency was found in the patients (40%) compared with that in 200 healthy controls (20%) (Pcorr less than 0.05). DR4 was significantly more frequent in GCA patients with polymyalgia rheumatica (PMR) than in those without PMR (58.8% versus 19.3%) (P less than 0.005). HLA-DR4 frequency in GCA patients without PMR was similar to that in the control population (20%). Patients with severe, disabling PMR had DR4 more frequently (90%) than did those with moderate symptoms who required medical care because of cranial arteritis manifestations (41.6%) (P less than 0.05). We conclude that, in GCA patients, association with DR4 is mainly related to the manifestation of the disease as PMR. We discuss clinical and immunogenetic similarities between PMR and other DR4-associated rheumatic disorders. Common immunopathogenic mechanisms leading to clinical overlap among them are suggested.