De Barsy syndrome: Report of a case,literature review,and elastin gene expression studies of the skin

Several “progeroid” syndromes have now been identified. The De Barsy syndrome is an autosomal recessive syndrome of dwarfism, mental deficiency, an “aged” appearance at birth, abnormal elastic fibers on skin biopsy, and lax skin, large helices, eye abnormalities, lax joints, hypotonia, and athetoid posturing. We report one case and review 11 cases from the literature. To understand the abnormal appearance of the elastic fibers on biopsy, we performed elastin gene expression studies on fibroblasts cultured from our patient's skin. Molecular hybridization studies revealed reduced elastin mRNA steady-state levels as compared with age matched control individuals. Assuming normal rates of mRNA translation, reduced elastin synthesis would occur. Diminished dermal elastin content could explain the altered cutaneous elasticity, decreased elastic fibers in the skin, and many clinical manifestations of individuals with this condition.     

Ki-67-determined growth fraction versus standard staging and grading parameters in colorectal carcinoma. A multivariate analysis.

BACKGROUND. The antibody Ki-67 binds to nuclei in all cell cycle phases except GO and can be used to measure growth fraction. Because proliferative activity has been linked to prognosis in neoplasia, the authors analyzed 100 cases of colorectal carcinoma, each with 3 or more years of follow-up, using Ki-67 immunostaining. METHODS. The Ki-67-positive nuclear area and total nuclear area of carcinoma cells in 20 microscopic fields were measured by computed morphometry. A Ki-67 score (percent positive nuclear area x 100) was calculated. The following characteristics also were recorded for each case: patient age and sex, tumor site and size, modified Dukes' stage, spread beyond bowel wall, lymph node status, tumor grade, histologic type, extramural venous spread, tumor growth pattern, fibrosis, lymphocytic infiltration, and mitotic rate. RESULTS. Ki-67 scores ranged from 1 to 90 (mean, 34.6). Ki-67 scores were higher in Stage A disease (versus Stage B, C, and D disease) but were not associated with survival. Survival curves differed by stage, lymph node metastases, infiltrative growth pattern, lymphocytic infiltration, fibrosis, extramural venous spread, and tumor grade in a univariate analysis. The infiltrative growth pattern (P = 0.04) and lymphocytic infiltration (P = 0.003) were features associated independently with survival after adjusting for modified Dukes' stage. Furthermore, the lack of a significant lymphocytic infiltrate was associated with a death rate 3.4 times greater than that occurring in patients with Stage B disease with a significant infiltrate. CONCLUSIONS. The authors conclude that proliferative activity in colorectal carcinoma as measured by Ki-67 immunostaining was not associated with prognosis.     

Interferon-alpha (IFN alpha) daily dose versus IFN alpha plus ribavirin for treatment-naive chronic hepatitis c patients infected by genotype 1b

INTRODUCTION: Infection with hepatitis C virus genotype 1b (HCV1b) is known to be a predictive factor of poor response to both interferon-alpha (IFN alpha) alone and IFN alpha plus ribavirin combination therapy.STUDY DESIGN, PATIENTS AND METHODS: This randomised study evaluated the efficacy and safety of daily IFN alpha administration versus the combination of IFN alpha plus ribavirin in treatment-naive patients infected with chronic HCV1b. Sixty-two patients were randomised to receive either human leucocyte IFN alpha 6MU three times weekly for 12 months plus ribavirin 15 mg/kg/day for the first 6 months (group A: 29 patients), or human leucocyte IFN alpha 3MU daily for 12 months (group B: 33 patients). Response was evaluated by monitoring serum alanine aminotransferase (ALT) and HCV-RNA levels during treatment and follow-up (12 months). RESULT AND CONCLUSION: Both treatment schedules were relatively well tolerated. Normal ALT levels and negative serum HCV-RNA were observed in 16 of 29 patients (55%) of group A and in 18 of 33 patients (54.5%) of group B at the end of treatment, as well as in 10 of 29 patients (34.5%) of group A and in 12 of 33 patients (36%) of group B at the end of the follow-up. There was no significant difference between the response rates obtained with the two regimens. In naive patients with chronic HCV1b infection, the efficacy of daily administration with IFN alpha is similar to that of IFN alpha plus ribavirin administered three times a week.     

Circadian variation of blood clotting time and circulating vitamin K in the athletic horse

In equine sport medicine, blood clotting and fibrinolysis variations are well investigated, given the practical implications of several pathophysiological conditions affecting the athlete horse such as exercise-induced pulmonary haemorrhage (EIPH) and other bleeding disorders whose etiology and pathogenesis mechanisms are not yet clearly understood. The purpose of the present investigation was to gain evidence of a daily rhythm of several blood clotting indices such as prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), plasma fibrinogen concentration and serum vitamin K concentration in the athletic horses. Blood samples from five thoroughbred mares were collected at 4-h intervals for 48 h (starting at 08:00 h on day 1 and finishing at 4:00 on day 2 via an intravenous catheter inserted into the jugular vein. Prothrombin time, activated partial thromboplastin time, thrombin time and plasma fibrinogen concentration were assessed by means of a Seac Clot 2 coagulometer (SEAC, Italy), while serum vitamin K concentration was measured by HPLC. Data analysis was conducted by one-way repeated analysis of variance (ANOVA) and by the single cosinor method. ANOVA showed a significant influence of time on all parameters investigated, in all horses, on either day. Cosinor analysis defined the periodic parameters and their acrophases (expressed in hours) during the 2 days of monitoring. PT showed a nocturnal acrophase, whereas serum vitamin K concentration acrophase occurred during the evening. The results of this study reflect the physiological peculiarities of the horse that is subjected to a number of exogenous (environmental, nutritional, physical) and endogenous stimuli capable of entraining the circadian rhythm specifically and thus producing time-dependent variations not always comparable with those observed in humans or laboratory animals.     

A cultural effect on brain function

We present behavioral and anatomical evidence for a multi-component reading system in which different components are differentially weighted depending on culture-specific demands of orthography. Italian orthography is consistent, enabling reliable conversion of graphemes to phonemes to yield correct pronunciation of the word. English orthography is inconsistent, complicating mapping of letters to word sounds. In behavioral studies, Italian students showed faster word and non-word reading than English students. In two PET studies, Italians showed greater activation in left superior temporal regions associated with phoneme processing. In contrast, English readers showed greater activations, particularly for non-words, in left posterior inferior temporal gyrus and anterior inferior frontal gyrus, areas associated with word retrieval during both reading and naming tasks.     

Impairment of neocortical metabolism predicts progression in Alzheimer's disease

Progression rates of Alzheimer's disease (AD) vary considerably, and they are particularly difficult to predict in patients with mild cognitive impairment. We performed a prospective multicenter cohort study in 186 patients with possible or probable AD, mostly with presenile onset. In a cross-sectional analysis at entry, impairment of glucose metabolism in temporoparietal or frontal association areas measured with positron emission tomography was significantly associated with dementia severity, clinical classification as possible versus probable AD, presence of multiple cognitive deficits and history of progression. A prospective longitudinal analysis showed a significant association between initial metabolic impairment and subsequent clinical deterioration. In patients with mild cognitive deficits at entry, the risk of deterioration was up to 4.7 times higher if the metabolism was severely impaired than with mild or absent metabolic impairment. Copyrightz1999S.KargerAG, Basel