A presenilin 1 mutation (L420R) in a family with early onset Alzheimer disease,seizures and cotton wool plaques,but not spastic paraparesis

Over 100 mutations in the presenilin‐1 gene (PSEN1) have been shown to result in familial early onset Alzheimer disease (EOAD), but only a relatively few give rise to plaques with an appearance like cotton wool (CWP) and/or spastic paraparesis (SP). A family with EOAD, seizures and CWP was investigated by neuropathological study and DNA sequencing of the PSEN1 gene. Aβ was identified in leptomeningeal vessels and in cerebral plaques. A single point mutation, p.L420R (g.1508T > G) that gives rise to a missense mutation in the eighth transmembrane (TM8) domain of PS1 was identified in two affected members of the family. p.L420R (g.1508T > G) is the mutation responsible for EOAD, seizures and CWP without SP in this family.     

Autoimmune hepatitis: a study of 50 patients.

INTRODUCTION: Autoimmune hepatitis (AIH) is a well-defined entity in the West but there are sparse Indian data on this disease. AIM: To study the clinical profile and response to treatment of Indian patients with AIH. METHODS: This is a part retrospective and part prospective study of 50 patients (median age 48 years, range 11-82; 43 women) seen between 1995 to 2001, diagnosed to have AIH as per the revised scoring system. Clinical and laboratory profile, response to treatment, and complications of treatment were analyzed. RESULTS: AIH accounted for 6% of all patients with liver disease seen during the period. The presenting symptoms were gastrointestinal in 43 and non-gastrointestinal in 7, with median symptom duration of 6 months (range 2 weeks to 40 years). Forty patients (80%) had chronic liver disease. Associated illnesses were present in 28 patients. Twenty-six patients were classified as definite and the rest as probable AIH. Forty-nine patients had Type 1 AIH. Five patients had overlap syndrome. Forty-five patients (90%) received immunosuppressive therapy. Twelve of 18 patients receiving only prednisolone and 21 of 27 patients receiving prednisolone and azathioprine combination responded. Thirteen (26%) patients had therapy-related complications (infectious 5, non infectious 8) with two treatment-related deaths. CONCLUSION: Type 1 AIH was the predominant type of AIH. The majority of patients with AIH presented with chronic liver disease. There was good response to immunosuppressive therapy. Therapy-related complications occurred in one-fourth of patients.     

灾难的时代错误:灾害医学的过去、现在和将来(一)

灾难,特别是地震、火山、洪水以及与战争有关的事件如饥饿和流行性传染病,是人类有记录的经历的一部分。从意大利庞贝的火山爆发,到约翰斯顿的洪水、第二次世界大战和黑色瘟疫,到西班牙流感,都发生了灾难,这不会被传说和历史书籍长期忘却。不过,在20世纪中叶以前,那些灾难的发生相对较少,且相距时间较长。从20世纪中叶以来,灾难的本质发生了变化。从恐怖分子使用“新技术”,到与气候有关的导致亿万美元经济损失的事件,表明这个世界正在发生变化。仅仅在最近的50~60年间,造成多种多样的伤亡事件,其危险性和频率的增加引人注目,并且注定要在接…     

Sex differences in the clinical presentation and management of airflow obstruction.

The aim of the present study was to explore differences in the clinical expression, clinical diagnoses and management of airway diseases in a primary-care setting. Patients aged >or=35 yrs who had ever smoked were enrolled when they presented for any reason to one of eight rural primary-care practices. Respiratory symptom questionnaires and spirometry were administered. In total, 1,034 patients had acceptable and reproducible spirometry, of whom 550 (53%) were males and 484 (47%) were females. Males smoked more than females (41.2 versus 29.2 pack-yrs) respectively, and were more likely to have a pre-bronchodilator forced expiratory volume in one second/forced vital capacity <0.70 at 22.4 versus 11.8%, respectively. However, more females than males reported breathlessness (51.0 versus 42.8%, respectively), a prior diagnosis compatible with airflow obstruction and taking respiratory medications (23.4 versus 14.9%, respectively). In conclusion, the current results suggest that females are more likely than males to report breathlessness and be prescribed respiratory medications independent of differences in the severity of airflow obstruction.     

Hypoxic ventilatory response in successful extreme altitude climbers.

A very high ventilatory response to hypoxia is believed necessary to reach extreme altitude without oxygen. Alternatively, the excessive ventilation could be counterproductive by exhausting the ventilatory reserve early on. To test these alternatives, 11 elite climbers (2004 Everest-K2 Italian Expedition) were evaluated as follows: 1) at sea level, and 2) at 5,200 m, after 15 days of acclimatisation at altitude. Resting oxygen saturation, minute ventilation, breathing rate, hypoxic ventilatory response, maximal voluntary ventilation, ventilatory reserve (at oxygen saturation = 70%) and two indices of ventilatory efficiency were measured. Everest and K2 summits were reached 29 and 61 days, respectively, after the last measurement. Five climbers summited without oxygen, the other six did not, or succeeded with oxygen (two climbers). At sea level, all data were similar. At 5,200 m, the five summiters without oxygen showed lower resting minute ventilation, breathing rate and ventilatory response to hypoxia, and higher ventilatory reserve and ventilatory efficiency, compared to the other climbers. Thus, the more successful climbers had smaller responses to hypoxia during acclimatisation to 5,200 m, but, as a result, had greater available reserve for the summit. A less sensitive hypoxic response and a greater ventilatory efficiency might increase ventilatory reserve and allow sustainable ventilation in the extreme hypoxia at the summit.     

Erythropoietin stimulates wound healing and angiogenesis in mice.

Erythropoietin exerts hematopoietic effects by stimulating proliferation of early erythroid precursors. Nonhematopoietic effects of erythropoietin have also been shown. It may act as a new angiogenic factor in wound healing. This study aimed to investigate the effect of systemic administration of recombinant human erythropoietin on wound healing in mice. Dorsal incisional wounds were performed in mice, which were then divided into two groups; a group treated for 7 days with recombinant human erythropoietin, and a control group. Sacrificing animals on day 7, the wound tissues were collected for analysis of wound breaking strength, malondialdehyde, a marker of lipid peroxidation, hydroxyproline, an index of reparative collagen deposition, reduced glutathione levels, and for histological evaluation. The immunohistochemical determination of vascular endothelial growth factor (VEGF) which is believed to be the most prevalent angiogenic factor throughout the skin repair process, was also studied. The treatment significantly increased wound breaking strength by decreasing malondialdehyde and increasing hydroxyproline levels on day 7 after wounding. No statistically meaningful change was observed in reduced glutathione content. VEGF was immunostained significantly more on wound tissue of treated animals compared to the control group. Recombinant human erythropoietin treatment may be effective in wound healing due to inhibition of lipid peroxidation, deposition of collagen, and VEGF expression in wound area.     

Isolation and analysis of partial cDNA sequence coding for superoxide dismutase in Wuchereria bancrofti.

Molecular characterization of Wuchereria bancrofti is essential to develop suitable anti-filarial drugs and vaccines. We describe here isolation, sequence analysis and cloning of a partial cDNA of an enzyme superoxide dismutase from this parasite. The immunoscreening of a lambda zap W. bancrofti microfilarial (Mf) cDNA library with microfilaremic sera had resulted in the isolation of several seroreactive clones including, WbSOD. This clone contained a 309 bp insert and showed significant nucleotide and deduced amino acid sequence homologies to the superoxide dismutases of other nematode parasites. The antioxidant property of this enzyme may have important contribution in the defense mechanism of the parasite against host immune response.     

Management of asthma in patients supervised by primary care physicians or by specialists.

French asthma patients may be supervised by general practitioners (GPs) and/or specialists. Therefore, this study examined asthma management in patients exclusively supervised by specialists (SPE), GPs, (GP) and both (GP+SPE group), and compared the findings. Asthma patients were consecutively recruited in 348 pharmacies. Each patient completed a questionnaire providing data on personal characteristics, asthma management, perception of disease and asthma supervision. Asthma control was measured using the Asthma Control Test. Questionnaires were linked to computerised records of medications which had been dispensed before inclusion in the study. From the 1,256 patients (mean age = 36.1 yrs, 54.3% females), 11.4, 36.6, and 52.0% were placed in the SPE, GP, and GP+SPE groups, respectively. During the previous 4 weeks, most patients in the SPE group were properly controlled (52.2 versus 26.4 and 21.5% in GP and GP+SPE groups, respectively). The SPE group made more use of fixed combinations of long-acting beta agonist and inhaled corticosteroid, while receiving less short-acting beta agonists, antitussives and antibiotics. Striking differences in symptoms and asthma management were observed according to the type of asthma supervision. The current results strongly support the need to improve the management of asthma in primary care, and the coordination of care between general practitioners and specialists.     

Spinocerebellar ataxia types 2 and 3 segregating simultaneously in a single family.

Spinocerebellar ataxia (SCA) types 2 and 3 are autosomal-dominant neurodegenerative disorders caused by mutations in two different genes. We identified mutations for SCA2 and SCA3 segregating simultaneously in a single Brazilian family. The index patient had SCA2, whereas her two second-degree cousins had SCA3. Disease was more rapidly progressive in the SCA2 patient, who presented severe brainstem and pancerebellar atrophy, as opposed to the two SCA3 patients, who had only mild cerebellar vermian atrophy. In such situations, molecular confirmation of all patients may avoid misdiagnosis of SCA subtypes and eventual errors in predictive testing of unaffected family members.