Mutations in PIK3CD Can Cause Hyper IgM Syndrome (HIGM) Associated with Increased Cancer Susceptibility

Autosomal dominant gain of function mutations in the gene encoding PI3K p110δ were recently associated with a novel combined immune deficiency characterized by recurrent sinopulmonary infections, CD4 lymphopenia, reduced class-switched memory B cells, lymphadenopathy, CMV and/or EBV viremia and EBV-related lymphoma. A subset of affected patients also had elevated serum IgM. Here we describe three patients in two families who were diagnosed with HIGM at a young age and were recently found to carry heterozygous mutations in PIK3CD. These patients had an abnormal circulating B cell distribution featuring a preponderance of early transitional (T1) B cells and plasmablasts. When stimulated in vitro, PIK3CD mutated B cells were able to secrete class-switched immunoglobulins. This finding implies that the patients’ elevated serum IgM levels were unlikely a product of an intrinsic B cell functional inability to class switch. All three patients developed malignant lymphoproliferative syndromes that were not associated with EBV. Thus, we identified a novel subset of patients with PIK3CD mutations associated with HIGM, despite indications of preserved in vitro B cell class switch recombination, as well as susceptibility to non-EBV-associated malignancies.     

The mental health system and the etiology of homelessness: A comparison study

Previous research suggests that former psychiatric hospital patients become homeless due to (1) their inability to make use of treatment services, (2) the lack of available services, or (3) the lack of available tangible economic supports. However, supportive studies tend to examine the homeless in isolation and therefore do not fully determine whether the three factors differentiate those former patients who become homeless from the large group who do not. They also fail to undertake multivariate analysis that can separate determinants from factors that are only spuriously related to the lack of a domicile. The current study thus compares homeless and other domiciled but vulnerable former psychiatric patients within a multivariate framework. Results suggest that, except for age, few measures representing the inability to use services or the lack of treatment services predict homelessness. In contrast, homelessness is related to traits that reflect the lack of tangible resources, including the lack of Supplemental Security Income (SSI), the lack of other income maintenance benefits, and the lack of work income. Such results suggest that homelessness might be avoided if vulnerable former patients receive special but not traditional types of care, if young people are retained in treatment, and if the vulnerable receive help in obtaining material support.     

红细胞输注前的质量标准

现行红细胞输注规则主要规定红细胞采集量和输注时存活红细胞的比例,即450ml的采集量,输注时24h平均体内的存活率至少75%。其他还限制了游离血红蛋白的含量,通常不超过红细胞总量的1．0%。特殊需求的红细胞产品又有额外的要求。每单位少白细胞的红细胞的残余白细胞不超过1×10~6。     

Hypothalamo-pituitary abnormalities in adult patients with langerhans cell histiocytosis: clinical, endocrinological, and radiological features and response to treatment

Langerhans cell histiocytosis (LCH) is a rare disorder in which granulomatous deposits occur at multiple sites within the body, but which often involves the hypothalamo-pituitary axis (HPA). Although diabetes insipidus (DI) is a well recognized complication, the frequency of anterior pituitary and other nonendocrine hypothalamic (NEH) involvement has not been well defined, particularly in adult patients with the disease. We have evaluated the frequency and progression of LCH-related anterior pituitary and other NEH dysfunction and their responses to treatment in 12 adult patients with histologically proven LCH and DI. They were followed up for a median of 11.5 yr (range, 3-28 yr) after the diagnosis of DI was made. Study evaluations comprised clinical (including formal psychometric assessment where appropriate), basal and dynamic pituitary function tests, and radiology with computed tomography and/or magnetic resonance imaging scanning. Eleven patients received systemic treatment, and 5 patients received external beam radiotherapy confined to the HPA. The median age at diagnosis of DI was 34 yr (range, 2-47 yr); DI was the presenting symptom in four patients, whereas the remaining eight each developed DI 1-20 yr (median, 2 yr) after the diagnosis of LCH. Eight patients developed one or more anterior pituitary hormonal deficiencies at a median of 4.5 yr (range, 2-22 yr) after the diagnosis of DI: GH deficiency developed in eight patients (median, 2 yr; range, 2-22 yr), FSH-LH deficiency in 7 patients (median, 7 yr; range, 2-22 yr), and TSH and ACTH deficiency in five patients (median, 10 yr; range, 3-16 and 3-19 yr), respectively; five patients developed panhypopituitarism. In addition, seven patients with anterior pituitary dysfunction also developed symptoms of other NEH dysfunctions at a median of 10 yr (range, 1-23 yr): five morbid obesity (body mass index, >35), five short term memory deficits, four sleeping disorders, two disorders of thermoregulation, and one adipsia. All patients developed disease outside of the hypothalamus during the course of the study, and no fluctuation of disease activity in the HPA region was noted. Radiological examination of the HPA was abnormal in each of the eight patients with anterior pituitary involvement and in the seven patients with NEH dysfunction (one or more abnormalities): seven had thickening of the infundibulum, and one had hypothalamic and thalamic signal changes. All patients who had a magnetic resonance imaging scan had absence of the bright spot of the posterior pituitary on the T1-weighted sequences, and in four patients with DI and normal anterior pituitary function this was the only abnormality. The five patients who received radiotherapy to the HPA achieved a partial or complete radiological response, and there was no evidence of tumor progression in this region. No form of therapy, including chemotherapy, improved any established hormonal deficiencies or symptoms of NEH. In summary, in our adult patients with hypothalamic LCH and DI, anterior pituitary hormonal deficiencies developed in 8 of 12 patients; these occurred over the course of 20 yr. They were frequently accompanied by structural changes of the HPA, although these were often subtle in nature. In addition, symptoms of NEH dysfunction developed in up to 90% of such patients and complicated management. Radiotherapy may be useful in achieving local control of tumor, but established anterior, posterior pituitary, and other NEH dysfunctions do not improve in response to current treatment protocols. Patients with LCH and DI, particularly those with multisystem disease and a structural lesion on radiology, should undergo regular and prolonged endocrine assessment to establish anterior pituitary deficiency and provide appropriate hormonal replacement.     

激光生物效应及医学应用研究

激光作用于生物体会产生物理、化学或生物学的效应,激光正是通过这些效应达到医学基础研究、诊断和治疗疾病的目的.本文简介了激光与生物组织相互作用所产生的生物效应,概述了激光生物效应在生物学和医学研究中的应用.     

Time course of left ventricular dilation after myocardial infarction: influence of infarct-related artery and success of coronary thrombolysis

Dilation of the left ventricle after myocardial infarction is common, occurs rapidly (within 2 weeks of infarction) and may be self-limited. To evaluate the time course of postinfarction left ventricular dilation and to assess the impact of successful coronary thrombolysis, serial radionuclide left ventricular volume analyses were performed in 36 patients undergoing attempted thrombolysis for acute transmural myocardial infarction. All patients underwent cardiac catheterization, coronary angiography and attempted thrombolysis within 7 h of the onset of symptoms. The site of coronary occlusion was the left anterior descending coronary artery in 17 patients, the right coronary artery in 18 and, in 1 patient, occluded bypass grafts to the right and left circumflex coronary arteries. Attempted reperfusion using a thrombolytic agent was successful in 22 individuals, occurring 5 +/- 1 h after the onset of symptoms. Gated radionuclide ventriculography was performed early (mean time 1 day after admission, n = 36), subacutely (mean time 11 days postinfarction, n = 36) and late after infarction (mean time 10.5 months, n = 25), and a geometric technique was used to measure serial left ventricular end-diastolic volume. Left ventricular end-diastolic volume for the entire group increased significantly (p less than 0.01) from 153 +/- 30 ml at baseline to 172 +/- 45 ml (at 11 days) to 220 +/- 63 ml (at 10.5 months). Twenty of 36 patients showed greater than 20% increase in left ventricular end-diastolic volume (dilation) with time. This appeared early in seven patients, occurred remote from infarction in seven others and showed a progressive pattern in six.(ABSTRACT TRUNCATED AT 250 WORDS)