Novel explant model to study mechanotransduction and cell-cell communication.

To understand in situ behavior of osteocytes, we characterized a model of osteocytes in their native bone matrix and demonstrated real-time biologic activity of osteocytes while bending the bone matrix. Using 43 male Sprague-Dawley rats, dumbbell-shaped explants were harvested from stainless steel femoral implants after 6-12 weeks and incubated in culture medium or fixed. Sixteen specimens were used to determine bone volume density (BV/TV), volumetric bone mineral density (BMD) and histology for different implantation periods. Osteocyte viability was evaluated by L-lactate dehydrogenase (LDH) activity in 12 cultured explants. Confocal microscopy was used to assess tracer diffusion in three explants and changes in osteocyte pH of a mechanically loaded explant. From 6 to 12 weeks, explant BV/TV and volumetric BMD trended up 92.5% and 101%, respectively. They were significantly and highly correlated. Tissues were uniformly intramembranous and all bone cell types were present. Explants maintained LDH activity through culture day 8. Diffusion at 200 microM was limited to 1,209 Da. Explants appeared capable of reproducing complex bone biology. This model may be useful in understanding osteocyte mechanotransduction in the context of a physiologically relevant bone matrix.     

Load-induced proteoglycan orientation in bone tissuein vivo andin vitro

Summary Previous studies of Alcian blue-induced birefringence in adult avian cortical bone showed that a short period of intermittent loading rapidly produces an increased level of orientation of proteoglycans within the bone tissue. In the absence of further loading, this persists for over 24 hours. We have proposed that this phenomenon could provide a means for “capturing” the effects of transient strains, and so provide a persistent, constantly updated strain-related influence on osteocyte populations related to the bones' averaged recent strain history, in effect, a “strain memory” in bone tissue. In our present study, we use the Alcian blue-induced birefringence technique to demonstrate that proteoglycan orientation also occurs after intermittent loading of both cortical and cancellous mammalian bonein vivo andin vitro. We also show that the change in birefringence is proportional to the magnitude of the applied strain, and that the reorientation occurs rapidly, reaching a maximal value after only 50 loading cycles. Examination of electron micrographs of bone tissue after staining with cupromeronic blue allows direct visualization and quantification of the change in proteoglycan orientation produced by loading. This shows that intermittent loading is associated with a realignment of the proteoglycan protein cores, bringing them some 5 degrees closer to the direction of collagen fibrils in the bone matrix.     

Immediate versus delayed chemotherapy in patients with asymptomatic incurable metastatic cancer

Aim: To examine the evidence of benefit in initiating immediate chemotherapy in patients with newly diagnosed asymptomatic metastatic incurable cancer, compared with delaying chemotherapy until symptomatic progression. Methods: Through an extensive review of published reports, we examined the biological, clinical, psychological and ethical background of the issue and reported on the available clinical trial evidence in a variety of tumor types. Results: Only a limited number of clinical trials have directly examined the role of immediate versus delayed chemotherapy in patients with incurable asymptomatic metastatic cancer. Small studies in mesothelioma, colorectal cancer, breast cancer, myeloma, and low‐grade lymphoma suggest no survival benefit for the immediate initiation of chemotherapy. However, there was no evidence in other tumor types. Conclusion: The appropriate timing of chemotherapy initiation in an asymptomatic patient with metastatic cancer remains a substantial question in oncology. Many factors are likely to impact on the decision. However, little if any evidence demonstrates a clear advantage in the immediate initiation of chemotherapy in this setting.     

Free plasma magnesium following glucose loading in healthy humans

The recognized existence of a circadian pattern in extracellular magnesium balance might mirror either an inherent rhythm in the homeostasis of this ion or dietary factors. Since in vitro insulin enhances cellular magnesium uptake, the circadian rhythm in extracellular magnesium metabolism might be modulated at least in part by carbohydrate intake. To assess this hypothesis, the effects of oral glucose loading on plasma total and ionized magnesium were investigted in lean healthy humans with a negative family history for essential hypertension and diabetes mellitus. Plasma total and ionized magnesium was similar before glucose loading and 30, 60, 90, 180, and 210 min thereafter. It is therefore concluded that in healthy humans the circadian pattern of extracellular magnesium is not modulated by the metabolic and hormonal mechanisms that adjust the concentration of glucose. Received: 5 February 1997 / Accepted in revised form: 14 April 1997     

战士体内VitB_1、VitB_2储备水平检测

选择南方热区某特种部队战士５２人，分两组分别口服５ｍｇＶｉｔＢ１和ＶｉｔＢ２，收集４ｈ尿液，用荧光法进行负荷试验。结果：ＶｉｔＢ１组，所测２９人中，１５人缺乏，９人不足，２人正常，３人充裕；ＶｉｔＢ２组，所测２３人中，１１人缺乏，１２人不足，反映该部队全年约５％的发病是由于ＶｉｔＢ１、ＶｉｔＢ２缺乏不足所致。其原因为膳食摄入不够     

POTASSIUM ACCELERATES URINARY SODIUM EXCRETION DURING SALT LOADING WITHOUT STIMULATING ATRIAL NATRIURETIC POLYPEPTIDE SECRETION

1. Effects of potassium (K) supplementation (100 mEq/day) on urinary sodium (Na) excretion and on the secretion of atrial natriuretic polypeptide (ANP) during salt loading (350 mEq/day) were studied in 12 healthy salt-resistant normotensives under strictly controlled metabolic ward conditions. 2. Urinary volume and Na excretion on the first day of the high salt period (HSP) were significantly greater in the K-supplemented group (KG) than in the control group (CG). 3. There was a significant gain in bodyweight after salt loading in both groups, with a significantly greater gain in CG on the second day of HSP. Haematocrit decreased significantly during salt loading in both groups, the degree of which was significantly greater in CG. 4. Plasma norepinephrine decreased significantly during salt loading in both groups, the degree of which was significantly less in KG than in CG. A significant increase in plasma ANP was observed in CG on and after the second day of HSP, while a significant increase in plasma ANP was observed on the fifth day of HSP in KG. 5. These findings indicate that K supplementation accelerates diuresis and natriuresis, resulting in moderate suppression of volume expansion induced by salt loading and that this accelerated diuresis and natriuresis is not a result of the action of ANP.     

IgE and atopy in perinatally HIV-infected children

Elevated serum immunoglobulin E (IgE) and increased prevalence of atopy is reported in patients infected with human immunodeficiency virus (HIV). The elevated serum IgE may be attributed to polyclonal stimulation of B cells or IgE production against allergens, viruses, fungi and bacteria. This study investigates the prevalence of atopy in perinatally HIV-infected children, and the relationships between serum IgE (and other serum immunoglobulins) with atopy, CD4+ cell count and HIV-disease stage. Serum immunoglobulin levels, epicutaneous skin test for common aeroallergens, clinical Centers for Disease Control and Prevention (CDC) classification, CD4+ cell counts and allergy history were extracted from the charts of perinatally HIV-infected children on highly active antiretroviral therapy. The prevalence of atopy (52%) and the pattern of aeroallergen sensitivity were comparable with the US pediatric population. Serum IgE levels did not correlate with clinical disease stage. However, in non-atopic patients, serum IgE levels increased with disease progression (p = 0.02). There was an inverse relationship between the prevalence of elevated serum IgE levels and atopy with progression of disease (p = 0.019). Serum IgE did not correlate with atopy, CD4+ cell count, or duration of HIV infection or levels of serum immunoglobulins. This is the first study to show no increased prevalence of atopy in perinatally HIV-infected children compared with the general population. In advanced stages of HIV, elevated serum IgE may be specific for antigens other than those known as allergens.     

Cow's milk-specific immunoglobulin E levels as predictors of clinical reactivity in the follow-up of the cow's milk allergy infants

Background IgE‐mediated cow's milk proteins (CMPs) allergy shows a tendency to disappear with age. The sooner tolerance is detected, the earlier the substitute diets can be suspended and the quicker family emotional hardship is alleviated. Objective To analyse the specific IgE levels to cow's milk and its proteins, which help to separate tolerant from no tolerant children in the follow‐up of infants with allergy to cow's milk. Patients and methods Sixty‐six infants diagnosed with IgE‐mediated allergy to CMPs were included in this prospective follow‐up study. Periodic reassessments were carried out every 6 months until they were 2‐years old and then, annually, until tolerance arose or until the last reassessment in which tolerance had not been achieved. Non‐tolerant infants were followed, at least, for a period of 3 years. In each visit, the same skin tests and determination of specific IgE (CAP System FEIA) for milk and its proteins were carried out. The open challenge test was repeated unless a clear transgression to milk, which came to be positive, had taken place within the previous 3 months in each of the follow‐up visits. Specific IgE levels to milk and its proteins, in different moments of the follow‐up were analysed by means of the receiver‐operating characteristic curve to predict clinical reactivity. Results Throughout the follow‐up 45 (68%) infants became tolerant. The follow‐up mean for tolerant infants was 21.2 months whereas for non‐tolerant infants it was 58 months. The specific IgE levels which were predictors of the clinical reactivity (positive predictive value (PPV)90%), grew as the age of the infants increased: 1.5, 6 and 14 kU_A/L for milk in the age range 13–18 and 19–24 months and in the third year, respectively. Specific IgE levels to casein: 0.6, 3 and 5 kU_A/L, respectively, predicted clinical reactivity (PPV90%) in the different analysed moments of the follow‐up. The cut‐off points: 2.7, 9 and 24 kU_A/L for milk and 2, 4.2 and 9 kU_A/L for casein, respectively, predicted clinical reactivity with an accuracy 95% corresponding to a specificity of 90%. Conclusions Monitorization of specific IgE concentration for milk and casein by means of the CAP system in allergic children to CMPs allows us to predict, to a high degree of probability, clinical reactivity. Age factor must be taken into account to evaluate the specific IgE levels which are predictors of tolerance or clinical reactivity.     

A typological model of schizophrenia based on age at onset,sex and familial morbidity

We investigated the age at onset distributions of schizophrenia in men and women and the relationship of age at onset and sex to the familial rates of schizophrenia and manic-depression in data from a Swedish family study of 270 schizophrenic probands. On the logarithmic scale, the age at onset distribution of schizophrenia in both male and female relatives was bimodal, suggesting that broadly defined schizophrenia may be a mixture of 2 (probably related) disorders. The risk of schizophrenia in relatives decreased as a function of the age at onset of the proband, irrespective of the sex of the proband or relative. In contrast, the risk of manic-depression was significantly higher in relatives of female probands with an age at onset in the twenties than in relatives of female probands with earlier or later onset, or in relatives of male probands. This suggests a third disorder related to affective psychosis, with an intermediate age at onset and female preponderance.