Seroconversion to human immunodeficiency virus (HIV) in hemophiliacs. Relation to lymphadenopathy

The authors studied the natural history of human immunodeficiency virus (HIV) exposure in 187 hemophiliacs followed for an average of 45 months. Overall, 55 percent developed antibody specific for HIV and 21 percent developed persistent generalized lymphadenopathy. Most patients seroconverted sometime between early 1982 and the end of 1984. Four patients developed acquired immune deficiency syndrome (AIDS) and four seropositive patients developed idiopathic thrombocytopenia (ITP). One of the four patients who developed AIDS and three of the four with ITP had preexisting lymphadenopathy. None of the 10 patients with lymphadenopathy or the 20 asymptomatic patients was seropositive for human T-lymphotropic virus, type I. Although seropositivity and lymphadenopathy have been found in many of the authors' patients, few have developed clinical disease that can be related to HIV infection.     

Genome scan for adiposity in Dutch dyslipidemic families reveals novel quantitative trait loci for leptin, body mass index and soluble tumor necrosis factor receptor superfamily 1A

OBJECTIVE: To search for novel genes contributing to adiposity in familial combined hyperlipidemia (FCH), a disorder characterized by abdominal obesity, hyperlipidemia and insulin resistance, using a 10cM genome-wide scan. DESIGN: Plasma leptin and soluble tumor necrosis factor receptor superfamily members 1A and 1B (sTNFRSF1A and sTNFRSF1B, also known as sTNFR1 and sTNFR2) were analyzed as unadjusted and adjusted quantitative phenotypes of adiposity, in addition to body mass index (BMI), in multipoint and single-point analyses. In the second stage of analysis, an important chromosome 1 positional candidate gene, the leptin receptor (LEPR), was studied. SUBJECTS: Eighteen Dutch pedigrees with familial combined hyperlipidemia (FCH) (n= 198) were analyzed to search for chromosomal regions harboring genes contributing to adiposity. RESULTS: Multipoint analysis of the genome scan data identified linkage (log of odds, LOD, 3.4) of leptin levels to a chromosomal region defined by D1S3728 and D1S1665, flanking the leptin receptor (LEPR) gene by approximately 9 and 3 cM, respectively. The LOD score decreased to 1.8 with age- and gender-adjusted leptin levels. Notably, BMI also mapped to this region with an LOD score of 1.2 (adjusted BMI: LOD 0.5). Two polymorphic DNA markers in LEPR and their haplotypes revealed linkage to unadjusted and adjusted BMI and leptin, and an association with leptin levels was found as well. In addition, the marker D8S1110 showed linkage (LOD 2.8) with unadjusted plasma concentrations of soluble TNFRSF1A. BMI gave a LOD score of 0.6. Moreover, a chromosome 10 q-ter locus, AFM198ZB, showed linkage with adjusted BMI (LOD 3.3). CONCLUSION: These data provide evidence that a human chromosome 1 locus, harboring the LEPR gene, contributes to plasma leptin concentrations, adiposity and body weight in humans affected with this insulin resistant dyslipidemic syndrome. Novel loci on chromosome 8 and 10 qter need further study.     

Klotho Prevents Renal Calcium Loss

Disturbed calcium (Ca²⁺) homeostasis, which is implicit to the aging phenotype of klotho-deficient mice, has been attributed to altered vitamin D metabolism, but alternative possibilities exist. We hypothesized that failed tubular Ca²⁺ absorption is primary, which causes increased urinary Ca²⁺ excretion, leading to elevated 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] and its sequelae. Here, we assessed intestinal Ca²⁺ absorption, bone densitometry, renal Ca²⁺ excretion, and renal morphology via energy-dispersive x-ray microanalysis in wild-type and klotho^−/− mice. We observed elevated serum Ca²⁺ and fractional excretion of Ca²⁺ (FE_Ca) in klotho^−/− mice. Klotho^−/− mice also showed intestinal Ca²⁺ hyperabsorption, osteopenia, and renal precipitation of calcium-phosphate. Duodenal mRNA levels of transient receptor potential vanilloid 6 (TRPV6) and calbindin-D_9K increased. In the kidney, klotho^−/− mice exhibited increased expression of TRPV5 and decreased expression of the sodium/calcium exchanger (NCX1) and calbindin-D_28K, implying a failure to absorb Ca²⁺ through the distal convoluted tubule/connecting tubule (DCT/CNT) via TRPV5. Gene and protein expression of the vitamin D receptor (VDR), 25-hydroxyvitamin D-1-α-hydroxylase (1αOHase), and calbindin-D_9K excluded renal vitamin D resistance. By modulating the diet, we showed that the renal Ca²⁺ wasting was not secondary to hypercalcemia and/or hypervitaminosis D. In summary, these findings illustrate a primary defect in tubular Ca²⁺ handling that contributes to the precipitation of calcium-phosphate in DCT/CNT. This highlights the importance of klotho to the prevention of renal Ca²⁺ loss, secondary hypervitaminosis D, osteopenia, and nephrocalcinosis.Characterization of a mouse that showed a phenotype comparable to human aging led to the identification of the hormone klotho.¹ Klotho^−/− mice have atherosclerosis, osteopenia, soft tissue calcifications, pulmonary emphysema, and altered glucose metabolism.¹ It has been suggested that the etiology of many of these findings is a primary defect in phosphorous [P(i)] and calcium (Ca²⁺) homeostasis.^2,3 Klotho^−/− mice have elevated serum levels of Ca²⁺.^1,4,5 The mechanism mediating hypercalcemia is poorly understood. A possible explanation invokes the role of klotho in vitamin D homeostasis. Klotho has been proposed to participate in a negative feedback circuit to inhibit 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] synthesis.^6,7 Specifically, klotho is necessary to transduce the signal of fibroblast growth factor 23 (FGF23) through the FGF receptor, thereby suppressing CYP1b expression, the enzyme that mediates the conversion of 25-hydroxyvitamin D into 1,25(OH)₂D₃. Thus, the absence of klotho results in increased serum levels of 1,25(OH)₂D₃ and reduced serum concentrations of the calciotropic hormone parathyroid hormone.^4,7,8 This would drive increased resorption of Ca²⁺ from bone, hyperabsorption from the intestine, increased serum levels of Ca²⁺, and consequently increase renal Ca²⁺ excretion. Definitive proof of this is lacking because the molecular control of Ca²⁺ homeostasis in klotho^−/− mice has yet to be delineated.Consistent with the above hypothesis is the observation that klotho^−/− mice display hypercalciuria^4,5,9 and that normalization of serum 1,25(OH)₂D₃ levels reverts many, but not all, of their abnormalities.⁶ The published literature supports an alternative, complementary hypothesis.^9–11 A primary defect in tubular Ca²⁺ handling might cause hypervitaminosis D and renal Ca²⁺ wasting observed in klotho^−/− mice. Consistent with this idea, in vitro, klotho mediates an increase in cell surface expression of transient receptor potential vanilloid 5 (TRPV5)^10,11 the distal convoluted tubule/connecting tubule (DCT/CNT) channel responsible for the transcellular absorption of Ca²⁺.¹² This process is itself implicit to Ca²⁺ homeostasis as TRPV5 is the predominant regulator of urinary Ca²⁺ excretion.¹³ Therefore, we set out to test the hypothesis that klotho^−/− mice have a primary renal Ca²⁺ leak that contributes to a secondary increase in 1,25(OH)₂D₃ synthesis and its consequences.     

结节性硬化症的CT诊断（附7例分析）

目的：探讨结节性硬化症（TSC）的CT表现和鉴别诊断。方法：分析7例诊断为结节性硬化症的CT资料。重点观察病变部位、大小、钙化程度及其他改变。结果：7例均有室管膜下结节,共计77个,其中钙化结节39个．80％结节位于侧脑室体部室管膜下;5例皮质及皮质下多发结节均无钙化,额枕叶为著,其次为颞顶叶：4例皮质下白质有不同程度低密度改变,主要围绕侧脑室体部及额角周围。4例合并其他畸形。结论：室管膜下多发结节并钙化,皮质异常脑回及不规则形低密度影、脑白质放射状分布的低密度改变是CT诊断结节性硬化症的主要征象,其中室管膜下结节并钙化是较有特征性的表现。CT结合临床可做出明确诊断并发现其他畸形。     

乌审旗3000名妇女宫颈癌筛查结果分析

目的：了解乌审旗妇女宫颈癌及癌前病变的发病现状,探讨子宫颈液基细胞学（Thinprep paptest,TCT）结合阴道镜检查的诊断价值。方法：对3 000名乌审旗妇女进行TCT筛查,对TCT阳性（细胞学TBS分类为不典型鳞状细胞以上）的妇女进行阴道镜及镜下多点活组织检查（活检）,分析TCT阳性者的阴道镜检查及活检结果,比较TCT阳性者中不同年龄段患者的活检结果。结果：3 000名受检者中,TCT阳性537例（17.9%）,其中经活检证实为宫颈上皮内瘤变（cervical intraepthelial neoplasia,CIN）190例（6.3%）,宫颈浸润癌2例（0.07%）,537例TCT阳性者中,阴道镜检查正常264例（49.2%）,其中活检结果为CIN34例,阴道镜的假阴性率为12.9%,异常273例（50.8%）,其中活检结果为湿疣34例,CIN或浸润癌158例,阴道镜与活检的诊断符合率达70.3%（192/273）。TCT为轻度鳞状上皮内病变、高度鳞状上皮内病变、鳞状细胞癌的病例与活检的诊断符合率分别为50.4%,88.3%和2/2,假阳性率则分别为49.6%、11%和0。537例TCT阳性者中,2030岁组、3140岁组,4147岁组的CIN检出率分别为33.7%、44.5%2、6.7%（P〈0.05）。结论：乌审旗妇女CIN的发生率高,是宫颈癌的高发人群。TCT结合阴道镜检查是较好的宫颈癌筛查手段之一。     

A crucial role for TNF-α in mediating neutrophil influx induced by endogenously generated or exogenous chemokines,KC/CXCL1 and LIX/CXCL5

Background and purpose:

Chemokines orchestrate neutrophil recruitment to inflammatory foci. In the present study, we evaluated the participation of three chemokines, KC/CXCL1, MIP-2/CXCL2 and LIX/CXCL5, which are ligands for chemokine receptor 2 (CXCR2), in mediating neutrophil recruitment in immune inflammation induced by antigen in immunized mice.

Experimental approach:

Neutrophil recruitment was assessed in immunized mice challenged with methylated bovine serum albumin, KC/CXCL1, LIX/CXCL5 or tumour necrosis factor (TNF)-α. Cytokine and chemokine levels were determined in peritoneal exudates and in supernatants of macrophages and mast cells by elisa. CXCR2 and intercellular adhesion molecule 1 (ICAM-1) expression was determined using immunohistochemistry and confocal microscopy.

Key results:

Antigen challenge induced dose- and time-dependent neutrophil recruitment and production of KC/CXCL1, LIX/CXCL5 and TNF-α, but not MIP-2/CXCL2, in peritoneal exudates. Neutrophil recruitment was inhibited by treatment with reparixin (CXCR1/2 antagonist), anti-KC/CXCL1, anti-LIX/CXCL5 or anti-TNF-α antibodies and in tumour necrosis factor receptor 1-deficient mice. Intraperitoneal injection of KC/CXCL1 and LIX/CXCL5 induced dose- and time-dependent neutrophil recruitment and TNF-α production, which were inhibited by reparixin or anti-TNF-α treatment. Macrophages and mast cells expressed CXCR2 receptors. Increased macrophage numbers enhanced, while cromolyn sodium (mast cell stabilizer) diminished, LIX/CXCL5-induced neutrophil recruitment. Macrophages and mast cells from immunized mice produced TNF-α upon LIX/CXCL5 stimulation. Methylated bovine serum albumin induced expression of ICAM-1 on mesenteric vascular endothelium, which was inhibited by anti-TNF-α or anti-LIX/CXCL5.

Conclusion and implications:

Following antigen challenge, CXCR2 ligands are produced and act on macrophages and mast cells triggering the production of TNF-α, which synergistically contribute to neutrophil recruitment through induction of the expression of ICAM-1.     

In situ preservation of kidneys from donors after cardiac death: results and complications

OBJECTIVES: To describe the results and complications of in situ preservation (ISP) of kidneys from donors after cardiac death (DCD). BACKGROUND: DCD donors are increasingly being used to expand the pool of donor kidneys. ISP reduces warm ischemic injury which is associated with DCD donation. METHODS: Insertion of a double-balloon triple-lumen catheter allows selective perfusion of the abdominal aorta to preserve the kidneys in situ. From January 2001 until August 2005, 133 ISP procedures were initiated in our procurement area. RESULTS: Fifty-six (42%) ISP procedures led to transplantation; in the remaining 77 cases (58%), the donation procedure was abandoned or both kidneys were discarded because of ISP complications (n = 31), poor graft quality (n = 23), no consent for donation (n = 13), medical contraindications (n = 8), or unknown cause (n = 2). Increasing donor age (odds ratio (OR) 1.06 per year, P < 0.001) and uncontrolled DCD donation (OR 5.4, P < 0.001) were independently correlated with ISP complications. After transplantation, prolonged double-balloon triple-lumen catheter insertion time was an independent predictor of graft failure (OR 2.0, P = 0.05). Selected controlled DCD donors were managed by rapid laparotomy and direct aortic cannulation; graft survival of these kidneys was superior to kidneys from controlled DCD donors managed by ISP. CONCLUSIONS: A minority of initiated ISP procedures led to transplantation, resulting in a high workload compared with donation after brain death. The association between increasing catheter insertion time and inferior graft outcome emphasizes the need for fast and effective surgery. Therefore, rapid laparotomy with direct aortic cannulation is preferred over ISP in controlled DCD donation. Despite these limitations, we have expanded our donor pool 3- to 4-fold by procuring DCD kidneys that were preserved in situ.     

乳腺癌早期诊断应用价值

目的分析乳腺肿物针吸细胞学对乳腺癌早期诊断应用价值。方法用5毫升一次性塑料注射器,对乳腺肿物及乳头溢液患者进行定位针吸细胞学诊断,并与临床病理组织学对照。结果乳腺针吸细胞学不仅对乳腺疾病诊断有重要适用价值,而且对乳腺癌早期诊断有重要价值,总诊断准确率达95.3%。结论乳腺针吸细胞学具有创伤小、简单快速、安全可靠、经济实用、结果准确等优点,各项技术指标明显高于传统诊断方法,是目前任何方法无法取代的,有较高推广实用价值。