Dual blockade of the renin-angiotensin system in type 1 patients with diabetic nephropathy.

BACKGROUND: Albuminuria and hypertension are predictors of poor renal and cardiovascular outcome in patients with diabetes. Approximately 30% of type 1 patients with diabetic nephropathy (DN) have albuminuria >1 g/day, and blood pressure >135 and/or >85 mmHg despite antihypertensive therapy with recommended doses of ACE inhibitor (ACEI) and diuretics. We tested the effect of dual blockade of the renin-angiotensin system (RAS) in these patients. METHODS: We performed a randomised double blind crossover trial with 2 months treatment with Irbesartan 300 mg o.d. and placebo added on top of previous antihypertensive treatment. We included 21 type 1 patients with DN responding insufficiently to ACEI and diuretics, as defined above. At the end of each treatment period, albuminuria, 24-h blood pressure and glomerular filtration rate (GFR) were measured. RESULTS: Addition of 300 mg Irbesartan to the patients' usual antihypertensive therapy induced a mean reduction in albuminuria of 37% (95% CI 20-49, P<0.001); from 1574 mg/24 h (95% CI 1162-2132) to 996 mg/24 h (95% CI 699-1419), a reduction in 24-h blood pressure of 8 mmHg systolic (95% CI -2 to 18) and 5 mmHg diastolic (95% CI 1-9) (P=0.11 and 0.01, respectively) (from placebo, mean (SE) 146 (4)/80 (2) mmHg). GFR remained unchanged. Serum potassium increased (mean 4.3 to 4.6 mmol/l, P=0.02). Intervention to reduce serum potassium was needed in two patients with GFR <35 ml/min/1.73 m(2). Otherwise the dual blockade with Irbesartan was safe and well tolerated. CONCLUSIONS: Dual blockade of the RAS may offer additional renal and cardiovascular protection in type 1 patients with DN responding insufficiently to conventional antihypertensive therapy, including recommended doses of ACEI and diuretics.     

Amplification or duplication of chromosome band 21q22 with multiple copies of the AML1 gene and mutation of the TP53 gene in therapy-related MDS and AML.

Amplification or duplication of the AML1 gene at chromosome band 21q22 was detected by FISH using a locus-specific probe in three out of 171 unselected patients with therapy-related myelodysplasia (t-MDS) or t-AML (1.7%). In two patients AML1 signals were located tandemly on derivative chromosomes, in one patient on a dic(9;21) and in the the other patient on a derivative chromosome 18 made up of interchanging layers of material from chromosomes 9, 14, 18, and 21. In the third patient three single supernumerary copies of AML1 were located on derivatives of chromosomes 19 and 21. All three patients were older, had previously received therapy with alkylating agents without topoisomerase II inhibitors, had complex karyotypes including abnormalities of chromosomes 5 or 7, and presented acquired point mutations of the TP53 gene. No point mutations of the AML1 gene were observed. The results support a pivotal role of impaired TP53 function in the development of gene amplification or duplication in t-MDS and t-AML.     

Improving toxicology testing protocols using computer simulations

Computer simulation can be used to integrate existing toxicity information within a biologically realistic framework. Simulation models calculate relevant measures of target tissue dose based on physiological, biochemical and physicochemical properties and readily support the dose, route, species and interchemical extrapolations necessary for human risk assessment. Because these models require very specific information, much of which can be obtained in vitro, they are much less dependent on extensive animal experiments than conventional risk assessment methods. With continuing development, simulation modeling will become an invaluable tool for improving experimental designs, for interpreting animal toxicity tests, and for estimating the importance of the animal toxicity observations for people.     

Effects of cooling and heating of the tooth on pulpal blood flow in man

Abstract Laser Doppler flowmetry (LDF) was used to study the changes in pulpal blood flow (PBF) evoked by application of cold or heat to the palatinal surfaces of teeth 11 or 21 in nine young subjects. Switching from a thermode temperature of 33° to 5° G on average induced a slow decrease of PBF to about 80% of control, and also warming to 39°C evoked a small reduction in most subjects. Inter individual differences were large, however, and both cooling and warming sometimes triggered a rise in PBF. In contrast, skin blood flow, as recorded with LDF in the forearm, invariably rose during warming and fell during local cooling. The results suggested a more complex interaction between local and nervously mediated effects of moderate changes in temperature in the tooth pulp than skin, and that the previous held view of cold and heat decreasing and increasing PBF, respectively, is wrong.     

人参茎叶总皂甙对实验性小鼠生殖细胞遗传物质损伤的影响

本文采用小鼠精原细胞姐妹染色单体互换（ＳＣＥ）实验方法，研究了人参茎叶总皂甙（ＧＮＳ）对丝裂霉素Ｃ（ＭＭＣ）引起的小鼠精原细胞遗传物质损伤的影响。结果表明，ＧＮＳ不能诱发小鼠精原细胞ＳＣＥ，而且在腹腔注射ＭＭＣ的同时给予ＧＮＳ，可使ＭＭＣ诱发的小鼠精原细胞ＳＣＥ频率明显降低。为此，我们认为ＧＮＳ对小鼠生殖细胞遗传物质具有保护作用。     

In vivo measurements show tensile axial strain in the proximal lateral aspect of the human femur

Two conflicting theories exist concerning the stress pattern for the proximal lateral aspect of the human femur. According to the classic theory of Pauwels, a bending moment on the femur leads to compression medially and to tension laterally. The alternative theory is that muscle forces contribute to a moment-free loading of the femur, with both the medial and lateral cortices subjected to compression. To examine these theories, we measured the strain at the external surface of the proximal lateral aspect of the femur of two female patients undergoing surgery for “snapping hip syndrome.” During the surgical procedure, a strain-gauge rosette was bonded to the lateral aspect of the femur and the cortical strains were monitored while the patient performed a series of activities. In both patients, principle tensile strain increased significantly during one-legged stance, walking, and stair climbing as compared with that during two-legged stance. During each loading situation, the principal tensile strain was aligned within 22° to the longitudinal femoral axis. Dynamic strain measurements consistently revealed tensile axial strain at the lateral aspect of the femur during each activity. The present studv supports the classic bending theory of Pauwels and demonstrates that the proximal lateral aspect of the femur is subjected to tension during the stance phase of gait.     

Diastematomyelia presenting as progressive weakness in an adult after spinal fusion for adolescent idiopathic scoliosis.

BACKGROUND CONTEXT: Diastematomyelia is uncommon and rarely presents in adulthood. This report draws attention to the fact that patients who underwent spinal fusion for deformity before the widespread use of computed tomography (CT) and magnetic resonance imaging (MRI) may have unrecognized spinal cord abnormalities. This should be considered if revision surgery is contemplated. PURPOSE: This case report focuses on the late presentation of lower-extremity weakness in a 44-year-old woman with a split cord malformation (diplomyelia), diastematomyelia and tethered cord syndrome. STUDY DESIGN/SETTING: METHODS: The patient underwent instrumented posterior spinal fusion with a Harrington rod as a child for progressive thoracolumbar scoliosis. As an adult, she developed paraparesis after a traumatic event.The patient underwent decompressive laminectomy, subtotal resection of the old fusion mass and resection of the osseous septum. Postoperatively, an anterior spinal fluid leak in the lower thoracic region required repeated fascial grafting, resection of a pseudomeningocele and reverse left latissimus dorsi flap transfer. The leak was controlled, and the patient had near complete resolution of her paraparesis 1 year after her surgery. RESULTS: The case described herein is unusual in that patients with diplomyelia and diastematomyelia rarely are symptomatic in adulthood. However, trauma may precipitate the onset of neurologic symptoms. This patient underwent spinal surgeries to address deformity, pain and progressive lower-extremity weakness. Preoperative CT and MRI studies showed a split cord malformation and diastematomyelia at L1-L2 with spinal stenosis and tethering of both hemicords. CONCLUSIONS: Progressive weakness without any previous neurologic deficit or neurocutaneous stigmas of an underlying spinal cord abnormality may develop in the adult with unrecognized diastemotomyelia. This case demonstrates that a thorough preoperative workup of patients with complex spinal deformities is imperative.     

夜间电子生物阻抗测量装置对阴茎勃起功能障碍的检测

目的 :探讨夜间电子生物阻抗测量装置 (NEVA)在阴茎勃起功能障碍的诊断中的应用价值。方法 :对 4 1例主诉阴茎勃起功能障碍者 (障碍组 ) 19例主诉无勃起功能障碍但有射精障碍者 (无障碍组 )进行NEVA检测。结果 :障碍组夜间试验中的夜间勃起的次数、阴茎勃起的最大体积改变、最长持续时间等客观指标均要差于无障碍组 ,差异有统计学意义 (P <0 .0 1)。结论 :NEVA为非侵入性检测、可鉴别心理性阴茎勃起功能障碍和严重的器质性勃起功能障碍 ,且对勃起功能障碍的定性和定量具有一定的客观性。