Requiring Consent vs. Waiving Consent for Medical Records Research: A Minnesota Law vs. the U.S. (HIPAA) Privacy Rule

The use of medical records in research can yield information that is difficult to obtain by other means. When such records are released to investigators in identifiable form, however, substantial privacy and confidentiality risks may be created. These risks become more common and more serious as medical records move to an electronic format. In 1996, the state of Minnesota enacted legislation with respect to consent requirements for the use of medical records in research. This legislation has been widely criticized because--it is claimed--it creates an unnecessary impediment to research. In this article, we show that these arguments rest upon misinterpretation and/or misrepresentation of the 1996 legislation. A consent requirement had actually been present in Minnesota since 1976 (though codified in a patient rights statute rather than a privacy statute). The 1996 law does not require specific consent, as often claimed, but rather only a general authorization. The campaign against the Minnesota legislation appears to have been motivated by concern with respect to the then impending federal privacy rule. The HIPAA rule, as enacted, is in fact less stringent with respect to consent than the Minnesota consent law. On the other hand, the Minnesota consent law has not been effectively applied or enforced. As we change the way we manage sensitive medical information, new efforts are needed to provide protection against the confidentiality risks in research. Patient consent is an important tool in this regard. New instrumentalities are needed to solicit and document consent.     

Total and free tissue factor pathway inhibitor in pregnancy hypertension.

OBJECTIVE: To clarify the role played by tissue factor pathway inhibitor (TFPI) in pregnancy hypertension. METHODS: Using enzyme-linked immunosorbent assays, hemostatic measurements were obtained for women with pre-eclampsia (n=51), nonproteinuric hypertension of pregnancy (n=62), postpartum pre-eclampsia 24 h after childbirth (n=31), and no hypertension (healthy pregnant controls, n=100). RESULTS: There was a significant increase in circulating free TFPI levels in women with pre-eclampsia (9.7+/-6.2 ng/mL) or nonproteinuric hypertension of pregnancy (8.3+/-5.3 ng/mL) compared with healthy controls (5.3+/-2.1 ng/mL). In women with pre-eclampsia the levels remained elevated after placental delivery (10.6+/-4.0 ng/mL). Free protein S levels were significantly higher in women with pre-eclampsia (40.0%+/-10.7%), nonproteinuric hypertension of pregnancy (37.1%+/-12.5%), or postpartum pre-eclampsia (39.3%+/-9.1%) than in healthy pregnant controls (32.2%+/-8.5%). CONCLUSION: Increased levels of the physiologically active free forms of TFPI and free protein S, 2 coagulation inhibitors, may protect women with pregnancy-induced hypertension from the risks of hemostatic activation.     

地塞米松对内毒素作用下人脐静脉内皮细胞表达组织因子、凝血酶调节蛋白和蛋白S的影响

目的观察地塞米松(DEX)对内毒素(LPS)作用于人脐静脉内皮细胞(HUVEC)后表达组织因子(TF)、凝血酶调节蛋白(TM)和蛋白S(PS)的影响.方法24孔板培养的第1～5代HUVEC,在含不同浓度LPS和DEX的无血清培养基中培养一定时间后裂解细胞,应用酶联免疫吸附法(ELISA)测定裂解液中的TF、TM和PS含量.结果在LPS刺激下,HUVEC表达TF的量呈剂量依赖性升高,在LPS0.1μg/ml下TF的表达量为对照组的4倍(P＜0.01),同时加入0.5 μg/ml和1.0 μg/ml DEX则可使TF的表达量由128.3±25.7 pg/105细胞分别降至94.9±19.4 pg/105细胞和98.8±7.8 pg/105细胞(P＜0.05);LPS(0.01～10μg/ml)可抑制HUVEC表达TM,在LPS 10 μg/ml下,TM表达量降至对照组的60%(P＜0.05).DEX可拮抗LPS抑制HUVEC表达TM的效应,0.1 μg/ml、0.5 μg/ml和1.0 μg/ml DEX可使LPS(10 μg/ml)作用下TM的表达量由0.282±0.014 ng/105细胞分别增至0.409±0.009、0.462±0.017和0.362±0.019 ng/105细胞(P＜0.05);LPS(0～10 μg/ml)可抑制HUVEC表达PS,在LPS浓度1.0 μg/ml及10 μg/ml时,PS的表达量分别为对照组的43%和38%(P＜0.01).DEX则拮抗LPS抑制HUVEC表达PS的效应,0.5 μg/ml DEX可使LPS刺激下PS的表达量由13.1±4.8%/2×105细胞增至48.5±10.2%/2×105细胞(P＜0.01).结论LPS促进HUVEC表达TF,抑制HUVEC表达TM和PS.DEX能部分拮抗上述作用,提示DEX可能纠正内毒素血症时的高凝状态.     

A case report of deficiency in an inhibitor of calcium-dependent association of protein S with C4B-binding protein suggested by a modified crossed immunoelectrophoresis

We have experienced a coagulation factor VIII-deficient patient whose plasma has normal protein S (PS) activity and masses of free PS and its bound form in complex with C4b-binding protein (C4BP). Although the patient's plasma showed a normal ratio of free PS to PS-C4BP complex in the presence of 5 mM EDTA, the plasma gave an abnormally retarding major C4BP peak together with a major PS peak in the crossed immunoelectrophoresis (CIE) in the presence of 2 mM CaCl₂. It was revealed that the major peak was formed by a mixture of PS-C4BP complex and free form. The addition of normal human plasma (NHP) to the patient's plasma inhibited the retardation of the major PS-C4BP complex. These suggest that the patient's plasma lacks some component(s) to inhibit Ca²⁺-dependent association of PS with C4BP.     

长链核酸扩增技术评价病毒灭活效果的研究

目的:探讨用长链核酸扩增技术评价病毒灭活效果的可行性.方法:针对伪狂犬病毒(pseudorabies virus,PRV)糖蛋白gD基因前后的保守区设计预计产物长短不一的5对引物,用半巢式PCR技术扩增经低pH法(4.0±0.1)、巴氏消毒法[(60±1.0)℃]和s/D法(有机溶剂/洗涤荆)处理后的PRV核酸,同时以细胞感染法做平行对照.结果:低pH对PRV核酸有破坏作用,处理时间越长,核酸损伤程度越明显,处理60 min时,6.62 lgTCID50的PRV完全被灭活.5条不同长度PCR扩增产物中,只有3.9 kb的长片段检出与细胞培养结果一致.7.25 lgTCID50的PRV经(60±1.0)℃处理20 min后即被完全灭活,7.13 lgTCID50的PRV经s/D法处理1 h后被完全灭活,但各长度核酸片段扩增均为阳性,与细胞感染试验结果不符.结论:低pH对PRV核酸的损伤程度随处理时间的延长而增加;用长链PCR(3.9 kb)技术来评价经低pH法灭活病毒的效果是可行的,而该法不适合评价巴氏消毒法和S/D法灭活病毒的效果.     

Co-segregation of the PROS1 locus and protein S deficiency in families having no detectable mutations in PROS1.

Inherited deficiency of protein S constitutes an important risk factor of venous thrombosis. Many reports have demonstrated that causative mutations in the protein S gene are found only in approximately 50% of the cases with protein S deficiency. It is uncertain whether the protein S gene is causative in all cases of protein S deficiency or if other genes are involved in cases where no mutation is identified. The aim of the current study was to determine whether haplotypes of the protein S gene cosegregate with the disease phenotype in cases where no mutations have been found. Eight protein S-deficient families comprising 115 individuals where previous DNA sequencing had failed to detect any causative mutations were analyzed using four microsatellite markers in the protein S gene region. Co-segregation between microsatellite haplotypes and protein S deficiency was found in seven of the investigated families, one family being uninformative. This suggests that the causative genetic defects are located in or close to the protein S gene in a majority of such cases where no mutations have been found.     

Executive functions processed in the frontal and lateral temporal cortices: Intracerebral study

OBJECTIVE: The study was designed to investigate the neurocognitive network in the frontal and lateral temporal cortices that is activated by the complex cognitive visuomotor tasks of letter writing. METHODS: Eight epilepsy surgery candidates with implanted intracerebral depth electrodes performed two tasks involving the writing of single letters. The first task consisted of copying letters. In the second task, the patients were requested to write any other letter. The cognitive load of the second task was increased mainly by larger involvement of the executive functions. The task-related ERD/ERS of the alpha, beta and gamma rhythms was studied. RESULTS: The alpha and beta ERD as the activational correlate of writing of single letters was found in the sensorimotor cortex, anterior cingulate, premotor, parietal cortices, SMA and the temporal pole. The alpha and beta ERD linked to the increased cognitive load was present moreover in the dorsolateral and ventrolateral prefrontal cortex, orbitofrontal cortex and surprisingly also the temporal neocortex. Gamma ERS was detected mostly in the left motor cortex. CONCLUSIONS: Particularly the temporal neocortex was activated by the increased cognitive load. SIGNIFICANCE: The lateral temporal cortex together with frontal areas forms a cognitive network processing executive functions.     

Differential Cellular Gene Expression in Ganglioglioma

Summary:  Purpose:  Gangliogliomas (GGs) are neuronal-glial tumors highly associated with epilepsy. We hypothesized that the expression of select gene families including neurotransmitter receptor subunits and growth factors would be distinct in neurons and astrocytes within GG compared with adjacent cortex and that these changes would yield insights into seizure onset and lesion formation.
Methods:  Candidate gene expression was defined in single immunohistochemically labeled neurons and astrocytes microdissected from GG specimens compared with neurons and astrocytes microdissected from morphologically intact cortex adjacent to the GG or normal control cortex.
Results:  Differential expression of 16 genes including glutamate transporter (EAAC1) and receptor (NMDA2C, mGluR5), growth factor (hepatocyte growth factor), and receptor (platelet derived growth factor receptor β, fibroblast growth factor receptor 3) mRNAs was detected in GG neurons compared with control neurons. In astrocytes, altered expression of p75NGF, mGluR3, TGFβ3 and Glt-1 mRNAs was detected. Nestin mRNA, a gene that exhibits enhanced expression in balloon cell cortical dysplasia, was increased in GG neurons. Because of the morphological similarities between GG and cortical dysplasia, we show that there is activation of the mTOR cascade in GG as evidenced by enhanced expression of phospho-p70S6kinase and phosphoribosomal S6 proteins.
Conclusion:  We find differential candidate gene expression in neurons and astrocytes in GG compared with adjacent cortex and show that there is activation of the mTOR pathway. These changes highlight pathways that may be pivotal for epileptogenesis and lesion growth.     

Epitope Context and Reshaping of Activated T Helper Cell Repertoire

In recent years, a growing interest in the study of peptide antigenicity in relation to the role of flanking sequences and protein topology in processing, presentation, and recognition has been observed. However, the information available on the antigenicity of recombinant fusion proteins and their effect on the selection of antigen receptor repertoires is limited. To analyze the role of molecular topology of T epitopes in a system relevant to human pathology, we have used the bacterially expressed Schistosoma japonicum glutathione S transferase (GST) to construct recombinant antigens containing HIV-1 derived T cell determinants, and human T cell clones specific for these determinants. We found that antigenicity of a given GST—peptide combination was not the same when T cells and antigen presenting cells from different individuals were tested. Our results show that differences in processing and presentation of chimeric proteins are not dictated by the use of diverse restriction elements. We also found that the context in which an antigenic peptide is delivered affects the recruited repertoire as defined according to T cell receptor Vβ usage and fine specificities of selected T cells.