Journal of Investigative Medicine

Clinical researchers need to share data to support scientific validation and information reuse and to comply with a host of regulations and directives from funders. Various organizations are constructing informatics resources in the form of centralized databases to ensure reuse of data derived from sponsored research. The widespread use of such open databases is contingent on the protection of patient privacy.

We review privacy-related problems associated with data sharing for clinical research from technical and policy perspectives. We investigate existing policies for secondary data sharing and privacy requirements in the context of data derived from research and clinical settings. In particular, we focus on policies specified by the US National Institutes of Health and the Health Insurance Portability and Accountability Act and touch on how these policies are related to current and future use of data stored in public database archives. We address aspects of data privacy and identifiability from a technical, although approachable, perspective and summarize how biomedical databanks can be exploited and seemingly anonymous records can be reidentified using various resources without hacking into secure computer systems.

We highlight which clinical and translational data features, specified in emerging research models, are potentially vulnerable or exploitable. In the process, we recount a recent privacy-related concern associated with the publication of aggregate statistics from pooled genome-wide association studies that have had a significant impact on the data sharing policies of National Institutes of Health-sponsored databanks.

Based on our analysis and observations we provide a list of recommendations that cover various technical, legal, and policy mechanisms that open clinical databases can adopt to strengthen data privacy protection as they move toward wider deployment and adoption.

Oxidative stress plays an important role in the pathogenesis of diabetic nephropathy (DN). This study examined if use of N-acetylcysteine for a month in moderate doses would reduce the oxidative stress in patients with DN and reduce the proteinuria.

Fifteen volunteers with DN participated in the study. Participants took capsule form of N-acetylcysteine 1 gm twice a day for a month. Spot urines were collected and tested for protein/creatinine on days 1 and 30. Sera were collected on days 1, 15, 30, and 60 and tested for several oxidative stress biomarkers.

There was no significant change in proteinuria or any of the oxidant stress markers at any point: protein-creatinine ratio (day 1, 1.6 ± 1.8; day 30, 1.3 ± 1.3), 8-isoprostane (day 1, 5.9 ± 4.2 pg/mL; day 15, 4.67 ± 2.4 pg/mL; day 30, 5.1 ± 2.8 pg/mL; and day 60, 4.7 ± 1.9 pg/mL), total antioxidant status (day 1, 1.5 ± 0.1 mM; day 15, 1.6 ± 0.2 mM; day 30, 1.5 ± 0.1 mM; and day 60, 1.5 ± 0.2 mM), aconitase (day 1, 7.9 ± 5.9 mU/mL; day 15, 10.1 ± 5.9 mU/mL; day 30, 8.9 ± 6.2 mU/mL; and day 60, 7.8 ± 5.5 mU/mL), glutathione peroxidase (day 1, 261.4 ± 56.4 mU/mL; day 15, 263.9 ± 57.2 mU/mL; day 30, 269.2 ± 66.0 mU/mL; and day 60, 257.5 ± 48.2 mU/mL), and superoxide dismutase (day 1, 242.6 ± 79.3 mU/mL; day 15, 252.1 ± 68.1 mU/mL; day 30, 262.0 ± 73.3 mU/mL; and day 60, 255.7 ± 61.5).

However, 4 patients with initial high isoprostane levels showed nonsignificant decline at each subsequent time point.

N-acetylcysteine in moderate doses given over a month did not have significant effect on the overall oxidative stress in patients with DN and did not reduce proteinuria.

The bladder's regulatory function is influenced by central serotonergic modulation. T102C polymorphism of the serotonin 2A (5-HT_2A) receptor gene is associated with urinary incontinence (UI) that has been reported by older community dwellers. We analyzed the association between 5-HT_2A receptor gene polymorphism and urodynamic tests for UI in older women.

A case-control study was performed with 68 older women submitted to urodynamic evaluation and 162 older women without urinary problems (self-reported), all community dwellers enrolled in the Gravataí-GENESIS Project, Brazil. Clinical interviews, complete urodynamic evaluation following the International Continence Society Report on Good Urodynamic Practice (case group), and molecular analyses were performed (case and control groups). Serotonin 2A receptor gene genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism using the restriction enzyme HpaII. We excluded patients with diabetes mellitus, neurologic damage, and diuretic intake.

The subjects' mean (SD) age was 68.1 (6.5) years (range, 60-92 years). We found an association between the TT genotype versus CC + CT genotypes and UI (P = 0.013; odds ratio, 2.69; 95% confidence interval, 1.37-5.29) and, in addition, an association with urgency UI, maximal cystometric capacity (TT, 349 mL; CC + CT, 429.5 mL [P = 0.047]), detrusor pressure at maximum cystometric capacity (TT, 11 cm H₂O; CC + CT, 6.75 cm H₂O [P = 0.032]), and detrusor compliance (TT, 34 mL/cm H₂O; CC + CT, 61.25 mL/cm H₂O [P = 0.006]).

We confirmed our previous findings of a genetic influence of the TT genotype on UI involving the serotonergic pathway among older women. Further investigations including 5-HT_2A expression in the bladder, pelvic floor, and striated sphincter muscle must be performed.

To investigate the potential influence of nuclear factor κB (NF-κB) activation on the inflammatory mediators secreted by alveolar macrophages (AMs) in rats with acute necrotizing pancreatitis (ANP) and to evaluate the effect of an inhibitor of NF-κB-N-acetylcysteine (NAC).

Ninety male Sprague-Dawley rats were randomly divided into 3 groups, 30 of each: control, ANP, and ANP plus NAC groups. The ANP rat models were established by a retrograde injection of 5% sodium taurocholate into the pancreatic duct. In addition to sodium taurocholate, the ANP plus NAC group received intravenous infusion of NAC (25 mg/100 g). At the sixth hour after modeling, the protein content of the bronchoalveolar lavage fluid, the myeloperoxidase in the lung tissue, and the transforming growth factor α and the nitric oxide (NO) secreted by AMs were determined. The histopathologic changes of the pancreas and the lung were observed under light microscope, and NF-κB activation of AMs was detected.

The protein content of the bronchoalveolar lavage fluid and the myeloperoxidase level of the lung tissue showed a significant increase in the ANP group as compared with the NAC-administered group. The levels of transforming growth factor α and NO secreted by AMs in the ANP and the ANP plus NAC group rose significantly over that in the control group, and there was a significant difference between them. Although they were still higher than those in the control group, the pancreas destruction and the lung injury were slighter in the ANP plus NAC group and the activation of NF-κB was lower in the ANP plus NAC group as compared with that in the ANP group.

The correlation between the NF-κB activation, the up-regulation of the inflammatory mediators secreted by AMs, and the tissue damage suggests a key influence of NF-κB in the pathogenesis of ANP. Inhibition of NF-κB activation may reverse the lung injury of ANP.