Data Obtained from Biopsy

The protocol should specify what should be recorded directly into the CRF and what will also be recorded in the medical records. The CRF will contain all the pertinent data associated specifically with the clinical trial but some will be repeated in the medical records, for example, the protocol identification number, date of consent, date of commencement of the study, key baseline medical findings, visit dates, start and finish dates of the study drug/placebo or treatment, concurrent medication, adverse events and key efficacy and any unscheduled or scheduled actions or interventions (such as escape medication). Additional information obtained from biopsy reports, radiographs and similar documents will provide confirmation that the data in the CRF are recorded correctly. Monitors, QA auditors and inspectors need to see all the medical records available to the investigator. It is not appropriate to create copies of data from CRFs or checklists derived from medical records and claim that these are source documents. 

By combining swab and scrub test methods on the same site, differential identification of both surface and subsurface microorganisms can be obtained [60]. A study by Chevalier [18] compared results of the scrub method to results of aerobic counts obtained from biopsies with remarkable similarity in data sets. From detailed studies using the scrub test method, the percentage of different species and types can be calculated for various parts of the body [107]. Due to the aggressiveness of this method, skin damage inevitably occurs and some studies of the human skin, under dynamic conditions, are precluded. 

Scientists need to classify and organize complex data, such as that yielded by medical tests or analysis via GC-MS (gas chromatography-mass spectrometry). The data may be multifaceted and difficult to interpret, as different tests may conflict or yield inconclusive results. Growing cell structures may be used to assess medical data for example, such as that obtained from patient biopsies, and determine whether the test results are consistent with a diagnosis of breast cancer.1... 

In conclusion, skeletal myoblast implantations require better investigation into the efficacy of implantation and the viability of injected myocytes by possibly obtaining the biopsy data from... 

Fig. 9. Ductal carcinoma in situ of the breast. H MR spectra (8.5 T, 37°C) of fine-needle biopsy specimens obtained from breast ductal carcinoma in situ (a) with micro-invasion present (b) without micro-invasion. Tissue sections of DCIS were taken 100 pm apart and are shown in (a) with micro-invasion present and (b) without micro-invasion. Spectra were acquired over a spectral width of 3597 Hz, 8192 data points, 256 accumulations, and relaxation delay of 2 s. Reprinted with permission from the Journal of Women s Imaging. Lippincott Williams Wilkins 2000.

Figure 6.4 Hyperspectral FT-IR data processing performed simultaneously on four adjacent tissue sections from a cervical biopsy sample. The numbers 1 to 4 identify the individual sections in the figure, (a) A univariate chemical image obtained from the integrated area under the 1275-1190cm region after baseline subtraction (b) A four-cluster map derived from analysis over the 1272-950cm spectral window. The cluster...

More recent spectroscopic work. Most of the recent advances in IR and Raman studies of mineralized tissue have been possible as a result of improvements in data analysis and instrumentation, particularly microscopic methods that allow spectra to be obtained from micron sized regions of tissue. For example, Paschalis et al. (1996) used FTIR microspectroscopy to study the mineral/matrix, (total carbonate)/phosphate, and CO3 Type A/Type B ratios across human osteons in 10 pm steps. The resolution was 4 cm for spectra from 20 x 20 pm areas. Similar instrumentation and data analysis have been used to study changes in mineral content and composition in biopsies of non-... 

In another study using flash-frozen liver biopsies obtained from 37 insulin-resistant, obese, nondiabetic individuals [51], it was found that hepatic DAG content in cytoplasmic lipid droplets was the best predictor of insulin resistance y = 0.80, p<0.001), and it was responsible for 64% of the variability in insulin sensitivity. Mechanistic studies showed that hepatic DAG content was strongly correlated with activation of hepatic PKCe (y = 0.67, p< 0.001), which impairs insulin signaling, and that there was no significant association between insulin resistance and other putative lipid metabolites or plasma or hepatic markers of inflammation. The investigators concluded that hepatic DAG content in lipid droplets was the best predictor of insulin resistance in humans, and the data supported the hypothesis that NAFLD-associated hepatic insulin resistance is caused by an increase in hepatic DAG content, which results in activation of PKCe. 

In the United States, the threshold mercury concentration for commercial sale of fish is determined by the Food and Drag Administration, whereas consumption advice for recreational (noncommercial) fish is developed by individual states and tribes. Mercury data collected for development of fish-consumption advisories are typically from analyses of filets (axial muscle tissue, with or without skin) for total mercury, with concentrations expressed on a wet-weight basis. Analysis of filets for total mercury yields a valid estimate of MeHg concentration (Grieb et al. 1990 Bloom 1992), whether the analyzed sample consists of a large filet or a small mass of tissue obtained with a biopsy needle (Cizdziel et al. 2002 Baker et al. 2004). 

Differences in the relative proportion of f-PSA and PSA-ACT can affect the result obtained for t-PSA because of the differences in the nature of calibration and the molar response, sensitivity, and specificity of antibodies used in various immunoassays. The efficiency of these immunoassays has been evaluated by several investigators. Because the proportion of free and complexed PSA varies in benign and malignant diseases, these immunoassays measure one form or the other, giving rise to different results for different patient groups. It is very important that data from clinical studies support the proposed intended uses of these assays, since as many as 5 percent of men with a negative free PSA test (free PSA values >25 percent) will have cancer and not be recommended for biopsy. Therefore, a goal for standardization is to detect total and free PSA accurately in equimolar fractions. 

In order to obtain comprehensive evidence bearing upon the question of this variation and the degree to which it is significant and important, it would be necessary to have extensive data regarding the enzymatic make-up of different individuals including that from repeated biopsy samples and autopsy material. A large part of the pertinent data which are at present available have to do with the enzymic composition of the blood. 

Changes in the distribution of VIP-immunoreactive nerves have also been reported in airways (or airway biopsy specimens) from patients with airway disease. Ollerenshaw et al. (1989) reported finding few, if any, VIP-containing nerves in the airways of asthmatic patients in contrast, such nerves were found in the airways of non-asthmatic subjects who served as controls. These data have not been widely reproduced another group who studied the VIP content of bronchoscopically obtained airway samples from mildly asthmatic and nonasthmatic subjects was unable to detect a difference... 

Multiple surgical biopsies (0.02-0.1 g) were obtained during resections from brain tumours and from the active site and underlying white matter of patients with intractable epilepsies. Proton MR spectra were obtained on a Bruker AM 8.5 T spectrometer at 37°C. The data set consisted of the H MR spectra of tissue specimens from meningiomas (M-95 24 cases) and astrocytomas (A-74 26 cases), and intractable epilepsy as the control (E-37 8 cases). 

A different approach to improving the clinical data on the significance of drug-resistance mechanisms might be to study the development of resistance in sequential biopsy samples from the same individual(s). Although this seems attractive in principle, the reality is that, for most patients, tissue samples are not easy to obtain. With hematological tumors, repeat samples of bone marrow or lymph node biopsies obtained pre- and post-chemotherapy are a possibility. However, with solid tumors it is often unfeasible, or unethical, to attempt to obtain tissue samples after chemotherapy or at relapse. 

---