Human Subject Studies

There are several future directions that NIR brain sensing and imaging research can take. In instrumentation, advances in time-resolve spectroscopic equipment may yield less expensive equipment and thus a more prolific use. This will allow for approximation of time of flight parameter providing a possible avenue for inferring path length. Theoretically, there is a need for better theoretical modeling to eliminate crosstalk noise. Possible improvements have already been introduced by Boas, et. al [8]. However, more human subject studies need to be conducted to... 

Hue, in color analysis, see also Color Hulled grains, starch isolation, 673 Human subjects/studies. see also specific studies... 

In the past decade Raman spectroscopy has assumed an important role in musculoskeletal tissue studies, especially in bone tissue studies. Applications to a wide range of problems in basic biology, biomechanics, and medicine have appeared in the journal literature. Most workers have used cell cultures or excised bone tissue, including human biopsy and cadaveric tissue. We expect that Raman spectroscopy will become increasingly important in such studies, as more life scientists and engineers learn how to employ it. Just as importantly, recent reports of non-invasive spectroscopy suggest that Raman spectroscopy may have a role in human subjects studies of bone development, function, and disease. 

Fischman AJ, Livni E, Babich J, Alpert NM, Liu YY, Thom E et al. Pharmacokinetics of [ F]fleroxacin in healthy human subjects studied by using positron emission tomography. Antimicrob Agents Chemother 1993 37 2144-52. 

Human Subject Study with Alcohol Feeding... 

The development of precise and reproducible methods of sensory analysis is prerequisite to the determination of what causes flavor, or the study of flavor chemistry. Knowing what chemical compounds are responsible for flavor allows the development of analytical techniques using chemistry rather than human subjects to characterize flavor (38,39). Routine analysis in most food production for the quaUty control of flavor is rare (40). Once standards for each flavor quaUty have been synthesized or isolated, they can also be used to train people to do more rigorous descriptive analyses. 

Health and Safety Factors. Results of acute oral toxicity studies of 2-pyrrohdinone on white rats and guinea pigs show the LD q to be 6.5 ml,/kg. Skin patch tests on 200 human subjects indicate that 2-pyrrohdinone is a skin kritant, but there is no indication of sensitising action. It is a mild eye irritant (79). 

In normal human subjects, ANP infusion for one hour causes increased absolute and fractional sodium excretion, urine flow, GFR, and water clearance (53—55). As shown in many in vitro and in vivo animal studies, ANP achieves this by direct effect on the sodium reabsorption in the inner medullary collecting duct, ie, by reducing vasopressin-dependent free-water and sodium reabsorption leading to diuresis and by indirect effect through increased hemodynamic force upon the kidney. ANP inhibits the release of renin and aldosterone resulting in the decreased plasma renin activity and aldosterone concentration (56,57). 

Hecdth effects data come from three types of studies clinical, epidemiological, and toxicological. Clinical and epidemiological studies focus on human subjects, whereas toxicological studies are conducted on animals or simpler cellular systems. Ethical considerations limit human exposure to low levels of air poUutants which do not have irreversible effects. Table 7-1 lists the advantages and disadvantages of each type of experimental informahon. 

Sulfuric acid (H1SO4) and ammonium bisulfate (NH4HSO4) contribute importantly to ambient acid aerosols, particularly in geographic locations where sulfur-rich coal is used for power plant fuel, such as the eastern United States.Studies on animals and human subjects have shown that H2SO4 and NH4HSO4 alter mucociliary transport in a dose-dependent fashion and... 

Knockout mice have been reported for several FATPs [1]. As insulin desensitization has been closely linked to excessive fatty acid uptake and intracellular diacylgly-cerol and TG accumulation, these animal models were particularly evaluated in the context of protection from diet-induced type 2 diabetes ( Type 2 Diabetes Mellitus (T2DM)). In addition, studies on human subjects have also established genetic links between polymorphisms in FATP genes and metabolic alterations [1]. 

Efficacy (E) dealing tvith clinical studies in human subjects. 

In-vitro models can provide preliminary insights into some pharmacodynamic aspects. For example, cultured Caco 2 cell lines (derived from a human colorectal carcinoma) may be used to simulate intestinal absorption behaviour, while cultured hepatic cell lines are available for metabolic studies. However, a comprehensive understanding of the pharmacokinetic effects vfill require the use of in-vivo animal studies, where the drug levels in various tissues can be measured after different dosages and time intervals. Radioactively labelled drugs (carbon-14) may be used to facilitate detection. Animal model studies of human biopharmaceutical products may be compromised by immune responses that would not be expected when actually treating human subjects. 

The overall objective of clinical trials is to establish a drug therapy that is safe and effective in humans, to the extent that the risk-benefit relationship is acceptable. The ICH process has developed an internationally accepted definition of a clinical trial as Any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of one or more investigational medicinal product(s), and/or to identify any adverse reactions to one or more investigational medicinal product(s) and/or to study absorption, distribution, metabolism and excretion of one or more investigational medicinal product(s) with the object of ascertaining its (their) safety and/or efficacy. ... 

Name and description of the investigational product(s). A summary of findings from non-clinical sfudies and from clinioal trials that is relevant to the trial. Summary of the known and potential risks and benefits, if any, to human subjects. Description of and justification for the route of administration, dosage, dosage regimen, and treatment period(s). A statement that the trial will be conducted in compliance with the protocol, GCP and the applicable regulatory requirement(s). Description of the population to be studied. References to literature and data that are relevant to the trial, and that provide background for the trial... 

Under US regulations, each institution conducting research with human subjects must have its own IRB. These perform the same functions as the Independent Ethics Committees in Europe, and should contain at least five members, one of which should be independent of the institution. There should be available a mixture of scientific and non-scientific expertise capable of assessing research proposals from legal, ethical and scientific perspectives. The IRB must grant written authorisation to the investigator before a study can commence. They are also responsible for on-going reviews of research, and must report to the FDA ... 

The sponsor is obliged to submit safety reports for SUSAR events to the same timelines as apply in Europe. They must also report within 15 days any findings from animal studies that would suggest an increased risk to human subjects, such as carcinogenidty or mutagenidty. 

This module should contain reports of all the clinical studies and other related data that were conducted to demonstrate the safety and efficacy of the drug in human subjects. The standard headings used to present this information are shown in Figure 6.5. An example of headings for a tabulated listing of clinical studies is shown in Table 6.4. 

Bolla KI, McCann UD, Ricaurte GA Memory impairment in abstinent MDMA ( ecstasy ) users. Neurology 51 1532—1537, 1998 Borgen L, Lane E, Lai A Xyrem (sodium oxybate) a study of dose proportionality in healthy human subjects. J Clin Pharmacol 40 1053, 2000 Borgen LA, Okerholm R, Morrison D, et al The influence of gender and food on the pharmacokinetics of sodium oxybate oral solution in healthy subjects. J Clin Pharmacol 43 59-65, 2003... 

Rider JA, Puletti EJ. 1969. Studies on the anticholinesterase effects of gardona, methyl parathion, and guthion in human subjects. Fed Proc 28 479. 

Rider JA, Swader Jl, Puletti EJ. 1971. Anticholinesterase toxicity studies with methyl parathion, guthion, and phosdrin in human subjects [Abstract]. Fed Proc 30 443. 

It is generally accepted (based on clinical and in vitro studies) that mast cells (and basophils), IgE and FceRI are involved in most cases of allergen-induced anaphylaxis in humans. However, it is difficult to define the exact roles and relative importance of mast cells, basophils, and other potential effector cells (e.g monocytes/macrophages, dendritic cells) in either IgE-dependent or IgE-independent human anaphylaxis. Unlike in mice, we neither have access to mast cell- or basophil-deficient humans nor can we genetically manipulate human subjects to produce such phenotypes. 

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