Subject prospects

Burger AJ, Sherman HB, Charlamb MJ, et al. Low prevalence of valvular heart disease in 226 phentermine-fenfluramine protocol subjects prospectively followed for up to 30 months. J Am Coll Cardiol 1999 34 1153-1158. 

The widespread use of biphenyl and methyl-substituted biphenyls as dye carriers (qv) in the textile industry has given rise to significant environmental concern because of the amount released to the environment in wastewater effluent. Although biphenyl and simple alkylbiphenyls are themselves biodegradable (48—50), the prospect of their conversion by chlorination to PCBs in the course of wastewater treatment has been a subject of environmental focus (51—53). Despite the fact that the lower chlorinated biphenyls are also fairly biodegradable (49,54,55) continued environmental concern has resulted in decreased use of biphenyl as a dye carrier (see Dyes, environmental chemistry). 

Chemical agents that increase the rate of grinding are an attractive prospect since their cost is low. However, despite a voluminous literature on the subject, there is no accepted scientific method to choose such aids there is not even agreement on the mechanisms by which they work. The subject has been recently reviewed [Fuerstenau, KONA Powder and Paiticle, 13,5-17 (1995)]. 

Few prospective studies of induced anaphylaxis have been performed in human subjects to imderstand the molecular basis of systemic anaphylaxis, because of the potentially rapid, Ufe-threatening outcome. Accordingly, various models of anaphylaxis have been estabUshed in laboratory animals, particularly mice, and extensively studied to clarify the underlying mechanisms. Such studies revealed that the classical pathway utilizing mast cells, IgE and histamine cannot explain all cases of anaphylaxis. 

Model equations can be augmented with expressions accounting for covariates such as subject age, sex, weight, disease state, therapy history, and lifestyle (smoker or nonsmoker, IV drug user or not, therapy compliance, and others). If sufficient data exist, the parameters of these augmented models (or a distribution of the parameters consistent with the data) may be determined. Multiple simulations for prospective experiments or trials, with different parameter values generated from the distributions, can then be used to predict a range of outcomes and the related likelihood of each outcome. Such dose-exposure, exposure-response, or dose-response models can be classified as steady state, stochastic, of low to moderate complexity, predictive, and quantitative. A case study is described in Section 22.6. 

Clearly the improved understanding of colloidal behaviour within living systems that we are developing offers the eventual prospect of our being able to manipulate such systems. The control of microarchitecture in both living and synthetic systems has many potential applications. The most important aspect is the ability to define the particular conditions under which a certain pattern or structure will be formed such that the products will be uniform. This clearly happens in Nature, but natural systems have been subject to trial and error for considerably longer than any experiment involving synthetic systems. 

Currently, treatment of DSP and ATN is similar to many other neuropathies that have predominantly painful sensory involvement (Mendell and Sahenk 2003 Gonzalez-Duarte et al. 2007). It is purely symptomatic as there are no proven regenerative therapies to reverse the underlying process. An 8-month prospective pilot study reported an improvement in subjective quantitative sensory testing (QST) in HIV-infected patients who responded to HAART (Martin et al. 2000). The patients who did not respond to HAART did not show any improvements in QST. It is possible that suppression of viral load will slow the progression of DSP. Some studies have found a correlation between viral load and incidence (Childs et al. 1999), or severity (Simpson et al. 2002) of sensory neuropathy. Others, however, did not find any correlation between plasma viral loads and incidence of DSP or ATN (Brew et al. 2003). 

The bulk of this paper will be concerned with the prospects of Ji-nitroso compound formation in the environment, and with environmental behaviors of selected nitroso compounds, as best we can describe or predict them from experimental work completed thus far. Obviously, once in the environment, a compound will to a large extent be subject to the same conditions whether it was formed there or introduced as a pesticide contaminant, and in this manuscript no attempt to differentiate between the two modes of introduction has been made. Such distinctions could, however, influence the location of a compound in the environment—say on a plant or soil surface if sprayed with a pesticide, admixed with soil if transported by leaching, etc., and some of the experiments cited will have been conceived with one or the other of the introduction modes in mind. 

A prospective, randomized, placebo-controlled trial of paroxetine in adults with chronic post-traumatic stress disorder (PTSD) was recently conducted (Marshall etal., 2007). The subjects were New Yorkers, predominantly female (67%) and Hispanic (65.4%). Seventy subjects entered the study and after a one week placebo lead-in, 52 subjects were randomized to placebo or paroxetine for ten weeks. The subjects were treated with a flexible dosage design (mean dosage, 40.4 mg/day). Dropout rates were 32% for paroxetine and 51.9% for placebo. There were no differences in rates of adverse effects between treatment arms. Paroxetine was superior to placebo in ameliorating the primary symptoms of PTSD (56% vs. 22.2%). 

Interim results of an investigation of 185 subjects and later results from the complete follow-up sample of 305 subjects in a prospective study of inner-city children (>80% black) bom in Cincinnati, Ohio, were reported by Dietrich et al. (1986, 1987a, 1987b). Maternal PbB levels were measured at the first prenatal visit cord PbB was measured at delivery infant PbB levels were measured at 10 days and at 3 months of age and neurobehavioral tests were performed at 3 and 6 months of age. Mean PbB levels were as follows prenatal (maternal)—8.0 pg/dL (range, 1-27 pg/dL) umbilical cord—6.3 pg/dL (range,... 

An analysis of eight cross-sectional and/or prospective studies which reported tooth lead and PbB levels of the same children found considerable consistency among the studies (Rabinowitz 1995). The mean tooth lead levels ranged from under 3 to over 12 pg/g. In a study of 63 subjects, dentin lead was found to be predictive of concentrations of lead in the tibia, patella, and mean bone lead 13 years after tooth lead assessment in half of them (Kim et al. 1996b). The authors estimated that a 10 pg/g increase in dentin lead levels in childhood was predictive of a 1 pg/g increase in tibia lead levels, a 5 pg/g in patella lead levels and a 3 pg/g increase in mean bone lead among the young adults. 

Wolbachia endosymbionts are abundant in arthropods, where they promote a variety of reproductive manipulations, including feminization of genetic males, parthenogenesis and cytoplasmic incompatibility. Wolbachia is also present in filarial nematodes and has recently attracted a great deal of attention. This chapter reviews the studies so far published and discusses potential implications and future research prospects. Since this is a relatively young field, the chapter will also refer to unpublished studies and will include some speculation. The aim is to stimulate further work on the subject. 

Under these circumstances, it may be unrealistic to expect research subjects to give scientists their DNA, family histories, and medical records for free. If the scientists are looking for millions, prospective research subjects may well wonder why their contribution should be uncompensated. On the other hand, it is extremely rare that any one individual research subject leads to a genetic breakthrough. Locating and cloning disease genes usually requires contributions of medical histories and DNA from thousands of subjects. Any one subject who held out for payment could be bypassed. 

Although there are several ethical concerns with biobanks and other large-scale research repositories (Rothstein, 2002), the most important issue is informed consent. Participants in research involving human subjects must be advised of the intended research to be performed with their specimens. With biobanks, however, the future research uses of the samples are unknown at the time of collection. It would be infeasible to contact each of the donors to obtain consent every time a new research use is contemplated, yet IRBs are reluctant to approve the use of blanket consent for unspecified uses. One way to avoid this problem is for prospective sample donors to be given a menu of possible uses of their samples. Such a list might include research in mental health, HIV/AIDS, cancer, cardiovascular disease, or other areas. The donors would then have the opportunity to approve the use of their specimens for all or some of the listed uses. Other disclosures necessary to obtain informed consent include the financial interests of the biobank and researchers, whether individuals may elect to be notified of research findings, and whether it is possible for an individual to withdraw his or her sample from the bank (Rothstein, 2002). 

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