Term Studies

Other investigators have carried out longer term studies. Eight type one patients (Miranda and Horwitz, 1978) undertook two dietary periods of 10 d each. Both diets contained identical amounts of carbohydrate, fat, and protein, but one had six times as much fiber as the other. Day profiles were performed at the end of each 10 days. Plasma glucose was sig- 

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Calcium Absorption. Phytates in cereal grains have also been reported to interfere with the absorption of calcium. However, a long-term study indicated a retention of calcium in subjects that consume large amounts of bread made with high extraction of flour (19). 

Administration of 5 ppm barium, the acetate, to mice in the drinking water in a life-time study had no observable effects on longevity, mortality, and body weights, or on the incidence of tumors (53). Long-term studies in rats exposed to Ba " in drinking water containing 5 mg/L, as acetate, or 10—250 mg/L, as chloride, resulted in no measurable toxic effects (47). 

Phosphodiesterase Inhibitors. Because of the complexity of the biochemical processes involved in cardiac muscle contraction, investigators have looked at these pathways for other means of dmg intervention for CHF. One of the areas of investigation involves increased cycHc adenosine monophosphate [60-92-4] (cAMP) through inhibition of phosphodiesterase [9025-82-5] (PDE). This class of compounds includes amrinone, considered beneficial for CHF because of positive inotropic and vasodilator activity. The mechanism of inotropic action involves the inhibition of PDE, which in turn inhibits the intracellular hydrolysis of cAMP (130). In cascade fashion, cAMP-catalyzed phosphorylation of sarcolemmal calcium-channels follows, activating the calcium pump (131). A series of synthetic moieties including the bipyridines, amrinone and milrinone, piroximone and enoximone, [77671-31-9], C22H22N2O2S, all of which have been shown to improve cardiac contractiUty in short-term studies, were developed (132,133). These dmgs... 

Ibid, Toxicity ofEPIKOTE 828 Results ofPreliminaj Short-Term Studies, SheU Report TLGR.0009.77. SheU Chemical Corp., Houston, Tex., 1977. 

Supplementation with high doses of vitamin K1 (1 mg/day for 14 days) or MK-4 (45 mg/day) resulted in decreased levels of undercarboxylated osteocalcin and increase of bone formation markers and in a significant reduction in bone loss, respectively. Using such high doses, any kind of effects besides vitamin K can not yet be ruled out and have to be further elucidated by long term studies. An overview can be found in a review by Palacios [4]. 

A long-term study of tar on beaches of Bermuda indicated that the amount stranded did not differ significantly between 1971-72 and 1978-79 (34). A subsequent study, however, indicated that a significant decrease occurred between 1978-79 and 1982-83, implying that the quantity of tar in... 

Kristenson H, Ohlin H, Hulten-Nousslin M, et al Identification and intervention of heavy drinking in middle-aged men results and follow-up of 24-60 months of long-term study with randomized controls. Alcohol Clin Exp Res 7 203-209, 1983... 

Reliable lifetime TDI values cannot be derived, since long-term studies at the appropriate doses and in the appropriate species are not available. Medium-term exposure TDIs for the estimation of risk were estimated (as the chlorides) as 0.0012 mg/kg body weight for monomethyltin and dimethyltin based on neurotoxicity, 0.003 mg/kg body weight for dibutyltin based on immunotoxicity, and 0.002 mg/kg body weight for dioctyltin, also based on immunotoxicity. No reliable TDI could be derived for monobutyltin or monooctyltin. 

Brief summaries were available for unpublished long-term studies for some of the organotins under consideration. These showed no carcinogenicity for mixtures of mono- and dimethyltins in rats and mono- or... 

Figure 3-5 graphically depicts the information that currently exists on the health effects of methyl parathion in humans and animals by various routes of exposure. The available literature reviewed concerning the health effects of methyl parathion in humans described case reports of longer-term studies of pesticide workers and case reports of accidental or intentional ingestion of methyl parathion. The occupational exposure is believed to be via the dermal and inhalation routes. The information on human exposure is limited in that the possibility of concurrent exposure to other pesticides or other toxic substances cannot be quantified. 

Danner SA, Carr A, Leonard JM, Lehman LM, Gudiol F, Gonzales J, Raventos A, Rubio R, Bouza E, Pintado V et al (1995) A short-term study of the safety, pharmacokinetics, and efficacy of ritonavir, an inhibitor of HIV-1 protease, European-Australian Collaborative Ritonavir Study Group, N Engl J Med 333 1528-1533... 

Muggleton, N.G., Smith, A.J., and Scott, E.A.M. et al. (2005). A long term study of the effects of diazinon on steep, the electrocorticogram and cognitive behaviour in common marmosets. Journal of Psychopharmacology 19, 455 66. 

Pure paper-based data collection systems are most suitable for small and short-term studies. Their advantages are that no computer hardware or software is needed at the participating sites because data are recorded manually on paper forms that are transferred to the centralized location in batches. A major drawback is that participating sites do not have real-time access to their data because no database is created locally. However, both hardware and software are needed at the centralized location for the data management system. The type of hardware and software used is determined by the configuration of the centralized computer. The most commonly used platforms include Open VMS, Unix, or PC, and one of the most widely used software packages is SAS [16]. 

Short term L-acetyl carnitine treatment has shown symptomatic benefits in ATN, although it is unclear if this effect is long lasting because of neuronal regeneration or is merely an analgesic effect (Scarpini et al. 1997 Oslo et al. 2006). Longer term studies showed improvements in epidermal nerve fiber density (Hart et al. 2004) as well as the symptoms of neuropathy when patients were treated with L-acetyl carnitine (Hart et al. 2004 Herzmann et al. 2005). A short term randomized, double-blind, placebo-controlled study showed reduction in pain over a 2 week period in HIV patients with TNA (Youle and Oslo 2007). 

The initial enthusiasm for tacrine and velnacrine, which are the anticholinesterases most studied clinically, has been tempered by the fact that not all patients respond. Most show the peripheral parasympathomimetic effects of cholinesterase inhibition, e.g. dyspepsia and diarrhoea, as well as nausea and vomiting, and about half of the patients develop hepatotoxicity with elevated levels of plasma alanine transaminase. While some peripheral effects can be attenuated with antimuscarinics that do not enter the brain, these add further side-effects and the drop-out rate from such trials is high (<75%) in most long-term studies. Donepezil appears to show less hepatotoxicity but its long-term value remains to be determined. 

Beneficial or adverse effects of phytoestrogens have to be more rigorously evaluated and long-term studies are necessary for most, if not all, diseases in... 

No long-term studies of toxicity or carcinogenicity were undertaken. 

Wilson, Kent Lewis (1970) in a long-term study found that most of the soluble phosphate was eluted from the cement in the first 24 hours. By contrast the rate of elution of zinc remained constant for 160 days, the length of the study. They concluded that long-term erosion took place at the surface of the oxide particles rather than in the matrix. 

McWalter, G. K., El-Kafrawy, A. H. Mitchell, D. F. (1976). Long term study of pulp capping in monkeys with three agents. Journal of the American Dental Association, 93, 105-111. 

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