Lead susceptibility factors

Mechanism and susceptibility factors Biguanides in high doses inhibit the oxidation of carbohydrate substrates by affecting mitochondrial function. Anoxidative carbohydrate metabolism stimulates the production of lactate. High lactate production leads to lactic acidosis (type B) with a low pH (<6.95). Hyperlactatemia was common in patients taking buformin, even without alcoholism or impaired liver, kidney, or cardiac function (70). 

Pancytopenia is a rare but potentially fatal complication, and numerous reports have been published. The characteristics and incidence of pancytopenia have been carefully re-evaluated from case reports and clinical trials published from 1980 to 1995 (38). Of 70 reported cases, 12 patients died (17%). Impaired renal function was the most important contributing factor (54%), particularly in fatal cases (10/12). Other important susceptibility factors included advanced age (over 65 years), hypoalbuminemia, concurrent infection, and/or concomitant multiple medications (particularly co-trimoxazole). The mean cumulative dosage was 675 (10-4800) mg, and the minimal cumulative methotrexate dose leading to fatal pancytopenia was 10 mg. This confirms that pancytopenia can occur at any time during treatment, even in the absence of known susceptibility factors. Bone marrow biopsy showed megaloblastosis and hypocellularity. Eosinophilia and increased mean corpuscular volume were rarely observed. In an overall review of five long-term prospective studies (511 patients), the calculated incidence of methotrexate-induced pancytopenia was 1.4%. Although severe myelo-suppression sometimes required folinic acid, there are as yet no data to determine whether prophylactic folate supplementation can reduce the incidence of pancytopenia. 

Mechanism and susceptibility factors The mechanism of cisplatin-induced neurotoxicity has not been fully explained. Cisplatin appears to affect neurons in the dorsal root ganglia. It has also been suggested that it can act as a calcium channel blocker, altering intracellular calcium homeostasis and leading to apoptosis of exposed neurons, such as those of the dorsal root ganglia. Cisplatin-induced sensory neuropathy is predominantly characterized by symptoms such as numbness and tingling, paresthesia of the upper and lower extremities, reduced deep-tendon reflexes, and leg weakness with gait disturbance. The first symptoms are often observed after a cumulative dose of 300-600 mg/m. Risk factors include diabetes mellitus, alcohol consumption, or inherited neuropathies. Advanced age has not been identified as an independent risk factor when there is no co-morbidity (67-70). 

Psychological and psychiatric The incidences of psychiatric and cognitive adverse events leading to withdrawal of zonisamide and the associated susceptibility factors have been retrospectively studied in 544 consecutive patients [372 ]. These adverse reactions were the most frequently identified reason for terminating zonisamide therapy. The... 

Susceptibility factors Genetic A 5-year-old child died after being given hydrocodone bitartrate 1 mg/ml, 1 teaspoon tds [97" ]. Genetic analysis showed that the child had reduced ability to metabolize hydrocodone via CYP2D6. Co-administration of clarithromycin and valproic acid had further reduced drug elimination, leading to accumulation of lethal concentrations. 

Urinary tract Acute renal failure, usually oliguric and transient, occurs rarely after treatment with intravenous immunoglobulin the incidence is less than 1%, but it is more frequent in patients with other susceptibility factors for renal failure [39 , 40 ,43, 57 ]. This reversible reaction occurs mostly (90%) with sucrose-containing products, leading to osmotic injury and tubular damage [30, 41. ... 

Susceptibility factors Genetic Impaired platelet function due to SSRIs has been well-documented, and is associated with clinical evidence of an increased bleeding tendency. The mechanism is related to the effect of SSRIs on the serotonin transporter (5-HTTLPR) in the platelet membrane, which leads to reduced platelet serotonin concentrations however, there have been no studies of the relation of genetic polymorphisms of 5-HTTLPR to this pharmacological action. In a prospective pre-post trial of paroxetine, the effect of paroxetine was most pronounced in patients with no La alleles or only a single allele, and was most marked in those with the S/S genotype [36. ... 

Add-base balance In some patients topiramate can cause metabolic acidosis, whose susceptibility factors, underlying mechanisms, and clinical effects have been reviewed [318 ]. Topiramate impairs both the normal reabsorption of filtered HCO by the proximal renal tubule and the excretion of by the distal renal tubule. This combination of defects is termed mixed renal tubular acidosis. The mechanism involves inhibition of carbonic anhydrase. This mechanism can make patients acutely ill, and chronically can lead to nephrolithiasis, osteoporosis, and in children growth retardation. The usefulness of monitoring HCO concentrations has not been proven and is not routine. Hence, there is no proven method for predicting or preventing the effect of topiramate on acid-base balance. However, patients with a history of renal calculi or known mixed renal tubular acidosis should not receive topiramate. 

Other specific considerations of perioperative use of ACE inhibitors The risk of angioedema with ACE inhibitors is a susceptibility factor in dental and maxillofacial surgery, during which orofacial manipulation can lead to localized angioedema. This adverse effect must be recognized when edema of the face, lips, oral cavity, or larynx occurs peri-operatively in patients taking ACE inhibitors. 

Susceptibility factors A study was intended to examine whether the high Petrol-Lead Emission Areas (PLEA) would result in an increase in the incidence rate of brain cancer based on a national data bank. The national brain... 

Factors other tlian tire Si/Al ratio are also important. The alkali-fonn of zeolites, for instance, is per se not susceptible to hydrolysis of tire Al-0 bond by steam or acid attack. The concurrent ion exchange for protons, however, creates Bronsted acid sites whose AlO tetraliedron can be hydrolysed (e.g. leading to complete dissolution of NaA zeolite in acidic aqueous solutions). 

In addition to reproductive effects, fish exposed to endocrine disrupters may have a decreased response to stress or decreased growth and metabolism which can affect their ability to survive, or to defend themselves against predators. All of these factors can affect the ability of the species to survive and to reproduce itself in sufficient numbers to maintain the stocks on which our commercial and sport fisheries are based. Not all fish species will be equally susceptible to the effects of endocrine disrupters. Selective sensitivity to such effects, especially those affecting reproduction, may well lead to major changes in the flora and fauna of some of our major aquatic ecosystems as the balance between fish, mammals, invertebrates and plants, and between predators and prey, is destabilised... 

Vessels with internal components may be susceptible to turbulence in the gas mixture, which can lead to detonations, which are not covered by this procedure. Hydrogen is particularly railnerable to detonations therefore, for such systems, a specialized expert should be consulted. The details of NFPA-68 should also be consulted as there are many factors that must be recognized. Also see reference [54]. 

This example of aluminium illustrates the importance of the protective him, and hlms that are hard, dense and adherent will provide better protection than those that are loosely adherent or that are brittle and therefore crack and spall when the metal is subjected to stress. The ability of the metal to reform a protective him is highly important and metals like titanium and tantalum that are readily passivated are more resistant to erosion-corrosion than copper, brass, lead and some of the stainless steels. There is some evidence that the hardness of a metal is a signihcant factor in resistance to erosion-corrosion, but since alloying to increase hardness will also affect the chemical properties of the alloy it is difficult to separate these two factors. Thus althou copper is highly susceptible to impingement attack its resistance increases with increase in zinc content, with a corresponding increase in hardness. However, the increase in resistance to attack is due to the formation of a more protective him rather than to an increase in hardness. 

A relationship between polyol pathway activity and reduction in endothelium-dependent relaxation in aorta from chronic STZ-diabetic rats has recently been reported (Cameron and Cotter, 1992). In agreement with several previous studies (Oyama et al., 1986 Kamata et al., 1989), endothelial-dependent relaxation was defective in the diabetic rats but the deficit was prevented by prior treatment with an AR inhibitor. The mechanism underlying the defect has been speculated to be due to decreased production of endothelium-derived relaxing factor (EDRF) or nitric oxide, NO (Hattori et al., 1991). It has been speculated that these vascular abnormalities may lead to diminished blood flow in susceptible tissues and contribute to the development of some diabetic complications. NO is synthesized from the amino-acid L-arginine by a calcium-dependent NO synthase, which requires NADPH as a cofactor. Competition for NADPH from the polyol pathway would take place during times of sustained hyperglycaemia and... 

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