End-organ Impairment Research Articles

QT prolongation with antimicrobial agents: understanding the significance.

Cardiac toxicity has been relatively uncommon within the antimicrobial class of drugs, but well described for antiarrhythmic agents and certain antihistamines. Macrolides, pentamidine and certain antimalarials were traditionally known to cause QT-interval prolongation, and now azole antifungals, fluoroquinolones and ketolides can be added to the list. Over time, advances in preclinical testing methods for QT-interval prolongation and a better understanding of its sequelae, most notably torsades de pointes (TdP), have occurred. This, combined with the fact that five drugs have been removed from the market over the last several years, in part because of QT-interval prolongation-related toxicity, has elevated the urgency surrounding early detection and characterisation methods for evaluating non-antiarrhythmic drug classes. With technological advances and accumulating literature regarding QT prolongation, it is currently difficult or overwhelming for the practising clinician to interpret these data for purposes of formulary review or for individual patient treatment decisions. Certain patients are susceptible to the effects of QT-prolonging drugs. For example, co-variates such as gender, age, electrolyte derangements, structural heart disease, end organ impairment and, perhaps most important, genetic predisposition, underlie most if not all cases of TdP. Between and within classes of drugs there are important differences that contribute to delayed repolarisation (e.g. intrinsic potency to inhibit certain cardiac ion currents or channels, and pharmacokinetics). To this end, a risk stratification scheme may be useful to rank and compare the potential for cardiotoxicity of each drug. It appears that in most published cases of antimicrobial-associated TdP, multiple risk factors are present. Macrolides in general are associated with a greater potential than other antimicrobials for causing TdP from both a pharmacodynamic and pharmacokinetic perspective. The azole antifungal agents also can be viewed as drugs that must be weighed carefully before use since they also have both pharmacodynamic and pharmacokinetic characteristics that may trigger TdP. The fluoroquinolones appear less likely to be associated with TdP from a pharmacokinetic perspective since they do not rely on cytochrome P450 (CYP) metabolism nor do they inhibit CYP enzyme isoforms, with the exception of grepafloxacin and ciprofloxacin. Nonetheless, patient selection must be carefully made for all of these drugs. For clinicians, certain responsibilities are assumed when prescribing antimicrobial therapy: (i) appropriate use to minimise resistance; and (ii) appropriate patient and drug selection to minimise adverse event potential. Incorporating information learned regarding QT interval-related adverse effects into the drug selection process may serve to minimise collateral iatrogenic toxicity.

Brain metabolic function in older men with chronic essential hypertension.

BACKGROUND AND METHODS. To determine the effects of hypertension on brain function, positron emission tomography (PET) studies using (18F)-2-fluoro-2-deoxy-D-glucose (FDG) were performed on a group of 17 otherwise healthy older hypertensive men (mean age +/- SD = 69 +/- 8 yr) and 25 age- and gender-matched controls. Subjects had medically treated essential hypertension for a minimum of 10 years (range = 10 to 24 yr) with no evidence of end-organ impairment from hypertension by routine clinical screening and by history. All hypertensive and control subjects were determined to be cognitively normal by extensive neuropsychological testing. The hypertensive subjects previously had been reported to have lateral ventricle enlargement and left hemisphere brain atrophy by quantitative MRI. PET data were analyzed using t-tests to look at group differences.

5-Year follow-up study of children with low-to-moderate lead absorption: Electrophysiological evaluation

Forty-nine children aged 6 to 12 years were evaluated for residual effects of lead exposure using psychometric, electrophysiological, and medical tests 5 years after initial assessment. The original range of blood lead (PbB) levels was 6–59 ( x ̄ = 28 ) μg/dl; the current range was 6–30 ( x ̄ = 14 ) μg/dl. A linear relationship between PbB and slow brain wave voltage during sensory conditioning was observed at initial evaluation and at 2-year follow-up. No significant relationship between PbB and slow wave voltage during passive conditioning was found at the 5-year follow-up, although a linear increase in slow wave negativity relative to the current PbB level during active conditioning was suggested by exploratory analyses. Another exploratory analysis revealed a significant linear relationship between the original PbB levels and the latency of waves III and V of the brainstem auditory evoked potential. The latency of both waves increased as a function of original PbB. Increased latency of these waves is suggestive of subclinical pathology of the auditory pathway rostral to the cochlear nucleus, although end-organ impairment cannot be ruled out. No threshold for the effect of Pb on auditory function was apparent.

Auditory processing disorders and problems with Hearing-Aid fitting in old age

The hearing handicap experienced by elderly subjects depends only partially on end-organ impairment. Not only the neural unit loss along the central auditory path-ways contributes to decreased speech discrimination, but also learning processes are slowed down. Diotic listening in elderly people seems to fasten learning of discrimination in critical conditions, as in the case of sensitized speech. This fact, and the binaural gain through the binaural release from masking, stress the superiority, on theoretical grounds, of binaural over monaural hearing-aid fitting.

Auditory processing disorders and problems with Hearing-Aid fitting in old age

The hearing handicap experienced by elderly subjects depends only partially on end-organ impairment. Not only the neural unit loss along the central auditory pathways contributes to decreased speech discrimination, but also learning processes are slowed down. Diotic listening in elderly people seems to fasten learning of discrimination in critical conditions, as in the case of sensitized speech. This fact, and the binaural gain through the binaural release from masking, stress the superiority, on theoretical grounds, of binaural over monaural hearing-aid fitting.