Use of sonography to evaluate carotid atherosclerosis in the elderly. The Cardiovascular Health Study. CHS Collaborative Research Group

Carotid sonography is being performed on more than 5,000 participants in the Cardiovascular Health Study, a prospective, multicenter study of cardiovascular disease in men and women aged 65 years and older. The sonographic methods used to examine and measure the extracranial carotid arteries are described. Initial validation studies were performed on 61 subjects with a mean age of 68.6 years. Analysis of within- and between-sonographer differences and between-reader differences were performed for selected variables. In general, the mean absolute differences for within- and between-sonographer comparisons were small, with even less variability between readers. Variability was less for the common carotid artery than for the internal carotid artery. These data suggest that carotid sonography is a reliable and reproducible method for use in the study of carotid atherosclerosis in population studies.     

Control of interfragmentary micromotion in Ilizarov distractional osteogenesis.

Growth of the regenerate is affected by various factors during the course of Ilizarov distractional osteogenesis. One of the chief biomechanical factors that influences the quality and rate of bone formation is fixator stiffness. A four-ring Ilizarov apparatus was configured around a synthetic tibia. In a series of trials involving a uniform axial load, different transfixing wire tensions, and the separation of paired proximal and distal rings, fragment displacement was measured. Preliminary results suggest that the effect produced by the distraction of ring pairs on interfragmentary micromotion is as significant as pretensioning of the wires.     

Use of Water-Soluble Vitamins in Patients with Chronic Renal. Failure

Little is actually known about the minimum daily requirement for most vitamins in the patient with end-stage renal disease. Many of the studies reviewed suffer from lack of adequate control populations and differing methodologies, making comparisons between these studies difficult. However, patients with renal failure have many restrictions on their dietary intake, frequently suffer from intercurrent illness, and would seem to be at risk for vitamin deficiency. Also, metabolic abnormalities associated with the loss of kidney function may increase the daily requirements for certain vitamins. It is unlikely that dialysis losses of the water-soluble vitamins alone could account for vitamin depletion, and these other factors are likely to play a much more important role. It is of interest to note that the studies which demonstrate little or no vitamin deficiencies are those studies which have been carried out more recently (8, 9, 17). The patients were usually given some vitamin supplementation prior to or during the period of study and thus it is not surprising that most patients failed to demonstrate vitamin deficiency. It is also likely that heightened awareness regarding the propensity for patients with renal failure to develop deficiencies of the water-soluble vitamins has resulted in better dietary instruction and earlier intervention with vitamin supplementation. More efficient dialytic methods have also reduced the restrictions on many foods, and patients are no longer instructed to boil all their fresh vegetables. Although there may be the risk of toxicity when vitamin supplementation is overzealously administered to patients with reduced renal excretory function, it seems prudent to administer some of these water-soluble vitamins to patients with end-stage renal disease who are treated with intermittent dialysis therapy (Table 1). Certainly, this is not a very costly approach. Further studies should be carried out to better evaluate vitamin nutriture in chronically uremic and maintenance dialysis patients and to more rigorously define the minimum dose that would prevent deficiency and avoid toxicity.     

Methamphetamine dependence increases risk of neuropsychological impairment in HIV infected persons.

Both HIV infection and methamphetamine dependence can be associated with brain dysfunction. Little is known, however, about the cognitive effects of concurrent HIV infection and methamphetamine dependence. The present study included 200 participants in 4 groups: HIV infected/methamphetamine dependent (HIV+/METH+), HIV negative/methamphetamine dependent (HIV-/METH+), HIV infected/methamphetamine nondependent (HIV+/METH-), and HIV negative/methamphetamine nondependent (HIV-/METH-). Study groups were comparable for age, education, and ethnicity, although the HIV-/METH- group had significantly more females. A comprehensive, demographically corrected neuropsychological battery was administered yielding a global performance score and scores for seven neurobehavioral domains. Rates of neuropsychological impairment were determined by cutoff scores derived from performances of a separate control group and validated with larger samples of HIV+ and HIV- participants from an independent cohort. Rates of global neuropsychological impairment were higher in the HIV+/METH+ (58%), HIV-/METH+ (40%) and HIV+/METH- (38%) groups compared to the HIV-/METH- (18%) group. Nonparametric analyses revealed a significant monotonic trend for global cognitive status across groups, with least impairment in the control group and highest prevalence of impairment in the group with concurrent HIV infection and methamphetamine dependence. The results indicate that HIV infection and methamphetamine dependence are each associated with neuropsychological deficits, and suggest that these factors in combination are associated with additive deleterious cognitive effects. This additivity may reflect common pathways to neural injury involving both cytotoxic and apoptotic mechanisms.     

Blinded comparison of a direct immunofluorescent monoclonal antibody staining method and a Giemsa staining method for identification of Pneumocystis carinii in induced sputum and bronchoalveolar lavage specimens of patients infected with human immunodeficiency virus.

A new direct immunofluorescence monoclonal antibody (DFA) method (Genetic Systems, Inc., Seattle, Wash.) for identification of Pneumocystis carinii in induced sputum and bronchoalveolar lavage specimens was compared in a blinded study with an established Giemsa stain method. We evaluated 148 consecutive clinical specimens from 104 patients with the following results. For the 67 patients (64%) infected with the human immunodeficiency virus (HIV), 49 were initially negative by both the DFA and the Giemsa methods, none were negative by DFA and positive by Giemsa, 6 were positive by DFA and negative by Giemsa, and 12 were positive by both methods, for a sensitivity and a negative predictive value of greater than 99%. For the six patients positive by DFA and negative by Giemsa, all were positive by both methods on evaluation of subsequently obtained clinical specimens, suggesting a specificity of greater than 99% and a false-positive rate of less than 1%. For 37 patients whose HIV status was negative or unknown, 35 were negative by both methods and 2 were positive by DFA and negative by Giemsa. The DFA method was simple to perform and required less time for scoring of stained slides than the Giemsa method, but care had to be taken to avoid false-positive readings due to extraneous fluorescence. This study indicates that the DFA method represents an advance as a sensitive, simple, and rapid way to identify P. carinii in induced sputum and bronchoalveolar lavage specimens from HIV-infected patients and suggests greater sensitivity of the DFA than the Giemsa method in this patient population.     

A reevaluation of the duration of survival after the onset of dementia

BACKGROUND: Dementia shortens life expectancy; estimates of median survival after the onset of dementia have ranged from 5 to 9.3 years. Previous studies of people with existing dementia, however, may have underestimated the deleterious effects of dementia on survival by failing to consider persons with rapidly progressive illness who died before they could be included in a study (referred to as length bias). METHODS: We used data from the Canadian Study of Health and Aging to estimate survival from the onset of symptoms of dementia; the estimate was adjusted for length bias. A random sample of 10,263 subjects 65 years old or older from throughout Canada was screened for cognitive impairment. For those with dementia, we ascertained the date of onset and conducted follow-up for five years. RESULTS: We analyzed data on 821 subjects, of whom 396 had probable Alzheimer's disease, 252 had possible Alzheimer's disease, and 173 had vascular dementia. For the group as a whole, the unadjusted median survival was 6.6 years (95 percent confidence interval, 6.2 to 7.1). After adjustment for length bias, the estimated median survival was 3.3 years (95 percent confidence interval, 2.7 to 4.0). The median survival was 3.1 years for subjects with probable Alzheimer's disease, 3.5 years for subjects with possible Alzheimer's disease, and 3.3 years for subjects with vascular dementia. CONCLUSIONS: Median survival after the onset of dementia is much shorter than has previously been estimated.     

Taking account of between-patient variability when modeling decline in Alzheimer's disease.

The pattern of deterioration in patients with Alzheimer's disease is highly variable within a given population. With recent speculation that the apolipoprotein E allele may influence rate of decline and claims that certain drugs may slow the course of the disease, there is a compelling need for sound statistical methodology to address these questions. Current statistical methods for describing decline do not adequately take into account between-patient variability and possible floor and/or ceiling effects in the scale measuring decline, and they fail to allow for uncertainty in disease onset. In this paper, the authors analyze longitudinal Mini-Mental State Examination scores from two groups of Alzheimer's disease subjects from Palo Alto, California, and Minneapolis, Minnesota, in 1981-1993 and 1986-1988, respectively. A Bayesian hierarchical model is introduced as an elegant means of simultaneously overcoming all of the difficulties referred to above.     

Pharmacokinetics of quinolones: Newer aspects

Differences in pharmacokinetic properties are emerging as important determinants in distinguishing among clinical uses of individual new quinolone antimicrobial agents. Selected data on pharmacokinetics, new pharmacokinetic studies, and pharmacodynamics are reviewed, with reference to norfloxacin, ciprofloxacin, ofloxacin, pefloxacin, enoxacin, fleroxacin, lomefloxacin, and other new quinolones. Considering pharmacokinetics, oral bioavailability is excellent (>95 %) for most quinolones. Differences in peak serum concentrations and -half-lives of elimination exist, however, and are reflected in up to ten-fold differences in values of the area under the curve of serum concentration versus time for administration of similar drug doses. As suggested by high apparent volumes of distribution and low binding to serum proteins, penetration into many body tissues and fluids is favorable. Considering new findings, orally administered ciprofloxacin has been found to be absorbed primarily in the duodenum and jejunum. Studies also suggest this drug to be cleared by transpithelial elimination into the bowel lumen as well as by the renal route. Oral bioavailability of quinolones has been demonstrated to be in general good in ill as well as healthy subjects but is reduced on co-administration with magnesium- and aluminum-containing acids, sucralfate (which contains aluminum), or ferrous sulfate. Pharmacodynamic parameters, such as the relationship of serum concentrations and drug potency in vitro to clinical response and suppression of bacterial resistance, have been little studied and merit further investigation.     

Health administration: devolution philosophy heads towards a better tomorrow

Reorganisation preached it; the Royal Commission commended it, the new Government has welcomed it. But the 'greater degree of delegation of authority and responsibility' that is the devolutionist's dream has already come true for Claybury Mental Illness Hospital on London's periphery. What Claybyry does today others might wish to try tommorrow. Authors believe they have seen that tomorrow--and it works.