Renal disease from habitual antipyretic analgesic consumption: an assessment of the epidemiologic evidence.

The quantitative evidence relating habitual antipyretic analgesic consumption to the development of renal disease is reviewed. For purposes of analysis, "abuse" of analgesics is defined as regular, usually daily consumption. The prevalence of habitual consumption demonstrates marked geographic variation for poorly defined reasons. Prevalence tended to be highest in those populations in which phenacetin was available and popular. The prevalence of nephropathy among habitual consumers also shows marked interpopulation variability. A highly significant linear relationship exists between the prevalence of habitual analgesic consumption in a given population and the prevalence of nephropathy in the subset of that population that habitually consumes analgesics. This relationship may represent a dose-response curve relating amount of analgesic intake to prevalence of nephropathy. Four cross-sectional studies, 1 longitudinal, and 1 case-control study have shown significant differences in prevalence of nephropathy between habitual users of phenacetin-containing analgesics and control populations. Conversely, 2 cross-sectional studies and 1 case control study showed no difference between habitual users of analgesics and control populations. However, those studies showing no difference were performed in populations with low prevalence of habitual consumption of compound analgesics and a lower prevalence of nephropathy than was found in those populations where differences were observed. The relative risk for developing various manifestations of analgesic nephropathy has been estimated in 4 studies and varies depending on which abnormality is considered. Data are available only for subjects consuming phenacetin-containing compound analgesics. The relative risk for elevated serum creatinine is in the range of 8 to 11, about twice that for an abnormal renal concentrating test (approximately 4). The relative risk for clinical papillary necrosis is approximately 18, and for cause-specific death (and by inference for end-stage renal disease) about 4. The difference in risk between most clinical manifestations of analgesic nephropathy and death (or end-stage renal disease) may be due to the fact that most patients with nephropathy do not progress to terminal renal failure. Rheumatology clinic studies indicate that the prevalence of nephropathy in habitual consumers of phenacetin-containing compounds is higher than that for habitual consumers of aspirin alone. Removal of phenacetin from compound analgesics in Scandinavian countries appears to have reduced the prevalence of papillary necrosis and death from interstitial nephritis.(ABSTRACT TRUNCATED AT 400 WORDS)

Extending the extenders. Compromise for the geriatric specialization-manpower debate.

This pilot study reports on issues germane to the geriatric specialization-manpower debate. The study found that a large amount of the functional responsibility required by older adults in an urban clinic setting could be delegated to physician extenders. Other findings included shorter hospitalizations, increased feelings of well-being, and high patient satisfaction with physician extended care. The implications are that rather than develop a new physician specialty, more geriatric manpower needs could be met by delegating responsibility to appropriately trained and supervised physician extenders.

Premature rupture of membranes: a prospective, randomized evaluation of steroids, latent phase, and expectant management.

A prospective, randomized study was conducted comparing the use of betamethasone and early delivery, early delivery alone, and expectant management in patients in the 28th to 34th week of pregnancy with premature rupture of the membranes (PROM). Tocolytic drugs were used to delay delivery until 24 hours had elapsed after the first dose of steroid or 24 to 48 hours of latent period had elapsed in the second group. There were no significant differences in maternal age, gestation at PROM, maximum maternal temperature, birth weights, maternal hospital days, respiratory distress, maternal sepsis, or delivery routes in the three groups. Comparisons with one other similar prospective, randomized study support the concept that expectant management offers less risk from tocolytic side effects.

Studies of low density lipoprotein molecular weight in human beings with coronary artery disease.

Low density lipoprotein molecular weight (LDL MW) correlates positively with coronary artery disease in cholesterol-fed nonhuman primates. To evaluate this in human beings with coronary artery disease (CAD) we measured LDL MW in 93 volunteers undergoing coronary angiography (47 controls and 46 CAD patients). LDL MW of CAD patients was less than that of controls (patients, 2.79 +/- 0.17 g/mumol; controls, 2.93 +/- 0.19 g/mumol; P less than 0.001). However, LDL MW decreased as plasma triglyceride increased and concentrations of triglyceride were greater in CAD patients than in controls. Since decreased LDL MW is likely to result, in part, from increased plasma triglyceride concentrations, we attempted to determine the effect of triglyceride on the relation of LDL MW to CAD in this study. After covariance adjustment for triglyceride, there was no LDL MW difference between CAD patients and controls. Because LDL heterogeneity has been identified in other studies and was apparent on inspection of agarose column profiles of LDL of these volunteers, we sought differences in the profiles that might distinguish coronary disease cases from controls. No differences could be found. In addition, we used density gradient ultracentrifugation to characterize LDL in more detail in a subset of volunteers who had a wide range of plasma triglyceride concentrations (50 mg/dl to 900 mg/dl). LDL mean hydrated density was inversely related to LDL MW and increased as triglyceride increased. The increase in peak density was reflected in an increase in percent of total protein in LDL found to have d greater than 1.045 g/ml and a decrease in protein in LDL of d 1.035-1.040 g/ml. These interrelationships were not apparently influenced by coronary artery status.

Comparison of tissue reactions produced by Haemophilus pleuropneumoniae vaccines made with six different adjuvants in swine.

Tissue damage caused by six different adjuvants incorporated in a Haemophilus pleuropneumoniae vaccine was compared in swine. The adjuvants compared were four mineral oil compounds, one peanut oil compound and aluminum hydroxide. Inoculations were given in the neck, quadriceps and semitendinosus muscles. The mineral oil adjuvants were highly irritant and caused extensive areas of granulomatous inflammation that were present at eight weeks after injection. The aluminum hydroxide produced smaller lesions that also persisted for eight weeks. Only the peanut oil adjuvant did not produce significant lesions at the site of injection. At two and four weeks, but not at eight weeks postinoculation, lesions in the quadriceps and semitendinosus muscles were approximately twice as extensive as those in the muscles of the neck.

The relationship between weight-height indices and the triceps skinfold measure among children age 5 to 12.

This study examines several weight for height indices--Quetelet's index W/H2, W/H, and Rohrer's index W/H3--for their appropriateness in estimating adiposity among young children. Data were obtained for a sample of 1,668 children age 5-12 residing in Forsyth County, North Carolina. Although W/H2 was found to be the most useful of these indices, the results suggest that no index, including the tricep skinfold measure, can be considered completely satisfactory in estimating adiposity among children.

An approach to the noninvasive periodic assessment of arterial elasticity in the young.

The detailed variation of the lumen diameter of common carotid arteries throughout the cardiac cycle was noninvasively measured using a pulse-echo ultrasonic technique in a population of 100 free-living, unrelated, human subjects between the ages of 6 and 25 years. The fractional diameter change (mean +/- SEM) during the cardiac cycle in the 50 male subjects (0.122 +/- 0.004) was found to be significantly (P less than 0.001) greater than the corresponding diameter change in the 50 female subjects (0.106 +/- 0.003). The pressure-strain elastic modulus, Ep, for the carotid arteries was also computed for these subjects by dividing the blood pulse pressure measured in the brachial artery by the fractional diameter change of the carotid. The male elastic modulus (67 +/- 3 kPa) was not significantly (P approximately 0.17) different from the female elastic modulus (62 +/- 2 kPa). Subject age and systolic blood pressure were able to explain approximately one-third of the variability in Ep. Reproductibility studies clearly demonstrated that only a small fraction of the remaining variability could be attributed to experimental technique or intrasubject variability. The results suggest that studies can now be safely performed on young human subjects to assess the effects of a variety of developmental, behavioral, and environmental factors on arterial elasticity. Such results could help to establish an important data base on arterial mechanics which might help in evaluating health promotion recommendations to societies.

Weight-for-height indices as measures of adiposity in children.

This study examines the weight-for-height index q = w/h lambda where the parameter lambda is chosen to maximize the correlation of q with triceps skinfold thickness, and thus provide an indirect measure of adiposity. Using a sample of 1668 children ages 5-12 years, we estimate lambda by an iterative procedure in each age/sex category. We find that lambda does not vary simply across the age/sex categories, and that the correlation of q and skinfold thickness is never more than marginally greater than that of the Quetelet index w/h2. We indicate that almost identical properties will be evidenced by the more general two-parameter index w alpha/h beta. Our conclusion is that there is no weight-for-height index generally useful as an indirect measure of adiposity in children.

Single versus biplane right and left ventricular volumetry: a cast and clinical study.

True volume (y) and measured volume (x) determined from 23 right and 22 left normal human casts in four biplane angiographic positions and in their eight single-plane components were used to find the correction factor (b) by regression through the origin (y = bx). The correction factors were applied to human studies to assess the validity of the various biplane and single-plane modalities in vivo. The casts studies yield excellent correlations in both right and left biplane methods (right volumetry: 0.555 less than or equal to b less than or equal to 0.708, 0.917 less than or equal to r less than or equal to 0.954, 4.10 less than or equal to SEE less than or equal to 6.01 left volumetry: 0.748 less than or equal to b less than or equal to 0.825, 0.974 less than or equal to r less than or equal to 0.982, 4.81 less than or equal to SEE 5.79). Good results were obtained with single-plane volumetries as well (right volumetry: 0.316 less than or equal to b less than or equal to 0.887, 0.750 less than or equal to r less than or equal to 0.917, 10.75 less than or equal to SEE less than or equal to 18.96; left volumetry: 0.728 less than or equal to b less than or equal to 0.881, 0.897 less than or equal to r less than or equal to 0.976 5.73 less than or equal to SEE less than or equal to 11.97). The correction factors for the single-plane studies depend much more strongly on the spatial position relative to the radiographic system, particularly in the case of the right ventricular volumes. Thus, the application of the appropriate correction factors is mandatory. The human studies (141 left and 60 right volumetric studies in various single-plane and biplane projections) showed a larger scatter of single-plane values, more pronounced for the right ventricle. In certain disease conditions, single plane volumetric studies using cast-derived correction factors cannot be used to obtain meaningful results. Correction factors for the following single or biplane mode volumetry are presented for the first time: biplane hepatoclavicular view (right and left ventricle), biplane long axial oblique view (right ventricle), and their single-plane components; lateral and 60 degree Left Anterior Oblique (LAO) single plane for the left-sided measurements, Postero-Anterior (PA), lateral, and 60 degree LAO for the single-plane right-sided calculations.

Is a left ventricular vent necessary for coronary artery bypass operations performed with cardioplegic arrest?

The need for ventricular venting with hypothermic cardioplegic arrest is controversial. We report an evaluation of the need for left ventricular venting in a canine model that closely simulates conditions during routine coronary artery bypass grafting (CABG). Thirty-five dogs were placed on cardiopulmonary bypass for 60 minutes of hypothermic cardioplegic arrest (18 vented, 17 nonvented) and then reperfused for 30 minutes. Myocardial temperature and left atrial pressure (LAP) were recorded continuously. Before and 30 minutes after hypothermic cardioplegic arrest, left ventricular function curves were generated (six vented, six nonvented), and biopsy specimens of the left ventricle were taken for adenosine triphosphate (ATP) determinations (11 vented, 10 nonvented) and semiquantitative grading of mitochondrial ultrastructure (six vented, six nonvented). LAP in nonvented dogs was 7.4 mm Hg during hypothermic cardioplegic arrest and 5.0 mm Hg during reperfusion. Temperature during hypothermic cardioplegic arrest was 12.3 degrees C in vented dogs and 11.3 degrees C in nonvented dogs (p = 0.5). There were no differences in left ventricular function or preservation of mitochondrial ultrastructure between vented and nonvented dogs. ATP after hypothermic cardioplegic arrest was 96.6% of control (4.30 microM/gm) in vented dogs and 94.6% (4.37 microM/gm) in nonvented dogs (p = 0.7). The absence of left ventricular venting did not lead to ventricular distention or more rapid rewarming. These data in vented dogs and nonvented dogs strongly support the belief that left ventricular venting is not necessary during routine CABG.

Objective measurement of physical activity in Macaca fascicularis.

The mean and standard deviation over 24 h for 3 groups of animals - active, intermediate and inactive - in physical activity units were 10948 +/- 3360, 2611 +/- 1973 and 484 +/- 316 respectively. The differences were significant (P = 0.004), demonstrating the ability of the method to distinguish between groups that can be visibly differentiated. The small within-animal physical activity standard deviation (18.85 PAU) obtained in another group, suggests that it also yields reliable physical activity measurements for non-human primates. The monitoring device used can discriminate between individual nonhuman primates physical activity levels in a free-living environment and does not alter daily behaviour. This makes possible the study of the relationship between physical activity and atherosclerosis in nonhuman primates.

A comparison of height, weight, and triceps skinfold thickness of children ages 5-12 in Michigan (1978), Forsyth County North Carolina (1978), and HANES I (1971-1974).

Height, weight, and triceps skinfold measurements were made on 1,668 Forsyth County, North Carolina students ages 5-12 during 1978. These data were compared to a representative sample of Michigan children taken during the same year and to their United States counterparts in HANES I (1971-74). The North Carolina children more closely resembled their US counterparts than did the Michigan group, casting doubt on the secular trend toward heavier children suggested by the Michigan researchers. (Am J Public Health 1982; 72:730-733.)

Breast cancer in hospitalized psychiatric patients.

Elevated serum prolactin levels caused by antipsychotic agents have been suspected of increasing the risk of breast cancer. The authors reviewed all the cases of breast cancer in 1969-1978 among the female population of a large psychiatric hospital and compared the incidence and prevalence rates of this group to expected rates. The rates of breast cancer among these psychiatric patients were not higher despite their use of antipsychotic drugs.

Analgesic-associated nephropathy and transitional cell carcinoma of the urinary tract.

Epidemiologic studies from Europe suggest that patients with analgesic-associated nephropathy have an increased risk of developing transitional cell carcinoma of the urinary tract. We did a similar epidemiologic study supporting this association. Six of 115 cases of transitional cell carcinoma diagnosed over 3 years had analgesic-associated nephropathy. The patients were predominantly female, younger, and had renal pelvis tumors instead of bladder tumors (P < 0.002), an mortality rate was higher (P < 0.05). In a historical prospective study, 146 patients with interstitial nephritis diagnosed between 1974 and 1976 were divided into those with and those without analgesic-associated nephropathy. In 4 of 84 patients with analgesic-associated nephropathy transitional cell carcinoma has developed. None of the 98 patients without analgesic associated nephropathy have developed transitional cell carcinoma (P < 0.001). These data strongly incriminate analgesic abuse as a risk factor for the development of transitional cell carcinoma.

Prevalence rate of renal stone disease in Forsyth County, North Carolina during 1977.

A count of all recorded hospitalized cases of Forsyth County, North Carolina residents with a primary discharge diagnosis of renal (kidneyand/or ureteral) stone in 1977 is obtained by age, race and sex, and used in conjunction with the census data to estimate age-adjusted prevalence rates. The over-all prevalence rate is 2.08 per thousand population, which agrees well with results of earlier investigations. For white male subjects the age-adjusted prevalence rate is 3.64 per thousand, for white female subjects 1.44, for non-white male subjects 0.97 and for non-white female subjects 0.34. The white to non-white ratio and the male to female rates are compared with earlier published values. For all groups the prevalence rate increases with age, attaining a maximum in the 40 to 60-year category for whites and somewhat later for non-whites. Beyond age 60 prevalence drops, reaching 0 or near 0 in the 80 to 89-year range. A simple phenomenological model is suggested to explain the observed race and sex differences in the prevalence rates.