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Clinical Competence↗
Biomedical subjects
D Merrill
Publications and source records attributed to D Merrill.
Relationship between nutritional status and the glomerular filtration rate: results from the MDRD study.
BACKGROUND: The relationship between the protein-energy nutritional status and renal function was assessed in 1785 clinically stable patients with moderate to advanced chronic renal failure who were evaluated during the baseline phase of the Modification of Diet in Renal Disease Study. Their mean +/- SD glomerular filtration rate (GFR) was 39.8 +/- 21.1 mL/min/1.73 m2. METHODS: The GFR was determined by 121I-iothalamate clearance and was correlated with dietary and nutritional parameters estimated from diet records, biochemistry measurements, and anthropometry. RESULTS: The following parameters correlated directly with the GFR in both men and women: dietary protein intake estimated from the urea nitrogen appearance, dietary protein and energy intake estimated from dietary diaries, serum albumin, transferrin, percentage body fat, skinfold thickness, and urine creatinine excretion. Serum total cholesterol, actual and relative body weights, body mass index, and arm muscle area also correlated with the GFR in men. The relationships generally persisted after statistically controlling for reported efforts to restrict diets. Compared with patients with GFR > 37 mL/min/1.73 m2, the means of several nutritional parameters were significantly lower for GFR between 21 and 37 mL/min/1.73 m2, and lower still for GFRs under 21 mL/min/1.73 m2. In multivariable regression analyses, the association of GFR with several of the anthropometric and biochemical nutritional parameters was either attenuated or eliminated completely after controlling for protein and energy intakes, which were themselves strongly associated with many of the nutritional parameters. On the other hand, few patients showed evidence for actual protein-energy malnutrition. CONCLUSIONS: These cross-sectional findings suggest that in patients with chronic renal disease, dietary protein and energy intakes and serum and anthropometric measures of protein-energy nutritional status progressively decline as the GFR decreases. The reduced protein and energy intakes, as GFR falls, may contribute to the decline in many of the nutritional measures.
Adult↗
Risk of repetition of a severe perineal laceration.
OBJECTIVE: To compare the outcome of subsequent delivery in women with a history of a third- or fourth-degree laceration with outcomes in women without such a history. METHODS: This retrospective study used a perinatal database and chart review from 1978 to 1995. Only women whose first delivery was at our institution at more than 36 weeks' gestation, vaginal singleton, vertex presentation, and birth weight greater than 2500 g, with a subsequent delivery were included. The women were grouped by presence or absence of a third- or fourth-degree (severe) perineal laceration in their first delivery. The subsequent delivery was analyzed for maternal age, weight, birth weight, gestational age, method of delivery, use of episiotomy, and occurrence of a severe laceration. Comparison of data was by Fisher exact and t tests. RESULTS: Four thousand fifteen women met our starting criteria. In their first delivery, the average birth weight, use of instrumentation, and episiotomy rate were significantly higher in those women sustaining a severe laceration. When compared with women without a history of severe perineal laceration, women with such a history were at more than twice the risk for another in their subsequent delivery. The women at highest risk (21.4%) were those sustaining a laceration in their first delivery who underwent instrumental vaginal delivery with episiotomy in their subsequent delivery. When episiotomy or instrumental delivery was performed in the second vaginal birth, 52 (11.6%) of 449 women with a history of a severe perineal laceration sustained another, compared with 98 (6.5%) of 1509 without such a history (P < .001, odds ratio 1.9, 95% confidence interval 1.3, 2.7). CONCLUSION: Women delivering their second baby, and in whom episiotomy or instrumentation is used, are at increased risk of severe perineal laceration compared with women delivery spontaneously.
Adolescent↗
Interactions between color and word processing in a flanker task.
To examine interactions between color and word attributes, participants responded, either manually or vocally, to a central target (color patch or word) flanked by a Stroop stimulus. Color and word attributes of the flanker affected both vocal and manual responding to color patches. Color and word flankers also affected manual responding to word targets, but only word flanker affected vocal responding to word targets. These results are not consistent with models (e.g., translational models) of Stroop tasks, which posit that interactions between colors and words occur only when vocal responding is required.
Adult↗
Effect of dietary protein restriction on nutritional status in the Modification of Diet in Renal Disease Study.
The safety of dietary protein and phosphorous restriction was evaluated in the Modification of Diet in Renal Disease (MDRD) Study. In Study A, 585 patients with a glomerular filtration rate (GFR) of 25 to 55 ml/min/1.73 m2 were randomly assigned to a usual-protein diet (1.3 g/kg/day) or a low-protein diet (0.58 g/kg/day). In Study B, 255 patients with a GFR of 13 to 24 ml/min/1.73 m2 were randomly assigned to the low-protein diet or a very-low-protein diet (0.28 g/kg/day), supplemented with a ketoacid-amino acid mixture (0.28 g/kg/day). The low-protein and very-low-protein diets were also low in phosphorus. Mean duration of follow-up was 2.2 years in both studies. Protein and energy intakes were lower in the low-protein and very-low-protein diet groups than in the usual-protein group. Two patients in Study B reached a "stop point" for malnutrition. There was no difference between randomized groups in the rates of death, first hospitalizations, or other "stop points" in either study. Mean values for various indices of nutritional status remained within the normal range during follow-up in each diet group. However, there were small but significant changes from baseline in some nutritional indices, and differences between the randomized groups in some of these changes. In the low-protein and very-low-protein diet groups, serum albumin rose, while serum transferrin, body wt, percent body fat, arm muscle area and urine creatinine excretion declined. Combining patients in both diet groups in each study, a lower achieved protein intake (from food and supplement) was not correlated with a higher rate of death, hospitalization or stop points, or with a progressive decline in any of the indices of nutritional status after controlling for baseline nutritional status and follow-up energy intake. These analyses suggest that the low-protein and very-low-protein diets used in the MDRD Study are safe for periods of two to three years. Nonetheless, both protein and energy intake declined and there were small but significant declines in various indices of nutritional status. These declines are of concern because of the adverse effect of protein calorie malnutrition in patients with end-stage renal disease. Physicians who prescribe low-protein diets must carefully monitor patients' protein and energy intake and nutritional status.
Adolescent↗
A placebo-controlled randomized trial of the terbutaline pump for prevention of preterm delivery.
To determine the efficacy of the terbutaline pump for the prevention of preterm delivery, patients in preterm labor defined by progressive cervical change underwent intravenous magnesium sulfate tocolysis (with or without oral indomethacin, as necessary), and once labor was arrested, were randomized to one of three treatment arms: terbutaline by pump, saline by pump (blinded), or oral terbutaline. If recurrent preterm labor occurred despite maximization of therapy, the treatment arm was determined and therapy was changed; saline pump and oral terbutaline were switched to terbutaline pump, terbutaline pump was switched to oral terbutaline. Patients who continued to labor were readmitted for aggressive intravenous therapy. Women randomized to the terbutaline pump (n = 15), saline pump (n = 12), and oral terbutaline (n = 15) groups were similar in terms of gravidity, parity, days of tocolysis before study entry, gestational age at entry, and cervical dilatation at entry. The mean gestational age at delivery was the same in all three groups (35 weeks), as were neonatal outcomes. Terbutaline by pump, saline by pump, and oral terbutaline appear equivalent for the prevention of preterm delivery. The terbutaline pump should remain experimental.
Administration, Oral↗
Epidural recording of nerve conduction studies and surgical findings in radiculopathy.
We developed a method of studying nerve conduction along proximal nerves and nerve roots by delivering supramaximal stimuli to the tibial and peroneal nerves within the popliteal space and recording compound nerve action potentials from an epidural needle electrode at the L4-L5 interspace. For the purpose of investigating lumbar radiculopathies, a battery of averaged potentials was developed that could be read side-to-side for symmetry of amplitude and latency. Decreased amplitude and/or increased latency in peroneal or tibial conduction studies was attributed to L5 or S1 root pathology respectively. We report on 22 patients who were studied with this method and subsequently went to surgery. To evaluate the ability of the procedure to predict surgical findings, we reviewed the last 155 patients that we studied using epidural recording to find those who had subsequently gone to surgery and were sufficiently documented to allow analysis. The review yielded 22 cases and 69 root levels whose condition had been reported at surgery and studied by our method. Agreement was above what might be expected by chance p < .0001 (7.462; sign). The agreement on nerve root condition between nerve conduction studies and surgical findings suggests that the procedure's usefulness for confirming and localizing pathology in nerve root entrapments is similar to that offered by nerve conduction studies for entrapment neuropathies elsewhere.
Action Potentials↗
Class II furcations treated by guided tissue regeneration in humans: case reports.
In the cases reported here, the response of Class II mandibular molar furcation defects to guided tissue regeneration (GTR) versus sham operation was evaluated. Base-line information, including probing pocket depth (PD) and clinical attachment level (CAL) measurements, was recorded after completion of the hygienic phase. Eleven experimental and six control furcations, randomly assigned, are included in this report. The furcations were surgically exposed, using a flap approach and the areas were debrided. On the experimental teeth, Gore-Tex periodontal material was adapted and sutured, using a suspensory suture. The flaps were then sutured tightly, assuring complete coverage to the material. For 1 month all patients were seen weekly and rinsed their mouths with an 0.12% chlorhexidine solution daily. After 4 to 6 weeks the Gore-Tex membranes were removed. Clinical measurements were repeated at 3 and 6 months following surgery. Changes from baseline in PD and CAL were calculated for each case. Results indicated that PD measurements were reduced by both procedures, but the reduction was better for GTR at 3 and 6 months. At six months the test sites showed 2.8 +/- 1.0 mm pocket reduction, while the control sites showed an average of 1.6 +/- 0.9 mm reduction in pocket depth. CAL recordings were improved by both treatments, but were better for GTR at 6 months, with an average gain in CAL of 1.8 mm for the GTR and 0.6 mm for the controls. These cases in which GTR was compared to sham-operated controls indicate that GTR can improve the response to therapy of Class II furcation defects.
Adult↗
Transformations of maps to investigate clusters of disease.
An approach is presented to display and analyze epidemiologic data using population density equalized maps (cartograms). The algorithm for generating these maps is discussed. A specific method for statistically analyzing plotted data is given, followed by an application of maps and analysis to 73 sets of age-, race-, sex-, and site-specific cancer incidence data. The data were obtained from the Surveillance, Epidemiology and End Results project for San Francisco City/County (1978-1981) and combined with 1980 U.S. Census data.
Adult↗
An examination of three spatial disease clustering methodologies.
Patterns of disease in space are often analysed to determine whether a relationship exists between a disease outcome and environmental exposures. This report examines the performance of three cluster analytical methods when applied to a single data set. These methods, designed to assess the purely spatial variation of events, have been examined to assess their ability to detect clustering in an area where disease rates have previously been shown to be significantly elevated. The ability of these methods to detect spatial clustering was also examined using simulation techniques. All three methods were found to be poor at detecting spatially localized disease rates which were approximately three time the expected rate, as measured by the relative risk.
California↗
Stereoselectivity of tocainide pharmacodynamics in vivo and in vitro.
Racemic tocainide [R,S-T], which is used in the treatment of ventricular arrhythmias, consists of an R(-)-enantiomer [R-T] and an S(+)-enantiomer [S-T]. The present experiments examined these substances for pharmacodynamic differences. The ability of various doses of R-T, S-T, and R,S-T to both induce ataxia (A) and protect against chloroform-induced ventricular arrhythmias (P) in mice were compared at 20 min after subcutaneous treatment. For A effects, the ED50S (95% Fieller Limits) of R-T, S-T, and R,S-T were 125 (78-802), 125 (84-283), and 90 (61-149) mg/kg, respectively. For P effects, the ED50S were 40 (11-71), 116 (82-204), and 86 (55-187) mg/kg. The ratios of A/P, a measure of the margin of safety, were 3.1, 1.1, and 1.0. Effects upon intracardiac conduction in isolated rabbit hearts also exhibited, qualitatively, similar patterns of selectivity. At 1 X 10(-4) M intraatrial, His-Purkinje, intraventricular conduction times, and the QT interval were prolonged with the following order of potency: R-T greater than R,S-T greater than S-T; A-V nodal conduction was unchanged. R-T also evoked the greatest decrease in contractility. With respect to separation of antiarrhythmic action and the production of ataxia, R-T has a greater margin of safety than either S-T or R,S-T.
Animals↗
Intra-oral effects on acid-softened enamel of NaF lozenges administered in divided daily doses.
The purpose of this investigation was to study the intra-oral effects of multiple daily applications of NaF lozenges upon acid-softened enamel. Bovine enamel slabs were softened with 0.1 mol/L lactate buffer at pH 4.0 for 14 hrs and subsequently mounted in a mandibular removable Hawley appliance. Control slabs were worn for seven days by eight adult male subjects who brushed their natural dentition daily with a fluoride-free dentifrice. Test slabs were exposed to one 0.55-mg NaF lozenge (0.25 mg F) 4x/day for seven days and the natural dentition brushed with a fluoride-free dentifrice. The efficacy of 0.25-mg F lozenges used 4x/day over that of a 1-mg F lozenge administered 1x/day was established by a pilot study with two subjects. Microhardness testing was performed after intra-oral exposure (IOE) and following immersion in 0.01 mol/L lactate buffer containing Ca and PO4 for 24 hrs at a pH of 4.0. Fluoride uptake was measured on separate control and test slabs after KOH wash and after acid-resistance-testing (ART). Recovery of microhardness following IOE was 40.9% for controls and 53.9% for treated slabs, while control slabs retained 1.3% resistance to ART, compared with 25.6% for test slabs. The F content of the control slabs was significantly less than that of lozenge-treated and lozenge-treated-ART slabs throughout the depth of the lesion. The F content of the lozenge-treated-ART slabs was significantly less than that of the lozenge-treated slabs only at the 0-5-microns depth.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗
The effect of renal function on enalapril kinetics.
Enalapril maleate (MK-421), a nonmercapto-containing angiotensin converting enzyme (ACE) inhibitor, is converted in vivo to enalaprilat (MK-422), the active diacid. We evaluated serum profiles and urinary excretion of oral enalapril maleate in patients with renal disease (group I, creatinine clearance less than 3 ml/min, patients undergoing dialysis, n = 10; group II, creatinine clearance 10 to 79 ml/min, n = 9) compared with healthy subjects (group III, creatinine clearance greater than 80 ml/min, n = 10). Group I received a 10 mg dose during a day while not receiving dialysis and a 10 mg dose 1 hour before dialysis 2 weeks later. Groups II and III received a single 10 mg dose. Blood samples and urine were collected for 48 hours. Impaired renal function resulted in elevated serum and plasma concentrations of enalapril maleate and decreased excretion rates and urinary recovery of enalapril maleate and enalaprilat. The data suggest an apparent increase in the extent of metabolism of enalapril maleate to enalaprilat or an increase in nonrenal elimination of unchanged enalapril maleate in renal disease compared with normal health. Enalaprilat was dialyzable.
Administration, Oral↗
Control of ACTH and vasopressin in neurohypophysectomized conscious dogs.
Adrenocorticotropin (ACTH), cortisol, and vasopressin responses to clamped decreases in blood pressure (MAP) and to ovine corticotropin-releasing factor (CRF) infusion (20 ng X kg-1 X min-1) in intact and neurohypophysectomized (NHX) conscious dogs were examined. Mean arterial blood pressure was decreased 28 mmHg by a controlled infusion of sodium nitroprusside. Hypotension induced large increases in ACTH (peak 164 +/- 25 pg/ml), cortisol (peak 12.5 +/- 2.5 micrograms/dl), and vasopressin (peak 221 +/- 64 pg/ml) in intact (n = 7) dogs. NHX (n = 7) significantly attenuated these responses to hypotension. CRF infusion induced increases in ACTH similar in intact (n = 4) and NHX (n = 4) dogs. However, cortisol responses were significantly attenuated by NHX. Interestingly, CRF infusion induced small but significant increases in vasopressin from 3.0 +/- 1.1 to 8.1 +/- 2.0 pg/ml. We conclude that NHX attenuates ACTH and vasopressin responses to hypotension and cortisol responses to CRF-induced increases in ACTH. CRF seems to stimulate vasopressin release.
Adrenocorticotropic Hormone↗
Influence of vasopressin and angiotensin on baroreflexes in the dog.
Cardiovascular responses to step-changes of carotid sinus pressure were evaluated at normal and elevated levels of plasma arginine vasopressin in anesthetized neurohypophysectomized dogs (n = 12). Arginine vasopressin influenced autonomic function in two ways: first, maximum carotid reflex gain increased; second, cardiac output was decreased. The enhancement of reflex strength was observed only in response to decreases of intrasinus pressure below the equilibrium point (pressures of between 60 and 105 mm Hg). Aortic pressure rose twice as high for a given decrease of intrasinus pressure, elevations of total peripheral resistance responses were triple those observed at normal plasma arginine vasopressin. In this way, arginine vasopressin more than doubled the ability of the carotid reflexes to return a drop in arterial pressure to normal. Arginine vasopressin enhancement of reflex gain was not observed with elevations of intrasinus pressures above the equilibrium point. Elevation of aortic pressure expected from the vasoconstrictor actions of infused arginine vasopressin were buffered by associated reductions in cardiac output. Vagally mediated bradycardia was consistently observed with elevated arginine vasopressin, but the reflex response of heart rate to step-changes of intrasinus pressure was unchanged. Time control studies in five neurohypophysectomized dogs indicated no significant change in carotid reflex response over the 3- to 4-hour protocol. Comparison of reflex responses in anephric dogs (n = 8) at low and elevated levels of angiotensin II indicated that this vasoactive peptide did not significantly alter reflex responsiveness. We conclude that arginine vasopressin enhances the ability of the carotid reflexes to normalize decreases of arterial pressure, but buffers a rise in pressure from its own vasoactive properties by initiating a fall of cardiac output.
Angiotensin II↗
Ecologic regression analysis and the study of the influence of air quality on mortality.
This presentation focuses entirely on the use and evaluation of regression analysis applied to ecologic data as a method to study the effects of ambient air pollution on mortality rates. Using extensive national data on mortality, air quality and socio-economic status regression analyses are used to study the influence of air quality on mortality. The analytic methods and data are selected in such a way that direct comparisons can be made with other ecologic regression studies of mortality and air quality. Analyses are performed by use of two types of geographic areas, age-specific mortality of both males and females and three pollutants (total suspended particulates, sulfur dioxide and nitrogen dioxide). The overall results indicate no persuasive evidence exists of a link between air quality and general mortality levels. Additionally, a lack of consistency between the present results and previous published work is noted. Overall, it is concluded that linear regression analysis applied to nationally collected ecologic data cannot be used to usefully infer a causal relationship between air quality and mortality which is in direct contradiction to other major published studies.
Air Pollutants↗
Inability of seven-pinhole myocardial tomography to obtain accurate 201Tl kinetic data.
Seven-pinhole myocardial tomography has been reported to enhance the accuracy of thallium-201 (201Tl) studies in detecting patients with coronary artery disease. To determine if this approach can accurately assess regional 201Tl kinetics, 12 dogs with temporary occlusion (mean 15 min) of either the left anterior descending (LAD) (n = 6) or left circumflex (LCX) (n = 6) coronary artery were studied. Thallium-201 was injected and serial 7-pinhole images were acquired during occlusion and following reflow (mean duration 175 min). Time-activity analysis was obtained from normal and ischemic regions of interest in the central pinhole image and the reconstructed tomographic images (TOMO-ROI). Time-activity data from corresponding normal and ischemic regions were also obtained using a circumferential graph program (TOMO-MAX). In addition, regional myocardial 201Tl activity was recorded continuously with a cadmium telluride radiation probe sutured directly to the posterior myocardial wall. Defects in 201Tl distribution with subsequent partial or complete redistribution were present in 11 of 12 central pinhole images and tomographic studies. In the normal and ischemic anterior myocardial segments the percentage change in 201Tl activity in the central pinhole image from occlusion to the end of reflow correlated well with the percentage change in activity for both TOMO-ROI (r = 0.93) and TOMO-MAX (r = 0.85). In the normal posterior segments the percentage change in 201Tl activity in the central pinhole image correlated well with TOMO-ROI (r = 0.98) and TOMO-MAX (r = 0.87).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
An alternative to ecologic regression analysis of mortality rates.
A number of recent papers have used geographically defined data and linear models to study the relationship between a series of epidemiologic factors and the frequency of disease. This "ecologic regression" approach involves serious problems of interpretation. An alternate approach is discussed that does not depend on statistical models, produces easily interpreted results and yields statistical summaries that approximately parallel regression analysis. This alternative procedure is illustrated by using acute lymphocytic leukemia mortality data on a county level from among white females less than five years of age between 1969-1977.
Child, Preschool↗