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Biomedical subjects

E D Mellits

Publications and source records attributed to E D Mellits.

At least 73 records · Page 4Linked to original sources

The relationship between the level of lead absorption in children and the age, type, and condition of housing.

A group of 184 preschool-aged children with pretreatment blood lead concentrations (PbB) greater than or equal to 50 micrograms/dl, who received inpatient chelation therapy, were followed prospectively as outpatients for 12 months after discharge. Of these, 160 were followed for 24-30 months. Serial PbB data were analyzed according to the type of housing to which each child was discharged. Following therapy, PbB stabilized by 3 months. Thereafter, highly significant differences (P less than 0.001) existed between those living in or visiting old houses in which lead-in-paint hazards had been abated according to local ordinances (m PbB = 38.5 micrograms/dl) and those discharged to "lead-free" public housing (m PbB = 28.8 micrograms/dl) or to recently, totally gutted and renovated old housing (m PbB = 28.7 micrograms/dl). During the period of study (1978-1982), no downward trend in PbB within housing groups was found during the first 12 months of follow-up. Of the 152 children discharged to old housing, 75 had 127 recurrences of PbB greater than or equal to 50 micrograms/dl. This emphasizes the need for close and prolonged follow-up in all cases. These data indicate that substantially improved methods of detection, classification, and abatement of lead hazards must replace traditional methods if lead exposure for young children in old housing is to be reduced to an acceptable level.

Child↗

Identification of language-impaired children on the basis of rapid perception and production skills.

Discriminant function analysis was used to determine whether performance on temporal perception and production tasks alone could correctly classify children as language-impaired or normal. The analysis identified six variables, all of which assessed temporal perceptual and production abilities, which taken in combination correctly classified 98% of participating subjects. None of these variables assess the higher-level linguistic abilities (semantic, syntactic, pragmatic) that have classically been considered to be deficient in language-impaired children, or have been used to diagnose them clinically.

Aphasia↗

Lack of evidence for interaction between tobramycin and shock in their effect on renal function.

We sought to determine whether there was an interaction between aminoglycoside use and shock in their effect on renal function among seriously ill patients suspected of having gram-negative sepsis. Serial serum creatinine determinations were used to estimate changes in creatinine clearance rates in 179 patients entered onto a prospective randomized trial of tobramycin-nafcillin versus cefotaxime. A 25% decline in estimated creatinine clearance was considered to be clinically important. Univariate chi-square analysis showed that both shock (P less than 0.01) and tobramycin use (P less than 0.001) were independently associated with decline in estimated creatinine clearance. A two-way analysis of variance showed that both shock (F = 10.44, P less than 0.01) and tobramycin use (F = 42.6, P less than 0.001) continued to be significantly associated with renal dysfunction in the presence of each other, but there was no significant interaction between shock and tobramycin in their effect (F = 0.62, P less than 0.43). A multiple logistic regression with an interaction term representing the occurrence of shock and tobramycin use simultaneously yielded similar results. Our study provided no analytic evidence supporting the existence of an interaction between shock and aminoglycoside use in their effect on renal function.

Analysis of Variance↗

Calcium-dependent enhancement of myocardial diastolic tone and energy utilization dissociates systolic work and oxygen consumption during low sodium perfusion.

The relationships and correlations among functional, metabolic, and ionic consequences of low sodium perfusion were studied in isovolumic, retrograde-aortic perfused working rat hearts by 31P nuclear magnetic resonance, oxygen consumption, and atomic absorption spectrometry. Reduction of perfusate sodium from 144 to 74, 51, 39, and 25 mM in four separate groups of hearts via lithium substitution for 15 minutes decreased cell sodium to mean values of 62, 51, 43, and 36 mumol/g dry weight, respectively (P less than 0.001 vs. control of 107). There was a transient rise and then a fall in developed pressure and a decline in phosphocreatine and adenosine triphosphate, all of which were graded and correlated with perfusate sodium (P less than 0.01 for all parameters vs. perfusate sodium). This was accompanied by a 2- to 7-fold elevation of diastolic pressure while oxygen consumption remained near control levels. All parameters except adenosine triphosphate returned toward baseline values when normal perfusate sodium was reintroduced. Although cell calcium as measured by atomic absorption spectrometry did not differ among the groups, the functional and metabolic changes did not occur if the sodium steps were performed in reduced perfusate calcium (0.08 mM). In hearts in which systolic function was obliterated by verapamil, exposure to zero sodium caused a 4-fold increase in oxygen consumption, an increase in diastolic pressure, and a reduction of high energy phosphates. In the presence of ryanodine, a specific inhibitor of sarcoplasmic reticulum calcium release, the metabolic changes did not occur, and the excess oxygen consumption in zero sodium was substantially reduced. Thus, the effect of lowered perfusate sodium in beating hearts, i.e., to dissociate oxygen consumption and systolic function, and to increase diastolic pressure and its effect in arrested hearts to increase oxygen consumption, are calcium dependent, energy consuming, and modulated by sarcoplasmic reticulum calcium cycling.

Adenosine Triphosphate↗

Serum immunoglobulins in the first year of life.

Serum IgG, IgM, and IgA were measured in 316 infants younger than 12 months of age. Information including the child's race, sex, age, and past history of infections or atopy was collected. Birth records were also reviewed to ascertain the child's birthweight and gestational age. Serum IgG levels were higher in black infants than in white infants after the age of 4 months. Serum IgM levels were higher in black females than in black males for infants older than 1 month. For infants younger than 4 months of age, those weighing less than 2500 g at birth had lower IgG levels than those weighing more than 2500 g. Infants younger than 1 month whose gestational age had been less than 36 weeks had lower IgG levels than those greater than 36 weeks. Infants aged 1 to 4 months whose gestational age had been less than 36 weeks had lower IgG levels than did those 40 or more weeks. Infants with a positive history for atopy had lower IgG levels than similarly aged infants with a negative history.

Age Factors↗

Lack of maternal metabolic, endocrine, and environmental influences in the etiology of cleft lip with or without cleft palate.

We studied metabolic, endocrine, and environmental factors in 59 women who had delivered a child with cleft lip with or without cleft palate (CL +/- CP) and compared these values with those of 56 mothers of unaffected children. There was no significant difference between the two groups with respect to race, age, weight, height, education, parity, menstrual history, medical illnesses, or the use of contraceptives, tobacco, alcohol, or caffeine. All patients had a normal XX karyotype confirmed by the fluorescent banding technique. The two groups demonstrated no significant difference in test results of serum chemistries, glucose tolerance, serum or erythrocyte folate, vitamin A, carotene, corticoids, prolactin T4, free T4, urine 17-ketosteroids, 17-hydroxysteroids, total estrogens, or pregnanediol. Urinalyses revealed no group differences in the presence of barbiturates, amphetamines, salicylates, or benzodiazepines. The percentage of immunologic studies reflecting susceptibility to toxoplasmosis, rubella, cytomegalic inclusion disease, and herpes was not different between the two groups. The only statistically significant metabolic differences between the two groups were serum alkaline phosphatase, creatinine, creatinine clearance, and creatinine clearance/m2. Phenytoin pharmacokinetics and urinary metabolic patterns were compared in a subgroup of ten mothers of affected children and ten mothers from the control group. No significant differences were observed. However, a brief course of phenytoin treatment induced a greater inhibition of the folate tolerance test in controls than in mothers of children with clefts.

Adult↗

Antiemetic efficacy of dexamethasone. Randomized, double-blind, crossover study with prochlorperazine in patients receiving cancer chemotherapy.

We conducted a randomized, double-blind, crossover study comparing the antiemetic efficacy of dexamethasone and prochlorperazine in 42 patients with cancer who were receiving outpatient chemotherapy, mainly without cisplatin. Patients experienced significantly less nausea and vomiting with dexamethasone than with prochlorperazine (P less than 0.02 and less than 0.03, respectively). Twenty-five patients experienced no nausea with dexamethasone, as compared with 14 patients taking prochlorperazine (P less than 0.001). Similarly, 29 patients receiving dexamethasone did not vomit, as compared with 18 receiving prochlorperazine (P less than 0.001). Somnolence was the most frequent side effect, occurring in 60 per cent of patients receiving prochlorperazine and in 12 per cent of those receiving dexamethasone (P less than 0.001). Patients also experienced less suppression of appetite while receiving dexamethasone (P less than 0.02). We conclude that dexamethasone is an effective and safe antiemetic in patients receiving cancer chemotherapy without cisplatin.

Adult↗

Neurologic outcome in children with inborn errors of urea synthesis. Outcome of urea-cycle enzymopathies.

We studied 26 children with inborn errors of urea synthesis who survived neonatal hyperammonemic coma. There was a 92 per cent one-year survival rate associated with nitrogen-restriction therapy and stimulation of alternative pathways of waste nitrogen excretion. Seventy-nine per cent of the children had one or more developmental disabilities at 12 to 74 months of age; the mean IQ was 43 +/- 6. There was a significant negative linear correlation between duration of Stage III or IV neonatal hyperammonemic coma and IQ at 12 months (r = -0.72, P less than 0.001) but not between the peak ammonium level (351 to 1800 microM) and IQ. There was also a significant correlation between CT abnormalities and duration of hyperammonemic coma (r = 0.85, P less than 0.01) and between CT abnormalities and concurrent IQ (r = -0.75, P less than 0.02). These results suggest that prolonged neonatal hyperammonemic coma is associated with brain damage and impairment of intellectual function. This outcome may be prevented by early diagnosis and therapy.

Amino Acid Metabolism, Inborn Errors↗

Acute nifedipine withdrawal: consequences of preoperative and late cessation of therapy in patients with prior unstable angina.

Reports of acute ischemic events after withdrawal of calcium antagonist therapy in outpatients and during bypass surgery in patients with prior angina at rest prompted the examination of the effect of nifedipine withdrawal in 81 patients who had completed a prospective, double-blind randomized trial of nifedipine versus placebo for rest angina. Thirty-nine patients underwent bypass surgery for uncontrolled angina or left main coronary artery disease. No significant difference between patients withdrawn from nifedipine or placebo was seen in the incidence of perioperative myocardial infarction, hypotension requiring intraaortic balloon counterpulsation, vasopressor or vasodilator requirements or incidence of significant arrhythmias. An additional 42 patients had completed 2 years on a protocol consisting of nitrates and propranolol in addition to nifedipine or placebo. During a mean of 66 hours of continuous monitoring after withdrawal of nifedipine or placebo, heart rate and blood pressure were unchanged. A worsening of previously present angina at rest occurred in five patients who had continued to experience rest angina before drug withdrawal, four of whom were withdrawn from nifedipine. No patient with class I to III angina experienced new onset of rest angina during drug withdrawal. No patient experienced myocardial infarction. There was no significant difference between patients withdrawn from nifedipine or placebo in the duration or frequency of ischemic ST changes on continuous electrocardiographic monitoring, or in duration or positive results of serial exercise treadmill testing. Thus, no early adverse effects of acute nifedipine withdrawal were found in patients with prior rest angina at the time of bypass surgery or in stable patients receiving long-term medical therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗

Variables predictive of successful medical therapy in patients with unstable angina: selection by multivariate analysis from clinical, electrocardiographic, and angiographic evaluations.

Although unstable angina can be initially controlled with medical therapy in most patients, there is a high incidence of subsequent death, myocardial infarction, or need for coronary bypass surgery to control symptoms. Identification at the time of presentation of the patient likely to do poorly on continued medical therapy would be useful in advising consideration of surgical therapy. Since coronary arterial spasm may have a significant role in the pathophysiology of unstable angina in some patients, the recently developed calcium channel antagonists may therefore be of particular benefit in the medical therapy of unstable angina. One hundred thirty-eight patients were entered into a randomized double-blind study of the efficacy of adding nifedipine to conventional treatment of unstable angina (nitrates and beta-blockers) and were followed for 18 months. Of these patients, 104 underwent coronary arteriography. A multivariate Cox's hazard function analysis was applied to variables selected from the history, electrocardiographic (ECG) changes during chest pain, and from scintigraphic and coronary arteriographic data to determine those variables most predictive of response to medical therapy. The percentage of the left ventricular myocardium supplied by vessels with 70% or greater luminal stenosis was the most significant variable in influencing failure of medical therapy defined as sudden death, myocardial infarction, or need for bypass surgery. Whether or not the patient received nifedipine was the second most powerful variable, with the use of nifedipine reducing by half the relative risk of failing medical therapy. These were followed by cigarette smoking and presence of global ST segment changes during ischemia. After 18 months the nifedipine group had fewer patients failing medical therapy (p = .02), with fewer patients undergoing coronary bypass surgery (p less than .01). However, nifedipine did not appear to have a preventive effect against myocardial infarction or death. Kaplan-Meier actuarial curves confirmed that medical therapy was significantly less successful in the presence of increasing numbers of significantly stenotic vessels (p = .03). However, nifedipine provided a significant beneficial effect in patients with two or more stenotic vessels (p less than .01) and in whom 50% or more of the myocardium was supplied by vessels with 70% or greater stenosis (p = .01). Thus, although patients with advanced obstructive coronary disease have the greatest likelihood of unfavorable outcomes, the addition of nifedipine is of significant benefit.(ABSTRACT TRUNCATED AT 400 WORDS)

Angina Pectoris↗

Body water measurements in premature and older infants using H218O isotopic determinations.

Total body water was measured by H218O stable isotope dilution in two groups: in premature infants without complications, who were studied from 8 d of age until discharge; and in Peruvian subjects aged 6-36 mo, who were in the long-term convalescent stage of recovery from malnutrition. Results indicated that reliable total body water estimates can be obtained from sample volumes as small as 50 microliters of urine or plasma using a gas-isotope-ratio mass spectrometer equipped with an automated purification inlet system. Results from 21 studies in 10 Peruvian infants indicated substantially completed isotope equilibration in plasma by 2 h after the dose; total body water estimates from the 2-h samples averaged 98.7% (+/- 4.1) of 6-h values. Samples obtained at 4-h postdose gave total body water estimates that averaged 99.0% (+/- 2.9) of the 6-h value, showing essentially complete equilibration and reduced variability. Total body water estimates from urine samples collected 3-5 h postdose were closely correlated with 6-h, plasma-based total body water values in both premature and older infants; however, some reduction in variability was observed when urine collection was extended to 5-7 h, at which time urine-based estimates averaged 98.8% (+/- 2.0) and 100.7% (+/- 3.1) of plasma-based values for prematures and older Peruvian infants, respectively. The correlation between 5-7 h urine-based estimates of total body water with plasma-based values was r = 0.96 for 30 studies in prematures and r = 0.99 for 57 studies in older Peruvian infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Composition↗

Risk factors for nephrotoxicity in patients treated with aminoglycosides.

Risk factors for nephrotoxicity in patients treated with aminoglycosides were determined from the case records of 214 patients in two prospective, randomized clinical trials of gentamicin and tobramycin. Nephrotoxicity, defined as a 50% or greater fall in calculated creatinine clearance, developed in 30 patients (14.1%). Patients with nephrotoxicity had higher initial calculated creatinine clearances, were more often women, and were more likely to have liver disease. Using stepwise discriminant analysis, these factors were selected with the initial 1-hour post-dose aminoglycoside level, patient age, and shock. An equation was generated that was accurate in discriminating between patients with and without nephrotoxicity when validated in an independent population. Factors that did not add significantly to the equation were diabetes, dehydration, serum bicarbonate, bacteremia, urinary tract infection, gentamicin or tobramycin use, duration of therapy, total aminoglycoside dose, or the use of clindamycin, furosemide, or cephalothin.

Aged↗

Cefotaxime compared with nafcillin plus tobramycin for serious bacterial infections. A randomized, double-blind trial.

In a prospective, randomized, double-blind study, we compared cefotaxime with nafcillin plus tobramycin in the treatment of serious bacterial infections. Of 195 patients with suspected or proven infections who were not neutropenic, definite bacterial infections were identified in 81; 34 of 38 patients given cefotaxime and 26 of 43 given nafcillin plus tobramycin (p less than 0.01) responded to treatment. The difference in response rates occurred primarily in patients with rapidly fatal underlying disease or with an infection outside the urinary tract. A logistic regression analysis showed that treatment with cefotaxime was still associated with a higher response rate after adjusting for several potential confounding factors. Among patients treated for 3 days or more, our criteria for nephrotoxicity were met in 2 of 68 (2.9%) given cefotaxime and 16 of 57 (28.1%) given nafcillin plus tobramycin (p less than 0.001). Prolongation of the prothrombin time and enterococcal colonization did not occur more frequently with cefotaxime. We conclude that cefotaxime may be more effective and less toxic than nafcillin plus tobramycin for patients with serious bacterial infections.

Adult↗

Predictive factors for acute graft-versus-host disease in patients transplanted with HLA-identical bone marrow.

To identify predictive parameters for incidence and severity of acute graft-versus-host disease (GVHD), 136 patients, transplanted with histocompatible marrow as therapy for aplastic anemia and hematologic malignancies, were examined using univariate and multivariate analyses. The risk of GVHD increased in patients with acute lymphocytic leukemia (p less than 0.05), in sex-mismatched donor-recipient pairs (p less than 0.01), and in patients older than 23.7 yr (p less than 0.05). No other commonly observed factors appeared to have any relationship to GVHD except the presence of certain alleles. The presence of a Cw4 allele or of the Bw21 specificities B49 and B50 were associated with significantly increased risks of GVHD (p less than 0.05), whereas the presence of Aw19 (or the related specificities A29, Aw30, Aw31 , Aw32, Aw33 ) was associated with a significantly decreased risk (p less than 0.01). Using these factors, a regression equation can be constructed that estimates the risk of a given patient to develop clinically significant acute GVHD.

Acute Disease↗

Effect of father's death or departure on growth of poor children in Peru.

Between 1966 and 1976, heights and weights were determined yearly on all available children from 163 families who had had at least one child successfully treated for malnutrition between 1961 and 1971 and from eight families who had adopted such a child. Between 1959 and 1976, a total of 72 fathers departed from these families: 12 died, 47 deserted, six were jailed, and seven left to look for work elsewhere. Heights and weights as Z scores and the weight age/height age ratios were analyzed, when available, during four periods around the date of the event: 6 to 18 months before (period 1B), 0 to 6 months before (period 2B), 0 to 6 months after (period 3A), and 6 to 18 months after (period 4A). Mean Z scores for all children measured in the period were already low (-0.26 +/- 0.93 and -0.25 +/- 0.95) during period 1B, were higher during period 2B, (-0.15 and 0.04), lower during period 3A (-0.39 and -0.46), and similar to original levels during period 4A (-0.37 and -0.27). Mean weight age/height age was low (0.93 +/- 0.17) only during period 3A for children 2 to 18 years of age. In paired comparisons for children measured during any two periods there were significant increases in Z height and Z weight from periods 1B to 2B and from periods 1B to 4A in children less than 2 years of age and a significant decrease in the weight age/height age ratio from periods 1B to 3A in those 2 to 18 years of age. Loss of father had little or no further impact on the already poor growth of these children.

Adolescent↗

Cognitive abilities of language-delayed children.

The performance and verbal IQ scores for the WPPSI and WISC-R were compared for two groups of children aged 5 to 8 1/2 years, one normal and one specifically language delayed (SLD). There 34 to 38 children in each group. In accordance with selection procedures, performance IQ scores were not significantly different across the two groups. Both verbal and full scale IQ were significantly lower for the SLD than for the normal group. Profiles of verbal subtest scores differed for normal and SLD children but profiles for performance subtest scores did not. Variability of performance subtest scores was not greater for the SLD than for the normal children. The results do not support the hypothesis that language delay in children is related to a nonverbal cognitive deficit.

Child↗

Comparison of early thallium-201 scintigraphy and gated blood pool imaging for predicting mortality in patients with acute myocardial infarction.

The extent of abnormality in early thallium-201 and gated cardiac blood pool scintigrams has been reported to be useful for predicting mortality in patients with acute myocardial infarction (AMI). To compare the two techniques, 91 patients admitted consecutively with evident or strongly suspected AMI underwent both imaging studies within 15 hours of the onset of symptoms. Patients with pulmonary edema or shock were excluded. AMI developed in 84% of patients, and 6-month mortality for the entire group was 16%. A thallium defect score of 7.0 or greater (corresponding to at least a moderate reduction of activity involving 40% of the left ventricular circumference) identified a subgroup of 14 patients with 64% 6-month mortality rate. Similarly, a left ventricular ejection fraction of 35% or less identified a high-risk subgroup of 10 patients with a 6-month mortality of 60%. Mortality in the remaining patients was 8% for thallium score less than 7 and 11% for ejection fraction greater than 35%. The mortality rate was highest among patients who had concordant high-risk scintigrams (five of six, 83%), lowest in those with concordant low-risk studies (five of 64, 8%) and intermediate in those with discordant results (four of 11, 36%). Of a number of clinical variables, only the appearance of Q waves, peak creatine kinase greater than 1000 IU/I, and history of infarction were significantly associated with mortality. High-risk thallium or blood pool scintigraphic results were significantly more predictive and a thallium score of 7 or greater was more sensitive for detecting nonsurvivors than ejection fraction 35% or less at a similar level of specificity. Stepwise multiple logistic analysis showed that the thallium score was the best predictor of mortality, but that appearance of Q waves and ejection fraction were additive. Using these three variables, 11 patients were calculated to have a 50% or greater chance of dying and eight (73%) actually died, compared with six of 70 (9%) with a calculated chance of death of less than 50%. These results in a prospectively identified and consecutive group of patients support the value of early thallium and blood pool scintigraphy for separating high- and low-risk subgroups of hemodynamically stable infarct patients.

Adult↗