ABSTRACT
PURPOSE: Immunosuppressed (IS) patients are at increased risk for developing Merkel cell carcinoma (MCC) with worsened outcomes compared to immunocompetent (IC) patients. We sought to determine the effects of immune status on the efficacy of adjuvant RT regarding OS for patients with stage I, II or III (localized) MCC of the head and neck. METHODS/PATIENTS: The National Cancer Database was queried for patients with resected, localized MCC of the head and neck with known immune status. Kaplan-Meier methods were used to describe OS. Log-rank tests, multivariable Cox regression models and interaction effect testing were used to compare OS by subgroup categorized by patient and treatment factors including immune status and adjuvant RT receipt. RESULTS: A total of 892 (89.6%) IC and 104 (10.4%) IS patients with MCC of the head and neck were included. Adjuvant RT was associated with improved 3-year OS rate for both IS patients (49.4% vs. 35.5%, p = 0.0467) and stage I/II IC patients (72.4% vs. 62.9%, p = 0.0092). Adjuvant RT was associated with decreased hazard of death (HR 0.77, 95% CI 0.62-0.95). Interaction effect testing did not demonstrate a difference in the efficacy of adjuvant RT on OS between IC and IS status (p = 0.157). CONCLUSIONS: In this NCDB analysis, adjuvant RT was associated with decreased hazard of death for patients with localized MCC of the head and neck regardless of immune status and should be considered for both IS and IC patients.
Subject(s)
Carcinoma, Merkel Cell/radiotherapy , Head and Neck Neoplasms/radiotherapy , Adult , Aged , Aged, 80 and over , Carcinoma, Merkel Cell/immunology , Carcinoma, Merkel Cell/mortality , Female , Head and Neck Neoplasms/immunology , Head and Neck Neoplasms/mortality , Humans , Male , Middle Aged , Proportional Hazards Models , Radiotherapy, Adjuvant , Retrospective StudiesABSTRACT
AIM: To investigate, with extended follow-up, cause-specific mortality among low-income Black and White Americans with Type 2 diabetes who have similar socio-economic status. METHODS: Black and White Americans aged 40-79 years with Type 2 diabetes (n = 12 498) were recruited from community health centres as part of the Southern Community Cohort Study. Multivariable Cox analysis was used to estimate mortality hazard ratios and 95% CIs for subsequent cause-specific mortality, based on both underlying and contributing causes of death. RESULTS: During the follow-up (median 5.9 years), 13.3% of the study population died. The leading causes of death in each race were ischaemic heart disease, respiratory disorders, cancer, renal failure and heart failure; however, Blacks were at a lower risk of dying from ischaemic heart disease (hazard ratio 0.70, 95% CI 0.54-0.91) or respiratory disorders (hazard ratio 0.70, 0.53-0.92) than Whites but had higher or similar mortality attributable to renal failure (hazard ratio 1.57, 95% CI 1.02-2.40), heart failure (hazard ratio 1.47, 95% CI 0.98-2.19) and cancer (hazard ratio 0.87, 95% CI 0.62-1.22). Risk factors for each cause of death were generally similar in each race. CONCLUSIONS: These findings suggest that the leading causes of death and their risk factors are largely similar among Black and White Americans with diabetes. For the two leading causes of death in each race, however, ischaemic heart disease and respiratory disorders, the magnitude of risk is lower among Black Americans and contributes to their higher survival rates.
Subject(s)
Black or African American/statistics & numerical data , Diabetes Mellitus, Type 2/mortality , Myocardial Ischemia/mortality , Neoplasms/mortality , Renal Insufficiency/mortality , Respiratory Insufficiency/mortality , White People/statistics & numerical data , Adult , Aged , Aged, 80 and over , Cause of Death , Cohort Studies , Diabetes Mellitus, Type 2/ethnology , Female , Follow-Up Studies , Health Services Accessibility , Health Status Disparities , Humans , Male , Middle Aged , Myocardial Ischemia/ethnology , Neoplasms/ethnology , Population Surveillance , Renal Insufficiency/ethnology , Respiratory Insufficiency/ethnology , Socioeconomic Factors , United States/epidemiologyABSTRACT
Objetivos: Principales: evaluar la seguridad y la efectividad (mediante el análisis de la conducta del paciente) con el uso de óxido nitroso durante la realización de procedimientos dolorosos en los servicios de urgencias pediátricos (SUP); secundarios: evaluar su manejabilidad y su aceptación por el equipo médico y el paciente. Pacientes y métodos: Estudio post-autorización, prospectivo, observacional, multicéntrico, no aleatorizado y abierto (noviembre 2007-diciembre 2008), en el que participaron 7 SUP nacionales. Se incluyó a los pacientes de 2-18 años en los que se utilizó óxido nitroso para la realización de procedimientos dolorosos. Resultados: Se incluyó a 213 pacientes (27,2% < 5 años). La conducta del paciente fue considerada «buena/muy buena» en el 79,7%. El porcentaje de casos con conducta «mala/acepta con dificultad» fue mayor en < 5 años (33,3% vs. 15,1%; p=0,006), no detectándose diferencias significativas en función del procedimiento. Se registraron efectos adversos en 17 casos (7,9%), sin diferencias significativas en función de la edad, estar o no en ayunas ni la asociación de otros fármacos. Los más frecuentes fueron mareo y/o cefalea (10), seguido de vómitos (3). La administración fue considerada fácil por parte del equipo médico en el 96,6%. En el 92,7%, los padres aceptarían que volviera a ser utilizado en su hijo en una situación similar. Conclusiones: La administración de óxido nitroso logra una adecuada sedoanalgesia para la realización de procedimientos dolorosos, sobre todo en niños mayores de 5 años. Los efectos adversos registrados son escasos, leves y conocidos. La mayoría de los padres aceptaría nuevamente su uso en condiciones similares (AU)
Objectives: Primary objectives: to assess the safety and the effectiveness (analysing the behaviour of the patient) with the use of nitrous oxide during the performance of painful procedures in the Paediatric Emergency Departments (PED); secondary objectives: to evaluate the manageability of the method and its acceptance by both the medical team and the patient. Patients and methods: Post-marketing observational, prospective, multicentre, non-randomised and open (November 2007-December 2008) study, which involved seven national PED. We included patients between 2 and 18 years-old on whom a painful procedure was performed in the PED and nitrous oxide was used. Results: A total 213 patients were included (27,2% < 5years). Patient behaviour was considered «good/very good» in 79,7%, with no statistically significant difference in relation to the procedure performed. Patient behaviour was more often classified as «bad/accept with difficulty» among those < 5years (33.3% vs 15.1%, P=0.006). Adverse events occurred in 17 cases (7.9%), with no significant difference in the rate in relation to the age, fasting or not or in association with other drugs; the most frequent were dizziness and/or headache (10), followed by vomiting (3). The administration was considered easy by the medical team in the 96.6% of the cases. Parents would accept the use of nitrous oxide in their child in a similar situation in 92.7% of the cases. Conclusions: Administration of nitrous oxide achieves proper sedation and analgesia during painful procedures, especially in children older than 5years. Adverse events reported were few, mild and expected. Most parents would accept its use again in a similar situation (AU)
Subject(s)
Humans , Male , Female , Child , Analgesia/methods , Pain/drug therapy , Nitrous Oxide/therapeutic use , Emergency Treatment/methods , Patient Satisfaction/statistics & numerical data , EffectivenessABSTRACT
PRIMARY OBJECTIVES: to assess the safety and the effectiveness (analysing the behaviour of the patient) with the use of nitrous oxide during the performance of painful procedures in the Paediatric Emergency Departments (PED); secondary objectives: to evaluate the manageability of the method and its acceptance by both the medical team and the patient. PATIENTS AND METHODS: Post-marketing observational, prospective, multicentre, non-randomised and open (November 2007-December 2008) study, which involved seven national PED. We included patients between 2 and 18 years-old on whom a painful procedure was performed in the PED and nitrous oxide was used. RESULTS: A total 213 patients were included (27,2% < 5 years). Patient behaviour was considered «good/very good¼ in 79,7%, with no statistically significant difference in relation to the procedure performed. Patient behaviour was more often classified as «bad/accept with difficulty¼ among those < 5 years (33.3% vs 15.1%, P=.006). Adverse events occurred in 17 cases (7.9%), with no significant difference in the rate in relation to the age, fasting or not or in association with other drugs; the most frequent were dizziness and/or headache (10), followed by vomiting (3). The administration was considered easy by the medical team in the 96.6% of the cases. Parents would accept the use of nitrous oxide in their child in a similar situation in 92.7% of the cases. CONCLUSIONS: Administration of nitrous oxide achieves proper sedation and analgesia during painful procedures, especially in children older than 5 years. Adverse events reported were few, mild and expected. Most parents would accept its use again in a similar situation.
Subject(s)
Analgesia , Analgesics, Non-Narcotic/therapeutic use , Conscious Sedation , Emergency Treatment , Nitrous Oxide/therapeutic use , Adolescent , Analgesics, Non-Narcotic/adverse effects , Child , Child, Preschool , Emergency Service, Hospital , Female , Humans , Male , Nitrous Oxide/adverse effects , Prospective StudiesABSTRACT
Two experiments were conducted to test the effect of a room with sensory equipment, or Snoezelen room, on the stereotypic behavior and engagement of adults with profound mental retardation. In Experiment 1, participants were observed in their living room before and after attending the Snoezelen room. Results showed that there tended to be a reduction in stereotypy and increase in engagement when participants went from their living room to the Snoezelen room, and a return of these behaviors to pre-Snoezelen levels in the living room. Positive effects in the Snoezelen room did not carryover to the living room. In Experiment 2, the living and Snoezelen rooms were compared to an outdoor activity condition with the same participants and target behaviors. Results showed that the outdoor condition was superior, the Snoezelen condition intermediate, and the living room least effective in their impact on stereotypic behavior and engagement. Conceptualizations regarding factors that maintain stereotypic behavior and engagement were discussed in the context of the three experimental conditions.
Subject(s)
Activities of Daily Living , Intellectual Disability/therapy , Stereotyped Behavior , Adult , Aged , Exploratory Behavior , Female , Housing , Humans , Intellectual Disability/psychology , Intellectual Disability/rehabilitation , Male , Middle Aged , PerceptionABSTRACT
Patterns of symptoms associated with depression and dementia were examined in 3 aging adults with Down syndrome. A case study approach (Yin, 1994) was employed to identify and link these symptoms. Results of the case analyses provide further insight into distinguishing between depression and dementia in older persons with Down syndrome.
Subject(s)
Depressive Disorder/diagnosis , Down Syndrome/diagnosis , Activities of Daily Living/psychology , Aged , Depressive Disorder/psychology , Diagnosis, Differential , Down Syndrome/psychology , Geriatric Assessment , Humans , Male , Middle AgedABSTRACT
In a landmark study, the Diabetes Control and Complications Trial proved that intensive insulin therapy (IIT) reduced the incidence and severity of the microvascular complications of insulin-dependent diabetes mellitus. Retinopathy, nephropathy, and neuropathy were all improved by IIT. The trial was conducted by endocrinologists experienced in the management of IIT. However, only a small minority of patients with diabetes are cared for by endocrinologists; the vast majority receive their care from primary care physicians. In this article, the authors describe the practical aspects of IIT for those physicians unfamiliar with IIT but who want to offer the benefits of this therapy to patients with diabetes. The authors define suitable candidates for IIT, describe the initiation and management of IIT, and emphasize the potential complications of this therapy. Severe hypoglycemia is the major risk of ITT, and caution must be used to reduce the incidence of this dangerous complication.
Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Insulin/administration & dosage , Insulin/therapeutic use , Practice Guidelines as Topic , Humans , Physicians, FamilyABSTRACT
The management of hypercalcemia of malignancy (HCM) is difficult if the underlying neoplasm cannot be treated successfully. The overexpression of parathyroid hormone-related protein (PTHrP) by various neoplasms is a common mechanism of HCM and usually is a premorbid event. Current pharmacologic measures to control HCM are directed more toward inhibiting the action rather than inhibiting the secretion of PTHrP. The somatostatin congeners are a novel class of drugs that can inhibit some excessive hormonal states. In this report, the authors summarize an observation made using lanreotide, an investigational somatostatin congener, in treating a patient with a neuroendocrine neoplasm. Lanreotide administration resulted in normalizing the serum calcium levels while decreasing plasma PTHrP concentrations. The chronic administration of lanreotide produced a stable radiographic response and controlled the HCM without adverse side effects. The somatostatin congeners potentially offer another therapeutic modality in managing HCM.
Subject(s)
Hypercalcemia/drug therapy , Neuroendocrine Tumors/complications , Pancreatic Neoplasms/complications , Peptides, Cyclic/therapeutic use , Somatostatin/analogs & derivatives , Aged , Calcium/blood , Female , Humans , Hypercalcemia/etiology , Neuroendocrine Tumors/metabolism , Pancreatic Neoplasms/metabolism , Parathyroid Hormone-Related Protein , Peptides, Cyclic/administration & dosage , Protein Biosynthesis , Proteins/metabolism , Somatostatin/administration & dosage , Somatostatin/therapeutic useABSTRACT
The development of diabetic ketoacidosis is an unusual complication of a glucagon-secreting pancreatic islet cell neoplasm, with only four reported cases in the literature. In this article, the authors report on a 46-year-old woman with a glucagonoma cosecreting pancreatic polypeptide, somatostatin, and serotonin diagnosed 8 months before the onset of diabetic ketoacidosis. She was treated with hydration, insulin, and octreotide, with improvement in her clinical course and a decrease in the glucagon, pancreatic polypeptide, and chromogranin A plasma levels. With the addition of weekly 5-FU, she has maintained a partial radiographic response and has had no further episodes of diabetic ketoacidosis for a 4.5-year period. Diabetic ketoacidosis can develop in the presence of a glucagonoma, and the pathophysiology remains unknown.
Subject(s)
Diabetic Ketoacidosis/etiology , Glucagonoma/complications , Pancreatic Neoplasms/complications , Female , Fluid Therapy , Fluorouracil/therapeutic use , Glucagonoma/diagnosis , Glucagonoma/drug therapy , Humans , Insulin/therapeutic use , Middle Aged , Octreotide/therapeutic use , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/drug therapy , Pancreatic Polypeptide/metabolism , Serotonin/metabolism , Somatostatin/metabolismABSTRACT
The effects of hypercalcemia on the heart and the resulting alterations of the electrocardiogram are well established. However, there are only rare reports of arrhythmias caused by hypercalcemia in primary hyperparathyroidism. This article describes a case of severe hypercalcemia secondary to hyperparathyroidism causing tachy-brady syndrome.
Subject(s)
Arrhythmias, Cardiac/etiology , Hypercalcemia/complications , Aged , Aged, 80 and over , Electrocardiography , Female , Humans , Hyperparathyroidism/complicationsABSTRACT
This study defines determinants of cost of treatment of diabetic ketoacidosis. A chart review for 92 cases of ketoacidosis from 1988 to 1992 in 40 females and 25 males (age range 18 to 81) showed a length of stay of 5.7 +/- 4.9 d. Length of stay did not correlate with the level of nursing care or any other component of the initial order set. Length of stay was shorter in cases managed by diabetologists. Length of stay was inversely proportional to the interval from arrival to the first shot of intermediate or long-acting insulin. Length of stay was longer in subjects with a positive bacterial culture (mean, 9.1 d) and was longer in subjects who arrived in the evening. There was a female predominance in total and recurrent cases of ketoacidosis. Female patients received fewer educational sessions than males. The grade of acidosis affected the duration of acidemia, but the grade of acidosis, APACHE scores, and admission lab values did not correlate with length of stay. The use of an intensive care unit (ICU) included more testing and expense without uniform clear benefit. Optimal transition from intensive to routine management includes resumption of long-acting insulins as soon as possible. Optimization of hospital care and reduction of incidence of ketoacidosis in females would have a marked effect on health care costs.
Subject(s)
Diabetic Ketoacidosis/therapy , Hospitals, University/statistics & numerical data , Length of Stay/statistics & numerical data , Utilization Review , Adolescent , Adult , Aged , Aged, 80 and over , Bacterial Infections/complications , Cost-Benefit Analysis , Diabetic Ketoacidosis/complications , Diabetic Ketoacidosis/diagnosis , Diabetic Ketoacidosis/nursing , Female , Hospital Costs , Hospitals, University/economics , Humans , Length of Stay/economics , Male , Middle Aged , Recurrence , Severity of Illness Index , Sex Factors , Tennessee , Treatment OutcomeABSTRACT
With variations in the concentrations of antibodies and blocking agents and reduction in incubation times, qualitative enzyme-linked immunosorbant assay can be performed in a matter of two hours, for more rapid identification of mutants and antigens.
Subject(s)
Bacteriological Techniques , Enzyme-Linked Immunosorbent Assay/methods , Escherichia coli/isolation & purification , Mutation , Time FactorsABSTRACT
Variation in the distribution of dietary nitrogen among the different amino acids is one factor that can modify the calorie equivalent per weight of amino acid or protein. This is important to consider when experimental diets with different amino acid compositions are compared and when indirect calorimetry is used to determine substrate oxidation rates. We developed a computer program to compute the energy content, oxygen equivalent, and respiratory quotient for arbitrary mixtures of amino acids and representative carbohydrates and fats. The calorie content of individual free amino acids was calculated by correction of the heat of combustion for the incomplete oxidation of amino acids characteristic of humans. Although these computations were presented before, we not report the limit of applicability of published values and the availability of the computer program to do these calculations.
Subject(s)
Amino Acids/analysis , Calorimetry , Diet , Amino Acids/metabolism , Amino Acids, Branched-Chain/analysis , Amino Acids, Branched-Chain/metabolism , Animals , Calorimetry/methods , Energy Metabolism , Humans , Rats , SoftwareABSTRACT
The effects of insulin-induced hypoglycemia (IIH) on leucine kinetics (mumol.kg-1.min-1) and interorgan flow of amino acids (AA) were examined in 2 groups of 18-h fasted conscious dogs. Insulin was infused at 5 mU.kg-1.min-1 for 3 h. IIH (40 +/- 5 mg/dl) resulted in a drop in plasma leucine (114 +/- 10 to 64 +/- 9 microM) and leucine rate of appearance (Ra) (3.1 +/- 0.1 to 2.4 +/- 0.2) within 1 h but gradually increased (P less than 0.05) to 145 +/- 30 microM and 3.8 +/- 0.5 by 3 h. Leucine oxidative rate of disposal (Rd) increased from 0.44 +/- 0.08 to 1.02 +/- 0.35 (P less than 0.01), and nonoxidative Rd dropped initially but was near basal levels by 3 h. When euglycemia was maintained, there was sustained drop in plasma leucine from 122 +/- 12 to 42 +/- 6 mumol/l, leucine Ra from 3.1 +/- 0.4 to 1.8 +/- 0.2, oxidative Rd from 0.36 +/- 0.03 to 0.22 +/- 0.04, and nonoxidative Rd from 2.75 +/- 0.4 to 1.6 +/- 0.2 (all P less than 0.01). IIH was associated with a significant net release of leucine (and other AA) across the gut (0.04 +/- 0.05 to 1.86 +/- 0.30 mumol.kg-1.min-1; P less than 0.05). In the group with euglycemia there was no significant change in the gut balance of leucine. We conclude that IIH is associated with a proteolytic response and that the gut is the major contributor to this response.
Subject(s)
Amino Acids/metabolism , Blood Glucose/metabolism , Hypoglycemia/metabolism , Insulin/pharmacology , Proteins/metabolism , Animals , Carbon Dioxide/analysis , Catecholamines/blood , Digestive System/metabolism , Dogs , Female , Hydrocortisone/blood , Hypoglycemia/chemically induced , Insulin/blood , Kinetics , Leucine/metabolism , Liver/metabolism , Male , Splanchnic CirculationABSTRACT
Patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) frequently report a history of theophylline use prior to arrival in the emergency department. The reliability of using this history to guide aminophylline therapy is, however, unclear. The authors studied patients with an acute exacerbation of COPD to determine the relation between the initial theophylline level and the medication history. Seventy-nine patients with a mean age of 64.3 years were entered into the study. The average theophylline level was 10.8 micrograms/mL. Forty-seven percent of the patients had subtherapeutic levels, 46% had therapeutic levels, and 7% had toxic levels. There were weak although statistically significant correlations between the theophylline level and the interval since the last theophylline dose (r = -.40, P less than .001), as well as with the last recorded outpatient theophylline level (r = .45, P less than .001). However, the theophylline level could not be predicted accurately in a number of patients. The authors conclude, because the prediction rule was often inaccurate, aminophylline therapy in patients with acute exacerbation of COPD should be based on direct measurement of the serum theophylline level.
Subject(s)
Lung Diseases, Obstructive/drug therapy , Theophylline/blood , Aged , Emergencies , Female , Humans , Lung Diseases, Obstructive/blood , Male , Maximal Expiratory Flow Rate/drug effects , Middle Aged , Smoking , Theophylline/therapeutic useABSTRACT
Determination of amino acids by reversed-phase chromatography of the adduct with orthophthalaldehyde and a thiol is rapid and sensitive. The major recognized adverse feature of this method is the instability of the reaction product, which requires precise control of reaction timing and chromatographic parameters for reliable quantitative application. We report another source of major variability: reagent instability. Deterioration of reagent was noted as low peak heights and peak broadening and was predictable if the premixed reagent was left at room temperature. Restoration of sharp chromatograms was accomplished by addition of mercaptoethanol or sodium metabisulfite. Reagent which was chromatographically inert contained minimal free thiol by direct assay. Free thiol disappearance was markedly slowed by addition of a chelating agent. Excess mercaptoethanol was deleterious. We conclude that reagent deterioration represents oxidation of the thiol, may be reversed by rereduction with minimal thiol or bisulfite, and may be minimized by inclusion of a metal chelator in the reagent.
Subject(s)
Amino Acids/analysis , o-Phthalaldehyde , Aldehydes , Chromatography/methods , Drug Stability , Oxidation-Reduction , Reference Standards , Sulfhydryl Compounds/metabolismABSTRACT
The calculation of a set of ratios from two sets of paired experimental data is a common practice. The ratio of the averages of two sets is in general not equal to the average of the ratios of individual pairs, and there is no predictable relation if both sets of data are unspecified real numbers. However, we prove here that the ratio of averages is the minimum bound for the average of ratios if the numerators of each ratio are identical. This is the practice for many steady-state turnover experiments, and thus summary data can be reliably utilized in this case.
Subject(s)
Data Interpretation, Statistical , Kinetics , Leucine/blood , MathematicsABSTRACT
The quantitative effect of plasmapheresis on concentrations of intravascular solutes is described by a minimal two-compartment model, which allows exit to and entry from a nonplasma body pool of the solute. This novel method is simple and capable of determining endogenous metabolic turnover of physiologically important plasma constituents in both therapeutic and experimental settings. The model was suggested by the therapeutic use of plasmapheresis in hyperlipidemia, and the turnover rates of triglyceride and cholesterol were calculated for one patient treated with chronic plasmapheresis. It is concluded that at least a two-compartment model is necessary to quantitatively describe the effect of plasmapheresis on any substance that undergoes appreciable endogenous turnover (metabolic clearance rate greater than 1.1 times plasmapheresis rate when both rates are in units of volume per time). Calculation of endogenous turnover rate with the use of measurements of the concentration of a solute in plasma before and after plasmapheresis and in the total plasmapheresate and measurement of the volume of plasma removed, volume of plasma substitute infused, and total plasmapheresis time is detailed. This method avoids the use of isotopic labeling experiments. In turn, the endogenous turnover rate may predict the efficacy of therapeutic plasmapheresis.
Subject(s)
Body Fluid Compartments , Body Fluids , Cholesterol/blood , Computer Simulation , Hyperlipoproteinemia Type III/blood , Models, Biological , Plasmapheresis , Triglycerides/blood , Blood Glucose/metabolism , Female , Humans , Metabolic Clearance Rate , Middle AgedABSTRACT
Amino acid availability rapidly regulates protein synthesis and degradation. Increasing amino acid concentrations above the levels found in post-absorptive plasma stimulates protein synthesis in a dose-dependent manner at the level of mRNA translation-initiation and inhibits protein degradation by inhibiting lysosomal autophagy. The anabolic effects of insulin on protein synthesis and protein degradation are exerted at the same sites (i.e., peptide chain initiation and lysosomal stabilization) allowing for a rapid synergistic response when both amino acids and insulin increase after a protein-containing meal. In perfused liver preparations, protein anabolic effects are exerted by a group of amino acids acting in concert. The BCAA are among the amino acids required for stimulation of hepatic protein synthesis, but there is no evidence that BCAA or leucine alone are effective. Leucine alone is an important inhibitor of hepatic protein degradation, but maximal inhibition requires in addition several other regulatory amino acids. In heart and skeletal muscle in vitro, increasing the concentration of the three BCAA or of leucine alone reproduces the effects of increasing the supply of all amino acids in stimulating protein synthesis and inhibiting protein degradation. Skeletal muscle is the largest repository of metabolically active protein and a major contributor to total body nitrogen balance. Supplying energy alone (i.e., carbohydrate and lipids) cannot prevent negative nitrogen balance (net protein catabolism) in animals or humans; only provision of amino acids allows the attainment of nitrogen balance. In rats and in humans nourished parenterally, provision of balanced amino acid solutions or of only the three BCAA cause similar improvements in nitrogen balance for several days. There is some evidence that infusions of leucine alone can stimulate muscle protein synthesis in vivo; the effect may be transitory and was not observed by all investigators; provisions of excess leucine alone does not seem to affect total body or muscle protein degradation in vivo. In postabsorptive rats, in vivo, infusion of the three BCAA together stimulates muscle protein synthesis as much as the infusion of a complete amino acid mixture or of a mixture of essential amino acids; the in vivo effect requires coinfusion of glucose or of small (physiological) doses of insulin, suggesting synergism between insulin and amino acids.(ABSTRACT TRUNCATED AT 400 WORDS)