Biomedical subjects
Publications and source records attributed to M E May.
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.
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.
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.
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.
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.
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.
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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.
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.
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.
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.
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.
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)
Previous studies have established spirometric criteria for arterial blood gas analysis during acute asthmatic attacks. However, only general guidelines have been available regarding the need for blood gas analysis during an acute exacerbation of chronic obstructive pulmonary disease (COPD). We conducted a study to determine the relationship between arterial blood gases and spirometry in 70 emergency department patients during acute exacerbations of COPD. Arterial blood gas analysis and spirometry were performed on arrival at the emergency department. All of the patients with a pCO2 of more than 45 mm Hg had an FEV1 of less than 35% of the predicted normal. We found patients with a pO2 of less than 60 mm Hg who had an FEV1 as high as 54% of the predicted normal. There was no correlation between the FEV1 and pO2. Because spirometry was not reliable for identifying patients with significant hypoxemia, we conclude that arterial blood gas analysis is indicated for patients presenting to the ED with acute exacerbations of COPD. Spirometric criteria that have been used to eliminate the need for arterial blood gases in asthmatic patients cannot be applied safely to patients with COPD.
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.
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.
We conducted a randomized, controlled double-blind study to determine whether intravenous administration of methylprednisolone early in the therapy for acute exacerbations of COPD would improve pulmonary function in the Emergency Department and reduce the need for hospitalization. Ninety-six patients completed the study. All were at least 50 years of age and had no history of asthma. Patients received aminophylline and hourly administration of aerosolized isoetharine. Methylprednisolone (100 mg) or physiologic saline solution was given within one-half hour of arrival in the Emergency Department. Spirometry was performed initially and after the third and fifth aerosol treatments. We found no greater improvement in FEV1 in the group receiving the steroid (37 percent) than in the control group (43 percent; NS). There was also no difference in the rate of hospitalization (33 percent in the steroid-treated group vs 30 percent in the control group; NS). We conclude that early administration of methylprednisolone does not affect the emergency phase of treatment for acute exacerbations of COPD.
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