Immune status and the efficacy of adjuvant radiotherapy for patients with localized Merkel cell carcinoma of the head and neck.

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.

Cause-specific mortality by race in low-income Black and White people with Type 2 diabetes.

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.

Efectividad y seguridad del uso de óxido nitroso para sedoanalgesia en urgencias / Safety and effectiveness of nitrous oxide for sedation-analgesia in emergency departments

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)

[Safety and effectiveness of nitrous oxide for sedation-analgesia in emergency departments]. / Efectividad y seguridad del uso de óxido nitroso para sedoanalgesia en urgencias.

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.

Effects of living room, Snoezelen room, and outdoor activities on stereotypic behavior and engagement by adults with profound mental retardation.

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.

Depression and dementia in aging adults with Down syndrome: a case study approach.

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.

A practical guide to intensive insulin therapy.

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.

Case report: lanreotide in the management of hypercalcemia of malignancy.

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.

Case report: diabetic ketoacidosis in a patient with glucagonoma.

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.

Case report: cardiotoxic calcemia.

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.

Resource utilization in treatment of diabetic ketoacidosis in adults.

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.

Enhanced enzyme-linked immunosorbant assay on membranes for the identification of mutants and pathogens.

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.

Energy content of diets of variable amino acid composition.

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.

Effect of insulin-induced hypoglycemia on protein metabolism in vivo.

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.

Theophylline concentrations in patients with acute exacerbation of COPD.

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.

Instability of orthophthalaldehyde reagent for amino acid analysis.

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.

Rapid assessment of average ratios: application to turnover studies.

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.

Multicompartment analysis of the effects of plasmapheresis. Application to lipid kinetics in humans.

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.

Relationship between arterial blood gases and spirometry in acute exacerbations of chronic obstructive pulmonary disease.

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.