Inaccurate measurement of a polymeric IgA myeloma protein by nephelometric and fluorometric instrumentation

The concentration of IgA in a serum was 5.99 g/L as assayed nephelometrically with reagent from one company, but varied between 5 and 3 g/L (for sixfold and 36-fold dilutions, respectively) without giving a definitive answer when assayed with reagent from another source. Immunofixation electrophoresis indicated an IgA lambda monoclonal protein of 45 g/L. Radial immunodiffusion showed two components, having a total concentration of 41 g/L. By fluorometry the IgA was 3.1 g/L. Increasing the dilution caused the (dilution-corrected) lower values to increase. Although the most frequent cause of such discrepant findings is an IgA2 myeloma, which occurs in about one of every 100 myeloma cases, Ouchterlony double diffusion indicated the major component to be IgA1. A polymer, Mr 670,000, was identified by column chromatography. Contrary to the usual behavior of polymers assayed with radial immunodiffusion, which underestimates their concentration, this polymer reached equivalency in agreement with its true concentration as assayed by the Mancini-Heremans technique.     

Cardiovascular and neuroendocrine responses to behavioral stress after central or peripheral barodenervation in rats

The cardiovascular and neuroendocrine responses to acute behavioral stress were evaluated in rats after disruption of the baro reflexes by electrolytic lesions of the nucleus tractus solitarii (NTS) or sinoaortic denervation (SAD). Rats with NTS lesions or SAD showed significantly greater increases in mean arterial pressure (MAP) and plasma norepinephrine (NE) concentrations than control rats during a single 30-min escape-avoidance test. In addition, the increases in MAP and plasma NE concentration of NTS lesion rats were significantly greater than those of SAD rats. However, NTS lesion raats showed no increase in plasma renin activity (PRA), as observed in the other groups. Thus, disruption of the baroreflexes by NTS lesions oraugments the arterial pressure and plasma NE responses to stress. Additionally, NTS lesions appeared to eliminate the neurons or fibers of passage participating in the sympathetically mediated increase in PRA.     

Safety of regadenoson, an adenosine A2A receptor agonist for myocardial perfusion imaging, in mild asthma and moderate asthma patients: A randomized, double-blind, placebo-controlled trial

Background. Patients with reactive airways are at risk for adenosine-induced bronchocon-striction, mediated via A_2B and/or A₃ adenosine receptors. Methods and Results. To examine the effects of regadenoson, a selective adenosine A_2A receptor agonist, on airway resistance, we conducted a randomized, double-blind, placebo-controlled crossover trial in asthmatic patients with a positive adenosine monophosphate challenge test. The mean ratio of the forced expiratory volume in 1 second (FEV₁) at each tested time point relative to the baseline FEV₁ was significantly higher after treatment with regadenoson compared with placebo from 10 to 60 minutes after treatment. One patient had a substantial but asymptomatic FEV₁ reduction (−36.2%) after regadenoson that reversed spontaneously. The most common adverse events with regadenoson were tachycardia (66%), dizziness (53%), headache (45%), and dyspnea (34%). The mean heart rate significantly increased with regadenoson (maximum of +10.4 beats/min) versus placebo. Conclusions. In this pilot safety study of 48 patients with mild or moderate asthma who had bronchial reactivity to adenosine monophosphate, regadenoson was safe and well tolerated. CV Therapeutics provided financial assistance for this study.     

Survival in patients operated on for pathologic fracture: implications for end-of-life orthopedic care.

PURPOSE: Life expectancy is routinely used as part of the decision-making process in deciding the value of surgery for the treatment of bone metastases. We sought to investigate the validity of frequently used indices in the prognostication of survival in patients with metastatic bone disease. METHODS: The study prospectively assessed 191 patients who underwent surgery for metastatic bone disease. Diagnostic, staging, nutritional, and hematologic parameters cited to be related to life expectancy were evaluated. Preoperatively, the surgeon recorded an estimate of projected life expectancy for each patient. The time until death was recorded. RESULTS: Kaplan-Meier survival analyses indicated that the survival estimate, primary diagnosis, use of systemic therapy, Eastern Cooperative Oncology Group (ECOG) performance status, number of bone metastases, presence of visceral metastases, and serum hemoglobin, albumin, and lymphocyte counts were significant for predicting survival (P < .004). Cox regression analysis indicated that the independently significant predictors of survival were diagnosis (P < .006), ECOG performance status (P < .04), number of bone metastases (P < .008), presence of visceral metastases (P < .03), hemoglobin count (P < .009), and survival estimate (P < .00005). Diagnosis, ECOG performance status, and visceral metastases covaried with surgeon survival estimate. Linear regression and receiver-operator characteristic assessment confirmed that clinician estimation was the most accurate predictor of survival, followed by hemoglobin count, number of visceral metastases, ECOG performance status, primary diagnosis, and number of bone metastases. Nevertheless, survival estimate was accurate in predicting actual survival in only 33 (18%) of 181 patients. CONCLUSION: A better means of prognostication is needed. In this article, we present a sliding scale for this purpose.     

Transcranial Doppler Ultrasound: A New Method of Monitoring Hemispheric Anesthetization During the Intracarotid Amobarbital Procedure

BACKGROUND: Electroencephalography (EEG) is traditionally used to assess the duration of hemispheric anesthetization and to monitor return of function in the anesthetized hemisphere during the intracarotid amobarbital procedure (IAP), but EEG changes are not consistently seen. The authors evaluated the role of continuous transcranial Doppler (TCD) monitoring as an alternative to EEG. METHODS: The authors performed both continuous TCD monitoring and EEG during the IAP in 10 patients with medically intractable partial epilepsy. Mean velocities were monitored continuously in both middle cerebral arteries (MCAs), and changes in MCA velocities on continuous TCD monitoring were time locked with the EEG changes. RESULTS: The average mean MCA velocities were within normal limits bilaterally (50-85 cm/s) in all patients at baseline. Mean MCA velocites increased in all patients to 95-115 cm/s at the start of the test when the patients were asked to raise their hands and start counting. After injection of sodium amobarbital, mean MCA velocities in all patients dropped dramatically on the ipsilateral side to values of 12-39 cm/s and returned to the baseline average value when the hemiparesis recovered. In 8 patients, the duration of delta activity on EEG coincided with the time interval during which the mean MCA velocities were low on TCD monitoring. In 2 patients, despite the presence of hemiparesis clinically and a drop in mean MCA velocities on the ipsilateral side on continuous TCD monitoring, EEG remained normal on the ipsilateral side. CONCLUSIONS: Continuous TCD monitoring may be a more sensitive method than EEG in determining the duration of hemispheric anesthetization during IAP. Because the items for assessment of memory are presented during the period of hemispheric anesthetization, TCD may be useful in more precisely defining the time window for memory testing.     

Prevention of chronic diseases: a call to action

Chronic (non-communicable) diseases—principally cardiovascular diseases, cancer, chronic respiratory diseases, and diabetes—are leading causes of death and disability but are surprisingly neglected elements of the global-health agenda. They are underappreciated as development issues and underestimated as diseases with profound economic effects. Achievement of the global goal for prevention and control of chronic diseases would avert 36 million deaths by 2015 and would have major economic benefits. The main challenge for achievement of the global goal is to show that it can be reached in a cost-effective manner with existing interventions. This series of papers in The Lancet provides evidence that this goal is not only possible but also realistic with a small set of interventions directed towards whole populations and individuals who are at high risk. The total yearly cost of the interventions in 23 low-income and middle-income countries is about US$5·8 billion (as of 2005). In this final paper in the Series we call for a serious and sustained worldwide effort to prevent and control chronic diseases in the context of a general strengthening of health systems. Urgent action is needed by WHO, the World Bank, regional banks and development agencies, foundations, national governments, civil society, non-governmental organisations, the private sector including the pharmaceutical industry, and academics. We have established the Chronic Disease Action Group to encourage, support, and monitor action on the implementation of evidence-based efforts to promote global, regional, and national action to prevent and control chronic diseases.     

The effect and safety after extended use of continuous negative pressure of 75 mmHg over mesh and allodermis graft on open sternal wound from oversized heart transplant in a 3‐month‐old infant*

Negative pressure therapy (NPT) has been reported to be effective in treating infants with open chest wounds. This report further supports its effectiveness by treating a 3‐month‐old infant with a 12 × 7 cm sized opening in its chest after an oversized heart transplantation. After applying a mesh and allodermis over the defect, 75‐mmHg continuous negative pressure was set and used for an extended period of 104 days. The haemodynamic status was evaluated during this period. The wound was closed with secondary intention and it healed well after NPT. There was no haemodynamic instability during the treatment course. The extended use of a continuous negative pressure of 75 mmHg over the mesh and alloderm graft was a reliable and safe option to close the massive defect in the chest of a 3‐month‐old infant.