Transmural distribution of calcium accumulation and glucose uptake in the calcium paradox in the rat left ventricle

The calcium paradox was induced in the isolated perfused rat heart and the transmural distributions of glucose uptake and calcium accumulations were determined using 2-deoxy-D-[3H]glucose and 45Ca2+ as tracers. The regional distribution of coronary flow was measured using radiolabelled microspheres. A significant transmural gradient was observed in left ventricular glucose uptake both in the control and the calcium paradox hearts: subendocardial and subepicardial glucose uptake rates were 5.70 +/- 0.65 mumol/min/g protein (mean +/- S.E.M.) and 4.29 +/- 0.35 mumol/min/g protein (P less than 0.05) in the control hearts, and 8.64 +/- 0.79 mumol/min/g protein and 4.09 +/- 0.71 mumol/min/g protein (P less than 0.01) in the paradox hearts. This increase in subendocardial glucose uptake in the calcium paradox was also significant (P less than 0.05), while the average left ventricular calcium accumulation was about 10-fold in the paradox hearts compared to the controls mumol x 10(-1)/min/g protein in the subendocardium and 14.02 +/- 0.93 mumol x 10(-1)/min/g protein in the subepicardium (P less than 0.001). The subendocardium received initially 30% more perfusion than subepicardium (P less than 0.01), but the subendocardial flow during the calcium depletion and replenishment periods was only 40% of that in the subepicardium (P less than 0.001) and the average myocardial flow was reduced by c. 60% (P less than 0.001). The data show clear transmural differences in the alterations associated with the calcium paradox. This suggests that the calcium paradox induced myocardial injury is unevenly distributed across the left ventricular wall, this uneven distribution possibly being due to regional differences in the damage of mitochondrial energy production.     

Further evidence of the in vivo role of erythropoietin or companion molecules induced by hypoxia on proliferation and continuing differentiation of BFU-e in PCDC

Normal and plethoric bone marrow cells were grown in plasma clot diffusion chambers (PCDC) implanted into the peritoneum of normal mice or mice submitted to 7 her of hypoxia (23,000 ft) daily, on a single day or on 2 consecutive days at different times after implantation of the PCDC's. Daily discontinuous hypoxia (DDH) produced more 6-day bursts than other treatments. Hypoxia on days 1 and 2 after implantation was nearly as effective as DDH on day-6 bursts. Later bouts of hypoxia or a singly hypoxic exposure on day 1 or 2 was less effective. Erythropoietin (Ep) levels were measured by bioassay on both diffusion chamber (DC) contents and serum. Serum Ep levels peaked at 160 mU/ml after a 7-hr hypoxic exposure while the DC content Ep levels were in the nondetectable range (less than 50 mU/ml). The data implies that either higher than normal Ep levels or a companion molecules (s) produced by hypoxia are required for 1-2 days early in the culture period of force an increasing number of BFU-d-e down the erythrocytic pathway and thus increase red cell production at times of need in vivo.     

Effect of posture on respiratory function and drive in preterm infants prior to discharge

Our objective was to determine the effect of posture on respiratory function and drive in prematurely born infants immediately prior to discharge. Twenty infants (6 oxygen-dependent), median gestational age 29 weeks (range, 25-32), were studied at a median postconceptional age (PCA) of 36 weeks (range, 33-39). On 2 successive days, infants were studied both supine and prone; each posture was maintained for 3 hr. The order on each day in which postures were studied was randomized between infants. At the end of each 3-hr period, tidal volume (Vt), inspiratory (Ti) and expiratory (Te) time, respiratory rate, and minute ventilation were measured. In addition, respiratory drive was assessed by measuring the pressure generated in the first 100 msec of an imposed airway occlusion (P(0.1)), and respiratory muscle strength was assessed by recording the maximum inspiratory pressure (Pimax) generated against an occlusion which was maintained for at least five breaths. Overall, tidal volume was higher (P < 0.05), but respiratory rate (P < 0.05), P(0.1) (P < 0.05), and Pimax (P < 0.05) were lower in the prone compared to the supine position. There were no significant differences in Ti or Te between the two postures. In oxygen-dependent infants only, minute volume was higher in the prone position (P < 0.05). In conclusion, posture-related differences in respiratory function are present in prematurely born infants studied prior to neonatal unit discharge.     

Thalidomide as salvage therapy for chronic graft-versus-host disease

Thalidomide has been reported to be an effective agent for treatment of chronic graft-versus-host disease (CGVHD). To determine the efficacy of this agent in patients with refractory CGVHD a total of 80 patients who failed to respond to prednisone (PSE) or PSE and cyclosporine (CSA) were treated with thalidomide. Sixteen patients (20%) had a sustained response, 9 with a complete remission and 7 with a partial response. Twenty-nine patients (36%) had thalidomide discontinued because of side effects, which included sedation, constipation, neuritis, skin rash, and neutropenia. Side effects were reversible with drug discontinuation except for mild residual neuritis in one case. Rashes and neutropenia have not previously been reported as thalidomide side effects when used for CGVHD treatment. We conclude thalidomide is immunosuppressive and active in the treatment of CGVHD. A high incidence of reversible side effects limited dose intensity and reduced the number of patients who could benefit from treatment.     

Novel approach to examining first cardiovascular events after hypertension onset

Hypertension confers risk for multiple types of cardiovascular events, but competing risks for these outcomes are unknown. We estimated the competing risks over 12 years after hypertension onset among cases and age-, sex-, and examination-matched controls using competing Cox cumulative incidence and proportional hazards models. We included all Framingham Heart Study subjects examined after 1977 with new-onset hypertension who were free of cardiovascular disease. There were 645 men and 702 women with new-onset hypertension (mean age: men, 55+/-12 years; women, 59+/-12 years). Compared with matched nonhypertensive controls, subjects with new-onset hypertension were more likely to experience a cardiovascular event first rather than noncardiovascular death. Among new-onset hypertensives, the 12-year competing cumulative incidence of any cardiovascular end point as a first event in men was 24.7%, compared with 9.8% for noncardiovascular death (hazards ratio [HR], 2.53; 95% confidence interval [CI], 1.83 to 3.50); in women, the competing incidences were 16.0% versus 10.1%, respectively (HR, 1.58; 95% CI, 1.13 to 2.20). The most common first major cardiovascular events were hard coronary disease (8.2%) in men and stroke (5.2%) in women. Type and incidence of first cardiovascular events varied by age and severity of hypertension at onset, with stroke predominating among older subjects with new-onset hypertension. After hypertension onset, cardiovascular events are more likely to occur first as opposed to noncardiovascular death. Types of initial events differ by gender, age, and severity of hypertension at onset. These results represent a novel approach to understanding the complications of hypertension and may help target therapies for patients with new-onset hypertension to optimize prevention strategies.     

Yearly diagnostic yield of colonoscopy in patients age 80 years or older,with a special interest in colorectal cancer

Aim: A high diagnostic yield of colonoscopy has been reported in elderly patients, but there is no data on the yearly yield. Our aim was to detect the yearly yield of colonoscopy in elderly patients. Methods: All consecutive endoscopies in the years 1992–2009 were included. Important endoscopic diagnoses were defined as colorectal cancer (CRC), polyps, diverticuli and inflammation. Results: In total, 19 569 endoscopies were performed, of which 1706 (8.7%) were in patients age 80 years or older. The number of women was significantly higher (P < 0.001). The percentage of patients who were 80 years or older was higher than in the general population and remained stable during the study period, though there has been a proportional increase of elderly people in the general population. Inconclusive procedures were present in 106 (6.2%) elderly patients compared with 277 (1.6%) patients under 80 years of age (P < 0.001). There were no significant changes in the consecutive years. A procedure revealing no endoscopic diagnosis was observed less often in patients who were 80 years or older (P < 0.001). CRC was diagnosed in 221 (19.6%) older patients. This figure remained more or less constant each year. Polyps were seen in 448 (8.8%) patients 80 years of age or older. The percentage of patients with diverticuli and inflammation was constant. The number of patients 80 years or older with CRC and polyps rose at a lower rate than the number of older people in the general population. Conclusion: The yield of colonoscopy in patients 80 years or older was high and constant over the years. The number of tumors rose less than expected compared to the increase of elderly in the general population. Geriatr Gerontol Int 2012; 12: 298–303.     

Perinatal cerebral insults alter auditory event-related potentials

Background

Auditory event-related potentials (AERPs) can be used as indices of neural information processing. Altered AERPs have been reported in children and young adults with frontal lobe infarction.

Aim

To test the hypothesis that perinatal brain injury affects cortical auditory processing.

Methods

We assessed AERPs at term, 6 and 12 months of age in preterm infants [n = 9, median gestational age (GA) 27.9, range 23.9-30.0 wk], term infants with perinatal intracerebral hemorrhage (ICH) [n = 5, GA 40.3, range 37.4-42.3 wk], and term infants with perinatal asphyxia [n = 4, GA 39.4, range 37.9-40.3 wk]. Healthy preterm (n = 16) and term infants (n = 22) served as controls. A harmonic tone of 500-Hz frequency was used as standard and of 750-Hz as deviant stimulus. Mean AERP amplitudes were calculated over 100 ms periods from 50 to 350 ms. The developmental outcome was followed until 2 years of age.

Results

The term ICH (p = 0.012) and asphyxia (p = 0.0016) group had smaller or more negative responses to the deviant, resulting in smaller or more negative MMR amplitudes than those of the controls. The preterm ICH group did not differ significantly from their preterm born controls. MMR varied in all patient groups and was not associated with adverse outcome.

Conclusion

AERP alterations suggest that perinatal cerebral insults affect cortical auditory processing.