Left heart disease: a frequent cause of early pulmonary hypertension in systemic sclerosis, unrelated to elevated NT-proBNP levels or overt cardiac fibrosis but associated with increased levels of MR-proANP and MR-proADM: retrospective analysis of a French Canadian cohort.

OBJECTIVES: Pulmonary hypertension (PH) causes mortality in systemic sclerosis (SSc). Pulmonary arterial hypertension (PAH) and left heart disease (LHD) are frequent causes of PH. Therefore, we studied PAH and LHD in early PH. METHOD: A total of 432 French Canadian SSc patients were studied retrospectively. All underwent screening for PH. We analysed clinical, serological, and radiographic data from 26 patients with early PH diagnosed by right heart catheterization (RHC). SSc patients with (n = 21) and without PH (n = 19) were prospectively re-evaluated by cardiac magnetic resonance imaging (MRI) and serial measurements of N-terminal pro-brain natriuretic peptide (NT-proBNP) and the haemodynamic biomarkers mid-regional pro-atrial natriuritic peptide (MR-proANP) and mid-regional pro-adrenomedullin (MR-proADM). RESULTS: The most frequent cause of early PH was LHD (58%). PAH was seen in 34% of patients. No association was found between the type of PH and autoantibodies. Early LHD-PH, but not early PAH, was associated with lower NT-proBNP (p = 0.024), but MR-proANP and MR-proADM levels were higher in early LHD-PH than in patients without PH (p = 0.014 and p = 0.012, respectively). Only one patient had abnormal cardiac MRI explaining LHD-PH. CONCLUSIONS: Early PH in SSc, like late PH, is heterogeneous and RHC is essential for determining its underlying cause. The most frequent cause of early PH was LHD. Levels of MR-proANP and MR-proADM, but not NT-proBNP, were increased in early LHD-PH, and may be more reliable than NT-proBNP as a biomarker of early PH in this subgroup of patients. Cardiac MRI did not explain LHD-PH. This study is the first to identify a high frequency of LHD in early PH correlating with normal NT-proBNP levels but increased MR-proANP and MR-proADM levels in SSc patients.

Morbidity following lower extremity fractures in men with spinal cord injury.

UNLABELLED: The Veterans Affairs Spinal Cord Dysfunction Registry from 2002 to 2007 was reviewed to determine whether men with spinal cord injury (SCI) and lower extremity fractures had an increased risk of complications compared to those without fractures. We determined that fractures are associated with significant consequences, particularly during the first month postfracture. INTRODUCTION: Despite increasing longevity, patients with SCI have a substantial number of illnesses and comorbid conditions. Lower extremity fractures are frequent events in these patients. However, whether these fractures are associated with any increased risk of complications in SCI is not certain. The purpose of this report was to determine the impact of lower extremity fractures on morbidities in men with SCI. METHODS: A population-based, nested, case-control (1,027 cases and 1,027 propensity-matched controls) of men enrolled in the Veterans Affairs Spinal Cord Dysfunction Registry from fiscal years 2002 to 2007 was reviewed to determine whether lower extremity fractures were associated with an increased risk for complications. RESULTS: In propensity score models matched for demographic (age, race) and SCI-related injury factors (level/completeness of SCI), Veterans Affairs-service connection status, and comorbidities, at 1 month following the fracture, there was an increased risk for respiratory infections, pressure ulcers, urinary tract infections, thromboembolic events, depression, and delirium (p ≤ 0.03 for all). Over 12 months, the only complication more common in fracture cases was pressure ulcers (p < 0.01), with an absolute difference of less than 2 % when compared to controls. There was no significant increased risk of cardiac arrhythmias at any time examined following fracture (≥0.12). CONCLUSIONS: Lower extremity fractures are associated with significant consequences in men with SCI during the first month postfracture, but they do not persist for a long term, except for pressure ulcers. Targeted interventions to prevent complications should be considered following lower extremity fractures in SCI, particularly in the first month following fracture.

Suppression of neuropeptide Y-elicited eating by adrenalectomy or hypophysectomy: reversal with corticosterone.

Neuropeptide Y (NPY) injected into the paraventricular hypothalamus (PVN) stimulates a robust eating response in the satiated rat. To examine whether the NPY-feeding system interacts with the pituitary-adrenal axis, the eating response to PVN injections of NPY (78 pmol) was tested in adult male rats before and after sham surgery, adrenalectomy (ADX), hypophysectomy (HYPX), and/or corticosterone (CORT) replacement therapy. In unoperated or sham groups, NPY elicited 5.7-8.8 g of food intake in 1 h as compared to 0.4-1.1 g for vehicle-injected animals. In ADX groups, the NPY-elicited response was reduced by 60-71%, to between 2.4 and 2.8 g. Likewise, the average response of the HYPX group was reduced by 69%, to 1.7 g. Corticosterone replacement, via subcutaneous implant of a 100 mg CORT pellet, normalized the NPY-induced feeding response in both the ADX and HYPX groups. These findings suggest that the hypothalamic NPY-feeding system is largely dependent upon circulating CORT and that no other adrenal or pituitary hormone is essential.

Paraventricular nucleus injections of peptide YY and neuropeptide Y preferentially enhance carbohydrate ingestion.

Neuropeptide Y (NPY) injected into the paraventricular nucleus (PVN) is known to elicit a powerful feeding response in satiated, brain-cannulated rats. The present experiment investigates the effect of peptide YY (PYY), a structurally-related peptide, on feeding behavior and, in addition, the effects of both PYY and NPY on the pattern of macronutrient selection. Injection of PYY directly into the PVN, in doses ranging from 7.8 to 235 pmol/0.3 microliters, caused a strong, dose-dependent stimulation of feeding behavior, as well as a small stimulation of drinking behavior, in satiated rats. The mean latency to eat was 9.3 min, with substantial feeding occurring within 30 min of the injection. At low doses, the increase in feeding was seen predominantly during the first hr. At the highest dose, in contrast, food intake continued to increase progressively over the next few hr. such that by 4 hr postinjection food intake was more than 20 g over vehicle baseline. In 1 hr tests with 3 pure macronutrient (protein, fat and carbohydrate) diets simultaneously available, PYY and NPY (78 pmol/0.3 microliters) both elicited a strong and selective increase in carbohydrate consumption, with little or no effect on protein or fat consumption. These results suggest that hypothalamic receptors sensitive to PYY and NPY may participate in the control of carbohydrate consumption.

Feeding and drinking elicited by central injection of neuropeptide Y: evidence for a hypothalamic site(s) of action.

Neuropeptide Y (NPY), which exists in very high concentrations in the brain, has been shown to elicit a powerful feeding response and a small drinking response in satiated rats. In order to delineate the brain sites sensitive to these effects, NPY was injected through chronic guide cannulas into seven different brain regions, and the food and water intake of satiated rats was measured one hr postinjection. Injection of NPY (78 pmoles) into hypothalamic areas, namely the paraventricular nucleus (PVN), ventromedial hypothalamus (VMH), and lateral hypothalamus (LH), elicited a strong feeding response; in contrast, injections into extra-hypothalamic areas, namely the amygdala, thalamus, and periaqueductal gray, were completely ineffective. Administration of NPY into the PVN and VMH also elicited a small drinking response; however, all other areas, including the LH, were insensitive to this effect. The findings that NPY was effective in the hypothalamus, as opposed to sites anterior, posterior, lateral or dorsal to this structure, suggest a hypothalamic site(s) of action for this neuropeptide.