Micronutrients in African-Americans with decompensated and compensated heart failure

Heart failure is thought to be more common and of greater severity in African-Americans (AAs). Potential mechanisms remain uncertain. The importance of micronutrient deficiencies in the pathophysiologic expression of congestive heart failure (CHF) in AAs remains to be explored, including hypovitaminosis D, which can promote secondary hyperparathyroidism (SHPT), together with hypozincemia and hyposelenemia, the 2 most crucial trace minerals integral to diverse biologic functions. Serum parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH)D), Zn, and Se were monitored in 30 AAs hospitalized during June through December 2005, with decompensated failure and reduced ejection fraction (EF) (<35%) of predominantly nonischemic origin treated with an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB), furosemide, and spironolactone. Based on their symptomatic status before hospitalization, 15 patients were stratified as having protracted (>or=4 weeks) CHF, whereas 15 patients had short-term (1-2 weeks) CHF. These hospitalized patients were compared with 10 AA outpatients with stable, similarly treated compensated failure and comparable EF, and 9 AA normal volunteers without cardiovascular disease. Serum PTH was elevated in all patients with protracted CHF and in 60% of patients with short-term CHF, but not in compensated patients or normal volunteers. However, serum 25(OH)D was reduced in all patients with >or=4 weeks and 80% with either 1-2 weeks CHF or compensated failure compared with volunteers. Serum Zn was below normal in 11 of 15 patients with protracted CHF, in 8 of 15 patients with shorter duration CHF, and in 5 of 10 patients with compensated failure. Serum Se was reduced in all patients with >or=4 weeks, 60% with short-term CHF, and 90% of compensated patients. Concomitant to hypovitaminosis D, hypozincemia, and hyposelenemia, SHPT is a covariant of CHF in housebound AAs.     

The basic property of Lys385 is important for potentiation of the human α1 glycine receptor by ethanol

Ethanol alters the function of several members of the Cys-loop ligand-gated ion channel superfamily. Recent studies have shown that the sensitivity of the α1 glycine receptor (GlyR) to ethanol can be affected by the state of G protein activation mediated by the interaction of Gβγ with intracellular amino acids in the GlyR. Here, we evaluated the physicochemical property of Lys385 that contributes to ethanol modulation by using mutagenesis, patch-clamp, and biochemical techniques. A conserved substitution (K385R) did not affect either the apparent glycine EC?? (40 ± 1 versus 41 ± 0.5 μM) or the ethanol-induced potentiation (53 ± 5 versus 46 ± 5%) of the human α1 GlyR. On the other hand, replacement of this residue with glutamic acid (K385E), an acidic amino acid, reduced the potentiation of the GlyR to 10 ± 1%. Furthermore, mutations with a hydrophobic leucine (K385L), a hydrogen bond donor glutamine (K385Q), or a neutral residue (K385A) also reduced ethanol modulation. Finally, substitution by a large and hydrophobic residue (K385F) and deletion of 385 (Lys385_) reduced ethanol modulation to 10 ± 4 and 17 ± 0.4%, respectively. Experiments using dynamic cysteine substitution with a methanethiosulfonate reagent and homology modeling indicate that the basic property and the position of Lys385, probably because of its interaction with Gβγ, is critical for ethanol potentiation of the receptor.     

Evolution of peripheral vs metabolic perfusion parameters during septic shock resuscitation. A clinical-physiologic study

Purpose

Perfusion assessment during septic shock resuscitation is difficult and usually complex determinations. Capillary refill time (CRT) and central-to-toe temperature difference (Tc-toe) have been proposed as objective reproducible parameters to evaluate peripheral perfusion. The comparative evolution of peripheral vs metabolic perfusion parameters in septic shock resuscitation has not been studied. We conducted a prospective observational clinical-physiologic study to address this subject.

Methods

Patients with sepsis-related circulatory dysfunction were resuscitated according to a standard local algorithm. Perfusion assessment included serial determinations of metabolic (central venous O₂ saturation [Scvo₂] and central venous to arterial Pco₂ gradient [P(cv-a)co₂]) and peripheral perfusion parameters (CRT and Tc-toe, among others). Successful resuscitation was defined as a normal plasma lactate at 24 hours.

Results

Forty-one patients were included. The presence of normal values for both CRT and Tc-toe considered together at 6 hours was independently associated with a successful resuscitation (P = .02), as compared with the behavior of metabolic parameters. Capillary refill time was the first parameter to be significantly normalized.

Conclusion

Early recovery of peripheral perfusion anticipates a successful resuscitation compared with traditional metabolic parameters in septic shock patients. Our findings support the inclusion of serial peripheral perfusion assessment in multimodal monitoring strategies for septic shock resuscitation.     

Health services utilization by the adult population in São Leopoldo, Rio Grande do Sul State, Brazil: a cross-sectional study

The aim was to describe healthcare utilization by adults in a Brazilian city. The outcomes were medical appointments in the previous month and use of public (Unified National Health System - SUS) versus private healthcare services. A population-based cross-sectional study with 1,098 adults aged 20 years or over was carried out. No medical appointment in the previous month was reported by 623 persons (56.7%, 95%CI: 53.8-59.7). Of the 487 individuals who had consulted a physician, 51.2% used the public healthcare system, 26.9% private care, and 22% other services. Consultation was associated with female gender and older age. Individuals in the intermediate categories for income, schooling, and socioeconomic status consulted less than the corresponding high and low categories. The results suggest that the middle class in this city lacks the purchasing power to seek care in the private sector while also using public services less, thus generally seeking healthcare less frequently.     

Unilateral headache with bilateral internal ophthalmoplegia

We describe the case of a young woman suffering from migraine. After some years, the headache started to be accompanied by internal ophthalmoplegia. Mydriasis was unilateral and after a few months became bilateral. The ophthalmoplegic migraine is a rare type of headache and it is characterized by paresis of one or more of the third, fourth or sixth cranial nerves. Migraine attacks associated with mydriasis (internal ophthalmoplegia) are extremely rare. Triptan therapy resolved mydriasis, but not the headache.     

PET-adapted therapy after three cycles of ABVD for all stages of Hodgkin lymphoma: results of the GATLA LH-05 trial

The role of Ann Arbor staging in determining treatment intensity after achieving a negative positron emission tomography (PET) has not been established in classical Hodgkin lymphoma (cHL). Patients with stage I–IV cHL, received three cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and an interim PET scan (PET3). PET3-negative patients received no further therapy. PET3-positive patients received three additional cycles of ABVD plus involved-field radiation therapy or salvage chemotherapy, if refractory to ABVD, and were re-evaluated by PET scan (PET6). Study endpoints were 3-year progression-free survival (PFS) and overall survival (OS) rates. Two hundred and thirty-nine patients with early-stage and 138 with advanced-stage were evaluable. Overall, 260 patients (70%) were PET3-negative and had higher 3-year PFS (90% vs. 65%; P < 0·0001) and OS (98% vs. 92%; P = 0·007) rates than PET3-positive patients. All PET3-negative patients, regardless of disease stage at diagnosis, achieved similarly good PFS (90–91%; P = 0·76) and OS (97–99%). The only independent prognostic factor for PFS was PET3-negativity (Hazard ratio 3·8; 95% confidence interval 2·4–6·3; P < 0·0001). This study suggests that cHL patients who achieve a negative PET3 following ABVD have an excellent outcome, regardless of stage at diagnosis. An appropriately powered, phase III trial will be necessary to confirm these findings.