Ejection Fraction/Velocity Ratio Identifies Prosthesis‐Patient Mismatches in Patients With Aortic Bioprosthetic Valves and Left Ventricular Dysfunction

Objectives. Recently, a new echocardiographic nonflow corrected index (ejection fraction/velocity ratio [EFVR] = percent left ventricular ejection fraction [EF]/maximum aortic gradient) has been introduced and has shown excellent accuracy in quantifying the effective orifice area (EOA) in native aortic valves and bio‐prostheses. The objective of this study was to assess the utility of the EFVR to quantify the indexed EOA in patients with an aortic bioprosthesis and left ventricular dysfunction considering an indexed EOA value of 0.85 cm²/m² or less to be indicative of a prosthesis‐patient mismatch (PPM), defined as an EOA of the inserted prosthetic valve of less than that of the normal human valve. Methods. We studied 100 patients (62 men and 38 women; mean age ± SD, 71 ± 8.6 years) with an aortic bioprosthesis and left ventricular dysfunction (EF ≤49%), and we evaluated the indexed EOA by both the continuity equation (CE) and EFVR. Results. We found a significant linear correlation between the CE and EFVR (r = 0.85; P < .0001) and good agreement between the two methods in identifying patients with an indexed EOA of 0.85 cm²/m² or less; the correlation began to become nonlinear for patients with an indexed EOA of greater than 1.2 cm²/m², which was not clinically relevant. Notably, all 11 patients with a discrepancy between the indexed EOA and EFVR (ie, EFVR ≤1.0 and indexed EOA >0.85 cm²/m²) also showed an indexed EOA of greater than 0.85 but less than or equal to 1.0 cm²/m² (meaning the presence of a mild PPM). Conclusions. The EFVR can be considered a reliable echocardiographic alternative to the CE, especially in conditions in which that is technically difficult, allowing identification of a PPM (indexed EOA ≤0.85 cm²/m²) with excellent sensitivity and specificity.     

Phenytoin/isradipine interaction causing severe neurologic toxicity

OBJECTIVE: To report a young man on phenytoin who developed acute neurologic symptoms after isradipine was introduced to his treatment regimen and discuss the possible causes of this drug interaction. CASE SUMMARY: A 21-year-old white man, with propionic acidemia and seizures treated with phenytoin and carbamazepine, was started on isradipine for essential hypertension. Soon thereafter, he developed acute and severe lethargy, ataxia, dysarthria, and weakness that resolved once isradipine was withheld. Phenytoin concentrations were within normal limits or elevated, despite sequential reductions of phenytoin dosage, during concomitant isradipine administration. DISCUSSION: Isradipine is a known inhibitor of the CYP450 isoenzyme family. Although the daily dose of phenytoin was decreased significantly, phenytoin blood concentrations remained high, suggesting a pharmacokinetic interaction. Previously, the patient had never had neurologic symptoms associated with increased phenytoin concentrations. This also indicates a likely pharmacodynamic interaction between phenytoin and the calcium-channel blocker. Both phenytoin and isradipine have been shown to bind to calcium channels and to inhibit calcium entry into the cells. Binding of isradipine to the brain has been described in humans and animals, and calcium-channel blockers have been shown to cause potentiation of anticonvulsant action of phenytoin. CONCLUSIONS: Acute pharmacokinetic and pharmacodynamic interactions between phenytoin and isradipine were probably responsible for the lethargy, dysarthria, ataxia, and weakness our patient developed. The combination of phenytoin and calcium-channel blockers should be used with caution.     

Long-term psychosocial functioning after Ilizarov limb lengthening during childhood: 37 patients followed for 2�C14 years

Background and purpose Few studies have been concerned with the patient''s perception of the outcome of limb lengthening. We describe the psychological and social functioning after at least 2 years of follow-up in patients who had had a leg length discrepancy and who had undergone an Ilizarov limb lengthening procedure.Patients and methods Self-esteem and perceived competence were measured in 37 patients (aged 17–30 years) both preoperatively and at a mean follow-up of 7 (2–14) years. At follow-up, health-related quality of life, functioning at school, daily activities, and treatment-related experiences were measured, and also retrospectively for the preoperative period.Results Preoperative and follow-up scores for self-esteem were similar. Overall perceived competence scores at follow-up were comparable to that of a healthy normal population. Patients'' perceived athletic competence was lower and their perceived level of behavioral conduct was higher. At follow-up, patients had more positive appraisal of their physical appearance. Most health-related quality of life scores were not significantly different to those of the healthy normal population, apart from a reduced gross motor function, less vitality, and more pain. Patients with a remaining leg length inequality (LLI) of more than 2 cm had lower quality of life scores for gross motor function, sleep, pain, vitality, and depressive feelings.Interpretation At an average of 7 years after an Ilizarov limb lengthening procedure, patients still have physical restraints, but they appear to have normal psychosocial functioning, self-esteem, and perceived competence. These patients have quality of life scores comparable to those of norm groups, apart from a reduced gross motor function, less vitality and more pain. Residual LLI of more than 2 cm remains important even after long-term follow-up; these patients report lower quality of life.     

Neurocognitive functioning in the early stages of bipolar disorder: visual backward masking performance in high risk subjects

Introduction  Cognitive deficits, including deficits in early information processing, are associated with remitted bipolar disorder. The temporal relationship between these deficits and the clinical course is not known. The current study investigated whether or not deficits in early information processing were present before the onset and/or during the early stages of bipolar disorder. Methods  Unaffected and remitted high risk offspring of well-characterized bipolar parents completed a visual backward masking task. For comparison we included a cohort of unaffected offspring of well parents and a clinically referred group of remitted bipolar patients. Results  There was no evidence of a deficit in early information processing in well high risk subjects. As expected, the referred patient group had the highest error rates. After excluding the patients, interaction effect showed that the affected remitted high risk subjects performed differently in terms of error rates than unaffected high risk and control subjects. There were no significant differences in response times across study groups. Exploratory analyses revealed an association between a lifetime history of psychosis and increased errors on the task. Conclusions  There was no evidence of a vulnerability in early information processing in offspring at risk for bipolar disorder. However, there were emergent changes in performance in the affected remitted high risk group. Psychosis appears to be an important clinical correlate associated with cognitive deficits. Mapping of the early course of bipolar disorder and associated changes in cognition has important implications for establishing critical periods for intervention.     

BDNF protein levels are decreased in transformed lymphoblasts from lithium-responsive patients with bipolar disorder

Objective

Brain-derived neurotrophic factor (BDNF) is a key factor in neuroplasticity and has been implicated in the affective disorders; studies have demonstrated elevated BDNF in patients taking lithium and other mood stabilizers. The objective of our study was to analyze BDNF in lithium-responsive patients with bipolar disorder (BD) to further understand the role of BDNF in the pathophysiology of BD.

Methods

Using enzyme-linked immunosorbent assay, we measured transformed B lymphocytes for BDNF protein.

Results

BDNF levels were 36% lower in lymphoblasts from patients with BD (n = 12), compared with matched control participants (n = 13), and 55% lower when compared with their unaffected relatives (n = 14). Lithium significantly decreased BDNF levels in patients with BD and healthy control participants, although BDNF levels remained lower (33%) in the BD group posttreatment.

Conclusion

Decreased BDNF may constitute part of the pathophysiologic process of BD in a lithium-responsive subgroup of individuals with this disease. A compensatory mechanism protecting the genetically predisposed unaffected relatives from phenotypic expression of BD is suggested.Medical subject headings: bipolar disorder, brain-derived neurotrophic factor, enzyme-linked immunosorbent assay, lithium     

Rapid cycling bipolar disorders in primary and tertiary care treated patients

Objective:  Rapid cycling (RC) affects 13–30% of bipolar patients. Most of the data regarding RC have been obtained in tertiary care research centers. Generalizability of these findings to primary care populations is thus questionable. We examined clinical and demographic factors associated with RC in both primary and tertiary care treated populations.
Method:  Clinical data were obtained by interview from 240 bipolar I disorder (BDI) or bipolar II disorder (BDII) community-treated patients and by chart reviews from 119 bipolar patients treated at an outpatient clinic of a teaching hospital.
Results:  Lifetime history of rapid cycling was present in 33.3% and 26.9% of patients from the primary and tertiary care samples, respectively. Among community-treated patients, lifetime history of RC was significantly associated with history of suicidal behavior and higher body mass index. There was a trend for association between RC and BDII, psychiatric comorbidity, diabetes mellitus, as well as lower age of onset of mania/hypomania. In the tertiary care treated sample there was a trend for association between lifetime history of RC and suicidal behavior. Tertiary versus primary care treated subjects with lifetime history of RC demonstrated markedly lower response to mood stabilizers.
Conclusions:  Lifetime history of RC is highly prevalent in both primary and tertiary settings. Even primary care treated subjects with lifetime history of RC seem to suffer from a more complicated and less treatment-responsive variant of bipolar disorder. Our findings further suggest relatively good generalizability of data from tertiary to primary care settings.     

Stimulation of new bone formation by the proteasome inhibitor, bortezomib: implications for myeloma bone disease

Impaired bone formation contributes to the lack of bone healing in multiple myeloma and there is a need for agents with bone anabolic properties to reverse the bone deficit in patients. Bortezomib, a proteasome inhibitor with antitumour efficacy in myeloma patients, enhanced new bone formation in mouse calvarial cultures; this effect was blocked by dickkopf 1(Dkk1), an antagonist of Wnt signalling implicated in myeloma bone disease. Bortezomib inhibited Dkk1 expression in calvariae and bone marrow-derived stromal cells, suggesting a novel mechanism by which bortezomib exerts its effects in bone. Clinical trials in patients with myeloma bone disease are needed to validate these results.     

Erythrocytic acid phosphatase genetic polymorphism and cardiovascular risk in health children and adolescents]

OBJECTIVE: To correlate, in a sample of healthy children and adolescents, the activity of the enzyme acid phosphatase (ACP) with its different genetic phenotypes and of these with some cardiovascular risk parameters such as body mass index (BMI), percentage of total fat mass (%TFM), trunk fat (TF), insulin resistance, and the arterial blood pressure (BP). DESIGN AND METHODS: The sample was composed of 173 healthy children and adolescents, 96 (55.5%) F and 77 (44.5%) M, with ages between 10 and 16 years (mean: 13.04 +/- 1.68). The ACP activity was determined through a spectrophotometric method and its phenotypes through isoelectric focusing electrophoresis. BMI (Kg/m2) and the BP were obtained by standardized methods. Glycemia determined by the glucose oxidase method and insulinemia by RIA method. Insulin resistance based on the homeostasis model assessment (HOMA) was calculated as: [fasting insulin (microU/ml) x fasting glucose (mmol/l)]: 22.5. The %TFM and TF were determined by dual energy x-ray absorptiometry (DXA). The statistical methods used were ANOVA, the Pearson correlation and the Student's test. RESULTS: The distribution of the phenotypes were the following--absolute versus relative frequencies: BB-74 (48.4%), AB-52 (34%), AA-16 (10.5%), BC-7 (4.6%), AC-3 (2%) and CC-1 (0.7%). ACP activities (mean: 321.04 +/- 84.56) were significantly different among the phenotypes (p < 0.001). The smallest activity was observed in the AA individuals, the highest in CC, followed by BC (247.17 +/- 66.52 and 767.30 and 362.44 +/- 91.56 respectively). Glycemia was higher in the AA individuals (4.61 +/- 0.37) compared to CC + BC (4.40 +/- 0.31) (p = 0.08). A direct correlation was verified between HOMA and BP, both diastolic (p = 0.013, r = 0.250) and systolic (p = 0.015, r = 0.246), as well as of these with BMI (mean: 20.57 +/- 3.24) and insulinemia (p = 0.016, r = 0.215; p = 0.004, r = 0.280 and p = 0.007, r = 0.240; p = 0.008, r = 0.261 respectively for diastolic and systolic BP). There were no significant difference of BMI between sexes, nor of this as well as of % TFM and TF among the different genetic phenotypes of ACP. CONCLUSIONS: The smallest enzymatic activity of ACP seems to be associated with the AA individuals, where a trend for higher glycemia was verified. BMI, HOMA and insulinemia, due to their significant direct relationship with diastolic and systolic BP in this sample of children and adolescents may warrant more future attention in the evaluation of cardiovascular risk. There were no significant differences of HOMA, BMI, %TFM, TF nor of BP among the different ACP genetic phenotypes.     

Impacts of non-transmissible chronic diseases on social security benefits

This paper strives to identify the current impact of Non-Transmissible Chronic Diseases (NTCDs) on sickness and disability benefits paid out by Brazil's National Social Security Institute (INSS) between 2000 and 2002. A total of 17,970 new cases were studied, registered at the two local agencies in Recife, Pernambuco State, Northeast Brazil. Initially the cases were divided up according by major diseases groups, following the CID-10 classification. Osteomuscular diseases (OMDs) and cardiovascular diseases (CVDs) were among the main reasons for granting sickness benefits. Among the disability benefits, CVDs, mental disorders (MDs), and OMDs, were the main reasons. In terms of specific diseases within the major DCNT groups, the main reasons for granting sickness benefits were high blood pressure, diabetes mellitus, arthrosis, breast and intestinal cancer, mood disorders and schizophrenia. For disability benefits, the main causes were cerebrovascular diseases, diabetes mellitus, cancer of the gastro-intestinal tract and schizophrenia. Most (66%) of the recipients were men between 39 and 58 years of age, and the initial value of the benefit was of up to three minimum wages per month.