Left ventricular volume and ejection fraction response to exercise in chronic congestive heart failure: difference between dilated cardiomyopathy and previous myocardial infarction

To determine if cause influences the left ventricular (LV) volume and ejection fraction (EF) response to exercise, 24 patients with chronic congestive heart failure (CHF) (13 dilated cardiomyopathy [DC], CHF-DC group; 11 previous myocardial infarction [MI], CHF-MI group) and 6 age-matched control subjects underwent simultaneous hemodynamic monitoring and radionuclide ventriculography during semiupright bicycle exercise. Both CHF groups had similar hemodynamic values, LV volumes and EF at rest. Exercise hemodynamics were also similar, but LV volume and EF responses to exercise were different. In the CHF-DC group LV end-diastolic volume increased by 15% during exercise, significantly less (p less than 0.01) than the 44% increase in CHF-MI group. During exercise, EF increased in CHF-DC group, but did not change in CHF-MI group because of a larger increase in end-systolic volume. The slope of mean pulmonary wedge pressure-LV end-diastolic volume relation was steeper in CHF-DC group than in CHF-MI group (p less than 0.01). The study suggests that LV volume and EF response to exercise in patients with CHF depends on the origin of the CHF.     

Psychiatric issues in the management of patients with HIV infection.

Approximately 1 million persons are now infected with human immunodeficiency virus (HIV) in the United States. Evidence exists that psychiatric disorders are common in patients with HIV and that these patients may not receive optimal care because their psychiatric disorders are a barrier to medical care, communication with clinicians, and adherence to medical recommendations. We describe herein a complex case seen at The Johns Hopkins Hospital with several psychiatric conditions that are common in our HIV clinic population. We describe the collaborative treatment of the patient by a multidisciplinary team including both medical and mental health practitioners. We briefly describe a coherent diagnostic and treatment approach to patients in HIV clinics and the supporting rationale from the literature. We discuss the need for comprehensive evaluation, a multidisciplinary treatment team, and therapeutic optimism.     

HIV Prevention and Treatment Behavior Change and the Situated Information Motivation Behavioral Skills (sIMB) Model: A Qualitative Evaluation of a Community Health Worker Intervention in Rakai,Uganda

AIDS and Behavior - A community health worker (CHW) model can promote HIV prevention and treatment behaviors, especially in highly mobile populations. In a fishing community in Rakai, Uganda, the...     

Quality of life after repair of tetralogy of Fallot

OBJECTIVE: To determine the quality of life in individuals with corrected tetralogy of Fallot. METHODS AND SUBJECTS: Questionnaires concerning quality of life were sent to all 87 surviving patients aged between 16 and 40 years who had undergone intracardiac repair of tetralogy of Fallot and follow-up in the Wessex Cardiothoracic Unit, and to 87 age and sex matched controls, with medically treated haemodynamically insignificant ventricular septal defects. RESULTS: The only significant difference found between the cases and controls was in requirements for schooling, where those with tetralogy of Fallot were more likely to require additional educational help at school (p = 0.044). For all other aspects of quality of life examined by the questionnaire, including social and genetic history, exercise ability, and health related quality of life, no significant differences were found. Different operative techniques, such as transjunctional patching, right ventriculotomy, and previous palliative shunting, did not affect the quality of life of our population with Tetralogy of Fallot, on average twenty years after their surgery, although the range of operative techniques was limited. Neither age at surgery, nor time since surgery, was correlated with measurements of quality of life. CONCLUSIONS: Those who have undergone surgical correction of tetralogy of Fallot have a normal quality of life, with few differences compared to controls.     

Haemostatic disturbances in patients bitten by Russell''s viper (Vipera russelli siamensis) in Burma

Patients who are severely envenomed by Russell's viper develop DIC which is frequently associated with spontaneous bleeding and incoagulable blood. These haemostatic disturbances may be responsible for death or organ/tissue damage both through haemorrhage and microvascular occlusion by fibrin thrombi. The most striking laboratory features of the coagulopathy developing after Russell's viper bite in the 42 patients studied were depletion of fibrinogen (mean 0.09 g/l, range 0-0.6), factor V (6.5 u/dl, range 0-17), factor X (35 u/dl, range 1-85), factor XIIIa (57 u/dl, range 15-82), plasminogen (61 u/dl, range 10-92), antiplasmin (36 u/dl, range 14-62). Protein C (49 u/dl, range 15-100) and platelets (104 x 10(9)/l, range 25-197). Intense fibrinolytic activity was detected in all cases with marked elevation of FDPs (1614 micrograms/ml, range 350-3000), a large proportion of which were cross-linked (1058 micrograms/ml, range 38-3000). The monospecific Burmese antivenom appeared to be very effective in neutralizing the venom procoagulants and in restoring blood coagulability. Moreover, the unexpectedly normal level of AT III provides a theoretical basis for the use of heparin to enhance the inactivation of those serine proteases present before antivenom administration.     

An important minority of prediabetic first-degree relatives of type 1 diabetic patients derives from seroconversion to persistent autoantibody positivity after 10?years of age

Aims/hypothesis

The appearance of autoantibodies (Abs) before diabetes onset has mainly been studied in young children. However, most patients develop type 1 diabetes after the age of 15?years. In first-degree relatives aged under 40?years, we investigated the frequency of seroconversion to (persistent) Ab positivity, progression to diabetes and baseline characteristics of seroconverters according to age.

Methods

Abs against insulin (IAA), glutamate decarboxylase (GADA), insulinoma-associated protein 2 (IA-2A) and zinc transporter 8 (ZnT8A) were measured during follow-up of 7,170 first-degree relatives.

Results

We identified 379 (5.3%) relatives with positivity for IAA, GADA, IA-2A and/or ZnT8A (Ab⁺) at first sampling and 224 (3.1%) at a later time point. Most seroconversions occurred after the age of 10?years (63%). During follow-up, Abs persisted more often in relatives initially Ab⁺ (76%) than in seroconverters (53%; p?Conclusions/interpretation Seroconversion to (persistent) Ab⁺ occurs regardless of age. Although the progression rate to diabetes is higher under age 10?years, later seroconverters (up to age 40?years) have similar characteristics when compared with age-matched initially Ab⁺ relatives and generate an important minority of prediabetic relatives, warranting their identification and, eventually, enrolment in prevention trials.     

BH3 mimetics and multi-kinase inhibition in AML

In this issue of Blood, Rahmani et al show in preclinical studies that the combination of the multi-kinase inhibitor sorafenib with the BH3 mimetic obatoclax results in enhanced antileukemic effects compared with the effects of each agent alone. This work has important clinical implications because it describes a novel approach to overcome acute myeloid leukemia (AML) cell resistance by combining agents that are currently being investigated in trials as single agents.     

Induction of tau pathology by intracerebral infusion of amyloid-beta -containing brain extract and by amyloid-beta deposition in APP x Tau transgenic mice

Alzheimer's disease presents morphologically with senile plaques, primarily made of extracellular amyloid-beta (A beta) deposits, and neurofibrillary lesions, which consist of intracellular aggregates of hyperphosphorylated tau protein. To study the in vivo induction of tau pathology, dilute brain extracts from aged A beta-depositing APP23 transgenic mice were intracerebrally infused in young B6/P301L tau transgenic mice. Six months after the infusion, tau pathology was induced in the injected hippocampus but also in brain regions well beyond the injection sites such as the entorhinal cortex and amygdala, areas with neuronal projection to the injection site. No or only modest tau induction was observed when brain extracts from aged nontransgenic control mice and aged tau-depositing B6/P301L transgenic mice were infused. To further study A beta-induced tau lesions B6/P301L tau transgenic mice were crossed with APP23 mice. Although A beta deposition in double-transgenic mice did not differ from single APP23 transgenic mice, double-transgenic mice revealed increased tau pathology compared to single B6/P301L tau transgenic mice predominately in areas with high A beta plaque load. The present results suggest that both extract-derived A beta species and deposited fibrillary A beta can induce the formation of tau neurofibrillary pathology. The observation that infused A beta can trigger the tau pathology in the absence of A beta deposits provides an explanation for the discrepancy between the neuroanatomical location of A beta deposits and the development and spreading of tau lesions in Alzheimer's disease brain.