Abnormalities of very low density lipoprotein apolipoprotein B-100 metabolism contribute to the dyslipidaemia of adult growth hormone deficiency

Increased cardiovascular mortality in adult growth hormone deficiency (GHD) may be, in part, explained by the dyslipidaemia associated with this condition. It is possible that abnormalities of very low density lipoprotein apolipoprotein B-100 (VLDL apoB) metabolism contribute to this dyslipidaemia. To test this hypothesis, we measured VLDL apoB kinetics in adult GH deficient patients (4 females, 3 males; age 50.1 +/- 4.7 yr (mean +/- SEM); BMI 28.2 +/- 1.1 kg/m2; total cholesterol (TC) 6.6 +/- 0.3 mmol/l; triglyceride (TG) 2.8 +/- 0.6 mmol/l; HDL cholesterol 1.1 +/- 0.1 mmol/l) and in control subjects (4 females, 3 male; age 47.0 +/- 4.7 yr; BMI 27.0 +/- 2.6 kg/m2; TC 5.0 +/- 0.4 mmol/l; TG 0.9 +/- 0.2 mmol/l; HDL cholesterol 1.4 +/- 0.1 mmol/l). [1-(13)C] leucine was administered by a primed (1 mg/kg), constant intravenous infusion (1 mg/kg/hr) and VLDL apoB enrichment with 13C leucine was determined using gas-chromatography mass-spectrometry. The GHD patients had a significantly higher hepatic secretion rate of VLDL apoB (15.5 +/- 1.8 mg/kg/day vs 9.4 +/- 0.6 mg/kg/day p = 0.007) and reduced catabolism ofVLDL apoB (metabolic clearance rate; 12.3 +/- 1.7 ml/min vs 24.3 +/- 4.8 ml/min p < 0.05) compared with control subjects. These findings suggest that GH is integrally involved in the regulation of VLDL apoB metabolism.

Scintigraphic and radiographic appearance of the sacroiliac region in horses with gait abnormalities or poor performance

Nuclear bone scintigraphy is commonly used in the diagnosis of sacroiliac disease in horses. The aim of the present retrospective study was to determine if there was an association between radiopharmaceutical uptake pattern and radiographic appearance of the sacroiliac region in horses. Seventy-nine horses undergoing bone scintigraphy with Tc-99 m-HDP and radiography of the pelvis because of lameness or poor performance were studied. Subjective and semiquantitative methods were used to characterize and compare radiopharmaceutical uptake between horses. Ventrodorsal radiographs of the region were obtained and were evaluated. Subjectively, 70 horses (88.6%) had an abnormal uptake pattern. In nine horses, the sacroiliac region was normal (11.4%). There was no association between subjective evaluation of the scintigraphic images and semiquantitative methods. There was a significant association between radiopharmaceutical uptake and conformation (T- or Y-like form) and shape (butterfly-, wing-, leaf-, or horn-like) of the sacrum. The radiopharmaceutical uptake of the tubera sacralia was significantly higher in males (left side P = 0.002, right side P = 0.003). In conclusion, the conformation of the sacrum may play an important role in the scintigraphic appearance and may be the cause of increased radiopharmaceutical uptake.

Eye-head coordination abnormalities in schizophrenia

Eye-movement abnormalities in schizophrenia are a well-established phenomenon that has been observed in many studies. In such studies, visual targets are usually presented in the center of the visual field, and the subject's head remains fixed. However, in every-day life, targets may also appear in the periphery. This study is among the first to investigate eye and head movements in schizophrenia by presenting targets in the periphery of the visual field.

An unmatched case controlled study of clinicopathologic abnormalities in dogs with Bartonella infection

We compared clinicopathologic findings in dogs with Bartonella infection to Bartonella spp. negative dogs suspected of a vector-borne disease. Cases (n=47) and controls (n=93) were selected on the basis of positive or negative enrichment culture PCR results, respectively. Signalment, clinicopathologic findings and treatments were extracted from medical records. DNA sequencing identified Bartonella henselae (n=28, 59.6%), Bartonella vinsonii subsp. berkhoffii (n=20, 42.6%), Bartonella koehlerae (n=3, 6.4%), Bartonella volans-like (n=3, 6.4%) and Bartonella bovis (n=1, 2.1%). There were no significant differences in age, breed, size, sex or neuter status between cases and controls. Dogs infected with Bartonella sp. often had a history of weight loss [OR=2.82; 95% CI: 1.08-7.56] and were hypoglobulinemic [OR=4.26; 95% CI: 1.31-14.41]. With the exception of weight loss and hypoglobulinemia, clinicopathologic abnormalities in Bartonella-infected dogs in this study were similar to dogs suspected of other vector-borne infections.

Left ventricular torsion abnormalities in septic shock and corrective effect of volume loading: a pilot study

BACKGROUND Ventricular torsion is an important component of cardiac function. The effect of septic shock on left ventricular torsion is not known. Because torsion is influenced by changes in preload, we compared the effect of fluid loading on left ventricular torsion in septic shock with the response in matched healthy control subjects. METHODS We assessed left ventricular torsion parameters using transthoracic echocardiography in 11 patients during early septic shock and in 11 age- and sex-matched healthy volunteers before and after rapid volume loading with 250 mL of a Ringer's lactate solution. RESULTS Peak torsion and peak apical rotation were reduced in septic shock (10.2 ± 5.2° and 5.6 ± 5.4°) compared with healthy volunteers (16.3 ± 4.5° and 9.6 ± 1.5°; P = 0.009 and P = 0.006 respectively). Basal rotation was delayed and diastolic untwisting velocity reached its maximum later during diastole in septic shock patients than in healthy volunteers (104 ± 16% vs 111 ± 14% and 13 ± 5% vs 21 ± 10%; P = 0.03 and P = 0.034, respectively). Fluid challenge increased peak torsion in both groups (septic shock, 10.2 ± 5.3° vs 12.6 ± 3.9°; healthy volunteers, 16.3 ± 4.5° vs 18.1 ± 6°; P = 0.01). Fluid challenge increased left ventricular stroke volume in septic shock patients (P = 0.003). CONCLUSIONS Compared with healthy volunteers, left ventricular torsion is impaired in septic shock patients. Fluid loading attenuates torsion abnormalities in parallel with increasing stroke volume. Reduced torsional motion might constitute a relevant component of septic cardiomyopathy, a notion that merits further testing in larger populations.

Association of electrocardiogram abnormalities and incident heart failure events

BACKGROUND Unless effective preventive strategies are implemented, aging of the population will result in a significant worsening of the heart failure (HF) epidemic. Few data exist on whether baseline electrocardiographic (ECG) abnormalities can refine risk prediction for HF. METHODS We examined a prospective cohort of 2,915 participants aged 70 to 79 years without preexisting HF, enrolled between April 1997 and June 1998 in the Health, Aging, and Body Composition (Health ABC) study. Minnesota Code was used to define major and minor ECG abnormalities at baseline and at year 4 follow-up. Using Cox models, we assessed (1) the association between ECG abnormalities and incident HF and (2) the incremental value of adding ECG to the Health ABC HF Risk Score using the net reclassification index. RESULTS At baseline, 380 participants (13.0%) had minor, and 620 (21.3%) had major ECG abnormalities. During a median follow-up of 11.4 years, 485 participants (16.6%) developed incident HF. After adjusting for the Health ABC HF Risk Score variables, the hazard ratio (HR) was 1.27 (95% CI 0.96-1.68) for minor and 1.99 (95% CI 1.61-2.44) for major ECG abnormalities. At year 4, 263 participants developed new and 549 had persistent abnormalities; both were associated with increased subsequent HF risk (HR 1.94, 95% CI 1.38-2.72 for new and HR 2.35, 95% CI 1.82-3.02 for persistent ECG abnormalities). Baseline ECG correctly reclassified 10.5% of patients with HF events, 0.8% of those without HF events, and 1.4% of the overall population. The net reclassification index across the Health ABC HF risk categories was 0.11 (95% CI 0.03-0.19). CONCLUSIONS Among older adults, baseline and new ECG abnormalities are independently associated with increased risk of HF. The contribution of ECG screening for targeted prevention of HF should be evaluated in clinical trials.

A RAB3GAP1 SINE Insertion in Alaskan Huskies with Polyneuropathy, Ocular Abnormalities and Neuronal Vacuolation (POANV) Resembling Human Warburg Micro Syndrome 1 (WARBM1)

We observed a hereditary phenotype in Alaskan Huskies, which was characterized by polyneuropathy with ocular abnormalities and neuronal vacuolation (POANV). The affected dogs developed a progressive severe ataxia, which led to euthanasia between 8 and 16 months of age. The pedigrees were consistent with a monogenic autosomal recessive inheritance. We localized the causative genetic defect to a 4 Mb interval on chromosome 19 by a combined linkage and homozygosity mapping approach. Whole genome sequencing of one affected dog, an obligate carrier and an unrelated control revealed a 218 bp SINE insertion into exon 7 of the RAB3GAP1 gene. The SINE insertion was perfectly associated with the disease phenotype in a cohort of 43 Alaskan Huskies and it was absent from 541 control dogs of diverse other breeds. The SINE insertion induced aberrant splicing and led to a transcript with a greatly altered exon 7. RAB3GAP1 loss-of-function variants in humans cause Warburg Micro Syndrome 1 (WARBM1), which is characterized by additional developmental defects compared to canine POANV, whereas Rab3gap1 deficient mice have a much milder phenotype than either humans or dogs. Thus the RAB3GAP1 mutant Alaskan Huskies provide an interesting intermediate phenotype that may help to better understand the function of RAB3GAP1 in development. Furthermore, the identification of the presumed causative genetic variant will enable genetic testing to avoid the non-intentional breeding of affected dogs.

Neurohistological abnormalities during early porcine endotoxemia.

BACKGROUND Brain dysfunction is common in sepsis. We aimed to assess whether cerebral perfusion, oxygenation, and/or metabolism are abnormal during early endotoxemia, and how they may relate to potential neurohistological changes. METHODS In this prospective animal study, we included 12 pigs (weight: 42 ± 4 kg; mean ± SD) that were exposed to Escherichia coli lipopolysaccharide (E. coli LPS B0111 : B4, 0.4 μg/kg/h) or saline infusion (n = 6, each) for 10 h. Systemic hemodynamics, cerebral blood flow, intracranial pressure, and brain tissue oxygen tension were continuously measured. At the end of the experiment, formalin-fixed brains were cut in coronal sections and embedded in paraffin. Afterwards, the sections were cut at 5 microns and stained with hematoxylin and eosin. RESULTS Stable systemic hemodynamics in both groups were associated with higher carotid arterial blood flow after 10 h of endotoxemia (9.0 ± 2.2 ml/kg/min) compared to controls (6.6 ± 1.2 ml/kg/min; time-group interaction: P = 0.014). Intracranial pressure, cerebral perfusion pressure, brain oxygen consumption, and brain tissue oxygen tension were similar in both groups. In four of the six endotoxemic animals but in none of the controls, cerebral tissue lesions were found (encephalomalacia with spongy degeneration of white matter, axonal swelling, and ischemic neuronal thalamic necrosis), including significant venous vascular alterations, predominantly in the brainstem, in three of the four animals. CONCLUSIONS Early endotoxemia seems to be associated with histological signs of brain damage unrelated to systemic or cerebral hemodynamics or oxygenation.

Cortical Abnormalities in Adults and Adolescents with Major Depression based on Brain Scans from 20 Cohorts Worldwide in the ENIGMA Major Depressive Disorder Working Group

The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen’s d effect sizes: −0.10 to −0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: −0.26 to −0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.

Electrophysiologic assessment of conduction abnormalities and atrial arrhythmias associated with amyloid cardiomyopathy.

BACKGROUND Arrhythmias in cardiac amyloidosis (CA) result in significant comorbidity and mortality but have not been well characterized. OBJECTIVE The purpose of this study was to define intracardiac conduction, atrial arrhythmia substrate, and ablation outcomes in a group of advanced CA patients referred for electrophysiologic study. METHODS Electrophysiologic study with or without catheter ablation was performed in 18 CA patients. Findings and catheter ablation outcomes were compared to age- and gender-matched non-CA patients undergoing catheter ablation of persistent atrial fibrillation (AF). RESULTS Supraventricular tachycardias were seen in all 18 CA patients (1 AV nodal reentrant tachycardia, 17 persistent atrial tachycardia [AT]/AF). The HV interval was prolonged (>55 ms) in all CA patients, including 6 with normal QRS duration (≤100 ms). Thirteen supraventricular tachycardia ablations were performed in 11 patients. Of these, 7 underwent left atrial (LA) mapping and ablation for persistent AT/AF. Compared to non-CA age-matched comparator AF patients, CA patients had more extensive areas of low-voltage areas LA (63% ± 22% vs 34% ± 22%, P = .009) and a greater number of inducible ATs (3.3 ± 1.9 ATs vs 0.2 ± 0.4 ATs, P <.001). The recurrence rate for AT/AF 1 year after ablation was greater in CA patients (83% vs 25%), and the hazard ratio for postablation AT/AF recurrence in CA patients was 5.4 (95% confidence interval 1.9-35.5, P = .007). CONCLUSION In this group of patients with advanced CA and atrial arrhythmias, there was extensive conduction system disease and LA endocardial voltage abnormality. Catheter ablation persistent AT/AF in advanced CA was associated with a high recurrence rate and appears to have a limited role in control of these arrhythmias.