Abnormal cardiovascular responses to carotid sinus massage also occur in vasovagal syncope - implications for diagnosis and treatment

Carotid sinus massage (CSM) is commonly used to identify carotid sinus hypersensitivity (CSH) as a possible cause for syncope, especially in older patients. However, CSM itself could provoke classical vasovagal syncope (VVS) in pre disposed subjects.

Abnormal bone geometry at the metacarpal bone shaft of rheumatoid arthritis patients with maintained muscle-bone relationship

OBJECTIVES:: Metacarpal juxta-articular bone is altered in Rheumatoid Arthritis (RA). However, a detailed analysis of disease related geometrical adaptations of the metacarpal shaft is missing. The aim of the present study was to assess the role of RA disease, forearm muscle cross-sectional area (CSA), age and sex on bone geometry at the metacarpal shaft. METHODS:: In 64 RA patients and 128 control subjects geometric properties of the third metacarpal bone mid-shaft and forearm muscle CSA were measured by peripheral quantitative computed tomography (pQCT). Linear models were performed for cortical CSA, total bone CSA, polar stress-strain Index (polar SSI, a surrogate for bone's resistance to bending and torsion), cortical thickness and Metacarpal Index (MI=cortical CSA/total CSA) with explanatory variables muscle CSA, age, RA status and sex. RESULTS:: Forearm muscle CSA was associated with cortical and total metacarpal CSA, and polar SSI. RA group status was associated with all bone parameters except cortical CSA. There was a significant interaction between RA status and age, indicating that the RA group had a greater age-related decrease in cortical CSA, cortical thickness and MI. CONCLUSIONS:: Bone geometry of the metacarpal shaft is altered in RA patients compared to healthy controls. While bone mass of the metacarpal shaft is adapted to forearm muscle mass, cortical thickness and MI are reduced but outer bone shaft circumference and polar SSI increased in RA patients. These adaptations correspond to an enhanced aging pattern in RA patients.

Cortical morphometry in narcolepsy with cataplexy

The sleep-wake disorder narcolepsy with cataplexy is associated with the loss of hypocretin-(orexin-) producing neurons in the lateral hypothalamus. Several studies have reported abnormal cerebral activation in patients with narcolepsy with cataplexy. It remains unclear, however, whether these functional changes are related to structural alterations, particularly at the cortical level. To quantify structural brain changes associated with narcolepsy with cataplexy, we used high-resolution T1-weighted magnetic resonance imaging (MRI) in 12 patients compared with 12 healthy participants matched for age and gender. Subcortical and regional cortical volumes were measured using a method unbiased by non-linear registration. Further whole-brain analyses were conducted, measuring cortical characteristics, such as cortical thickness and gyrification, at thousands of points across each hemisphere using validated algorithms. Statistical analyses accounted for an effect of age and gender. We observed decreased cortical volume in the left paracentral lobule and increased cortical volume in the left caudal part of the middle frontal gyrus in narcoleptic patients compared with controls. Cortical thickness in prefrontal areas was inversely correlated with the severity of narcolepsy. Further, we observed several clusters of cortical thinning in patients with childhood or adolescent onset of narcolepsy compared with patients with adult onset of the disease. Our results suggest that specific anatomical changes may differentiate subgroups of narcolepsy patients with different clinical profiles (such as varying symptom severity or different age at onset). Future studies with larger groups of sleepy patients are required to assess whether distinct patterns of anatomical changes may distinguish narcolepsy from non-hypocretin-deficient hypersomnia disorders.

Reverse-translational biomarker validation of Abnormal Repetitive Behaviors in mice: an illustration of the 4P's modeling approach

The NIMH's new strategic plan, with its emphasis on the "4P's" (Prediction, Pre-emption, Personalization, and Populations) and biomarker-based medicine requires a radical shift in animal modeling methodology. In particular 4P's models will be non-determinant (i.e. disease severity will depend on secondary environmental and genetic factors); and validated by reverse-translation of animal homologues to human biomarkers. A powerful consequence of the biomarker approach is that different closely related disorders have a unique fingerprint of biomarkers. Animals can be validated as a highly specific model of a single disorder by matching this 'fingerprint'; or as a model of a symptom seen in multiple disorders by matching common biomarkers. Here we illustrate this approach with two Abnormal Repetitive Behaviors (ARBs) in mice: stereotypies and barbering (hair pulling). We developed animal versions of the neuropsychological biomarkers that distinguish human ARBs, and tested the fingerprint of the different mouse ARBs. As predicted, the two mouse ARBs were associated with different biomarkers. Both barbering and stereotypy could be discounted as models of OCD (even though they are widely used as such), due to the absence of limbic biomarkers which are characteristic of OCD and hence are necessary for a valid model. Conversely barbering matched the fingerprint of trichotillomania (i.e. selective deficits in set-shifting), suggesting it may be a highly specific model of this disorder. In contrast stereotypies were correlated only with a biomarker (deficits in response shifting) correlated with stereotypies in multiple disorders, suggesting that animal stereotypies model stereotypies in multiple disorders.

Incidence of spinal compressive lesions in chondrodystrophic dogs with abnormal recovery after hemilaminectomy for treatment of thoracolumbar disc disease: a prospective magnetic resonance imaging study

OBJECTIVE: To investigate causes of the lack of clinical improvement after thoracolumbar disc surgery. STUDY DESIGN: Case-control magnetic resonance imaging (MRI) study. ANIMALS: Chondrodystrophic dogs with acute thoracolumbar disc disease treated by hemilaminectomy: 10 that had no short-term clinical improvement and 12 with "normal" clinical improvement. METHODS: Dogs that had surgery for treatment of intervertebral disc extrusion (2003-2008) where thoracolumbar disc disease was confirmed by MRI were evaluated to identify dogs that had lack of clinical improvement after surgery. Ten dogs with delayed recovery or clinical deterioration were reexamined with MRI and compared with 12 dogs with normal recovery and MRI reexamination after 6 weeks (control group). RESULTS: Of 173 dogs, 10 (5.8%) had clinical deterioration within 1-10 days after surgery. In 8 dogs, residual spinal cord compression was identified on MRI. Bleeding was present in 1 dog. In 3 dogs, the cause was an incorrect approach and insufficient disc material removal. In 3 dogs, recurrence occurred at the surgical site. In 1 dog, the centrally located extruded material was shifted to the contralateral side during surgery. These 8 dogs had repeat surgery and recovery was uneventful. In 2 dogs, deterioration could not be associated with a compressive disc lesion. Hemorrhagic myelomalacia was confirmed by pathologic examination in 1 dog. The other dog recovered after 6 months of conservative management. CONCLUSION: Delayed postsurgical recovery or deterioration is commonly associated with newly developed and/or remaining compressive disc lesion. CLINICAL RELEVANCE: We recommend early MRI reexamination to assess the postsurgical spinal canal and cord, and to plan further therapeutic measures in chondrodystrophic dogs with delayed recovery after decompressive hemilaminectomy for thoracolumbar disc disease.

Congenital hypothyroidism in a kitten resulting in decreased IGF-I concentration and abnormal liver function tests

A 7-month-old male kitten was presented with chronic constipation and retarded growth. Clinical examination revealed disproportional dwarfism with mild skeletal abnormalities and a palpable thyroid gland. The presumptive diagnosis of congenital hypothyroidism was confirmed by low serum total thyroxine (tT(4)) concentration prior to and after the administration of thyroid stimulation hormone (TSH), increased endogenous TSH concentration and abnormal thyroid scintigraphic scan. The kitten had abnormal liver function tests and decreased insulin-like growth factor 1 (IGF-1) concentration, both of which returned to normal in correspondence with an improvement of the clinical signs after 6 weeks of thyroxine therapy. Congenital hypothyroidism is a rare disease that may present with considerable variation in clinical manifestation. In cases in which clinical signs are ambiguous, disorders such as portosystemic shunt and hyposomatotropism have to be taken into account as differential diagnosis. As hypothyroidism may be associated with abnormal liver function tests and low IGF-1 concentrations, test results have to be interpreted carefully.

Alveolar bone grafting in association with polyostotic fibrous dysplasia and bisphosphonate-induced abnormal bone turnover in a bilateral cleft lip and palate patient: a case report

A case is presented of extensive alveolar bone grafting in a patient with bilateral cleft lip and palate and polyostotic fibrous dysplasia. The patient previously underwent bisphosphonate therapy. Because of an abnormal and often decreased bone turnover caused by the fibrous dysplasia and the bisphosphonate therapy, bone grafting in such a patient poses several potential difficulties. In addition, the histomorphometric analysis of the bone grafts showed markedly decreased bone turnover. However, alveolar bone grafting using the iliac crest was performed successfully. Sufficient occlusion was achieved by postoperative low-loading orthodontic treatment.

Elimination of local abnormal ventricular activities: a new end point for substrate modification in patients with scar-related ventricular tachycardia

Catheter ablation of ventricular tachycardia (VT) is effective and particularly useful in patients with frequent defibrillator interventions. Various substrate modification techniques have been described for unmappable or hemodynamically intolerable VT. Noninducibility is the most frequently used end point but is associated with significant limitations, so the optimal end point remains unclear. We hypothesized that elimination of local abnormal ventricular activities (LAVAs) during sinus rhythm or ventricular pacing would be a useful and effective end point for substrate-based VT ablation. As an adjunct to this strategy, we used a new high-density mapping catheter and frequently used epicardial mapping.

Impaired pericyte recruitment and abnormal retinal angiogenesis as a result of angiopoietin-2 overexpression

Angiopoietin-2 (Ang2) is among the relevant growth factors induced by hypoxia and plays an important role in the initiation of retinal neovascularizations. Ang2 is also involved in incipient diabetic retinopathy, as it may cause pericyte loss. To investigate the impact of Ang2 on developmental and hypoxia-induced angiogenesis, we used a transgenic mouse line overexpressing human Ang2 in the mouse retina. Transgenic mice displayed a reduced coverage of capillaries with pericytes (-14%; p < 0.01) and a 46% increase of vascular density of the capillary network at postnatal day 10 compared to wild type mice. In the model of oxygen-induced retinopathy (OIR), Ang2 overexpression resulted in enhanced preretinal (+103%) and intraretinal neovascularization (+29%). Newly formed intraretinal vessels in OIR were also pericyte-deficient (-26%; p < 0.01). The total expression of Ang2 in transgenic mice was seven-fold, compared with wild type controls. Ang2 modulated expression of genes encoding VEGF (+65%) and Ang1 (+79%) in transgenic animals. These data suggest that Ang2 is involved in pericyte recruitment, and modulates intraretinal, and preretinal vessel formation in the eye under physiological and pathological conditions.