Grey-matter abnormalities in boys with Tourette syndrome: magnetic resonance imaging study using optimised voxel-based morphometry

The genesis of Tourette syndrome is still unknown, but a core role for the pathways of cortico-striatal-thalamic-cortical circuitry (CSTC) is supposed. Volume-rendering magnetic resonance imaging data-sets were analysed in 14 boys with Tourette syndrome and 15 age-matched controls using optimised voxel-based morphometry. Locally increased grey-matter volumes (corrected P < 0.001) were found bilaterally in the ventral putamen. Regional decreases in grey matter were observed in the left hippocampal gyrus. This unbiased analysis confirmed an association between striatal abnormalities and Tourette syndrome, and the hippocampal volume alterations indicate an involvement of temporolimbic pathways of the CSTC in the syndrome.

Paracellin-1 gene mutation with multiple congenital abnormalities

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is an autosomal recessive renal tubular disorder characterized by renal magnesium wasting, hypercalciuria, advanced nephrocalcinosis and progressive renal failure. Mutations in the paracellin-1 (CLDN16) gene have been defined as the underlying genetic defect. The tubular disorders and progression in renal failure are usually resistant to magnesium substitution and hydrochlorothiazide therapy, but hypomagnesemia may improve with advanced renal insufficiency. We present a patient with a homozygous truncating CLDN16 gene mutation (W237X) who had early onset of renal insufficiency despite early diagnosis at 2 months. He also had additional abnormalities including horseshoe kidney, neonatal teeth, atypical face, cardiac abnormalities including coarctation of the aorta associated with atrial and ventricular septal defects, umbilical hernia and hypertrichosis. To the best of our knowledge, this is the youngest case diagnosed as familial hypomagnesemia with hypercalciuria and nephrocalcinosis and the first case having such additional congenital abnormalities independent of the disease itself.

[Retinal abnormalities in adult acute myeloid leukemia: semeiological features and prognostic correlations. Analysis of 178 cases]

INTRODUCTION: Adult patients with acute myeloid leukemia (AML) frequently present retinal abnormalities. We tried to find a relationship between fundus lesions and treatment responsiveness, prognosis, and several hematologic parameters. PATIENTS AND METHODS: We examined 178 adult patients with newly diagnosed AML. All patients were assigned to two groups regarding retinal parameters (1 or 2) and age (A or B). Group 1 included cases with retinal dysfunction classified as retinal abnormalities with impaired visual acuity; group 2 included cases with no or only minor retinal changes. Subgroup A included patients younger than 60 years (n=97), subgroup B patients older than 60 years (n=81). RESULTS: In this study, higher age and a lower Hb value were associated with retinal findings (group 1). Among the younger patients (subgroup A), 78% of those with complete remission had no retinal findings (group 2) compared to 18% of the nonresponders. In the elderly population (subgroup B), this ratio was 58% versus 19%. In the younger patients (subgroup A), the mean overall survival was 50 months if they had no retinal abnormalities (group 2) and 7 months in the case of retinal changes (group 1). In the older population (subgroup B), the ratio was 15 months versus 3 months, respectively. CONCLUSION: Retinal abnormalities in AML are generally associated with higher age, although they correlate with a shorter survival in both age groups. This association is stronger in younger patients.

Imaging structural abnormalities in the hip joint: instability and impingement as a cause of osteoarthritis

Osteoarthritis is thought to be caused by a combination of intrinsic vulnerabilities of the joint, such as anatomic shape and alignment, and environmental factors, such as body weight, injury, and overuse. It has been postulated that much of osteoarthritis is due to anatomic deformities. Advances in surgical techniques such as the periacetabular osteotomy, safe surgical dislocation of the hip, and hip arthroscopy have provided us with effective and safe tools to correct these anatomical problems. The limiting factor in treatment outcome in many mechanically compromised hips is the degree of cartilage damage which has occurred prior to treatment. In this regard, the role of imaging, utilizing plain radiographs in conjunction with magnetic resonance imaging, is becoming vitally important for the detection of these anatomic deformities and pre-radiographic arthritis. In this article, we will outline the plain radiographic features of hip deformities that can cause instability or impingement. Additionally, we will illustrate the use of MRI imaging to detect subtle anatomic abnormalities, as well as the use of biochemical imaging techniques such as dGEMRIC to guide clinical decision making.

Thromboelastometry for the assessment of coagulation abnormalities in early and established adult sepsis: a prospective cohort study

INTRODUCTION: The inflammatory response to an invading pathogen in sepsis leads to complex alterations in hemostasis by dysregulation of procoagulant and anticoagulant factors. Recent treatment options to correct these abnormalities in patients with sepsis and organ dysfunction have yielded conflicting results. Using thromboelastometry (ROTEM(R)), we assessed the course of hemostatic alterations in patients with sepsis and related these alterations to the severity of organ dysfunction. METHODS: This prospective cohort study included 30 consecutive critically ill patients with sepsis admitted to a 30-bed multidisciplinary intensive care unit (ICU). Hemostasis was analyzed with routine clotting tests as well as thromboelastometry every 12 hours for the first 48 hours, and at discharge from the ICU. Organ dysfunction was quantified using the Sequential Organ Failure Assessment (SOFA) score. RESULTS: Simplified Acute Physiology Score II and SOFA scores at ICU admission were 52 +/- 15 and 9 +/- 4, respectively. During the ICU stay the clotting time decreased from 65 +/- 8 seconds to 57 +/- 5 seconds (P = 0.021) and clot formation time (CFT) from 97 +/- 63 seconds to 63 +/- 31 seconds (P = 0.017), whereas maximal clot firmness (MCF) increased from 62 +/- 11 mm to 67 +/- 9 mm (P = 0.035). Classification by SOFA score revealed that CFT was slower (P = 0.017) and MCF weaker (P = 0.005) in patients with more severe organ failure (SOFA >or= 10, CFT 125 +/- 76 seconds, and MCF 57 +/- 11 mm) as compared with patients who had lower SOFA scores (SOFA <10, CFT 69 +/- 27, and MCF 68 +/- 8). Along with increasing coagulation factor activity, the initially increased International Normalized Ratio (INR) and prolonged activated partial thromboplastin time (aPTT) corrected over time. CONCLUSIONS: Key variables of ROTEM(R) remained within the reference ranges during the phase of critical illness in this cohort of patients with severe sepsis and septic shock without bleeding complications. Improved organ dysfunction upon discharge from the ICU was associated with shortened coagulation time, accelerated clot formation, and increased firmness of the formed blood clot when compared with values on admission. With increased severity of illness, changes of ROTEM(R) variables were more pronounced.

Beta1 integrin deficiency results in multiple abnormalities of the knee joint

The lack of beta1 integrins on chondrocytes leads to severe chondrodysplasia associated with high mortality rate around birth. To assess the impact of beta1 integrin-mediated cell-matrix interactions on the function of adult knee joints, we conditionally deleted the beta1 integrin gene in early limb mesenchyme using the Prx1-cre transgene. Mutant mice developed short limbed dwarfism and had joint defects due to beta1 integrin deficiency in articular regions. The articular cartilage (AC) was structurally disorganized, accompanied by accelerated terminal differentiation, altered shape, and disrupted actin cytoskeleton of the chondrocytes. Defects in chondrocyte proliferation, cytokinesis, and survival resulted in hypocellularity. However, no significant differences in cartilage erosion, in the expression of matrix-degrading proteases, or in the exposure of aggrecan and collagen II cleavage neoepitopes were observed between control and mutant AC. We found no evidence for disturbed activation of MAPKs (ERK1/2, p38, and JNK) in vivo. Furthermore, fibronectin fragment-stimulated ERK activation and MMP-13 expression were indistinguishable in control and mutant femoral head explants. The mutant synovium was hyperplastic and frequently underwent chondrogenic differentiation. beta1-null synoviocytes showed increased proliferation and phospho-focal adhesion kinase expression. Taken together, deletion of beta1 integrins in the limb bud results in multiple abnormalities of the knee joints; however, it does not accelerate AC destruction, perturb cartilage metabolism, or influence intracellular MAPK signaling pathways.

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.

Skeletal abnormalities in mice lacking extracellular matrix proteins, thrombospondin-1, thrombospondin-3, thrombospondin-5, and type IX collagen.

Thrombospondin-5 (TSP5) is a large extracellular matrix glycoprotein found in musculoskeletal tissues. TSP5 mutations cause two skeletal dysplasias, pseudoachondroplasia and multiple epiphyseal dysplasia; both show a characteristic growth plate phenotype with retention of TSP5, type IX collagen (Col9), and matrillin-3 in the rough endoplasmic reticulum. Whereas most studies focus on defining the disease process, few functional studies have been performed. TSP5 knockout mice have no obvious skeletal abnormalities, suggesting that TSP5 is not essential in the growth plate and/or that other TSPs may compensate. In contrast, Col9 knockout mice have diminished matrillin-3 levels in the extracellular matrix and early-onset osteoarthritis. To define the roles of TSP1, TSP3, TSP5, and Col9 in the growth plate, all knockout and combinatorial strains were analyzed using histomorphometric techniques. While significant alterations in growth plate organization were found in certain single knockout mouse strains, skeletal growth was only mildly disturbed. In contrast, dramatic changes in growth plate organization in TSP3/5/Col9 knockout mice resulted in a 20% reduction in limb length, corresponding to similar short stature in humans. These studies show that type IX collagen may regulate growth plate width; TSP3, TSP5, and Col9 appear to contribute to growth plate organization; and TSP1 may help define the timing of growth plate closure when other extracellular proteins are absent.