Doppler in non-immune hydrops fetalis.

Fetal ultrasound studies were performed on 24 fetuses with non-immune hydrops to evaluate echocardiographic and cardiovascular Doppler parameters that may be useful in assessing hemodynamics and in predicting outcome. Of all cardiovascular parameters analyzed, only the presence of abnormal pulsations in the umbilical vein (p < 0.001) was found to be significantly different between the 11 survivors and 13 non-survivors. In a smaller subset of 12 fetuses, in whom inferior vena caval waveforms were recorded, survivors (n = 6) had a significantly lower percentage of retrograde flow in the inferior vena cava (p < 0.001) and higher inferior vena caval E/V velocity ratio (p < 0.001) than non-survivors (n = 6). Sixteen of the 24 cases examined had abnormal umbilical venous pulsations; 12 of the 16 (75%) died including all fetuses with hydrops due to twin-to-twin transfusion or congenital heart disease. When fetuses with pulsatile flow in the umbilical vein were compared with fetuses with normal umbilical venous flow, the following significant differences were found: lower right and left ventricular output velocities, larger inferior vena caval diameter, decreased shortening fractions of the right and left ventricles, and lower peak velocities at the aortic and pulmonary valves and in the ductus arteriosus.     

T-lymphocyte subsets in the human lacrimal gland

This study examines the microscopical appearance, location, distribution, subdivision and density of T-lymphocytes in the human lacrimal gland. Fourteen glands, 7 from either sex, were removed and frozen shortly after the donors' death, and processed for immunoperoxidase staining, utilizing a biotinavidin system and one of the following monoclonal antibodies: Anti-Leu-1 and -Leu-4, which recognize T-lymphocytes, anti-Leu-2a, which binds to suppressor/cytotoxic T-cells, and anti-Leu-3a + 3b, which recognizes helper/inducer cells. The T-lymphocytes in the human lacrimal gland were small to medium sized, mainly located in the interacinar tissue, often adjacent to an acinus or close to a collecting duct. The median number of each T-cell subset per defined field (0.086 mm2) at x 500 magnification was as follows: Males: Leu-1: 3.1, Leu-2a: 4.9, Leu-3a + 3b: 2.8, Leu-4: 4.5. Females: Leu-1: 4.3, Leu-2a: 5.0, Leu-3a + 3b: 3.7 and Leu-4:5.8. The sex difference was not statistically significant. The helper/suppressor cell ratio in the human lacrimal gland was 0.57 for males and 0.74 for females.     

Skin deposits in hereditary cystatin C amyloidosis

Summary Clinically normal skin from 47 individuals aged 9–70 years was investigated. Cystatin C amyloid deposits were found in various locations of the skin by light and/or electron microscopy, in all 12 patients with a clinical history of hereditary cystatin C amyloidosis (HCCA). Six asymptomatic individuals, who had the Alu 1 restriction fragment length polymorphism (RFLP) marker reported to cosegregate with the disease, also had cystatin C amyloid deposits in the skin. Three asymptomatic individuals (age 17–46) belonging to the HCCA families were without amyloid in the skin but had Alu 1 RFLP marker. Skin from 12 individuals who served as controls and skin from 14 close relatives of the patients was negative for amyloid. Punch biopsy of the skin is a simple procedure which is of value for the diagnosis of HCCA, even before the appearance of clinical symptoms. This method might also be of use in following progression of the disease.     

Vitamin D Enhances Neutrophil Generation and Function in Zebrafish (Danio rerio)

Vitamin D (VD) is a major regulator of calcium metabolism in many living organisms. In addition, VD plays a key role in regulating innate and adaptive immunity in vertebrates. Neutrophils constitute an important part of the first line of defense against invading microbes; however, the potential effect of VD on neutrophils remains elusive. Thus, in this study zebrafish in different developmental stages were utilized to identify the potential role of VD in the basal homeostasis and functions of neutrophils. Our results showed that addition of exogenous VD₃ promoted granulopoiesis in zebrafish larvae. Reciprocally, neutrophil abundance in the intestine of adult zebrafish with a cyp2r1 mutant, lacking the capacity to 25-hydroxylate VD, was reduced. Moreover, VD-mediated granulopoiesis was still observed in gnotobiotic zebrafish larvae, indicating that VD regulates neutrophil generation independent of the microbiota during early development. In contrast, VD was incapable to influence granulopoiesis in adult zebrafish when the commensal bacteria were depleted by antibiotic treatment, suggesting that VD might modulate neutrophil activity via different mechanisms depending on the developmental stage. In addition, we found that VD₃ augmented the expression of il-8 and neutrophil recruitment to the site of caudal fin amputation. Finally, VD₃ treatment significantly decreased bacterial counts and mortality in zebrafish infected with Edwardsiella tarda (E. tarda) in a neutrophil-dependent manner. Combined, these findings demonstrate that VD regulates granulopoiesis and neutrophil function in zebrafish immunity.     

Left ventricular early diastolic inflow velocity and atrial ventricular plane downward velocity: useful parameters to test diastolic function in clinical practice? Diastolic parameters tested in a clinical setting.

AIMS: To study the clinical value of the colour-M-mode slope of the early diastolic left ventricular filling phase (Vp) and the early diastolic downward M-mode slope of the left atrioventricular plane displacement (EDS), compared with diastolic function assessed by traditional Doppler evaluation. METHODS AND RESULTS: In 65 consecutive patients EDS and Vp were compared with a four-degree traditional diastolic function classification, based on pulsed Doppler assessment of the early to atrial transmitral flow ratio (E/A), the E-wave deceleration time (Edt), and the systolic to diastolic (S/D) pulmonary venous inflow ratio. Vp (P=0.006) and EDS (P=0.045) were related to traditional diastolic function (Kruskal--Wallis analysis). EDS showed a trend brake between the moderate and severe diastolic dysfunction groups by traditional Doppler evaluation. Vp and EDS correlated weakly in simple linear regression analysis (r=0.33). Vp and EDS discriminated poorly between normal and highly abnormal diastolic function. CONCLUSIONS: Vp and EDS were significantly related to diastolic function by traditional Doppler evaluation. They were, however, not useful as single parameters of left ventricular diastolic function due to a small difference between normal and highly abnormal values, allowing for little between-measurement variability. Consequently, these methods for the evaluation of left ventricular diastolic function do not add significantly to traditional Doppler evaluation.     

Real-time perfusion adenosine stress echocardiography in the coronary care unit: a feasible bedside tool for predicting coronary artery stenosis in patients with acute coronary syndrome.

Myocardial contrast echocardiography using power modulation real-time perfusion (RTP) is an appealing method for bedside risk stratification of patients with acute coronary syndrome. In this study, we aimed to evaluate the accuracy in predicting significant coronary stenosis of a bedside RTP adenosine stress protocol in patients with acute coronary syndrome. METHODS: Prior to coronary angiography, 36 consecutive in-patients with acute coronary syndrome underwent a bedside adenosine stress echocardiography with RTP in the coronary care unit. Visual assessment of both perfusion and wall motion was made, comparing rest and hyperaemia images. Each segment was attributed to one of the three main coronary vessel areas. RESULTS: The sensitivity of predicting significant stenosis was 87, 83 and 81% for left anterior descending, circumflex and right posterior descending areas, respectively. Specificity was 69, 67 and 60%, respectively. The positive predictive values were 83, 79 and 74%, respectively. CONCLUSIONS: RTP using adenosine is a feasible bedside tool in predicting the area of significant coronary stenosis and could be helpful as a bedside decision-making tool in the clinical setting. More studies are required to assess the clinical value of RTP adenosine stress echocardiography.     

Legg‐Calvé‐Perthes Disease Produces Chronic Hip Synovitis and Elevation of Interleukin‐6 in the Synovial Fluid

Legg‐Calvé‐Perthes disease (LCPD) is a childhood hip disorder of ischemic osteonecrosis of the femoral head. Hip joint synovitis is a common feature of LCPD, but the nature and pathophysiology of the synovitis remain unknown. The purpose of this study was to determine the chronicity of the synovitis and the inflammatory cytokines present in the synovial fluid at an active stage of LCPD. Serial MRI was performed on 28 patients. T2‐weighted and gadolinium‐enhanced MR images were used to assess synovial effusion and synovial enhancement (hyperemia) over time. A multiple‐cytokine assay was used to determine the levels of 27 inflammatory cytokines and related factors present in the synovial fluid from 13 patients. MRI analysis showed fold increases of 5.0 ± 3.3 and 3.1 ± 2.1 in the synovial fluid volume in the affected hip compared to the unaffected hip at the initial and the last follow‐up MRI, respectively. The mean duration between the initial and the last MRI was 17.7 ± 8.3 months. The volume of enhanced synovium on the contrast MRI was increased 16.5 ± 8.5 fold and 6.3 ± 5.6 fold in the affected hip compared to the unaffected hip at the initial MRI and the last follow‐up MRI, respectively. In the synovial fluid of the affected hips, IL‐6 protein levels were significantly increased (LCPD: 509 ± 519 pg/mL, non‐LCPD: 19 ± 22 pg/mL; p = 0.0005) on the multi‐cytokine assay. Interestingly, IL‐1β and TNF‐α levels were not elevated. In the active stage of LCPD, chronic hip synovitis and significant elevation of IL‐6 are produced in the synovial fluid. Further studies are warranted to investigate the role of IL‐6 on the pathophysiology of synovitis in LCPD and how it affects bone healing. © 2015 American Society for Bone and Mineral Research