Six cases of silicosis: implications for health surveillance of stonemasons.

BACKGROUND: Silicosis is one of the oldest occupational lung diseases, but it continues to cause significant morbidity and mortality worldwide. AIMS: To report cases of silicosis presenting to two specialist respiratory clinics. METHODS: A retrospective analysis of prospectively collected data of cases of silicosis in workers referred to specialist respiratory clinics. RESULTS: Over the course of 6 years, six cases were identified. The patients were all male with an age range between 24 and 39 years. The duration of silica exposure ranged between 7 and 20 years (mean 13 years). Four cases were entirely asymptomatic at presentation, and two cases described minimal shortness of breath on exertion. Pulmonary function tests were normal in three cases, and a mild restrictive ventilatory defect was documented in the other cases. All had a low apparent predicted probability of pneumoconiosis based on health questionnaires, spirometry and duration of silica exposure. The initial chest X-ray was abnormal in all six cases with radiological evidence of silicosis (International Labour Office profusion category ≥1/1) on imaging, and all had evidence of silicosis on high-resolution computed tomography (HRCT). Three patients had already progressed to progressive massive fibrosis on HRCT scanning at the time of referral to specialist respiratory services. CONCLUSIONS: The appearances of these six cases of silicosis in young, asymptomatic construction workers emphasizes the importance of enforcing effective exposure control and comprehensive surveillance programmes. Our observations highlight the importance of having a low threshold for early radiological screening to promote early and effective detection of this disease.

Cross-sectional and longitudinal analysis of bone age maturation during peri-pubertal growth in children with type I, III and IV osteogenesis imperfecta.

Osteogenesis imperfecta (OI)is a rare genetically heterogeneous disorder caused by changes in the expression or processing of type I collagen. Clinical manifestations include bone fragility, decreased linear growth, and skeletal deformities that vary in severity. In typically growing children, skeletal maturation proceeds in a predictable pattern of changes in the size, shape, and mineralization on the hand and wrist bones that can be followed radiographically known at the bone age. Assessment of bone age can be clinically used to assess time remaining for linear growth, and the onset and duration of puberty, both of which can be useful in determining the timing of some surgeries or the interpretation of other imaging modalities such as bone densitometry. Additionally, deviations in the expected maturation process of the bone age may prompt or assist in the work up of a significant delay or advancement in a child's growth pattern. The primary aim of our study was to determine whether the bone age in children with a skeletal disorder such as OI follow the same pattern and rate of bone maturation compared to a control population. Using participants from the Natural History Study of the Brittle Bone Disorders Consortium, we analyzed 159 left hand and wrist radiographs (bone age) for a cross-sectional analysis and 55 bone ages repeated at approximately 24 months for a longitudinal analysis of skeletal maturation. Bone ages were read by a pediatric endocrinologist and by an automated analysis using a program called BoneXpert. Our results demonstrated that in children with mild-to-moderate OI (types I and IV), the skeletal maturation is comparable to chronological age-mated controls. For those with more severe forms of OI (type III), there is a delayed pattern of skeletal maturation of less than a year (10.5 months CI 5.1-16) P = 0.0012) at baseline and a delayed rate of maturation over the two-year follow up compared to type I (P = 0.06) and type III (P = 0.02). However, despite these parameters being statistically different, they may not be clinically significant. We conclude the bone age, with careful interpretation, can be used in the OI population in a way that is similar to the general pediatric population.

Alterations of a serum marker of collagen X in growing children with osteogenesis imperfecta.

Abnormalities in the structure and/or processing of type I collagen cause osteogenesis imperfecta and result in bone fragility, abnormal bone growth and short stature. Type I collagen is expressed in the growth plate but the mechanisms by which abnormalities in collagen I contribute to growth plate dysfunction and growth retardation are unknown. The non-collagenous domain (NC1) of type X collagen (CXM) is released from the hypertrophic zone of active growth plates and is a marker for new endochondral bone formation. Serum CXM levels are strongly correlated with the rate of growth in healthy children. We hypothesized that CXM levels in children with OI would be abnormal when compared to normally growing children. Using participants from the Brittle Bone Disease Consortium Natural History Study we analyzed the distribution of CXM over the ages of 8 months to 40 years in 187 subjects with OI (89 type I and 98 types III/IV) as well as analyzed the relationship between growth velocity and CXM levels in a subset of 100 children <16 years old with OI (44 type I and 56 types III/IV). CXM levels in both control and OI children demonstrated a similar pattern of variation by age with higher levels in early life and puberty followed by a post-pubertal drop. However, there was greater variability within the OI cohort and the relationship with growth velocity was weaker. The ratio of CXM level to growth velocity was elevated in children with type III/IV OI compared to controls. These results suggest that the relationship between hypertrophic zone function and the end point of skeletal growth is disrupted in OI.

CENP-B binds a novel centromeric sequence in the Asian mouse Mus caroli.

Minor satellite DNA, found at Mus musculus centromeres, is not present in the genome of the Asian mouse Mus caroli. This repetitive sequence family is speculated to have a role in centromere function by providing an array of binding sites for the centromere-associated protein CENP-B. The apparent absence of CENP-B binding sites in the M. caroli genome poses a major challenge to this hypothesis. Here we describe two abundant satellite DNA sequences present at M. caroli centromeres. These satellites are organized as tandem repeat arrays, over 1 Mb in size, of either 60- or 79-bp monomers. All autosomes carry both satellites and small amounts of a sequence related to the M. musculus major satellite. The Y chromosome contains small amounts of both major satellite and the 60-bp satellite, whereas the X chromosome carries only major satellite sequences. M. caroli chromosomes segregate in M. caroli x M. musculus interspecific hybrid cell lines, indicating that the two sets of chromosomes can interact with the same mitotic spindle. Using a polyclonal CENP-B antiserum, we demonstrate that M. caroli centromeres can bind murine CENP-B in such an interspecific cell line, despite the absence of canonical 17-bp CENP-B binding sites in the M. caroli genome. Sequence analysis of the 79-bp M. caroli satellite reveals a 17-bp motif that contains all nine bases previously shown to be necessary for in vitro binding of CENP-B. This M. caroli motif binds CENP-B from HeLa cell nuclear extract in vitro, as indicated by gel mobility shift analysis. We therefore suggest that this motif also causes CENP-B to associate with M. caroli centromeres in vivo. Despite the sequence differences, M. caroli presents a third, novel mammalian centromeric sequence producing an array of binding sites for CENP-B.

Assessment of endothelial damage and cardiac injury in a mouse model mimicking thrombotic thrombocytopenic purpura.

Essentials Endothelial injury is thought to be a key event in thrombotic thrombocytopenic purpura (TTP). Endothelial and cardiac damages were assessed in a model of TTP using ADAMTS-13 knockout mice. Damages of cardiac perfusion and function were associated with nitric oxide pathway alteration. Endothelial dysfunction constitutes a critical event in TTP development and cardiac injury. SUMMARY: Background Cardiac alterations represent a major cause of mortality in patients with thrombotic thrombocytopenic purpura (TTP). Endothelial injury remains poorly defined, but seems to be a key initiating event leading to the formation of platelet-rich thrombi in TTP patients. Objectives To assess the changes in endothelial function and the induced cardiac damage in a mouse model of TTP. Patients/methods We used an animal model in which TTP-like symptoms are triggered by injection of 2000 units kg-1 of recombinant von Willebrand factor in ADAMTS-13 knockout mice. Results These mice developed TTP-like symptoms, i.e. severe thrombocytopenia, schistocytosis, and anemia. On day 2, magnetic resonance imaging demonstrated a decrease in left ventricular perfusion associated with alteration of left ventricular ejection fraction, fractional shortening, and cardiac output, suggesting early systolic dysfunction. This was associated with decrease in endothelium-mediated relaxation responses to acetylcholine in mesenteric and coronary arteries, demonstrating severe early endothelial dysfunction. In parallel, we showed decreased cardiac expression of endothelial nitric oxide (NO) synthase and increased expression of antioxidant enzymes, suggesting alteration of the NO pathway. At this time, cardiac immunohistochemistry revealed an increase in the expression of VCAM-1 and E-selectin. Conclusion This study provides evidence that the heart is a sensitive target organ in TTP, and shows, for the first time, strong mesenteric and coronary endothelial dysfunction in an induced-TTP model. The mechanisms incriminated are the occurrence of a pro-oxidant state, and proadhesive and proinflammatory phenotypes. This previously largely unrecognized vascular dysfunction may represent an important contributor to the systemic organ failure occurring in TTP.

BMP-4 inhibits follicle-stimulating hormone secretion in ewe pituitary.

Activins and inhibins, members of the transforming growth factor-beta family are able to stimulate and inhibit, respectively, FSH synthesis and release. Other members of this superfamily, the bone morphogenetic proteins (BMPs), may also affect FSH synthesis in the mouse. The aim of this work was to determine whether BMPs are expressed in the ovine pituitary and whether they play a role in the regulation of FSH release. The mRNAs encoding BMP-2, BMP-4, BMP-7 and the oocyte-derived growth factor, growth differentiation factor (GDF)-9 were detected in the pituitaries of cyclic ewes by reverse-transcriptase PCR, as well as the mRNAs encoding the BMP type I receptors, BMPR-IA (activin-receptor-like kinase (ALK)-3) and BMPR-IB (ALK-6), and type II receptors (BMPR-II). Immunolabeling of pituitary sections revealed the presence of BMPR-IA (ALK-3) and BMPR-II in gonadotrope cells. To investigate the potential effects of BMPs on FSH secretion, ewe pituitary cell cultures were treated with BMP-4 (10(-11) M to 10(-9) M) for 48 h. Interestingly, FSH release was decreased in a dose-dependent manner. At 10(-9) M BMP-4 both FSH concentration and FSHbeta mRNA expression were reduced by 40% of control values. In contrast, there was no inhibitory effect on either LH or LHbeta mRNA expression. A similar result was found with BMP-6. BMP-4 triggered the phosphorylation of Smad1, suggesting that the effect of BMP-4 on FSH secretion is due to the activation of the BMPs signaling pathway. Furthermore, BMP-4 blocked the stimulatory effect of activin on both FSH release and FSHbeta mRNA and amplified the suppression of FSH release and FSHbeta mRNA levels induced by 17beta-estradiol. These results indicate that a functional BMP system operates within the sheep pituitary, at least in vitro, to decrease FSH release and to modulate the effect of activin.

Maternal exposure to octylphenol suppresses ovine fetal follicle-stimulating hormone secretion, testis size, and sertoli cell number.

We have tested the hypothesis that maternal exposure to octylphenol, a putative endocrine disrupting chemical, will suppress gonadotropin secretion with a concomitant decrease in testis size and Sertoli cell number during fetal life in the lamb. In Exp 1, pregnant ewes received a continuous iv infusion of diethylstilbestrol (DES; 50 microg/kg x day), octylphenol (1000 microg/kg x day), or vehicle (1:4, alcohol-saline) from days 110-115 of gestation. The fetuses were chronically catheterized in utero, and blood samples were collected every 8 h to monitor gonadotropin secretion. In Exp 2, pregnant ewes received twice weekly sc injections of DES (0.5 microg/kg x day), octylphenol (1000 microg/kg x day), or corn oil from day 70 of gestation to birth. The pituitary gland and testes were collected from the lambs at the end of the treatment period. In Exp 1, maternal exposure to octylphenol suppressed (P < 0.05) FSH concentrations without any effect (P > 0.05) on LH concentrations compared with those in control fetuses. In Exp 2, long-term maternal exposure to octylphenol or a 1000-fold lower dose of DES suppressed (P < 0.05) FSH, messenger RNA levels and the number of FSHbeta-immunopositive cells in the pituitary gland and reduced testis weight and the number of Sertoli cells in the testis compared with those in control lambs. We conclude that maternal exposure to octylphenol inhibits the secretion of FSH in the fetus with a concomitant decrease in testis size and Sertoli cell number at birth.

Differential secretion of gonadotrophins: investigation of the role of secretogranin II and chromogranin A in the release of LH and FSH in LbetaT2 cells.

This study investigated the role of the secretory granule proteins, secretogranin II (SgII) and chromogranin A (CgA), in the differential secretion of FSH and LH from LbetaT2 mouse gonadotroph cells. Exogenous activin, which synergises with GnRH, is essential for the release of FSH from these cells, but also has stimulatory effects on LH and enhances GnRH-induced LH secretion. Two experiments are reported. In experiment 1, cultures were supplemented with activin (0-50 ng/ml), with and without a daily 1 h treatment of 10 nM GnRH, for 3 days. Protein secretion and mRNA levels were measured. In experiment 2, cells were treated with activin (50 ng/ml) alone, a daily 1 h treatment of 10 nM GnRH, or a combination of both for 6 days. In addition, cells exposed to activin+GnRH for 3 days were subsequently left untreated or given activin or GnRH alone for a further 3 days for comparison with cells maintained in activin+GnRH for 6 days. Protein secretion, intracellular protein and mRNA levels were measured. FSH secretion was stimulated, dose dependently, by activin and this effect increased synergistically in the presence of GnRH. The close correlation between secreted and intracellular FSH and FSHbeta mRNA levels was maintained in cells that had undergone treatment withdrawal after previous exposure to activin+GnRH, but there was no correlation between FSH and the granins. These results are consistent with the view that FSH released in response to activin/GnRH is constitutively secreted via a granin-independent pathway. SgII secretion mirrored the GnRH-induced secretion of LH, but was unaffected by activin, which stimulated LH secretion and had a detrimental effect on CgA mRNA transcription. This confirms previous observations that the LH released in response to GnRH is co-released with SgII via a regulated, granin-dependent pathway, and, in addition, suggests that activin may stimulate LH secretion through a constitutive, granin-independent pathway.

Influence of steroids and GnRH on biosynthesis and secretion of secretogranin II and chromogranin A in relation to LH release in LbetaT2 gonadotroph cells.

The granin proteins secretogranin II (SgII) and chromogranin A (CgA) are commonly found associated with LH and/or FSH within specialised secretory granules in gonadotroph cells, and it is possible that they play an important role in the differential secretion of the gonadotrophins. In this study we have examined the regulation of the biosynthesis and secretion of SgII and CgA, in relation to LH secretion, in the LbetaT2 mouse pituitary gonadotroph cell line. Three experiments were carried out to investigate the effects of oestradiol (E2) and dexamethasone (Dex) in the presence and absence of GnRH (experiment 1), differing GnRH concentrations (experiment 2) and alterations in GnRH pulse frequency (experiment 3). In experiment 1, exposure to E2, Dex or E2+Dex, either with or without GnRH treatment, resulted in increased LH secretion. Steroids alone had no effect on LHbeta mRNA levels, but in the presence of GnRH LHbeta mRNA levels were increased in Dex- and E2+Dex-treated cells. GnRH receptor (GnRH-R) mRNA levels were up-regulated by Dex and E2+Dex, but were unaffected by GnRH. There were no steroid-induced changes in SgII or CgA mRNA, but increased levels of CgA mRNA were observed after GnRH treatment in cells cultured in the presence of Dex. In experiment 2, increasing concentrations of GnRH resulted in increases in LH secretion that were inversely dose-dependent. No changes in LHbeta, GnRH-R or SgII mRNA levels were observed, but there were dose-dependent increases in CgA mRNA levels. In experiment 3, GnRH was given as either 1 pulse/day or 4 pulses/day for 3 days. Both pulse regimes resulted in increased LH, SgII and CgA secretion compared with controls during the first 15 min pulse on day 3. Exposure to GnRH at 4 pulses/day increased LH and SgII secretion compared with controls during all 4 pulses, but secretion of both proteins was reduced during pulses 2-4 compared with pulse 1. CgA secretion also increased due to GnRH in pulse 1, but was decreased by GnRH treatment during pulse 2, and unchanged by GnRH during pulses 3 and 4. Total daily secretion of LH and SgII from cells given 1 pulse/day of GnRH increased compared with controls on all three treatment days, while total CgA secretion increased in response to GnRH on days 2 and 3 only. Intracellular levels of SgII, but not LH, decreased after GnRH treatment. In contrast, intracellular CgA was increased, but only after 4 pulses/day of GnRH. Levels of LHbeta, but not SgII, mRNA were increased by both pulse regimes, while CgA mRNA levels increased after 1 pulse/day of GnRH. These results indicate that there is a close correlation between the GnRH-stimulated release of LH and SgII from LbetaT2 cells, suggesting that SgII may have an influential role in the regulated secretion of LH, possibly by inducing LH aggregation to facilitate trafficking into secretory granules. CgA secretion does not appear to be closely associated with that of LH, but CgA expression does appear to be regulated by GnRH, which may indicate involvement in the control of LH secretion, possibly by influencing the proportion of LH in the different types of secretory granules.

Study of respiratory effect of short- and long-term cotton gin exposure.

No excess of obstructive airway disease was found in a group of 265 cotton gin workers when compared with other San Joaquin Valley agricultural workers. After an average of eight weeks' employment in San Joaquin Valley cotton gins, 125 workers showed no appreciable deterioration of pulmonary function compared with pre-employment measurements. In studies of pulmonary function during a workshift, cotton gin workers showed slightly greater mean decrements than control agricultural workers. These differences did not reach a level of statistical significance and were lower than those usually found in byssinosis. The unusual temporal pattern of employment in cotton gins in California precludes a simple approach to diagnosis by symptoms. No correlation was found in this study between symptoms of byssinosis and objective decrements in FEV1. The questionnaire as proposed by the Cotton Dust Standard was found to be of no value in detecting reactors in this study of gin workers.

Gadolinium-enhanced fast three-dimensional angiography of the neck: technical aspect.

RATIONAL AND OBJECTIVES: This study sought to assess the feasibility of a contrast-enhanced three-dimensional (3D) magnetic resonance (MR) angiographic sequence for imaging the cervical arteries. METHODS: Ninety-eight consecutive patients underwent contrast MR angiography using a 3D sequence in the coronal plane, including both carotid and vertebral arteries. Gadolinium was injected at the beginning of the sequence. When the contrast was not optimal, a second injection was performed 5 to 10 minutes later. Qualitative assessment was performed for each arterial portion in a consensus manner by three radiologists who judged contrast enhancement, imaging coverage, and artifacts. RESULTS: A second injection was required in 11 patients, and two examinations were not assessable because of motion artifacts. Among the vessels analyzed, 19% were not assessable owing to the limited coverage in 11% and to the low contrast in 9%. Carotid bifurcations were assessable in 95%, whereas vertebral arteries were visualized from their origins to their intradural portions in only 82% of cases. A longitudinal signal-void artifact was found in the center of the arterial lumen of carotid arteries in six patients. CONCLUSIONS: Contrast MR angiography constitutes a promising tool to assess cervical arteries. Some limitations including spatial resolution, timing of injection, and imaging coverage should be overcome in the near future.

Contrast-enhanced MR angiography of supraaortic vessels: the effect of voxel size on image quality.

BACKGROUND AND PURPOSE: Several acquisition strategies may be used for imaging supraaortic vessels by using contrast-enhanced MR angiography. The purpose of this study was to assess the effect of voxel size on image quality of MR angiograms. METHODS: Fourty-four patients underwent 3D MR angiography in the coronal plane. Patients were randomly assigned into two groups according to the voxel size of MR angiograms: group 1 referred to a 1.3 x 1.29 x 1.25-mm voxel size and group 2 to a 0.95 x 0.76 x 0.82 mm voxel size. Signal-to-noise ratios (SNRs) were measured and image artifacts were analyzed by consensus between observers. The delineation of the arterial lumen was independently ranked on a four-point scale (1 = not assessable; 2 = poor delineation; 3 = fair delineation; 4 = optimal delineation). RESULTS: The overall interobserver agreement for the delineation of the arterial lumen was good (K = .84, P < .0001), with a rank significantly higher in group 2 (68% of arteries graded as 4) compared with group 1 (76% graded as 3). SNRs were significantly higher by using the conventional resolution technique, with a negative correlation between SNRs and artery delineation (P < .0001). Image artifacts, however, were more frequent with the high-resolution technique, including wrap-around artifacts and signal fall-off at the origin of the great vessels. CONCLUSION: MR angiograms with a decreased voxel size improve the delineation of cervical carotid and vertebral arteries, despite reduced SNRs and additional artifacts.

Preliminary experience using contrast-enhanced MR angiography to assess vertebral artery structure for the follow-up of suspected dissection.

BACKGROUND AND PURPOSE: Important advances have been made recently in MR angiography with the use of contrast medium injection, which has proved valuable for the imaging of vertebral arteries (VAs) obtained during short scanning times. Our purpose was to assess the feasability of contrast-enhanced fast 3D MR angiography for imaging VAs and to evaluate the long-term follow-up of VA dissections. METHODS: Sixteen consecutive patients with 18 angiographically documented VA dissections (seven occlusive dissections and 11 stenotic dissections, including two each with a pseudoaneurysm) were followed up using both contrast-enhanced 3D MR angiography and cervical T1-weighted MR imaging at a median delay of 22 months. Ten patients underwent MR imaging at the acute phase as well, and nine underwent early follow-up angiography at a median delay of 3 months. MR angiographic findings were determined by consensus, focussing on image quality, presence of residual stenosis, luminal irregularities, and occlusion. RESULTS: Of the 32 VAs, a segment of the artery was not assessable on contrast-enhanced MR angiography in each of four small VAs. A central signal void artifact of cervical arteries was seen in one patient and motion artifacts were seen in two, but images could be interpreted. A venous enhancement was detected in 10 of 16 examinations, but this did not prevent image analysis. Ten of 11 stenotic dissections returned to normal, whereas one stenotic dissection progressed to occlusion. Two pseudoaneurysms detected by initial angiography resolved spontaneously; one was revealed only by delayed MR angiography, and one was detected on an early MR angiogram and proved resolved on a late MR angiogram. Of the seven initially occluded VAs, five reopened, with a hairline residual lumen in each of three. CONCLUSION: This preliminary experience showed that contrast-enhanced MR angiography is a promising tool for imaging VAs; it allows the assessment of VA dissection changes over time. Most lesions tended to heal spontaneously, but persisting occlusion or pseudoaneurysm could be detected during the late course.

No effect of a low-frequency pulsed magnetic field on the brain blood flow among mice.

For thirty minutes Swiss mice were exposed to a 60 G 12 Hz or a 460 Hz pulsed magnetic field. The blood-brain flow was then calculated thanks to an i.v. injection of 99mTc HM-PAO, 0, 3 or 24 hours after the end of the exposure. In the end, it was in fact impossible to discriminate between the exposed mice and the controls.

The value of diaphragmatic breathing in the patient with obstructive airways disease.

It has been assumed that, by diaphragmatic breathing, a patient could vary his basal expansion.

Immunohistochemical localization of estrogen receptors in the vulva and vagina.

A rat monoclonal antibody against human estrogen receptor (ER) was used to localize nuclear ER in frozen tissue sections with the peroxidase-antiperoxidase technique. Premenopausal and postmenopausal vaginal, vulvar and nongenital skin was examined. ER was demonstrated in some but not all of the nuclei of basal and suprabasal differentiated epithelial cells of the vagina. ER was seen in the fibroblasts and smooth muscle, but not in the vessel endothelium, of the underlying stroma. ER was demonstrated in epidermal keratinocytes and dermal fibroblasts of the vulva and perineum, hair and non-hair bearing, but at a much lower frequency than in the vagina. Specific ER staining was not detected in the majority of skin specimens for extragenital sites. These findings have implications for the hormonal regulation of the vulva and for the use of estrogen cream in managing vulvar conditions.

[Evaluation of aortocoronary bypass using exercise myocardial thallium 201 scintigraphy]. / Evaluation des pontages aorto-coronaires par scintigraphie myocardique au thallium 201 à l'effort.

The surveillance of aortocoronary bypass grafts is a difficult problem. Clinical examination and exercise testing are unable to give a complete evaluation of the operative results and cardiac catheterisation with radiological opacification of the grafts are not without risk and cannot be repeated periodically. Therefore, radioisotopic methods have been proposed as a means of assessing aortocoronary bypass grafts. The aim of this study was to evaluate postoperative myocardial perfusion by Thallium 201 scintigraphy. The authors compared pre and postoperative scintigraphies in 37 patients undergoing aortocoronary bypass surgery (36 men and 1 woman, average age: 53.9 years). Preoperative coronary angiography showed 9 cases of single vessel disease, 11 cases of double vessel diseases and 17 cases of triple vessel disease. Seventy one bypass grafts were performed (average 1.92 grafts/patient): 37 on the LAD, 15 on the circumflex, 10 on the diagonal and 9 on the right coronary. All patients were submitted to the same protocol before surgery and during the third postoperative month; Clinical examination, ECG, exercise stress testing and Thallium 201 myocardial scintigraphy. The results confirm the improvement in myocardial perfusion after coronary bypass surgery. The percentage of pathological scintigraphic segments fell from 42 per cent before surgery to 27 per cent after surgery (p less than 0.01). The total Thallium perfusion index improved significantly after surgery from 9.3 +/- 2 to 7.7 +/- 1.9 (p less than 0.01). Thallium 201 scintigraphy was superior to clinical examination and exercise testing in the assessment of graft patency, identifying 2 postoperative infarctions inapparent on clinical examination, excluding postoperative non-anginal chest pain and evaluating myocardial perfusion in patients who had sub maximal postoperative exercise stress tests. The relatively non traumatic character of Thallium 201 scintigraphy makes it the best non-invasive method of assessing aortocoronary bypass graft patency.

[Does NMR provide information complementary to cardiac catheterization in aortic coarctation?]. / L'imagerie par résonance magnétique nucléaire apporte-t-elle des éléments complémentaires dans le bilan de la coarctation de l'aorte par rapport au cathétérisme cardiaque?

The results of magnetic resonance imaging (MRI) in the investigation of coarctation of the aorta were assessed and compared with those of cardiac catheterisation. This was a retrospective study of a series of 24 patients aged 14 +/- 4 years with a coarctation treated and documented by MRI. The investigation was performed with a high field 1.5 tesla (Vision, Siemens) system. Twenty-one children underwent comparative retrograde cardiac catheterisation with angiography and measurement of the peak-to-peak pressure gradient across the isthmus. No significant difference in the measurements of the aorta in MRI spin echo, gradient echo and retrograde aortic angiography were observed. On the other hand, there was a slight correlation between the degree of stenosis measured by MRI and the peak-to-peak haemodynamic gradient (r = 0.40). Seven patients had a loss of signal at the level of the aortic isthmus on MRI angiography which correlated with the haemodynamic gradient (p = 0.04). The authors conclude that MRI is a reliable non-invasive technique of investigating coarctations of the aorta. It gives accurate morphological data concerning the stenosis and blood flow. MRI should be part of the investigations of coarctation of the aorta, especially in poor indication to be able to correct it or consider the results of angioplasty or surgical correction.

Pancreatic inflammation and increased islet macrophages in insulin-resistant juvenile primates.

Chronic high caloric intake has contributed to the increased prevalence of pediatric obesity and related morbidities. Most overweight or obese children, however, do not present with frank metabolic disease but rather insulin resistance or subclinical precursors. The innate immune system plays a role in the pathophysiology of type 2 diabetes but how it contributes to early metabolic dysfunction in children on chronic high-fat diet (HFD) is unclear. We hypothesize that such inflammation is present in the pancreas of children and is associated with early insulin resistance. We used nonhuman primate (NHP) juveniles exposed to chronic HFD as a model of early pediatric metabolic disease to demonstrate increased pancreatic inflammatory markers before the onset of significant obesity or glucose dysregulation. Pancreata from 13-month-old Japanese macaques exposed to a HFD from in utero to necropsy were analyzed for expression of cytokines and islet-associated macrophages. Parameters from an intravenous glucose tolerance test were correlated with cytokine expression. Before significant glucose dysregulation, the HFD cohort had a twofold increase in interleukin 6 (IL6), associated with decreased first-phase insulin response and a sexually dimorphic (male) increase in IL1ß correlating with increased fasting glucose levels. The number of islet-associated macrophages was also increased. Pancreata from juvenile NHP exposed to HFD have increased inflammatory markers and evidence of innate immune infiltration before the onset of significant obesity or glucose dysregulation. Given the parallel development of metabolic disease between humans and NHPs, these findings have strong relevance to the early metabolic disease driven by a chronic HFD in children.