Long-term integrity of 53 iliac vein stents after catheter-directed thrombolysis.

BACKGROUND: Long-term surveillance data on venous stent integrity is sparse. There is limited knowledge on whether duplex ultrasound (DUS) can detect potential stent deformities such as kinking, straightening, and fracture, which may impact long-term patency of the stented veins. PURPOSE: To assess venous stent integrity after at least five years of follow-up and to establish the efficacy of DUS as surveillance in patients with venous stent. MATERIAL AND METHODS: A total of 45 patients with acute iliac-femoral deep vein thrombosis (DVT) treated with catheter directed thrombolysis (CDT) and stenting >5 years before follow-up. Stents were evaluated with 3D volume low dose non-contrast computed tomography (CT) and DUS for kinking, straightening, stent fracture, and patency. Results from CT scans and DUS were compared to assess the overall agreement between the methods. RESULTS: Median follow-up was 13.2 years (mean = 11.2 years; range = 5.2-15.8 years). 3D CT reconstructions showed normal stent configuration in 47 stents (89%). All intact stents were identified by DUS. In the remaining six stents, 3D CT reconstructions showed compression, tapering, kinking, and minor fracture. DUS recognized all stent complications except the minor fracture. Overall agreement between CT and DUS was 98% (kappa = 0.90). Two cases of stent occlusion were found. CONCLUSION: The long-term physical resilience of iliac vein stents evaluated with 3D CT in patients treated with CDT for iliofemoral DVT was high. Stent deformities were mostly compression, whereas fracture was rarely seen. DUS seems to be sufficient to evaluate venous stent integrity.

Hepatic microbiome in healthy lean and obese humans.

BACKGROUND & AIMS: Dysbiosis of the gut microbiota in response to an energy-rich Western diet and the potential leak of bacteria and/or bacterial products from the intestine to the liver is perceived as a potential risk factor for the development of non-alcoholic fatty liver disease (NAFLD). We investigated the microbiome in liver biopsies from healthy lean and obese individuals and compared it with their blood microbiome. METHODS: We examined liver biopsies from 15 healthy lean and 14 obese individuals (BMI of 18.5-25 and 30-40 kg/m2, respectively). Bacterial 16S ribosomal DNA (rDNA) was analysed by quantitative polymerase chain reaction (qPCR) and 16S metagenomic sequencing targeting the hypervariable V3-V4 region. Metagenomic analysis was performed using the linear discriminant analysis effect size (LEfSe) algorithm. Data are medians with IQRs in brackets. RESULTS: Histology revealed hepatic steatosis in 13 obese individuals and in 2 lean individuals. A robust signal from qPCR revealed significantly higher amounts of bacterial rDNA copies in liver samples from obese individuals compared with those from lean individuals (148 [118-167] vs. 77 [62-122] 16S copies/ng DNA, p <0.001). Liver biopsies from the obese group were characterised by lower alpha diversity at the phylum level (Shannon index 0.60 [0.55-0.76] vs. 0.73 [0.62-0.90], p = 0.025), and metagenomic profiling revealed a significantly higher proportion of Proteobacteria in this group (81.0% [73.0-82.4%] vs. 74.3% [68.4-78.4%], p = 0.014). CONCLUSIONS: We provide evidence for the presence of bacterial rDNA in the healthy human liver. Based on differences in the hepatic microbiome between obese individuals and healthy lean individuals, we suggest that changes in the liver microbiome could constitute an additional risk factor for the development of NAFLD. LAY SUMMARY: Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disease globally, and new evidence suggests that obesity is associated with a disturbed gut bacterial composition, which may influence the development of NAFLD. We examined the composition of bacterial DNA in liver biopsies from healthy lean and obese individuals and found a different composition of bacterial DNA in liver biopsies from the obese group. We propose that the increased bacterial DNA load in the livers of obese individuals could constitute an early risk factor for the progression of NAFLD. CLINICAL TRIAL NUMBER: NCT02337660.

Metabolic effects of 1-week binge drinking and fast food intake during Roskilde Festival in young healthy male adults.

AIMS/HYPOTHESIS: Metabolic effects of intermittent unhealthy lifestyle in young adults are poorly studied. We investigated the gluco-metabolic and hepatic effects of participation in Roskilde Festival (1 week of binge drinking and junk food consumption) in young, healthy males. METHODS: Fourteen festival participants (FP) were studied before, during and after 1 week's participation in Roskilde Festival. Fourteen matched controls (CTRL) who did not participate in Roskilde Festival or change their lifestyle in other ways were investigated along a similar timeline. RESULTS: The FP group consumed more alcohol compared to their standard living conditions (2.0 ± 3.9 vs 16.3 ± 8.3 units/day, P < 0.001). CTRLs did not change their alcohol consumption. AUC for glucose during OGTT did not change in either group. C-peptide responses increased in the FP group (206 ± 24 vs 236 ± 17 min × nmol/L, P = 0.052) and the Matsuda index of insulin sensitivity decreased (6.2 ± 2.4 vs 4.7 ± 1.4, P = 0.054). AUC for glucagon during oral glucose tolerance test (OGTT) increased in the FP group (1037 ± 90 vs 1562 ± 195 min × pmol/L, P = 0.003) together with fasting fibroblast growth factor 21 (FGF21) (62 ± 30 vs 132 ± 72 pmol/L, P < 0.001), growth differentiation factor 15 (GDF5) (276 ± 78 vs 330 ± 83 pg/mL, P = 0.009) and aspartate aminotransferase (AST) levels (37.6 ± 6.8 vs 42.4 ± 11 U/L, P = 0.043). Four participants (29%) developed ultrasound-detectable steatosis and a mean strain elastography-assessed liver stiffness increased (P = 0.026) in the FP group. CONCLUSIONS/INTERPRETATION: Participation in Roskilde Festival did not affect oral glucose tolerance but was associated with a reduction in insulin sensitivity, increases in glucagon, FGF21, GDF15 and AST and lead to increased liver stiffness and, in 29% of the participants, ultrasound-detectable hepatic steatosis.

One Year's Treatment with the Glucagon-Like Peptide 1 Receptor Agonist Liraglutide Decreases Hepatic Fat Content in Women with Nonalcoholic Fatty Liver Disease and Prior Gestational Diabetes Mellitus in a Randomized, Placebo-Controlled Trial.

Prior gestational diabetes mellitus (pGDM) is associated with increased risk of nonalcoholic fatty liver disease (NAFLD). Treatment with glucagon-like peptide 1 (GLP-1) receptor agonists has shown beneficial effects in NAFLD patients. We evaluated the effect of the GLP-1 analogue liraglutide on NAFLD features in women with pGDM. Eighty-two overweight/obese, nondiabetic women with pGDM were included. We performed abdominal ultrasound, transient elastography with controlled attenuation parameter (CAP), and blood sampling at baseline and after 1 year. Thirty-seven women were randomized to liraglutide (1.8 mg once-daily) and 45 to placebo. Based on the ultrasound scan, 18 women (22%) had ultrasound-verified NAFLD at baseline and of these, 10 (56%) received liraglutide treatment. After 1 year, eight participants no longer had steatosis, four in each treatment group. The number of participants who developed NAFLD was similar in the two treatment groups; five in the liraglutide group and six in the placebo group (p = 0.74). Compared to placebo, liraglutide reduced the CAP-assessed intrahepatic fat content (-28 (-44;-11) vs. 2 (-13;18) dB/m, p < 0.01) and body weight (-4.7 (-6.4;-2.9) vs. -1.4 (-3;0.3) kg, p < 0.01). One-year's liraglutide treatment had no effect on the presence of ultrasound-diagnosed NAFLD in overweight/obese nondiabetic women with pGDM, but reduced body weight and steatosis assessed by transient elastography with CAP.

Glucagon Resistance at the Level of Amino Acid Turnover in Obese Subjects With Hepatic Steatosis.

Glucagon secretion is regulated by circulating glucose, but it has turned out that amino acids also play an important role and that hepatic amino acid metabolism and glucagon are linked in a mutual feedback cycle, the liver-α-cell axis. On the basis of this knowledge, we hypothesized that hepatic steatosis might impair glucagon's action on hepatic amino acid metabolism and lead to hyperaminoacidemia and hyperglucagonemia. We subjected 15 healthy lean and 15 obese steatotic male participants to a pancreatic clamp with somatostatin and evaluated hepatic glucose and amino acid metabolism when glucagon was at basal levels and at high physiological levels. The degree of steatosis was evaluated from liver biopsy specimens. Total RNA sequencing of liver biopsy specimens from the obese steatotic individuals revealed perturbations in the expression of genes predominantly involved in amino acid metabolism. This group was characterized by fasting hyperglucagonemia, hyperaminoacidemia, and no lowering of amino acid levels in response to high levels of glucagon. Endogenous glucose production was similar between lean and obese individuals. Our results suggest that hepatic steatosis causes resistance to the effect of glucagon on amino acid metabolism. This results in increased amino acid concentrations and increased glucagon secretion, providing a likely explanation for fatty liver-associated hyperglucagonemia.

Significance of Partial or Complete Thrombosis of the Common and Deep Femoral Vein in Patients With Deep Vein Thrombosis.

OBJECTIVE: The aim was to assess the anatomical distribution of acute deep venous thrombosis (DVT) with a focus on iliofemoral DVT, and, in particular, to characterise thrombus in the common femoral vein (CFV) and the deep femoral vein (DFV). METHODS: A one year prospective study including patients older than 18 years of age with an acute first time DVT according to ultrasound examination at one of three university hospitals in Copenhagen, Denmark. Thrombus location and extent were registered and divided into five segments: calf veins; popliteal vein; femoral and deep femoral vein; common femoral vein; and iliac veins and/or the inferior vena cava. Thrombus appearance of the CFV and the DFV (partial or occlusive) was examined in detail. RESULTS: Acute DVTs were identified in 203 extremities in 200 patients (58% male). The median age of the patients was 68 years (range 19-92 years), and left-sided DVT was observed in 56%. Iliofemoral DVT was present in 54 (27.0%) patients. Thrombus involving the CFV but not the iliac veins (CFV group) was seen in 28 patients; the remaining 26 had involvement of the iliac veins (iliac group). Thrombus in the CFV was more likely to be occlusive in the iliac group than in the CFV group (77% vs. 4%; p < .001). Thrombus in the DFV was more often occlusive in the iliac group than in the CFV group (81% vs. 11%; p < .001). The DFV was free of thrombus in 12% of patients in the iliac group and in 64% of those in the CFV group. CONCLUSION: The presence of occlusive thrombus in the CFV and/or in the DFV pointed to a DVT also involving the ipsilateral iliac veins. Thrombosis of the deep leg veins extending into the CFV below the inguinal ligament was more likely to be partial in the CFV, mainly due to inflow from the DFV.

Hepatic transcriptome signatures in patients with varying degrees of nonalcoholic fatty liver disease compared with healthy normal-weight individuals.

Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of conditions ranging from simple steatosis (NAFL), over nonalcoholic steatohepatitis (NASH) with or without fibrosis, to cirrhosis with end-stage disease. The hepatic molecular events underlying the development of NAFLD and transition to NASH are poorly understood. The present study aimed to determine hepatic transcriptome dynamics in patients with NAFL or NASH compared with healthy normal-weight and obese individuals. RNA sequencing and quantitative histomorphometry of liver fat, inflammation and fibrosis were performed on liver biopsies obtained from healthy normal-weight ( n = 14) and obese ( n = 12) individuals, NAFL ( n = 15) and NASH ( n = 16) patients. Normal-weight and obese subjects showed normal liver histology and comparable gene expression profiles. Liver transcriptome signatures were largely overlapping in NAFL and NASH patients, however, clearly separated from healthy normal-weight and obese controls. Most marked pathway perturbations identified in both NAFL and NASH were associated with markers of lipid metabolism, immunomodulation, extracellular matrix remodeling, and cell cycle control. Interestingly, NASH patients with positive Sonic hedgehog hepatocyte staining showed distinct transcriptome and histomorphometric changes compared with NAFL. In conclusion, application of immunohistochemical markers of hepatocyte injury may serve as a more objective tool for distinguishing NASH from NAFL, facilitating improved resolution of hepatic molecular changes associated with progression of NAFLD. NEW & NOTEWORTHY Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries. NAFLD is associated with the metabolic syndrome and can progress to the more serious form, nonalcoholic steatohepatitis (NASH), and ultimately lead to irreversible liver damage. Using gold standard molecular and histological techniques, this study demonstrates that the currently used diagnostic tools are problematic for differentiating mild NAFLD from NASH and emphasizes the marked need for developing improved histological markers of NAFLD progression.

Vector and Doppler Ultrasound Velocities Evaluated in a Flow Phantom and the Femoropopliteal Vein.

Ultrasound is used for evaluating the veins of the lower extremities. Operator and angle dependency limit spectral Doppler ultrasound (SDUS). The aim of the study was to compare peak velocity measurements in a flow phantom and the femoropopliteal vein of 20 volunteers with the angle-independent vector velocity technique vector flow imaging (VFI) and SDUS. In the flow phantom, VFI underestimated velocity (p = 0.01), with a lower accuracy of 5.5% (p = 0.01) and with no difference in precision, that is, error factor, compared with SDUS (VFI: 1.02 vs. SDUS: 1.02, p = 0.58). In vivo, VFI estimated lower velocities (femoral: p = 0.001; popliteal: p = 0.001) with no difference in precision compared with SDUS (femoral: VFI 1.09 vs. SDUS 1.14, p = 0.37; popliteal: VFI 1.13 vs. SDUS 1.06, p = 0.09). In conclusion, the precise VFI technique can be used to characterize venous hemodynamics of the lower extremities despite its underestimation of velocities.

Nonalcoholic Fatty Liver Disease Is Prevalent in Women With Prior Gestational Diabetes Mellitus and Independently Associated With Insulin Resistance and Waist Circumference.

OBJECTIVE: Type 2 diabetes increases the risk of nonalcoholic fatty liver disease (NAFLD), which is a potentially reversible condition but is also associated with progressive fibrosis and cirrhosis. Women with prior gestational diabetes mellitus (pGDM) have a higher risk for NAFLD. RESEARCH DESIGN AND METHODS: One hundred women without diabetes who had pGDM (median [interquartile range]: age 38.6 [6.4] years; BMI 31.0 [6.2] kg/m2) and 11 healthy control subjects without NAFLD (age 37.9 [7.8] years; BMI 28.1 [0.8] kg/m2) underwent a 75-g oral glucose tolerance test (OGTT), DXA whole-body scan, and ultrasonic evaluation of hepatic steatosis. RESULTS: Twenty-four (24%) women with pGDM had NAFLD on the basis of the ultrasound scan. None had cirrhosis. Women with NAFLD had a higher BMI (P = 0.0002) and waist circumference (P = 0.0003), increased insulin resistance (P = 0.0004), and delayed suppression of glucagon after the OGTT (P < 0.0001), but NAFLD was not associated with the degree of glucose intolerance (P = 0.2196). Visceral fat mass differed among the three groups, with the NAFLD group having the highest amount of fat and the control subjects the lowest (P = 0.0003). By logistic regression analysis, insulin resistance (P = 0.0057) and waist circumference (P = 0.0109) were independently associated with NAFLD. CONCLUSIONS: NAFLD was prevalent in this cohort of relatively young and nonseverely obese women with pGDM who are considered healthy apart from their increased risk for diabetes. Insulin resistance and a larger waist circumference were independently associated with the presence of NAFLD, whereas glucose intolerance was not.

[Ultrasound is the first choice when chronic venous disease in the lower extremities is suspected].

Chronic venous disease affects one quarter of the population and is routinely examined with Doppler ultrasound. The veins are evaluated in terms of diameter, compressibility and blood flow. The examination is performed with the patient in the standing position but can be complemented in the supine position, if disease of the deep veins is suspected. New angle-independent ultrasound techniques may contribute with more complex visualization of the blood flow and may in the future replace Doppler ultrasound in some areas of vein diagnostics.

[Transabdominal bowel sonography].

This focused review describes the current use and future perspectives regarding transabdominal bowel sonography (TABS). The technique for B-mode and Doppler is described and the use of ultrasound contrast and elastography is discussed. Pathology and subsequent imaging findings are focused on appendicitis, diverticulitis, inflammatory bowel diseases and within paediatric conditions along with other common intestinal pathology. In conclusion we find that TABS is a fast, efficient, low-cost and non-ionization imaging technique without any patient discomfort.

Ultrasonographic examination in juvenile idiopathic arthritis is better than clinical examination for identification of intraarticular disease.

INTRODUCTION: The diagnosis of juvenile idiopathic arthritis (JIA) is formally based on clinical examination, but ultrasound (US) examination is used increasingly. Our purpose was to compare US and clinical examination in the assessment of synovitis in JIA. MATERIAL AND METHODS: This study was retrospective and included 62 consecutive patients with newly diagnosed JIA admitted to the Department of Paediatrics at Gentofte Hospital, Denmark from 2003 to 2010. The included patients were examined clinically and by US at their first visit. All peripheral joints were examined clinically, 24% of these joints were examined by US. The development of new, clinically arthritic joints was followed during the next six months. RESULTS: The mean sensitivity of clinical examination was 48% with a clear hierarchy among joints, knees having the highest sensitivity, small joints of hands and feet the lowest. On average, 0.4 joints per child, which were arthritic by clinical examination, were negative by US. Inversely, US detected 1.3 more arthritic joints than clinical examination did per child. The latter is a minimum estimate since only 24% of the joints were examined by US. Subclinically arthritic joints had a 29% probability of developing clinical arthritis within the first six months following the initial examination. CONCLUSION: Although there is no formal validation of US examination in children suspected for JIA, we recommend that it is used routinely and performed by a highly experienced US operator. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

[Diagnostic strategy in patients with clinically suspected deep vein thrombosis]. / Diagnostisk strategi hos patienter, der er henvist til skadestuen på mistanke om dyb venøs trombose.

INTRODUCTION: The standard method for diagnosing deep vein thrombosis (DVT) involves determination of D-dimer and ultrasound scanning. In an attempt to reduce the number of ultrasound examinations we have supplemented this with a clinical probability estimate for DVT (DVT-score) over one year. MATERIALS AND METHODS: A total of 508 consecutive patients presenting in the emergency room with suspected DVT had D-dimer and DVT-score performed. Patients with non-elevated D-dimer and a low or moderate DVT score received no treatment. The remainder had ultrasound scanning from the groin to the popliteal fossa. If no DVT was revealed, the patient was contacted by telephone 7-10 days later, and was offered a repeat examination if symptoms persisted. RESULTS: Three patients with chronic DVT were excluded. Normal D-dimer and low or moderate DVT-score was found in 103 patients, none had DVT. Only five patients with normal D-dimer had high DVT-scores, none had DVT, so that the benefit from determining DVT-scores was modest. Ultrasound scanning revealed DVT in 85 out of 397 patients with elevated D-dimer. A repeat examination was performed in 91 patients with persisting symptoms, and disclosed DVT in two. CONCLUSION: We recommend that ambulatory patients with clinically suspected DVT have a D-dimer test. If D-dimer is elevated, compression ultrasound should be performed in the groin and the popliteal fossa.

[Ultrasound in the diagnosis and treatment of developmental dysplasia of the hip. Evaluation of a selective screening procedure]. / Ultralydskanning ved diagnostik og behandling af hoftedysplasi. Vurdering af en selektiv screeningsprocedure.

INTRODUCTION: With the intention of reducing the treatment frequency of Developmental Dysplasia of the Hip (DDH), two hospitals in Copenhagen implemented a screening and treatment procedure based on selective referral to ultrasonography of the hip (US). This paper describes and evaluates the procedure. MATERIALS AND METHODS: The procedure defines procedures for referral, diagnosis, treatment and follow-up of DDH. From 1998 to 2003 children with risk factors or with positive Ortolanis or Barlows test were referred to US. RESULTS: The treatment rate was 0.47%, and the rate of late diagnosed cases 0.03%. No relationship was seen between morphological parameters at the first US and the outcome of hips classified as minor dysplastic or not fully developed (NFD). A statistically significant relationship was seen between the degree of dysplasia and the time until US normalization of the hips (p= 0.02). There was no relapse of dysplasia after treatment. The median duration of treatment was six, eight and nine weeks for mild, moderate and severe dysplasia respectively. CONCLUSION: The procedure resulted in a low rate of treatment and a small number of late diagnosed cases. Prediction of the outcome of minor dysplastic/NFD hips must be based on a minimum of two US. An individualization of the treatment length was possible, and treatment length could be shortened in many cases. Compared with the incidence of DDH in Gentofte Hospital before the use of US, we suggest that this selective ultrasound screening procedure is worthwhile.

Ultrasonography of the metacarpophalangeal and proximal interphalangeal joints in rheumatoid arthritis: a comparison with magnetic resonance imaging, conventional radiography and clinical examination.

Signs of inflammation and destruction in the finger joints are the principal features of rheumatoid arthritis (RA). There are few studies assessing the sensitivity and specificity of ultrasonography in detecting these signs. The objective of the present study was to investigate whether ultrasonography can provide information on signs of inflammation and destruction in RA finger joints that are not available with conventional radiography and clinical examination, and comparable to the information provided by magnetic resonance imaging (MRI). The second to fifth metacarpophalangeal and proximal interphalangeal joints of 40 RA patients and 20 control persons were assessed with ultrasonography, clinical examination, radiography and MRI. With MRI as the reference method, the sensitivity, specificity and accuracy of ultrasonography in detecting bone erosions in the finger joints were 0.59, 0.98 and 0.96, respectively; they were 0.42, 0.99 and 0.95 for radiography. The sensitivity, specificity and accuracy of ultrasonography, with signs of inflammation on T1-weighted MRI sequences as the reference method, were 0.70, 0.78 and 0.76, respectively; they were 0.40, 0.85 and 0.72 for the clinical examination. With MRI as the reference method, ultrasonography had higher sensitivity and accuracy in detecting signs of inflammation and destruction in RA finger joints than did clinical and radiographic examinations, without loss of specificity. This study shows that ultrasonography has the potential to improve assessment of patients with RA.

Contrast-enhanced power Doppler ultrasonography of the metacarpophalangeal joints in rheumatoid arthritis.

The aim of this study was to examine, with dynamic contrast-enhanced MRI as the reference, if contrast-enhanced power Doppler ultrasonography (CE PDUS) of rheumatoid arthritis (RA) metacarpophalangeal (MCP) joints provides additional information for evaluation of synovial inflammation compared with PDUS. One MCP joint in each of 15 RA patients and 3 healthy control persons were examined with PDUS before and after intravenous bolus Levovist contrast injection. Corresponding rates of early synovial enhancement (RESE), previously shown to be closely related to histopathological synovitis, were calculated from dynamic contrast-enhanced MR images obtained the same day. Prior to ultrasonography, the joint was evaluated clinically. Levovist increased the flow signal in 7 of 9 joints with pre-contrast flow-signal and in 0 of 9 without pre-contrast signal. No healthy controls showed CE PDUS signal. The results of CE PDUS and dynamic MRI were closely related: RESE in joints with CE PDUS signal was significantly higher than in joints without CE PDUS signal (Mann-Whitney test, p<0.001). Among the patients with pre-contrast PDUS signal no statistically significant difference in RESE values was found between joints with and without post-contrast flow-signal increase. No correlation was found between clinical examination and CE PDUS. Based on comparisons with dynamic contrast-enhanced MRI, PDUS appears to be reliable for assessment of synovitis in RA MCP joints. Intravenous contrast injection may provide additional information in selected cases but did not in the present study increase the sensitivity of the method.

Thymic involvement in immune recovery during antiretroviral treatment of HIV infection in adults; comparison of CT and sonographic findings.

In adult HIV-infected patients, thymic size evaluated from CT scans seems to be important to the degree of immune reconstitution obtainable during treatment with highly active antiretroviral therapy (HAART). To examine whether ultrasound is as reliable as CT for estimating thymic size and predicting immune recovery, CT and ultrasound scans were performed in 25 adult HIV-infected patients and 10 controls. CD4 counts and naive CD4 counts were measured in order to determine immune reconstitution. Furthermore, the CD4+ T-cell receptor excision circle (TREC) frequency and T-cell receptor (TCR) repertoire were determined. The study demonstrated no correlation between the 2 scanning methods (r = 0.201, p = 0.358 in patients and r = 0.457, p = 0.184 in controls). Among the patients, no association was found between the sonographically estimated thymic size and immunological parameters such as CD4 count (r = 0.083, p = 0.706), naive CD4 count (r = 0.067, p = 0.762), CD4 + TREC frequency (r = 0.028, p = 0.900) and CD4 + TCR repertoire (r = -0.057, p = 0.828). These findings show that CT remains superior for assessing thymic size in adults and is preferable to ultrasound when evaluating the importance of a large thymus to immune recovery during HAART.

Threshold electrical stimulation (TES) in ambulant children with CP: a randomized double-blind placebo-controlled clinical trial.

A randomized double-blind placebo-controlled clinical trial was carried out to determine whether a group of stable children with cerebral palsy (36 males, 21 females; mean age 10 years 11 months, range 5 to 18 years) would improve their motor skills after 12 months of threshold electrical stimulation (TES). Two thirds received active and one third received inactive stimulators. For the primary outcome we constructed a set of plausible motor function tests and studied the change in summary indices of the performance measurements. Tests were videotaped and assessed blindly to record qualitative changes that might not be reflected in performance measurements. We also judged range of motion, degree of spasticity, and muscle growth measured by CT. Fifty seven of 82 outpatients who were able to walk at least with a walker, completed all 12 months of treatment (hemiplegia n=25, diplegia n=32). There was no significant difference between active and placebo treatment in any of the tested groups, nor combined. Visual and subjective assessments favoured TES (ns), whereas objective indices showed the opposite trend. We conclude that TES in these patients did not have any significant clinical effect during the test period.

Association between larger thymic size and higher thymic output in human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy.

To examine the impact of thymic size on immune recovery in patients with human immunodeficiency virus (HIV) infection, the thymus was visualized, using computed tomographic scans, in 25 HIV-infected patients who had received highly active antiretroviral therapy (HAART) for 6-18 months and had levels of viremia <500 copies/mL. For comparison, 10 control subjects were included in the study. Total and naive CD4+ cell counts were determined by flow cytometry. To determine thymic output, the number of CD4+ cells containing T cell receptor excision circles (TRECs) was measured. Qualitative immune recovery was evaluated by determination of CD4+ T cell receptor repertoire in 19 of the HIV-infected patients. Larger thymic size was associated with higher CD4+ cell counts (r=0.498; P=.011) and higher CD4+ TREC frequency (r=0.652; P<.001). Furthermore, patients with abundant thymic tissue seemed to have broader immunologic repertoires, compared with patients with minimal thymic tissue (P=.054). These findings suggest that thymopoiesis is ongoing in the adult thymus and contributes to immune reconstitution in HIV-infected patients receiving HAART.