Pivotal advance: CTLA-4+ T cells exhibit normal antiviral functions during acute viral infection

Previous studies have shown that T cells, which are genetically deficient in CTLA-4/CD152 expression, will proliferate uncontrollably, resulting in lethal autoimmune disease. This and other evidence indicate that CTLA-4 plays a critical role in the negative regulation of effector T cell function. In contrast to expectations, BrdU incorporation experiments demonstrated that CTLA-4 expression was associated with normal or even enhanced in vivo proliferation of virus-specific CD4+ and CD8+ T cells following acute lymphocytic choriomeningitis virus or vaccinia virus infection. When compared with CTLA-4- T cells directly ex vivo, CTLA-4+ T cells also exhibited normal antiviral effector functions following stimulation with peptide-coated cells, virus-infected cells, plate-bound anti-CD3/anti-CTLA-4, or the cytokines IL-12 and IL-18. Together, this indicates that CTLA-4 does not directly inhibit antiviral T cell expansion or T cell effector functions, at least not under the normal physiological conditions associated with either of these two acute viral infections.     

Multicentre analysis of 178,992 type 2 diabetes patients revealed better metabolic control despite higher rates of hypertension,stroke, dementia and repeated inpatient care in patients with comorbid Parkinson's disease

BackgroundEspecially in older people, physicians are faced with the coexistence of type 2 diabetes mellitus (T2DM) and Parkinson's disease (PD). Therefore, this research aimed to compare diabetes endpoints between T2DM with and without PD.MethodsBased on the standardized, multicenter, prospective DPV database, 178,992 T2DM patients (≥40 years) were analyzed. 1579 were diagnosed with PD and/or received specific treatment. Hierarchical multivariable regression models were used for group comparisons; adjusted estimates based on observed marginal frequencies were calculated.ResultsPD patients were significantly older (77.9 vs. 70.0 years; p < 0.0001) and had a longer diabetes duration (10.3 vs. 8.4 years; p < 0.0001). In young PD patients (<50 years), percentage of females was significantly higher compared to age-matched T2DM patients without PD or people of the German population (66.7 vs. 38.1 vs. 49.0%; p < 0.0001, p < 0.02).After demographic adjustment, T2DM patients with PD showed a significantly lower HbA1c (58.0 vs. 60.3 mmol/mol; p < 0.0001), OAD/GLP-1 treatment (41.9 vs. 45.9%; p < 0.01) and frequency of dyslipidemia (62.0 vs. 64.5%; p < 0.05). In contrast, rates of insulin therapy (57.8 vs. 54.8%; p < 0.05), hypertension (73.3 vs. 68.6%; p < 0.001), antihypertensive medication (60.4 vs. 56.1%; p < 0.01), stroke (12.0 vs. 7.3%; p < 0.0001), dementia (9.2 vs. 2.6%; p < 0.0001) and repeated inpatient care (15.7 vs. 12.0%; p < 0.0001) were significantly higher and duration of hospital stay (6.2 vs. 4.7 days; p < 0.0001) was significantly longer in T2DM with PD.ConclusionClear demographic and clinical differences were observed between T2DM with and without PD. In PD patients, metabolic control is better, potentially due to more intensive medical care.     

Virtual colon dissection with CT colonography compared with axial interpretation and conventional colonoscopy: preliminary results

OBJECTIVE: The aim of this study was to determine whether a new virtual colon dissection 3D visualization technique for CT colonography has a shorter analysis time and better sensitivity for detection of colonic polyps than interpretation of axial CT images. SUBJECTS AND METHODS. CT colonography was performed in 22 patients using 4-MDCT followed by conventional colonoscopy on the same day. The CT colonography data sets were analyzed by virtual colon dissection, which virtually bisects and unfolds the colon along its longitudinal axis to inspect the inner colonic surface for polyps. The same CT data sets were independently evaluated using axial interpretation. All data sets were independently interpreted by two radiologists in a blinded manner. RESULTS: Conventional colonoscopy revealed 31 colonic lesions in 20 patients. Twenty two of the lesions were smaller than 10 mm; nine were 10 mm or larger. Two of the original 22 patients were excluded, one because of residual stool and fluid and the other because of an impassable stenosing rectal wall cancer. For virtual colon dissection, the per-lesion sensitivity was 42% for observer 1 and 68% for observer 2; for axial interpretation, the respective sensitivities were 48% and 61%. For polyps 10 mm or larger, the respective sensitivities were 67% and 89% for virtual colon dissection and 89% and 100% for axial interpretation. The average time for reconstruction and analysis of virtual colon dissection was 36.8 min versus 29.2 min for axial images. Virtual colon dissection was feasible in both the supine and the prone positions in 45.5% of colonic segments, in either the supine or the prone position in 24.5%, and in neither position in 30% of segments. CONCLUSION: Although virtual colon dissection may facilitate detection of colonic polyps in isolated cases, its detection rate is not superior to axial interpretation, which is mainly attributable to failed rendering of insufficiently distended colonic segments or regions with residual feces. Virtual colon dissection is also the more time-consuming of the two procedures. With further improvement of path-finding and image segmentation, however, virtual colon dissection has the potential to be a useful interpretation tool for CT colonography.     

Factors predicting tracer uptake in somatostatin receptor and MIBG scintigraphy of metastatic gastroenteropancreatic neuroendocrine tumors.

Radiolabeled octreotide analogs (Oct) and metaiodobenzylguanidine (MIBG) offer 2 different approaches for imaging and targeting metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NET). Despite successful establishment of the revised World Health Organization (WHO) classification, which distinguishes between low- and high-grade malignant GEP-NET, there is a lack of scintigraphic studies comparing uptake behavior on the basis of this categorization. This study aims to define predisposing factors of tracer uptake for both imaging principles implementing the updated tumor criteria of the current WHO classification. METHODS: Fifty-seven consecutive patients with histologically confirmed metastatic GEP-NET evaluated with both 111In-pentetreotide and 123I/131I-MIBG scintigraphy were included in this study. Intensity of tracer uptake was graded according to the different metastatic regions. Patients were classified as overall positive when avid uptake in the clinically relevant tumor lesions was present. Correlation was tested between the proportion of positive patients and tumor origin, function, and malignancy. RESULTS: Overall, 52 patients (91.2%) were Oct positive and 28 patients (49.1%) were MIBG positive. The proportion of tracer-positive patients was significantly higher (P < 0.05) in low-grade malignant tumors for both tracers and in functioning as well as in gastroenteral NET for MIBG. Five patients were negative for both tracers. None of the Oct-negative patients proved to be MIBG positive. CONCLUSION: Oct affinity is observed with high frequency throughout the subgroups of metastatic GEP-NET, whereas corresponding MIBG uptake is overall less prevalent and more group dependent. Tumor differentiation significantly impacts both Oct and MIBG uptake, whereas functionality predisposes only for MIBG accumulation. Though clearly inferior to Oct-based radioimaging in most GEP-NET, MIBG achieves a remarkable rate of radioligand accumulation in functioning midgut enterochromaffin cell metastases (>80% of patients positive). These results may have implications for patient management and potentially for selection and performance of targeted therapy.     

Elevated bilirubin and visual perception in pilots

BACKGROUND: A fatal aircraft accident of a Bo-105 helicopter on May 20, 1996 led to the suspicion that the pilot's raised serum bilirubin level could have contributed to the accident. It was suspected that an increase of bilirubin beyond 20.52 micromol x L(-1) could disturb visual perception. METHODS: In 1998 and 1999, 101 pilots with functional hyperbilirubinemia, diagnosed as Gilbert's syndrome, were subjected to perceptual-psychological testing (signal detection test) during their periodic medical examinations at the German Air Force Institute of Aviation Medicine. The results of the psychophysiological testing were compared with a control group. RESULTS: Reaction time and perception range increased with age and were independent of serum bilirubin level. CONCLUSION: There is no evidence that raised serum bilirubin levels can diminish visual perceptional performance.     

Triage of patients with suspected coronary artery disease using multislice computed tomography

RATIONALE AND OBJECTIVES: Several studies have shown that multislice computed tomography (MSCT) has a high sensitivity and specificity for detecting coronary artery stenoses. The aim of the present study was to investigate whether MSCT can reliably triage patients with suspected coronary artery disease (CAD) to coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or no revascularization. MATERIALS AND METHODS: A total of 123 patients with suspected CAD who were referred for conventional coronary angiography (CATH) additionally underwent MSCT (16*0.5 mm detector collimation). Therapeutic decisions made on the basis of CATH and MSCT strictly following current guidelines for treatment of CAD were compared with decisions made by a cardiac surgeon and an interventional cardiologist. Only MSCTs with at least adequate image quality in all coronary segments were included in the analysis (94/123). RESULTS: Decisions made on the basis of MSCT and CATH according to guidelines did not differ significantly (agreement of 88%, 82 of 94, P = .319). The therapeutic decisions made by the interventional cardiologist and the cardiac surgeon based on CATH differed significantly (overall agreement of 79%, 74 of 94 cases, P < .001; cardiologist: 78% PCI and 22% CABG versus surgeon: 38% PCI and 62% CABG), whereas there was 100% agreement regarding decisions for or against invasive treatment. CONCLUSIONS: MSCT shows good agreement with CATH in triaging patients with suspected CAD to CABG, PCI, or no revascularization. The choice of revascularization procedure is significantly more strongly influenced by whether an interventional cardiologist or a cardiac surgeon makes the decision than by the diagnostic test on which the decision is based.     

Continuously moving table MRI with sliding multislice for rectal cancer staging: Image quality and lesion detection

Purpose

To determine image quality and lesion detection of sliding multislice (SMS), a recently developed moving table MRI technique, in patients with rectal cancer.

Materials and methods

Twenty-seven paired SMS (Avanto, Siemens Medical Solutions) and MDCT (Sensation 64, Siemens Medical Solutions) examinations of abdomen and pelvis were performed in patients with rectal cancer and compared for detection of liver, lymph node and bone metastases by two independent observers. A contrast-enhanced, fat saturated 2D gradient echo sequence (TE, 2.0 ms; TR, 102 ms; slice, 5 mm) was acquired with SMS and a standard contrast-enhanced protocol (100 ml @ 2.5 ml/s; slice, 5 mm) was used for abdominal MDCT. Standard of reference consisted of a consensus evaluation of SMS, MDCT, and all available follow-up examinations after a period of 6 months.Artifact burden and image quality of SMS was assessed in comparison to stationary gradient echo sequences obtained in an age-matched group of 27 patients.

Results

Whereas SMS achieved a mean quality score of 3.65 (scale, 0-4) for the liver, representing very good diagnostic properties, strong breathing artifacts in the intestinal region were observed in 19 cases by both observers. The retroperitoneum still achieved a mean quality score of 3.52, although breathing artifacts were noted in 12 and 15 cases (observers 1 and 2, respectively). The sensitivities of SMS to detect hepatic metastases were 91.2% and 94.1% for both observers, respectively, compared to 98.5%/98.5% for MDCT. The sensitivities for lymph node metastases were 87.5%/81.3% for SMS compared to 78.1%/81.3% for MDCT. The sensitivities for bone metastases were 91.7%/100% for SMS compared to 8.3%/16.7% for MDCT.

Conclusion

With slightly reduced image quality in the intestinal region, SMS exhibits equal detection of lymph node and liver metastases compared to MDCT. SMS MRI proved to be superior to MDCT in detection of bone metastases.     

Oral High-Dose Vitamin D Dissolved in Oil Raised Serum 25-Hydroxy-Vitamin D to Physiological Levels in Obese Patients After Sleeve Gastrectomy—A Double-Blind,Randomized, and Placebo-Controlled Trial

Background

Osteomalacia and cardiometabolic disorders are favored in morbidly obese patients due to an inadequate vitamin D (VD) status. Former trials supplementing orally VD (20–50 μg/day) in crystalline form after sleeve gastrectomy (SG) could not stabilize serum 25-hydroxycholecalciferol levels at predefined concentrations (≥50 nmol/l). We hypothesized that VD in an oily suspension would increase its bioavailability resulting in normal serum VD levels minimizing markers of cardiometabolic risk.

Methods

Morbidly obese patients (n?=?94, BMI 51.8?±?11.5 kg/m²) received orally 80 μg/day VD₃ dissolved in oil or placebo (pure oil) in a randomized, double-blind, parallel-group study for 12 weeks after SG. 25-hydroxycholecalciferol, parathyroid hormone, albumin, alkaline phosphatase, phosphate, magnesium, calcium, creatinine, C-reactive protein, lipids, glucose, and glycated hemoglobin were determined in serum/plasma before surgery and after 4 and 12 weeks of supplementation. Intake of energy, fat, and VD were monitored using a 3-day food record.

Results

Seventy-nine patients were included in statistical analysis. Preoperatively, 77.2 and 40.5 % presented 25-hydroxycholecalciferol levels <75 and <50 nmol/l, respectively. After 12 weeks of supplementation, significantly more patients in the VD group exhibited levels >50 nmol/l (92 %) and >75 nmol/l (68 %) compared to the placebo group (54 and 22 %, respectively). Parameters of mineral metabolism and cardiometabolic risk were not modulated by intervention.

Conclusion

Supplementation of 80 μg/day VD₃ by oil is an effective and safe measure to prevent VD deficiency and to treat a preexisting undersupply in patients after SG. Cardiometabolic risk factors were, however, not affected; probably, higher VD doses might be necessary.

Clinical Trial Registration

This trial was registered retrospectively on November 14, 2014, at the German Clinical Trials Register as DRKS00007143.

     

Embolia cutis medicamentosa (Nicolau syndrome) after endodontic treatment: a case report

Introduction

Embolia cutis medicamentosa (Nicolau syndrome) is a rare iatrogenic event of tissue necrosis after intramuscular or intraarticular application of cristalloid suspensions. Clinically, it presents as a livid discoloration of the skin, local pain, and signs of inflammation.

Methods

This article presents the first case of Nicolau syndrome after the endodontic application of calcium hydroxide paste into the distal root canal of tooth 18. The patient presented to the Department for Maxillofacial Surgery and hospitalized for several days.

Results

The application of calcium hydroxide paste led to a thrombosis of the inferior alveolar artery and various branches of the maxillary artery. A definite necrosis of the left-side infraorbital skin area and concomitant hypaesthesia of the infraorbital nerve and of the mental nerve were observed.

Conclusions

Calcium hydroxide paste is appropriate for the medicamentous treatment of root canals, but is not suitable to stanch bleeding from periapical arteries.     

Endosonography of pararectal lymph nodes

One hundred thirteen patients with carcinoma of the rectum were evaluated for lymph node metastases by endorectal ultrasound. With the use of 7.5 MHz and based on different echo patterns, two main groups of lymph nodes can be differentiated: hypoechoic and hyperechoic lymph nodes. Compared with pathologic findings, hypoechoic lymph nodes represent metastases, whereas hyperechoic lymph nodes are visualized due to unspecific inflammation. Lymph node metastases can be predicted with a sensitivity of 72 percent and inflammatory lymph nodes with a specificity of 83 percent. The physical basis of the differentiation of lymph nodes was assessed in vitro by the determination of ultrasound parameters (speed of sound, acoustic impedance, attenuation, and backscattered amplitude). The attenuation coefficient of benign lymph nodes [2.5 dB/(MHz×cm)] is significantly higher than the mean value of lymph node metastases [1.3 db/(MHz×cm)]. The results demonstrate that involved nodes can principally be differentiated from not involved nodes. Micrometastases, mixed lymph nodes, and changing echo patterns within inflammatory nodes explain the accuracy rate of 78 percent.Supported by a grant from the Deutsche Forschungsgemeinschaft Hi 385/1-1