Automated CTA quantification of internal carotid artery stenosis: a pilot trial.

PURPOSE: To evaluate the feasibility and accuracy of automated analysis software for use with multidetector computed tomographic angiography (CTA) in the exact grading of internal carotid artery stenosis. METHODS: A retrospective pilot trial was performed using CTA datasets from 87 stenotic carotid arteries in 46 consecutive patients (34 men; median age 73.5 years) with known cerebrovascular disease. Internal carotid artery (ICA) stenosis was graded according to NASCET criteria by 2 experienced vascular radiologists in consensus using axial source images as well as curved planar reformations and digital subtraction angiography (DSA). These results were then compared to those obtained from the automated CTA analysis software and the results of manually adapted automated CTA analysis. RESULTS: Measurements from automated CTA analysis as well as manually adapted automated CTA analysis correlated significantly to those of axial/reformatted CTA and DSA (r=0.53 and r=0.82, r=0.58 and 0.70, respectively, all p<0.05). Compared to axial/reformatted CTA measurements, automated CTA analysis had a median difference of -16%, while manually adapted automated CTA had a difference of -10%. Corresponding differences in a comparison with DSA were +4% and -2%, respectively. Circumferential calcification or kinking of the ICA origin did not significantly interfere with these differences (all p>0.05). Sensitivities for the detection of ICA stenosis >70% by manually adapted automated CTA analysis and automated measurement were 44.2% and 34.9%, respectively, versus axial/reformatted CTA. Compared with DSA as the gold standard, the sensitivities were 54.2% and 62.5%, respectively. Specificities for both methods and gold standards all exceeded 90%. CONCLUSION: Commercially available automated CTA analysis is a feasible tool, but sensitivities are still not sufficient for clinical application.     

Antioxidant defence during cardiopulmonary bypass surgery.

OBJECTIVE: Cardiac surgery may lead to severe oxidative stress due to formation of oxidation products generated during ischemia and reperfusion. We investigated to which extent oxidative stress influences a number of endogenous antioxidants and markers of cellular activation. METHODS: At six time points blood was withdrawn from patients undergoing coronary artery bypass grafting, using the on-pump procedure. RESULTS: Both glutathione peroxidase and superoxide dismutase show a gradual and strong increase in activity during surgery (40 and 30%, respectively), returning to baseline values 24 h after surgery. The total antioxidant capacity has a maximum increase of 60%. Markers of cellular activation, such as eosinophil cationic protein and tryptase also increase during the procedure. CONCLUSION: Cardiac surgery results in systemic inflammation accompanied or caused by severe oxidative stress. The human body has a strong innate oxidative defence screen, which is probably not sufficient to fully compensate for the total amount of oxidative damage.     

Fusion of bone marrow-derived stem cells with cardiomyocytes in a heterologous in vitro model.

OBJECTIVE: Recent studies have demonstrated that transplanted bone marrow-derived stem cells (BMCs) possess a broad differentiation potential and are able to form new cardiomyocytes. However, the identity of BMCs as true cardiomyocytes is still ambiguous. Therefore, we investigated the fate of transplanted fluorescence labeled BMCs and cardiomyocytes in co-culture. METHODS: For cell tracking we used two different fluorescent probes, Vybrant/DiO and Vybrant/DiI. BMCs were taken from human sternal marrow, purified using a Ficoll-gradient-centrifugation, treated with 5-azacytidine and stained with Vybrant/DiO. Furthermore, isolated spontaneous beating cardiomyocytes of neonatal rats (CM) were labeled with Vybrant/DiI. Thereafter, the BMCs were transplanted into CM-cultures and investigated on day 1, 4, 7, 14 and 28 using two-color fluorescence phenotyping by laser-scanning-cytometry (LSC). Two-color positive cells were harvested by patch-clamp technique and beta-MHC mRNA expression was analyzed by single-cell PCR. RESULTS: Two different morphological phenotypes were observed by LSC. First, isolated DiO labeled BMCs without contact or with direct cell contact to DiI labeled CMs. Second, some BMCs and CMs were double positive for DiO/DiI spontaneously forming hybrids. This population increased by 18% from day 1 to 4 and decreased only slightly until day 28. Additionally, few two-color positive cell formations expressed both human and rat specific beta-MHC mRNA as well as only human beta-MHC mRNA indicating that cell-fusion and transdifferentiation has occurred. CONCLUSION: These observations provide in vitro evidence for spontaneous cell fusion and transdifferentiation of BMCs in co-culture, raising the possibility that the observed phenomenons may contribute to development or maintenance of these cell types.     

Comparative in vivo evaluation of technetium and iodine labels on an anti-HER2 affibody for single-photon imaging of HER2 expression in tumors.

In vivo diagnosis with cancer-specific targeting agents that have optimal characteristics for imaging is an important development in treatment planning for cancer patients. Overexpression of the HER2 antigen is high in several types of carcinomas and has predictive and prognostic value, especially for breast cancer. A new type of targeting agent, the Affibody molecule, was described recently. An Affibody dimer, His6-(ZHER2:4)2 (15.4 kDa), binds to HER2 with an affinity of 3 nmol/L and might be used for the imaging of HER2 expression. The use of 99mTc might improve the availability of the labeled conjugate, and Tc(I)-carbonyl chemistry enables the site-specific labeling of the histidine tag on the Affibody molecule. The goals of the present study were to prepare 99mTc-labeled His6-(ZHER2:4)2 and to evaluate its targeting properties compared with the targeting properties of 125I-4-iodobenzoate-His6-(ZHER2:4)2 [125I-His6-(ZHER2:4)2]. METHODS: The labeling of His6-(ZHER2:4)2 with 99mTc was performed with an IsoLink kit. The specificity of 99mTc-His6-(ZHER2:4)2 binding to HER2 was evaluated in vitro with SK-OV-3 ovarian carcinoma cells. The comparative biodistributions of 99mTc-His6-(ZHER2:4)2 and 125I-His6-(ZHER2:4)2 in tumor-bearing BALB/c nu/nu mice were determined. RESULTS: The labeling yield for 99mTc-His6-(ZHER2:4)2 was approximately 60% (50 degrees C), and the radiochemical purity was greater than 97%. The conjugate was stable during storage and under histidine and cysteine challenges and demonstrated receptor-specific binding. The biodistribution study demonstrated tumor-specific uptake levels (percentage injected activity per gram of tissue [%IA/g]) of 2.6 %IA/g for 99mTc-His6-(ZHER2:4)2 and 2.3 %IA/g for 125I-His6-(ZHER2:4)2 at 4 h after injection. Both conjugates provided clear imaging of SK-OV-3 xenografts at 6 h after injection. The tumor-to-nontumor ratios were much more favorable for the radioiodinated Affibody. CONCLUSION: The use of Tc(I)-carbonyl chemistry enabled us to prepare a stable, site-specifically labeled 99mTc-His6-(ZHER2:4)2 conjugate that was able to bind to HER2-expressing cells in vitro and in vivo. The indirectly radioiodinated conjugate provided better tumor-to-liver ratios. The labeling of Affibody molecules with 99mTc should be investigated further.     

Molecular and signaling mechanisms of atherosclerosis in insulin resistance.

Although the prevalence of cardiovascular complications is increased in insulin-resistant individuals, the underlying causes of this link have been elusive. Recent work suggests that several intracellular signal transduction pathways are inappropriately activated by hyperinsulinemia, hyperglycemia, increased free fatty acids, dyslipidemia, various inflammatory cytokines and adipokines--factors that are increased in insulin resistance. Once activated, substantial cross talk occurs between these pathways, especially a self-reinforcing cascade of vascular inflammation and cell dysfunction, greatly increasing the risk and severity of atherosclerosis in the insulin-resistant individual. We review several key cell-signalling pathways, describe how they are activated in they insulin-resistant state and the damage they induce, and discusses possible therapeutic approaches to limit vascular damage.     

Predictors of Partner Notification for C. trachomatis and N. gonorrhoeae: An Examination of Social Cognitive and Psychological Factors

Efforts to control chlamydial and gonococcal infections include notifying eligible sexual partners of possible infection, primarily by asking the diagnosed patient to notify their partners. This approach, known as patient referral, is widely used but poorly understood. The current study examined psychosocial and cognitive factors associated with patient referral among an urban, minority sample of 168 participants recently diagnosed with Chlamydia trachomatis or Neisseria gonorrhoeae. At a follow-up interview 1-month from diagnosis, participants were more likely to have notified all eligible partners if they had greater intention to notify at baseline (OR = 3.72; 95% CI = 1.34, 10.30) and if they had only one partner at baseline (OR = 4.08; 95% CI = 1.61, 10.31). There were also gender differences as well as differences based on type of partner (i.e., regular, casual, one-time). The implications of these findings for the design of programs to promote patient referral for sexually transmitted infections are discussed. Schwartz, Malka, Augenbraun, McCormack, and Wilson are with the State University of New York, Downstate Medical Center, Brooklyn, NY, USA; Rubin is with the New York City Department of Health, Bureau of STD Control, New York, NY, USA; Rubin, Hogben, and Liddon are with the Centers for Disease Control and Prevention, Atlanta, GA, USA; Schwartz is with the Department of Preventive Medicine and Community Health, SUNY Downstate Medical Center, Box 1240, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.     

Treatment of cremaster synkinesias with botulinum toxin A: a video case report.

Synkinesias secondary to nerve lesions and aberrant re-innervation are well-known phenomena especially after lesions of the facial nerve. Synkinesias can successfully be treated with botulinum toxin A (BTx A). Synkinesias of the cremaster muscle have not been described or treated to date. We present the case of a 62-year-old man who developed synkinesias of both cremaster muscles after extensive laparatomy for esophageal cancer. Treatment of synkinesias with various oral medications had been unsuccessful. Electromyography-guided injections of BTx A in both cremaster muscles (15 MU on the right and 10 on the left) led to significant symptom relief for an average of 8 weeks. We present the case including pre- and posttreatment video clips.     

Mapping scores onto stages: mini-mental state examination and clinical dementia rating.

OBJECTIVE: Although the clinical course of Alzheimer disease (AD) is gradual, it is useful for a number of reasons to distinguish between different levels of severity. The Clinical Dementia Rating (CDR) has demonstrated high validity and reliability for this purpose, but it requires a considerable amount of data to be collected both from the patient and from an informant. In the present study, the authors mapped Mini-Mental State Examination (MMSE) scores onto CDR categories to determine how well the MMSE performs as a surrogate of the CDR as a timesaving method of staging dementia. METHOD: Eight hundred sixty-three probands, including 524 patients with probable AD, 92 patients with questionable dementia, and 247 with memory complaints but no objective cognitive impairment, were included. Cutoff scores were identified on one-half of the sample using a receiver operating characteristic analysis. The cutoff values were then applied to the other half of the sample, and the agreement between MMSE score ranges and CDR stages was determined by calculating Cohen's kappa. RESULTS: The MMSE discriminated well between CDR stages 0.5, 1, 2, and 3 but performed poorly in the separation between CDR stages zero and 0.5. The MMSE ranges were 30 for no, 26-29 for questionable, 21-25 for mild, 11-20 for moderate, and 0-10 for severe dementia. Substantial agreement between the two instruments was obtained for the categories mild (kappa=0.62, p<0.001, N=115), moderate (kappa=0.69, p<0.001, N=114), and severe dementia (kappa=0.76, p<0.001, N=39), whereas the agreement was moderate for no (kappa=0.44, p<0.001, N=120) and only fair for questionable dementia (kappa=0.28, p<0.001, N=42). CONCLUSION: The MMSE can be used as a surrogate measure for the CDR for the staging of dementia in AD.