Technical and Clinical Aspects of Coronary Computed Tomography Angiography

Coronary computed tomography angiography is an emerging imaging technique that has attracted much scientific attention over the past years. Improved scanner technology and dedicated protocols have made noninvasive coronary a reliable diagnostic test in patients with suspected coronary artery disease (CAD). Several technical steps such as the introduction of 64-slice scanners, multisegment reconstruction, and dual-source computed tomography have substantially improved temporal and spatial resolution. With these sophistications, coronary computed tomography angiography enables reliable exclusion of CAD in patients with low to intermediate pretest probability of having CAD or with inconsistent ischemia test results.     

Visceral artery aneurysms—follow-up of 23 patients with 31 aneurysms after surgical or interventional therapy

Purpose  

Visceral artery aneurysms (VAA) are rare forms of vascular pathology, with an incidence of 0.1% to 0.2% in routine autopsies [1–4]. They frequently present as a life-threatening, often fatal, emergency, if associated with rupture and intra- or retroperitoneal bleeding. The clinical symptoms, natural history, and mortality of VAAs vary depending on the vessels involved. The mortality rates range from 8.5% up to 25% and, in pregnant women, up to 75% [1, 4, 6, 7]. A retrospective analysis of all VAAs diagnosed at our institution from 1991 to 2006 was performed. The presentation, management, and outcome of therapy was evaluated for each patient.     

Hepatic events associated with atomoxetine treatment for attention-deficit hyperactivity disorder

OBJECTIVE: This study describes and assesses potential hepatobiliary events related to atomoxetine therapy, as reported in clinical trials and as spontaneous adverse event reports post-launch in 2002. METHODS: Case reports that contained potential hepatobiliary events were identified by a computerized search of the Eli Lilly and Company atomoxetine spontaneous adverse events and clinical trials databases. All cases were reviewed by at least two company physicians, one with expertise in hepatology, to determine the relevance of the information in respect of potential liver toxicity. RESULTS: Of 7961 paediatric and adult patients treated with atomoxetine in clinical trials, 41 were identified as having hepatobiliary events requiring additional analysis. Most of these events were mild increases in ALT and AST levels. None of these cases met Hy's rule criteria or progressed to liver failure. During the 4 years after market launch, 351 spontaneous reports of adverse events were related to the liver, of which 69 had other explanations unrelated to atomoxetine. Of the remaining 282 cases, 133 contained possible confounding factors (and were deemed to be possibly related), 146 presented too little information to assess, and three suggested atomoxetine as a probable cause of liver injuries. One of the three had a positive rechallenge. All three patients recovered after discontinuation of the drug. CONCLUSIONS: Since the launch of atomoxetine therapy, three spontaneously reported cases of reversible drug-induced liver injury were deemed probably related to it. Atomoxetine should be discontinued in patients with jaundice or laboratory evidence of liver injury and should not be restarted.     

Preclinical evaluation of a new, stabilized neurotensin(8--13) pseudopeptide radiolabeled with (99m)tc.

The rapid degradation of neurotensin (NT) limits its clinical use in cancer imaging and therapy. Thus, a new NT(8--13) pseudopeptide, NT-VIII, was synthesized. Some changes were introduced in the sequence of NT(8--13) to stabilize the molecule against enzymatic degradation: Arg(8) was N-methylated, and Lys and Tle replaced Arg(9) and Ile(12), respectively. Finally, (NalphaHis)Ac was coupled to the N-terminus for (99m)Tc(CO)(3) labeling. This peptide was characterized both in vitro and in vivo. METHODS: The new analog was labeled with (99m)Tc(CO)(3). Its metabolic stability was analyzed both in human plasma and in HT-29 cells. Binding properties, receptor downregulation, and internalization were tested with HT-29 cells. Biodistribution was evaluated in nude mice with HT-29 xenografts. RESULTS: (99m)Tc(CO)(3)NT-VIII showed a high stability in plasma, where most of the peptide remained intact after 24 h of incubation at 37 degreesC. However, the degradation in HT-29 cells was more rapid (46% of intact (99m)Tc(CO)(3)NT-VIII after 24 h at 37 degreesC). Binding to NT1 receptors (NTR1) was saturable and specific. Scatchard analysis showed a high affinity for (99m)Tc(CO)(3)NT-VIII, with a dissociation constant similar to (125)I-NT (1.8 vs. 1.6 nmol/L). After interacting with NTR1, (99m)Tc(CO)(3)NT-VIII was rapidly internalized, with more than 90% internalized after 30 min. It also distributed and cleared rapidly in nude mice bearing HT-29 xenografts. The highest rates of accumulation were found in kidney and tumor at all time points tested. Tumor uptake was highly specific because it could be blocked by coinjection with a high dose of (NalphaHis)Ac-NT(8--13). Tumors were clearly visualized in scintigraphy images. CONCLUSION: The changes that were introduced stabilized the molecule against enzymatic degradation without affecting binding properties. Moreover, the increase in stability enhanced tumor uptake, making this derivative a promising candidate for clinical use.     

Stumpfe Schultergelenkverletzungen und ihre Begutachtung

It is difficult to assess blunt injuries in the region of the shoulder girdle because of the overlying acute and chronic processes. In assessments of rotator cuff ruptures in particular, in over 50% of cases the rupture could be explained by a degenerative process. This makes the assessment difficult, and also the decision as to whether or not the injury is due to an occupational accident. The diagnostic procedures applied should exclude a degenerative aetiology immediately after an accident in all cases. Rupture of the rotator cuff is often associated with an impingement syndrome and leads to corresponding symptoms in the subacromial space. Treatment of a rotator cuff rupture always involves a diagnostic arthroscopy as the first step, after which a reconstruction can be undertaken, either by way of the anterolateral approach after Neer or, in many cases, arthroscopically. Reconstruction of the rotator cuff must include outward mobilization of the muscles and a secure, mostly transosseous suture. Transference of a pedunculated tendon is indicated for large defects in the rotator cuff. In the case of dislocation of the shoulder with subsequent shoulder instability degenerative change and any possible multidirectional instability should be defined. Unidirectional instability with a demonstrable Bankart lesion has a good prognosis when surgery is performed without delay. In view of the high recurrence rate early treatment is indicated especially in young persons and in patients with a high activity level. Following detection of the Bankart lesion an arthroscopic procedure with refixation of the capsule–labrum complex is the method of choice.     

Reducing the risk of stroke in type 2 diabetes: pathophysiological and therapeutic perspectives

Reducing the excess cerebrovascular burden in patients with type 2 diabetes remains a major therapeutic challenge, especially with respect to the high risk of recurrent events. Targeting the traditional metabolic risk factors of hypertension, dyslipidemia, and hyperglycemia has failed to remove this excess risk, and agents targeting thrombotic risk (i.e., antiplatelet and anticoagulant drugs) remain poorly studied in the context of stroke in diabetes. This may relate to the accumulation of risk factors in type 2 diabetes as well as to diabetes-specific pathophysiologic factors. Regrettably, there is a lack of prospective evidence to support the efficacy of interventions in the secondary prevention of cerebrovascular events in type 2 diabetes, particularly recurrent stroke events. Overall, there is a need for rigorous evaluations of new therapeutic approaches in both primary and secondary prevention of stroke and management of acute stroke in patients with type 2 diabetes. This systematic review of the published literature summarizes the evidence regarding current therapeutic interventions and their impact on the risk of stroke in people with type 2 diabetes, and highlights potential strategies for improving outcomes.