Different vascular smooth muscle cell apoptosis in the human internal mammary artery and the saphenous vein. Implications for bypass graft disease

BACKGROUND: The remarkable patency of internal mammary artery (MA) grafts compared to saphenous vein (SV) grafts has been related to different biological properties of the two blood vessels. We examined whether proliferation and apoptosis of vascular smooth muscle cells (VSMC) from human coronary artery bypass vessels differ according to patency rates. METHODS AND RESULTS: Proliferation rates to serum or platelet-derived growth factor (PDGF)-BB were lower in VSMC from MA than SV. Surface expression of PDGF beta-receptor was slightly lower, while that of alpha-receptor was slightly higher in MA than SV. Cell cycle distribution, expression of cyclin E, cdk2, p21, p27, p57, and cdk2 kinase activity were identical in PDGF-BB-stimulated cells from MA and SV. However, apoptosis rates were higher in MA than SV determined by lactate dehydrogenase release, DNA fragmentation, and Hoechst 33258 staining. Moreover, caspase inhibitors (Z-VAD-fmk, Boc-D-fmk) abrogated the different proliferation rates of VSMC from MA versus SV. Western blotting and GSK3-beta kinase assay revealed lower Akt activity in VSMC from MA versus SV, while total Akt expression was identical. Adenoviral transduction of a constitutively active Akt mutant abrogated the different proliferation rates of VSMC from MA versus SV. CONCLUSIONS: Higher apoptosis rates due to lower Akt activity rather than different cell cycle regulation account for the lower proliferation of VSMC from MA as compared to SV. VSMC apoptosis may protect MA from bypass graft disease.

Absence of histamine-induced nitric oxide release in the human radial artery: implications for vasospasm of coronary artery bypass vessels

Radial artery (RA) bypass grafts can develop severe vasospasm. As histamine is known to induce vasospasm, its effect on RA was assessed compared with the classic bypass vessels internal mammary artery (MA) and saphenous vein (SV). The vessels were examined in organ chambers for isometric tension recording. Histamine induced contractions on baseline; the sensitivity was higher in RA and SV than MA. After precontraction with norepinephrine, histamine did not evoke relaxations of RA but induced relaxations of MA and less of SV at lower concentrations; it induced contractions at higher concentrations, reaching similar levels in all three vessels. Indomethacin did not affect the response of MA and RA but potentiated relaxations and reduced contractions of SV. Endothelium removal, N(omega)-nitro-L-arginine methyl ester (L-NAME), or the H2-receptor blocker cimetidine did not affect the response of RA, but inhibited relaxations and enhanced contractions in MA and inhibited relaxations in SV; in the latter, only L-NAME enhanced contractions. Real-time PCR detected much lower expression of endothelial H2-receptor in RA than MA or SV. Western blots revealed similar endothelial nitric oxide (NO) synthase expression in all three vessels. Relaxations to acetylcholine were identical in RA and MA. Thus histamine releases NO by activating the endothelial H2-receptor, the expression of which is much lower in RA than MA or SV. H2-receptor activation also releases prostaglandins in SV, partially antagonizing NO. The lack of histamine-induced NO production represents a possible mechanism of RA vasospasm.

Feline herpes dermatitis treated with interferon omega

This case report describes the diagnosis, demonstration and treatment of feline herpes virus-induced facial dermatitis in a cat. The cat was successfully treated with interferon omega (IFN-omega).

Pontocerebellar hypoplasia type 2: variability in clinical and imaging findings

We report 24 children (14 girls) who presented with the typical neuroimaging findings of pontocerebellar hypoplasia (PCH) to describe the clinical spectrum of type 2. Twenty-one presented with the classical form described by Barth; characteristic features (15/21) were breathing and/or sucking problems during neonatal period and early onset hyperkinetic movement disorder. Eighteen were normocephalic at birth, but all developed microcephaly during infancy. Development was severely affected with none of the children being capable of sitting, walking, or talking. Social contact and visual fixation were persistently poor. Dyskinetic movement disorder was present in all, in some together with mild spasticity. Seizures occurred in 14 (in 7 as neonates). Eight children died (age 1 day-6 years). Neuroimaging showed an absent or severely flattened pons, different degrees of vermian hypoplasia, with cerebellar hemispheres (wing-like structures) being equally or more affected. Three (all girls) were less severely affected clinically and did not develop the dyskinetic movement disorder, motor and cognitive development were somewhat better. Microcephaly was also a prominent sign. Severity of pontocerebellar neuroimaging findings did not differentiate between the typical and atypical clinical group and did not correlate with clinical outcome.

Post-mortem forensic neuroimaging: correlation of MSCT and MRI findings with autopsy results

Multislice-computed tomography (MSCT) and magnetic resonance imaging (MRI) are increasingly used for forensic purposes. Based on broad experience in clinical neuroimaging, post-mortem MSCT and MRI were performed in 57 forensic cases with the goal to evaluate the radiological methods concerning their usability for forensic head and brain examination. An experienced clinical radiologist evaluated the imaging data. The results were compared to the autopsy findings that served as the gold standard with regard to common forensic neurotrauma findings such as skull fractures, soft tissue lesions of the scalp, various forms of intracranial hemorrhage or signs of increased brain pressure. The sensitivity of the imaging methods ranged from 100% (e.g., heat-induced alterations, intracranial gas) to zero (e.g., mediobasal impression marks as a sign of increased brain pressure, plaques jaunes). The agreement between MRI and CT was 69%. The radiological methods prevalently failed in the detection of lesions smaller than 3mm of size, whereas they were generally satisfactory concerning the evaluation of intracranial hemorrhage. Due to its advanced 2D and 3D post-processing possibilities, CT in particular possessed certain advantages in comparison with autopsy with regard to forensic reconstruction. MRI showed forensically relevant findings not seen during autopsy in several cases. The partly limited sensitivity of imaging that was observed in this retrospective study was based on several factors: besides general technical limitations it became apparent that clinical radiologists require a sound basic forensic background in order to detect specific signs. Focused teaching sessions will be essential to improve the outcome in future examinations. On the other hand, the autopsy protocols should be further standardized to allow an exact comparison of imaging and autopsy data. In consideration of these facts, MRI and CT have the power to play an important role in future forensic neuropathological examination.

Initial clinical experience with the 4-F self-expanding XPERT stent system for infrapopliteal treatment of patients with severe claudication and critical limb ischemia

PURPOSE: To evaluate the primary success and short-term patency associated with a new 4-F sheath-compatible self-expanding nitinol stent after failed conventional angioplasty of distal popliteal and infrapopliteal lesions in severe lifestyle-limiting claudication (LLC) and chronic critical limb ischemia (CLI). MATERIALS AND METHODS: Between May 2003 and July 2005, 35 patients with Rutherford category 3-5 disease (16 patients with CLI, 19 patients with LLC) underwent percutaneous transluminal angioplasty (PTA) and stent implantation. Indications for stent placement were residual stenosis, flow-limiting dissections, or elastic recoil after PTA. Before and after the intervention and during the 6-month follow-up, clinical investigation, color-flow and duplex Doppler ultrasonography, and digital subtraction angiography were performed. Technical success, primary patency at 6 months, clinical improvement as defined by Rutherford with clinical and hemodynamic measures, and complications were evaluated. RESULTS: A total of 22 patients underwent distal popliteal artery stent placement and 13 underwent tibioperoneal artery stent placement. Stent implantation was successfully performed in all patients. After stent placement, the primary cumulative patency rate for the study group at 6 months was 82%. The mean resting ankle-brachial index at baseline was 0.50 +/- 0.16 and significantly increased to 0.90 +/- 0.17 at 12-24 hours after intervention and 0.82 +/- 0.24 at latest follow-up (P < .001 for both). The sustained clinical improvement rate was 80% at the 6-month follow-up. The 6-month limb salvage rate regarding major amputation was 100%. The rate of major complications was 17%. CONCLUSIONS: Infrapopliteal application of the new nitinol stent is a safe, feasible, and effective method with good short-term patency rate in the treatment of severe LLC and chronic CLI.

Should 3K zoom function be used for detection of pneumothorax in cesium iodide/amorphous silicon flat-panel detector radiographs presented on 1K-matrix soft copies?

The purpose of the study was to evaluate observer performance in the detection of pneumothorax with cesium iodide and amorphous silicon flat-panel detector radiography (CsI/a-Si FDR) presented as 1K and 3K soft-copy images. Forty patients with and 40 patients without pneumothorax diagnosed on previous and subsequent digital storage phosphor radiography (SPR, gold standard) had follow-up chest radiographs with CsI/a-Si FDR. Four observers confirmed or excluded the diagnosis of pneumothorax according to a five-point scale first on the 1K soft-copy image and then with help of 3K zoom function (1K monitor). Receiver operating characteristic (ROC) analysis was performed for each modality (1K and 3K). The area under the curve (AUC) values for each observer were 0.7815, 0.7779, 0.7946 and 0.7066 with 1K-matrix soft copies and 0.8123, 0.7997, 0.8078 and 0.7522 with 3K zoom. Overall detection of pneumothorax was better with 3K zoom. Differences between the two display methods were not statistically significant in 3 of 4 observers (p-values between 0.13 and 0.44; observer 4: p = 0.02). The detection of pneumothorax with 3K zoom is better than with 1K soft copy but not at a statistically significant level. Differences between both display methods may be subtle. Still, our results indicate that 3K zoom should be employed in clinical practice.

Mycobacterium avium subspecies paratuberculosis and Crohn's disease: a systematic review and meta-analysis

This systematic review assesses the evidence for an association between Mycobacterium avium subspecies paratuberculosis (MAP) and Crohn's disease. We analysed 28 case-control studies comparing MAP in patients with Crohn's disease with individuals free of inflammatory bowel disease (IBD) or patients with ulcerative colitis. Compared with individuals free of IBD, the pooled odds ratio (OR) from studies using PCR in tissue samples was 7.01 (95% CI 3.95-12.4) and was 1.72 (1.02-2.90) in studies using ELISA in serum. ORs were similar for comparisons with ulcerative colitis patients (PCR, 4.13 [1.57-10.9]; ELISA, 1.88 [1.26-2.81]). The association of MAP with Crohn's disease seems to be specific, but its role in the aetiology of Crohn's disease remains to be defined.

Matched-pair study showed higher quality of placebo-controlled trials in Western phytotherapy than conventional medicine

OBJECTIVES: Herbal medicine (phytotherapy) is widely used, but the evidence for its effectiveness is a matter of ongoing debate. We compared the quality and results of trials of Western phytotherapy and conventional medicine. STUDY DESIGN AND SETTING: A random sample of placebo-controlled trials of Western phytotherapy was identified in a comprehensive literature search (19 electronic databases). Conventional medicine trials matched for condition and type of outcome were selected from the Cochrane Central Controlled Trials Register (issue 1, 2003). Data were extracted in duplicate. Trials described as double-blind, with adequate generation of allocation sequence and adequate concealment of allocation were assumed to be of higher methodological quality. RESULTS: Eighty-nine herbal medicine and 89 matched conventional medicine trials were analyzed. Studies of Western herbalism were smaller, less likely to be published in English, and less likely to be indexed in MEDLINE than their counterparts from conventional medicine. Nineteen (21%) herbal and four (5%) conventional medicine trials were of higher quality. In both groups, smaller trials showed more beneficial treatment effects than larger trials. CONCLUSIONS: Our findings challenge the widely held belief that the quality of the evidence on the effectiveness of herbal medicine is generally inferior to the evidence available for conventional medicine.

Placebo-controlled trials of Chinese herbal medicine and conventional medicine - comparative study

BACKGROUND: Chinese herbal medicine (CHM) is increasingly used in the West, but the evidence on its effectiveness is a matter of debate. We compared the characteristics, study quality and results of clinical trials of CHM and conventional medicine. METHODS: Comparative study of placebo-controlled trials of CHM and conventional medicine. Eleven bibliographic databases and searches by hand of 48 Chinese-language journals. Conventional medicine trials matched for condition and type of outcome were randomly selected from the Cochrane Controlled Trials Register (issue 1, 2003). Trials described as double-blind, with adequate generation of allocation sequence and adequate concealment of allocation, were assumed to be of high quality. Data were analysed using funnel plots and multivariable meta-regression models. RESULTS: 136 CHM trials (119 published in Chinese, 17 published in English) and 136 matched conventional medicine trials (125 published in English) were analysed. The quality of Chinese-language CHM trials tended to be lower than that of English-language CHM trials and conventional medicine trials. Three (2%) CHM trials and 10 (7%) conventional medicine trials were of high quality. In all groups, smaller trials showed more beneficial treatment effects than larger trials. CHM trials published in Chinese showed considerably larger effects than CHM trials published in English (adjusted ratio of ORs 0.29, 95% confidence intervals 0.17-0.52). CONCLUSIONS: Biases are present both in placebo-controlled trials of CHM and conventional medicine, but may be most pronounced in CHM trials published in Chinese-language journals. Only few CHM trials of adequate methodology exist and the effectiveness of CHM therefore remains poorly documented.

Source of funding and results of studies of health effects of mobile phone use: systematic review of experimental studies

OBJECTIVES: There is concern regarding the possible health effects of cellular telephone use. We examined whether the source of funding of studies of the effects of low-level radiofrequency radiation is associated with the results of studies. We conducted a systematic review of studies of controlled exposure to radiofrequency radiation with health-related outcomes (electroencephalogram, cognitive or cardiovascular function, hormone levels, symptoms, and subjective well-being). DATA SOURCES: We searched EMBASE, Medline, and a specialist database in February 2005 and scrutinized reference lists from relevant publications. DATA EXTRACTION: Data on the source of funding, study design, methodologic quality, and other study characteristics were extracted. The primary outcome was the reporting of at least one statistically significant association between the exposure and a health-related outcome. Data were analyzed using logistic regression models. DATA SYNTHESIS: Of 59 studies, 12 (20%) were funded exclusively by the telecommunications industry, 11 (19%) were funded by public agencies or charities, 14 (24%) had mixed funding (including industry), and in 22 (37%) the source of funding was not reported. Studies funded exclusively by industry reported the largest number of outcomes, but were least likely to report a statistically significant result: The odds ratio was 0.11 (95% confidence interval, 0.02-0.78), compared with studies funded by public agencies or charities. This finding was not materially altered in analyses adjusted for the number of outcomes reported, study quality, and other factors. CONCLUSIONS: The interpretation of results from studies of health effects of radiofrequency radiation should take sponsorship into account.

Fast DNA serotyping of Escherichia coli by use of an oligonucleotide microarray

Classical antibody-based serotyping of Escherichia coli is an important method in diagnostic microbiology for epidemiological purposes, as well as for a rough virulence assessment. However, serotyping is so tedious that its use is restricted to a few reference laboratories. To improve this situation we developed and validated a genetic approach for serotyping based on the microarray technology. The genes encoding the O-antigen flippase (wzx) and the O-antigen polymerase (wzy) were selected as target sequences for the O antigen, whereas fliC and related genes, which code for the flagellar monomer, were chosen as representatives for the H phenotype. Starting with a detailed bioinformatic analysis and oligonucleotide design, an ArrayTube-based assay was established: a fast and robust DNA extraction method was coupled with a site-specific, linear multiplex labeling procedure and hybridization analysis of the biotinylated amplicons. The microarray contained oligonucleotide DNA probes, each in duplicate, representing 24 of the epidemiologically most relevant of the over 180 known O antigens (O antigens 4, 6 to 9, 15, 26, 52, 53, 55, 79, 86, 91, 101, 103, 104, 111, 113, 114, 121, 128, 145, 157, and 172) as well as 47 of the 53 different H antigens (H antigens 1 to 12, 14 to 16, 18 to 21, 23 to 34, 37 to 43, 45, 46, 48, 49, 51 to 54, and 56). Evaluation of the microarray with a set of defined strains representing all O and H serotypes covered revealed that it has a high sensitivity and a high specificity. All of the conventionally typed 24 O groups and all of the 47 H serotypes were correctly identified. Moreover, strains which were nonmotile or nontypeable by previous serotyping assays yielded unequivocal results with the novel ArrayTube assay, which proved to be a valuable alternative to classical serotyping, allowing processing of single colonies within a single working day.