Time-of-flight angiography: a viable alternative to contrast-enhanced MR angiography and fat-suppressed T1w images for the diagnosis of cervical artery dissection?

OBJECTIVES: To compare the use of an unenhanced high-resolution time-of-flight MR angiography sequence (Hr-TOF MRA) with fat-suppressed axial/coronal T1-weighted images and contrast-enhanced angiography (standard MRI) for the diagnosis of cervical artery dissection (cDISS). METHODS: Twenty consecutive patients (9 women, 11 men, aged 24-66 years) with proven cDISS on standard MRI underwent Hr-TOF MRA at 3.0 T using dedicated surface coils. Sensitivity (SE), specificity (SP), positive and negative predictive values (PPV, NPV), Cohen's kappa (к) and accuracy of Hr-TOF MRA were calculated using the standard protocol as the gold standard. Image quality and diagnostic confidence were assessed on a four-point scale. RESULTS: Image quality was rated better for standard MRI (P = 0.02), whereas diagnostic confidence did not differ significantly (P = 0.27). There was good agreement between Hr-TOF images and the standard protocol for the presence/absence of cDISS, with к = 0.95 for reader 1 and к = 0.89 for reader 2 (P < 0.001). This resulted in SE, SP, PPV, NPV and accuracy of 97 %, 98 %, 97 %, 98 % and 97 % for reader 1 and 93 %, 96 %, 93 %, 96 % and 95 % for reader 2. CONCLUSIONS: Hr-TOF MRA can be used to diagnose cDISS with excellent agreement compared with the standard protocol. This might be useful in patients with renal insufficiency or if contrast-enhanced MR angiography is of insufficient image quality. KEY POINTS: • New magnetic resonance angiography sequences are increasingly used for vertebral artery assessment. • A high-resolution time-of-flight sequence allows the diagnosis of cervical artery dissection. • This technique allows the diagnosis without intravenous contrast medium. • It could help in renal insufficiency or when contrast-enhanced MRA fails.

[New aspects of MRI for diagnostics of large vessel vasculitis and primary angiitis of the central nervous system]. / Neue Aspekte der MRT-Bildgebung zur Diagnostik der Großgefäßvaskulitiden sowie der primären Angiitis des zentralen Nervensystems.

Vasculitis is a rare disease and clinical symptoms are often unspecific. Accurate and early diagnosis is mandatory in order to prevent complications, such as loss of vision or stroke. Imaging techniques can contribute to establishing a definite diagnosis and to evaluate disease activity and the extent of the disease in various vascular regions. Conventional imaging methods, such as computed tomography (CT) and magnetic resonance (MR) angiography, as well as digital subtraction angiography allow the vessel lumen but not the vessel wall to be depicted. However, vasculitis is a disease which primarily affects the vessel wall, therefore conventional imaging modalities often fail to make a definite diagnosis. Recently black-blood high resolution MR in vivo imaging has been used to visualize cervical and intracranial vasculitis. This review article presents imaging protocols for intracranial and cervical black-blood MR imaging and clinical cases with large vessel vasculitis and vasculitis of the central nervous system. Furthermore the current literature, examples of the most common differential diagnoses of cervical and cranial arteriopathy and the potential of other imaging modalities, such as PET/CT and ultrasound will be discussed.

High-resolution black-blood contrast-enhanced T1 weighted images for the diagnosis and follow-up of intracranial arteritis.

Primary arteritis of the central nervous system (CNS) comprises a heterogeneous group of CNS disorders, which is characterised by non-atheromatous inflammation and necrosis of the arterial wall. The clinical presentation is highly variable, with stroke being the most common manifestation. Conventional angiography is considered to be the best imaging tool for diagnosing the disease. However, angiographic findings, which usually show lumen irregularities and stenosis, are often unspecific and can occur with a variety of other vascular disorders, such as atherosclerosis and arterial dissection. Therefore, brain biopsies are often needed to confirm the diagnosis. Recent reports have shown that MRI is able to visualise contrast enhancement in subjects with known primary CNS arteritis.

[Validity of clinical trials: are there differences between conventional and complementary alternative medicine?]. / Studienvalidität: Gibt es Unterschiede zwischen Schul- und Komplementärmedizin?

So far there has been no consensus on the criteria which confirm the validity of scientific contributions in conventional medicine (CM) and complementary/ alternative medicine (CAM). An interdisciplinary group of experts from various disciplines within each of the areas of medicine held six well-documented sessions in an effort to reach a consensus. The group agreed that the methods to confirm the validity of clinical trials are identical in CM and CAM. There are differences in research strategies and there may also be differences in interpreting the results, depending on the concept of medicine.

[The situation of patients with dementia may be rectified by Ginkgo biloba. Results of a health services research study concerning the ability of patients with dementia, quality of life of the nursing family members and total treatment costs]. / Versorgungssituation von Demenzkranken kann durch Ginkgo biloba verbessert werden. Ergebnisse einer Studie zur Versorgungsforschung hinsichtlich der Leistungsfähigkeit der Demenzkranken, der Lebensqualität der Pflegenden und der Gesamtkosten der Behandlung.

UNLABELLED: BACKGROUND AND ISSSUES: Ginkgo biloba-extracts are often used in therapy of patients with dementia. In this study, benefit and structure of Ginkgo biloba-extract EGb 761 in treatment of patients with dementia was examined. PATIENTS AND METHODS: For the assessment of quality of life of care-taking relatives and patients as well as treatment costs were documented. The study was conducted as a non-randomised, two-armed cohort study with an open design for 683 slightly or moderately demented patients, aged between 65 and 80 years. Society's perspective was taken. Barthel-Index and MMST were also documented. Because of significant differences at inclusion of both cohorts, a matched-pairs-analysis and multiple regression analysis conducted. RESULTS: According to PLC a significant improvement in quality-of-life of care-taking relatives (p < 0.001) and patients (positive mood p = 0.018, negative mood p < 0.001) was only observed in the Ginkgo-cohort. Also Barthel-Index indicated an improvement in the Ginkgo-cohort (p < or = 0,001). MMST-scores increased significantly only in the Ginkgo-cohort (p < 0.001). Average total cost per patient amounted to 3.614,75 euro in the standard-cohort, whereas these costs per patient in the Ginkgo-cohort amounted to 3.031,78 euro (p = 0.067). Results were confirmed by matched-pairs-analysis. RESULTS: Ginkgo treatment has a valid place in caretaking structure of health services. Gingko attributes to a higher quality of life for both care-takers and patients, the progression of disease is slowed down and treatment costs are lower.

Prospective, comparative cohort studies and their contribution to the benefit assessments of therapeutic options: heart failure treatment with and without Hawthorn special extract WS 1442.

BACKGROUND: In addition to testing a drug for its efficacy, pharmacological quality and safety, current policies are increasingly demanding evaluations of the therapeutic benefits provided by a drug in general practice with "non-selected" patients and increasingly restrictive economic considerations. OBJECTIVE: One of the trials which addresses this task is the WISO cohort study (Efficacy and socio-economic relevance of treatment of chronic heart failure stage NYHA II with Crataegus extract WS 1442). It compares two different therapeutic strategies in the treatment of heart failure stage NYHA II, i.e. a conventional medication and a therapy which also includes hawthorn special extract WS 1442 (Crataegutt novo 450) in addition to chemical-synthetic drugs. In contrast to clinical trials, the patients in cohort studies are expressly not randomised and the physician in charge independently chooses the administered treatment. This comparative, non-interventional observation provides well-founded evidence of the "real-world effectiveness" of the tested preparation. PATIENTS AND METHODS: 952 patients with heart failure (NYHA II) were enrolled in the study by 217 general practitioners. 588 patients received Crataegus special extract WS 1442 (Crataegutt novo 450) either as an add-on therapy or as a monotherapy (Crataegus cohort) and 364 patients received therapy without hawthorn (comparative cohort). These two groups had the same indication (heart failure NYHA II) but were significantly different regarding gender, age and concomitant cardiovascular disease. Basically, in view of the free choice of therapy made by the physician in charge, such differences are to be expected in comparative observational studies. A sufficient degree of patient comparability was provided by means of the matched-pairs technique, which replaced the randomisation procedure normally used in clinical studies. After 2 years, 130 patient pairs generated by this technique could be included in the interim assessment. RESULTS: The clinical symptoms with regard to all parameters investigated showed the same or a more pronounced improvement in the Crataegus cohort in the course of 2 years. After 2 years, the three cardinal symptoms of heart failure--fatigue (p = 0.036), stress dyspnoea (p = 0.020) and palpitations (p = 0.048)--were significantly less marked in the Crataegus cohort than in the comparative cohort. DISCUSSION: The particular design of the cohort study also provides valuable additional information: (1) Hawthorn special extract WS 1442 was prescribed in registered cardiological practices for the treatment of patients with heart failure stage NYHA II, partly as an alternative and partly as a supplement to the used chemical-synthetic drugs. (2) Favourable effects on the clinical symptoms were achieved although the patients in the Crataegus cohort received markedly fewer chemical-synthetic drugs than the patients in the comparative cohort (ACE-inhibitors: 36 vs. 54%, p = 0.004; cardiac glycosides: 18 vs. 37%, p = 0.001; diuretics: 49 vs. 61%, p = 0.061; beta-blockers: 22 vs. 33%, p = 0.052). CONCLUSION: The data show a clear benefit for patients with heart failure stage NYHA II treated with WS 1442. The single or add-on administration in addition to a chemical-synthetic medication resulted in objective improvements at comparable costs.

Influence of perinatal nicotine administration on transplacental carcinogenesis in Sprague Dawley rats by N-methylnitrosourea.

The administration of nicotine during the perinatal stages of life resulted in a significant decrease in tumours occurring after transplacental induction by N-methylnitrosourea (MNU). The overall tumour incidence following p.o. application of MNU to dams was 85% in rats of the F1-generation, the main occurrence being related to the neurogenic system (62% of the animals). Regular injections of nicotine before or after birth resulted in a reduction of malignancies by 17% and 22% (P = 0.08 and 0.0015), respectively. The difference in the incidence of neurogenic tumours proved to be highly significant (P less than 0.002) in rats of either sex, when nicotine was applied over 26 weeks following birth. There was a gender-specific imbalance in rats which received the carcinogen only, in favour of a lower tumour yield in females (P less than 0.04), which became less apparent when nicotine was given additionally. These findings suggest that nicotine is capable of modulating the expression of chemically induced tumours of the neurogenic system in a favourable way.

Influence of the application mode of N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide on the localization of its carcinogenic expression in female NMRI-mice.

The administration of N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide FANFT) by gavage to female NMRI-mice resulted in a high incidence of neoplasms of the forestomach. From 117 effective animals which were pooled from 3 dosed groups, 30 squamous cell carcinomas and 26/117 papillomas of the forestomach were diagnosed. Only 5/117 neoplasms of the urinary bladder occurred. The average cumulative dose administered was 1180 mg/mouse, and the mean latent period for the induction of forestomach tumours was 574 days. The mode of application seems to be an important factor in the carcinogenicity of FANFT.

Long-term toxicology effects of prednimustine in comparison with chlorambucil, prednisolone, and chlorambucil plus prednisolone in Sprague-Dawley rats.

Chlorambucil was linked to prednisolone to improve the therapeutic and toxic properties of this potent alkylating agent, which is known to induce second tumors in humans. To compare the carcinogenic potency of the linked compound with that of the respective individual agents and of their unlinked mixture, prednimustine (I), chlorambucil (II), prednisolone (III), chlorambucil plus prednisolone (IV), or vehicle were administered to groups of 120 female Sprague-Dawley rats for 18 months. The following doses were administered nine, four, five, two times, or once a month per subgroup of 30 rats: I, 12 mg/kg; II, 3 mg/kg; III, 3 mg/kg; IV, 3 mg/kg. After natural death of animals, median survival times were analyzed, and percentages of malignant tumors were recorded. An increased tumor risk was found in the following organs compared with those of vehicle-treated controls: I, external auditory canal (EAC); II, mammary gland (MG), central and peripheral nervous tissue (CPNT), hematopoietic and lymphatic tissue (HLT), and EAC; III, none; and IV, MG, CPNT, and EAC. There is evidence of carcinogenic activity of prednimustine compared with untreated controls, but the cancer-inducing potential of the linked compound is distinctly lower than that of the unlinked mixture of chlorambucil plus prednisolone or that of chlorambucil.

Carcinogenicity of methapyrilene hydrochloride, mepyramine hydrochloride, thenyldiamine hydrochloride, and pyribenzamine hydrochloride in Sprague-Dawley rats.

Four histamine antagonists, methapyrilene, thenyldiamine, mepyramine and pyribenzamine were tested for carcinogenicity in rats by continuous application in drinking water. Only methapyrilene displayed significant carcinogenic effects, inducing liver tumors in a dose-related pattern. Analogues not containing a thiophene ring (mepyramine, pyribenzamine) did not exhibit neoplastic effects under the experimental conditions.

Comparison of liver tumor frequencies after intermittent oral administration of different doses of N-nitrosopyrrolidine in Sprague-Dawley rats.

N-Nitrosopyrrolidine (N-Pyr) was administered orally to 400 Sprague-Dawley rats. An additional group of 80 rats served as an untreated control. There were 5 individual groups in which the effects of different periods of dosing and varying intervals without treatment were compared. Individual doses corresponded to 0.0, 1.0, 1.2 and 2.0 mg/kg per day. The total dose (600 days after the start of the trial) always amounted to 600 mg/kg N-Pyr. Significantly different incidences of liver tumors were observed in the individual N-Pyr-treated groups. The findings support the assumption that tumor risks not only depend on individual and total doses of the administered carcinogen, but are also an age-related function.

Comparative carcinogenic activity of prednimustine, chlorambucil, prednisolone and chlorambucil plus prednisolone in Sprague-Dawley rats.

This study compares long term toxic effects of equivalent doses of prednimustine (12 mg/kg) chlorambucil (3 mg/kg), prednisolone (3 mg/kg) and chlorambucil plus prednisolone (3 mg/kg each) in comparison to vehicle treated controls after regular administration over a period of 18 months to 600 female Sprague Dawley rats. Frequency of administration to subgroups (30 rats each) varied between 9 (a), 4.5 (b), 2 (c) times or once (d) a month. When comparing organ specific, age-adjusted expected versus observed incidences after natural death of animals an increased tumor risk was found in organ systems of all treatment modalities but prednisolone. Prednimustine-administration was related to an elevated risk of developing squamous-cell carcinomas of the external auditory canal only (alpha = 0.013), whereas simultaneous application of chlorambucil plus prednisolone induced significantly higher rates of adenocarcinomas of the mammary gland, of malignant tumors of the central and peripheral nervous tissue and of squamous cell carcinomas of the external auditory canal (alpha less than 0.01 for each tissue). Chlorambucil alone caused a significantly higher rate of malignancies of the hematopoietic and lymphatic tissue (alpha less than 0.01) additionally to effects observed after the unlinked mixture of chlorambucil plus prednisolone. There is evidence of carcinogenic activity of prednimustine compared to untreated controls, but the cancer-inducing potential of the linked compound is distinctly lower than that of the unlinked mixture of chlorambucil plus prednisolone or of chlorambucilalone.

Reduction of acetoxymethyl-methylnitrosamine-induced large bowel cancer in rats by indomethacin.

The nonsteroid anti-inflammatory drug indomethacin, a potent prostaglandin synthesis inhibitor, may play a role in preventing chemically-induced large bowel cancer development in rats. 250 male Sprague-Dawley rats were given weekly intrarectal doses of 2 mg/kg body weight of acetoxymethyl-methylnitrosamine (AMMN) in the first 10 weeks of the experiment to induce large bowel tumors. Experimental groups received a 0.001% aqueous solution of indomethacin ad libitum as drinking water for different time intervals. At autopsy in week 21, the indomethacin treatment in the first and second 10-week periods, or only in the second 10-week period significantly reduced the number of large bowel tumors compared to non-treatment control groups, while the treatment in the first 10-week period alone did not affect the tumor development. It was observed at autopsy in week 31 that the 10-week cessation of treatment after the effective treatments permitted the growth of tumors, but the treatment in the first and second 10-week periods was effective enough to suppress tumor appearance compared to other groups. It can be concluded that indomethacin has an antiproliferative activity on large bowel carcinogenesis.

[Prevention of tumor formation in the bladder by sodium-2-mercaptoethane sulfonate (mesna). Experimental studies and clinical consequences]. / Prophylaxe der Tumorentstehung in der Harnblase durch Natrium-2-mercaptoethansulfonat (Mesna). Experimentelle Untersuchungen und klinische Konsequenzen.

An experimental model was developed, in which urinary bladder cancer was induced by cyclophosphamide in rats, thus reproducing cyclophosphamide-induced urinary bladder carcinogenesis observed in humans. It was possible in this model to achieve a highly significant reduction of cyclophosphamide-induced urinary bladder cancer by concomitant administration of sodium 2-mercaptoethane sulfonate (mesna). A significant delay of urinary bladder carcinogenesis by administration of the uroprotective substance mesna was also observed when using butylbutanolnitrosamine for inducing urinary bladder cancer. It was thus for the first time possible to assure chemoprevention of this tumor type by administration of a specific antidote.