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.

Carcinogenicity and mutagenicity testing of three isomeric N-nitroso-N-methylaminopyridines in rats.

Three isomeric N-nitroso-N-methylaminopyridines (NMPY's) were investigated for their carcinogenic activity in BD VI rats following chronic oral administration and for their mutagenic properties in the Ames assay. On the basis of postulated reaction mechanisms, it was expected that 3-NMPY would react differently than 2- and 4-NMPY, but the outcome of both carcinogenicity and mutagenicity assays did not show this. 2-NMPY induced tumors of the esophagus and possibly also of the liver; 3- and 4-NMPY had no activity as carcinogens under the experimental conditions used. Similarly, high concentrations of 2-NMPY showed mutagenic activity toward Salmonella typhimurium TA100, whereas 3- and 4-NMPY did not have such an effect.

Carcinogenicity of N-nitrosodiethanolamine in rats at five different dose levels.

N-nitrosodiethanolamine, an N-nitroso compound of environmental significance, has been tested for carcinogenicity in male Sprague-Dawley rats at five different dose levels. Administration p.o. in the drinking water of 1.5, 6, 25, 100, or 400 mg N-nitrosodiethanolamine per kg per day was tolerated well. Median total doses administered were between 0.86 g/kg body weight at the highest and 100.3 g/kg body weight at the lowest dose level. Treatment-related tumors were observed in the liver and the nasal cavity. The induction of hepatocellular carcinomas was clearly dose related, low doses also inducing benign lesions. Other liver tumors were of mesenchymal and ductal origin and nasal cavity neoplasms were diagnosed as squamous-cell carcinomas and neuroepitheliomas of the olfactory epithelium. Statistical evaluation of the 1.5-mg/kg dose regimen clearly indicates that even such low doses are carcinogenic. This potent carcinogenic activity is surprising since a high percentage (60 to 90%) of an administered dose of N-nitrosodiethanolamine is excreted unchanged in the urine. Thus, we propose that an as yet unidentified metabolite may possess high carcinogenic potential.

[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.

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.

Influence of five different postnatal lifelong treatments on the transplacental carcinogenicity of ethylnitrosourea in Sprague-Dawley rats.

Sprague-Dawley rats received in 10 mg/kg body weight (group I) or 30 mg/kg body weight (group II) ethylnitrosourea (ENU) orally on the 19th day of pregnancy. Their offspring were treated with Bacille Calmette-Guerin, human albumin, hydrocortisone, cyclophosphamide or nicotine starting on the 6th day of life. The ENU treatment significantly reduced the life expectancy of all offspring. Treatment of the offspring did not influence tumor frequency, induction time or localization of neurogenic malignant tumors. Cyclophosphamide treatment of group II offspring increased the number of females bearing mammary carcinomas.

Effect of the pretreatment with disulfiram on the toxicity and antitumor activity of 1-(2-hydroxyethyl)-3-(2-chloroethyl)-3-nitrosourea in Sprague--Dawley rats.

Pretreatment with disulfiram (DSF, 1000 mg/kg p.o.) 2 h prior to intraperitoneal injection of 1-(2-hydroxyethyl)3-(2-chloroethyl)-3-nitrosourea (HECNU, NSC 29485) reduced the acute toxicity of HECNU by 50% in Sprague--Dawley rats. Thereafter the effect of this additional treatment on the chemotherapeutic activity of HECNU was investigated. After intraperitoneal transplantation of Yoshida sarcoma ascites cells untreated rats had a median survival time of 8 days. The therapeutic response to a single application of HECNU alone or of DSF followed by HECNU was compared. HECNU was injected intravenously at logarithmically increasing doses from 15 to 61.8 mg/kg. The maximum survival time was increased to about 14 days in rats treated with HECNU. Pretreatment with DSF (1000 mg/kg) resulted in identical or slightly higher life expectancies; it thus reduced the toxic side effects of HECNU without inhibiting its antitumor potency.

Carcinogenic activity in Sprague-Dawley rats of 2-[3-(2-chloroethyl)-3-nitrosoureido]-D-gluco-pyranose (chlorozotocin).

Sprague--Dawley rats of both sexes received 2 mg/kg body wt (group 1) or 0.4 mg/kg body wt (group 2) of 2-[3-(2-chloroethyl)-3-nitrosoureido]-D-glucopyranose (chlorozotocin) intraperitoneally in weekly injections for life. A dose-dependent carcinogenic effect of chlorozotocin was found (animals with malignant tumors in group 1: males 88%, females 89%, in group 2: males 83%, females 63%, in controls: males 10%, females 24%). Chlorozotocin reduced the life expectancy of treated animals significantly, compared to solvent controls. Histologically, the chlorozotocin-induced tumors were shown to be mesotheliomas or sarcomas of the peritoneal cavity (undifferentiated type, fibrosarcomas, myosarcomas).

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.

Delay of bladder cancer induction in rats treated with N-nitroso-N-butyl-N-(4-hydroxybutyl)amine by administration of sodium-2-mercaptoethanesulfonate (Mesna).

The influence of sodium-2-mercaptoethanesulphonate (Mesna) on urinary bladder cancer induced by N-nitroso-N-butyl-N-(4-hydroxybutyl)amine (BBNOH) was studied in male Sprague-Dawley rats. The treatment consisted of 5 g/kg BBNOH per gavage and 63 g/kg Mesna in drinking water over a period of 39 weeks. A positive control group was given the same dose of BBNOH as the treated group. Although Mesna did not reduce the incidence of bladder carcinomas, it significantly increased the lifespan of the animals, thus suggesting a partial general protective action.

Carcinogenicity of di(N-nitroso)-perhydropyrimidine (DNPP) after intraperitoneal application to rats.

Male Sprague-Dawley rats received 30 mg/kg body wt. (group I) or 15 mg/kg (group II) di(N-nitroso)-perhydropyrimidine (DNPP) by the intraperitoneal route once a week for life. The DNPP treatment significantly reduced the life expectancy in both groups. DNPP induced tumors of the esophagus (27% incidence in group I, 33% in group II) and possibly also of the liver (4% incidence in group I, 8% in group II).

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.

Negative dose-response study for carcinogenicity of orally administered rutin sulfate in Sprague-Dawley rats.

Rutin is a ubiquitous naturally occurring flavonoid, which is used in a number of drugs. It was tested for carcinogenicity in Sprague--Dawley rats as a water-soluble mixture of sodium salts of sulfuric acid esters. Over 2 years, doses ranging from 10 to 500 mg/kg body wt of rutin sulfate (expanding factor 2.66) were administered by gavage 3 times a week to 4 groups of rats comprising 12 males and 12 females each. A control group was treated with tap water. Age-adjusted analysis of tumor rates did not provide any evidence for rutin sulfate to be carcinogenic under the conditions of this bioassay.

Chemotherapy studies in autochthonous rat tumors: carcinomas of the forestomach.

Tumors of the forestomach were induced in male Sprague-Dawley rats by oral application of acetoxymethyl-methylnitrosamine (AMMN) in single weekly doses of 3.5 mg/kg body weight for 10 weeks. 100 +/- 5 days after the beginning of carcinogen treatment exploratory laparotomy was performed. One hundred animals in the same stage of tumor development were divided at random into one control group and four groups treated with cytostatics. Bleomycin (BLM), methotrexate (MTX), 5-fluorouracil (5FU), and 1,2-bis-(2-chloroethyl)-1-nitrosourea (BCNU) were tested in groups of 20 rats each. Only in animals receiving repeated doses of BLM a slight tumor response was observed but no increase in median survival times was seen. No therapeutic effects of the other drugs used were demonstrable.

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.

Comparative metabolism and carcinogenicity of ring-halogenated 3,3-dimethyl-1-phenyltriazenes.

The objective of this study was to compare urinary metabolism of parent 3,3-dimethyl-1-phenyltriazene with that of its ring-substituted 1-(4-chlorophenyl)-3,3-dimethyltriazene and 1-(2,4,6-trichlorophenyl)-3,3-dimethyltriazene congeners, in an attempt to evaluate the molecular requirements for systemic carcinogenic activity. Complementary carcinogenicity assays were conducted at low equimolar dose levels using both 4- und 2,4,6-chlorinated and brominated analogues. Ring halogenation was found to prolong metabolic detoxification and to reduce carcinogenic activity.

Chemotherapeutic study on Yoshida sarcoma ascites cells implanted into the glandular stomach of rats. Monotherapy with 5-fluorouracil, methyl-CCNU, mitomycin C, adriamycin, and cytosine arabinoside, and combination therapy with respective two-drug combinations.

The chemotherapeutic activity of five cytostatic drugs was investigated experimentally in monotherapy and in two-drug combinations, using Yoshida sarcoma cells implanted into the wall of the glandular stomach of Sprague-Dawley rats. In monotherapy, the antibiotic agent mitomycin C and the nitrosourea methyl-CCNU exhibited the highest cytotoxic activity in this tumor model. In combination therapy, the combination of these two drugs was superior to all the other therapeutic schemes tested. In general, the results demonstrate a marked superiority of combination therapy in comparison with monotherapy.

Induction of tumors of the forestomach in rats by oral application of N-methyl-N'-nitro-nitrosoguanidine.

After 12 oral applications of 80 mg/kg MNNG as a suspension in 30% aqueous ethanol at weekly intervals, 98 Sprague-Dawley rats died with multiple tumors of the forestomach after a medium latency period of 226 days. Histological examination showed generalized papillomatosis developing into keratinizing squamous cell carcinomas with infiltrative growth in 88/98 (89%) animals. Tumorigenic lesions in the glandular stomach ware only observed in 3/98 rats. In two of these animals, mucosal adenocarcinomas were found and in the third a leiomyosarcoma. In about 30% of the animals treated with MNNG, degenerative liver changes were found, especially single cell and focal necroses, cystic alterations, and bile-duct proliferations.