Comparison of Readout-Segmented Echo-Planar Imaging and Single-Shot TSE DWI for Cholesteatoma Diagnostics.

BACKGROUND AND PURPOSE: The high diagnostic value of DWI for cholesteatoma diagnostics is undisputed. This study compares the diagnostic value of readout-segmented echo-planar DWI and single-shot TSE DWI for cholesteatoma diagnostics. MATERIALS AND METHODS: Thirty patients with newly suspected cholesteatoma were examined with a dedicated protocol, including readout-segmented echo-planar DWI and single-shot TSE DWI at 1.5T. Acquisition parameters of both diffusion-weighted sequences were as follows: b=1000 s/mm,2 axial and coronal section orientations, and section thickness of 3 mm. Image quality was evaluated by 2 readers on a 5-point Likert scale with respect to lesion conspicuity, the presence of susceptibility artifacts mimicking cholesteatomas, and overall subjective image quality. Sensitivity and specificity were calculated using histology results as the gold standard. RESULTS: Twenty-five cases of histologically confirmed cholesteatomas were included in the study group. Lesion conspicuity was higher and fewer artifacts were found when using TSE DWI (both P < .001). The overall subjective image quality, however, was better with readout-segmented DWI. For TSE DWI, the sensitivity for readers 1 and 2 was 92% (95% CI, 74%-99%) and 88% (95% CI, 69%-97%), respectively, while the specificity for both readers was 80% (95% CI, 28%-99%). For readout-segmented DWI, the sensitivity for readers 1 and 2 was 76% (95% CI, 55%-91%) and 68% (95% CI, 46%-85%), while the specificity for both readers was 60% (95% CI, 15%-95%). CONCLUSIONS: The use of TSE DWI is advisable for cholesteatoma diagnostics and preferable over readout-segmented DWI.

Structured Digital Self-Assessment of Patient Anamnesis Prior to Computed Tomography: Performance Evaluation and Added Value.

The aim of this study was to evaluate the performance of a tablet-based, digitized structured self-assessment (DSSA) of patient anamnesis (PA) prior to computed tomography (CT). Of the 317 patients consecutively referred for CT, the majority (n = 294) was able to complete the tablet-based questionnaire, which consisted of 67 items covering social anamnesis, lifestyle factors (e.g., tobacco abuse), medical history (e.g., kidney diseases), current symptoms, and the usability of the system. Patients were able to mark unclear questions for a subsequent discussion with the radiologist. Critical issues for the CT examination were structured and automatically highlighted as "red flags" (RFs) in order to improve patient interaction. RFs and marked questions were highly prevalent (69.5% and 26%). Missing creatinine values (33.3%), kidney diseases (14.4%), thyroid diseases (10.6%), metformin (5.5%), claustrophobia (4.1%), allergic reactions to contrast agents (2.4%), and pathological TSH values (2.0%) were highlighted most frequently as RFs. Patient feedback regarding the comprehensibility of the questionnaire and the tablet usability was mainly positive (90.9%; 86.2%). With advanced age, however, patients provided more negative feedback for both (p = 0.007; p = 0.039). The time effort was less than 20 min for 85.1% of patients, and faster patients were significantly younger (p = 0.046). Overall, the DSSA of PA prior to CT shows a high success rate and is well accepted by most patients. RFs and marked questions were common and helped to focus patients' interactions and reporting towards decisive aspects.

Effect of long term CPAP therapy on cardiac parameters assessed with cardiac MRI.

The obstructive sleep apnoea syndrome (OSAS) is a disorder with a high prevalence and is associated with an elevated cardiovascular risk and increased morbidity and mortality. For longitudinal studies and functional analysis cardiac MRI is regarded as the gold standard. Aim of this study was to evaluate the long-term effect of continuous positive airway pressure (CPAP) therapy on cardiac functional parameters with cardiac Magnetic Resonance Imaging (cMRI). 54 patients with OSAS (mean apnea hypopnea index-AHI: 31) were prospectively enrolled in this study and cMRI was performed before and after 7 months of CPAP therapy. Data were acquired on a 1.5 T MRI and right and left ventricular cardiac function were analysed. CPAP treatment was considered compliant when used ≥ 4 h per night. 24-h blood pressure was measured at baseline and follow up. 33 patients could be assigned to the compliance group. Left ventricular stroke volume (LV SV) and right ventricular ejection fraction (RV EF) improved significantly with CPAP therapy (LV SV from 93 ± 19 to 99 ± 20 ml, p = 0.02; RV EF from 50 ± 6 to 52 ± 6%, p = 0.04). All other cardiac parameters did not change significantly while mean systolic and diastolic blood pressure improved significantly (p < 0.01). 21 patients were assigned to the non-compliance group and were considered as a control group. There were no relevant differences in cardiac parameters between baseline and follow up examination in these patients. CPAP therapy seems to improve LV SV, RV EF, systolic and diastolic blood pressure in OSAS patients, but reproducibility of our results need to be confirmed in a larger patient population.

Effect of Mammography Screening on Mortality by Histological Grade.

Background: It has been asserted that mammography screening preferentially benefits those with less aggressive cancers, with lesser or no impact on more rapidly progressing and therefore more life-threatening tumors.Methods: We utilized data from the Swedish Two-County Trial, which randomized 77,080 women ages 40 to 74 to invitation to screening and 55,985 for usual care. We tabulated cancers by histologic grade and then compared mortality from cancers specific to histologic grade between the invited and control group using Poisson regression, with specific interest in the effect on mortality from grade 3 cancers. We used incidence-based mortality from tumors diagnosed within the screening phase of the trial. Finally, we cross-tabulated grade with tumor size and node status, to assess downstaging within tumor grades.Results: There was a major reduction in mortality from grade 3 tumors (RR = 0.65; 95% CI, 0.53-0.80; P < 0.001), and more deaths prevented from grade 3 tumors (n = 95) than grade 1 and 2 tumors combined (n = 48) in the invited group. The proportions of tumors ≥15 mm or larger and node-positive tumors were substantially reduced in the grade 3 tumors in the invited group.Conclusions: The combination of prevention of tumors progressing to grade 3 and detection at smaller sizes and lesser rates of lymph node metastases within grade 3 tumors results in a substantial number of deaths from grade 3 cancers being prevented by invitation to mammographic screening.Impact: Mammography screening prevents deaths from aggressive cancers. Cancer Epidemiol Biomarkers Prev; 27(2); 154-7. ©2017 AACR.

Cardiac MRI in Children and Adolescents Who Have Undergone Surgical Repair of Right-Sided Congenital Heart Disease: Automated Left Ventricular Volumes and Function Analysis and Effects of Different Manual Adjustments.

PURPOSE: To evaluate automated segmentation and the effects of different manual adjustments regarding left ventricular parameter quantification in cardiac magnetic resonance (MR) data on children and adolescents who have undergone surgical repair of right-sided congenital heart disease (CHD). MATERIALS AND METHODS: Dedicated software (syngo.via, Siemens AG) was used to automatically segment and/or manually adjust the end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), myocardial mass (MM) and ejection fraction (EF) before/after manual apex/base adjustment (ADJ-step 1) and after manual apex/base/myocardial contour adjustment (ADJ-step 2; reference standard). MR data of 40 patients (13.1 ± 3. y, 4 - 17 y) with repaired CHD with decreased pulmonary blood flow (CHD-DPBF) were evaluated. Intra- and inter-rater reliability was determined for 10 randomly selected patients. RESULTS: The software correctly detected the left ventricle in 38/40 (95%) patients. EDV after automated segmentation: 119.1 ± 44.0 ml; after ADJ-step 1: 115.8 ± 9.5 ml; after ADJ-step 2: 116.2 ± 39.4 ml. The corresponding results for ESV were 52.0 ± 18.5/49.6 ± 6.9/49.7 ± 16.4 ml; for SV 67.1 ± 28.5/66.2 ± 25.4/66.5 ± 25. ml; for EF 55.5 ± 7.3/56.7 ± 6.6/56.7 ± 6.3%; for MM 83.7 ± 35.9/76.2 ± 8.3/74.6 ± 27.2 g. Significant differences were found for ESV/MM/EF comparing the automated segmentation results with these after ADJ-step 1 and ADJ-step 2. No significant differences were found when comparing all results of ADJ-step 1 and ADJ-step 2 or when comparing EDV/SV results. Intra- and inter-rater reliability was excellent. The mean time effort was 63.4 ± 6.9 s for the automated segmentation, 74.2 ± 8.9 s for ADJ-step 1 and 269.5 ± 39.4 s for ADJ-step 2. CONCLUSION: Automated left ventricular volumes and function analysis in children and adolescents with surgically treated CHD proved to be feasible with excellent intra- and inter-rater reliability. Automated segmentation with manual apex/base adjustment provided clinically acceptable results. KEY POINTS: Automated left ventricular volume and function analysis in children and adolescents with surgically treated right-sided heart disease is feasible with excellent intra- and inter-rater reliability. Automated segmentation with manual apex/base adjustment provides clinically acceptable results. Additional manual myocardial contour adjustment does not significantly improve the results.

Improved Image Quality in Head and Neck CT Using a 3D Iterative Approach to Reduce Metal Artifact.

BACKGROUND AND PURPOSE: Metal artifacts from dental fillings and other devices degrade image quality and may compromise the detection and evaluation of lesions in the oral cavity and oropharynx by CT. The aim of this study was to evaluate the effect of iterative metal artifact reduction on CT of the oral cavity and oropharynx. MATERIALS AND METHODS: Data from 50 consecutive patients with metal artifacts from dental hardware were reconstructed with standard filtered back-projection, linear interpolation metal artifact reduction (LIMAR), and iterative metal artifact reduction. The image quality of sections that contained metal was analyzed for the severity of artifacts and diagnostic value. RESULTS: A total of 455 sections (mean ± standard deviation, 9.1 ± 4.1 sections per patient) contained metal and were evaluated with each reconstruction method. Sections without metal were not affected by the algorithms and demonstrated image quality identical to each other. Of these sections, 38% were considered nondiagnostic with filtered back-projection, 31% with LIMAR, and only 7% with iterative metal artifact reduction. Thirty-three percent of the sections had poor image quality with filtered back-projection, 46% with LIMAR, and 10% with iterative metal artifact reduction. Thirteen percent of the sections with filtered back-projection, 17% with LIMAR, and 22% with iterative metal artifact reduction were of moderate image quality, 16% of the sections with filtered back-projection, 5% with LIMAR, and 30% with iterative metal artifact reduction were of good image quality, and 1% of the sections with LIMAR and 31% with iterative metal artifact reduction were of excellent image quality. CONCLUSIONS: Iterative metal artifact reduction yields the highest image quality in comparison with filtered back-projection and linear interpolation metal artifact reduction in patients with metal hardware in the head and neck area.

Thoracic non-osseous lesions in cancer patients detected in low-dose CT images acquired as part of skeletal SPECT/CT examinations.

AIM: Hybrid single-photon emission tomographic (SPECT) and X-ray computed tomography (CT) systems are increasingly used in oncologic imaging. With SPECT/CT not only the thoracic spine but also the surrounding soft tissue needs to be evaluated for pathological findings. The purpose of this study was to assess the prevalence of non-osseous findings detectable on low-dose CT datasets from patients studied by thoracic 99mTc-dicarboxypropane diphosphonate (DPD)-SPECT/CT. PATIENTS, METHODS: 119 consecutive oncologic patients (81 breast cancer, 38 with other cancer) who underwent DPD-SPECT CT of the thoracic region were included in this study. Non-osseous findings on CT were classified as either probably benign or suspicious. Suspicious findings were correlated with retrievable previous imaging and if performed with follow up imaging (MRI, CT with contrast medium, Ultrasound) or biopsy results. RESULTS: In 80/119 (67%) patients no imaging was performed before SPECT/CT. Only 7/119 subjects (6%) had no other lesions than bone lesions. In 101/119 (85%) patients lesions found on SPECT/CT images were rated as benign and in 65/119 (55%) patients as suspicious. In 8/119 (7%) patients with previously unknown suspicious lesions on SPECT/CT images suspicious findings were confirmed by biopsy. CONCLUSION: 7% of patients referred to SPECT/CT of the thoracic spine for staging of malignant disease had previously unknown suspicious non-osseous lesions detectable on the low-dose CT images which were confirmed by biopsy. This could be especially relevant for cancer entities like breast and prostate, in which no thorax-CT is routinely intended for staging.

Imaging the Parasinus Region with a Third-Generation Dual-Source CT and the Effect of Tin Filtration on Image Quality and Radiation Dose.

BACKGROUND AND PURPOSE: CT is the imaging technique of choice in the evaluation of midface trauma or inflammatory disease. We performed a systematic evaluation of scan protocols to optimize image quality and radiation exposure on third-generation dual-source CT. MATERIALS AND METHODS: CT protocols with different tube voltage (70-150 kV), current (25-300 reference mAs), prefiltration, pitch value, and rotation time were systematically evaluated. All images were reconstructed with iterative reconstruction (Advanced Modeled Iterative Reconstruction, level 2). To individually compare results with otherwise identical factors, we obtained all scans on a frozen human head. Conebeam CT was performed for image quality and dose comparison with multidetector row CT. Delineation of important anatomic structures and incidental pathologic conditions in the cadaver head was evaluated. RESULTS: One hundred kilovolts with tin prefiltration demonstrated the best compromise between dose and image quality. The most dose-effective combination for trauma imaging was Sn100 kV/250 mAs (volume CT dose index, 2.02 mGy), and for preoperative sinus surgery planning, Sn100 kV/150 mAs (volume CT dose index, 1.22 mGy). "Sn" indicates an additional prefiltration of the x-ray beam with a tin filter to constrict the energy spectrum. Exclusion of sinonasal disease was possible with even a lower dose by using Sn100 kV/25 mAs (volume CT dose index, 0.2 mGy). CONCLUSIONS: High image quality at very low dose levels can be achieved by using a Sn100-kV protocol with iterative reconstruction. The effective dose is comparable with that of conventional radiography, and the high image quality at even lower radiation exposure favors multidetector row CT over conebeam CT.

Dose reduction in computed tomography of the chest: image quality of iterative reconstructions at a 50% radiation dose compared to filtered back projection at a 100% radiation dose.

PURPOSE: The aim of this study was to evaluate the potential of iterative reconstruction (IR) in chest computed tomography (CT) to reduce radiation exposure. The qualitative and quantitative image quality of standard reconstructions with filtered back projection (FBP) and half dose (HD) chest CT data reconstructed with FBP and IR was assessed. MATERIALS AND METHODS: 52 consecutive patients underwent contrast-enhanced chest CT on a dual-source CT system at 120 kV and automatic exposure control. The tube current was equally split on both tube detector systems. For the HD datasets, only data from one tube detector system was utilized. Thus, FD and HD data was available for each patient with a single scan. Three datasets were reconstructed from the raw data: standard full dose (FD) images applying FBP which served as a reference, HD images applying FBP and IR. Objective image quality analysis was performed by measuring the image noise in tissue and air. The subjective image quality was evaluated by 2 radiologists according to European guidelines. Additional assessment of artifacts, lesion conspicuity and edge sharpness was performed. RESULTS: Image noise did not differ significantly between HD-IR and FD-FBP (p = 0.254) but increased substantially in HD-FBP (p < 0.001). No statistically significant differences were found for the reproduction of anatomical and pathological structures between HD-IR and FD-FBP, subsegmental bronchi and bronchioli. The image quality of HD-FBP was rated inferior because of increased noise. CONCLUSION: A 50 % dose reduction in contrast-enhanced chest CT is feasible without a loss of diagnostic confidence if IR is used for image data reconstruction. Iterative reconstruction is another powerful tool to reduce radiation exposure and can be combined with other dose-saving techniques. KEY POINTS: • Iterative reconstructions allow for image noise and artifact reduction.• Comparable image data can thus be attained even at 50 % radiation dose.• Diagnostic confidence remains unaffected.

Frequency split metal artefact reduction in pelvic computed tomography.

OBJECTIVES: Artefacts from total hip replacement affect image quality and the visualisation of pelvic lesions on computed tomography (CT). We propose a frequency split (FS) approach in addition to the normalised metal artefact reduction (NMAR) algorithm that aims to suppress artefacts and improves image quality in patients with orthopaedic hardware. METHODS: Data from ten consecutive patients with metal artefacts from uni- (n = 5) and bilateral (n = 4) total hip replacement or osteosynthesis (n = 1) were reconstructed with filtered back projection (FBP), linear interpolation MAR (LIMAR), NMAR, FSLIMAR and FSNMAR and analysed for image quality and severity of artefacts. RESULTS: NMAR and FSNMAR significantly improved the assessment of the pelvic organs, lymph nodes and vessels compared with FBP, LIMAR or FSLIMAR (P < 0.05). Assessment of the metal hardware, joint and capsule was improved with the addition of FS (FSLIMAR, FSNMAR). No algorithm-related artefacts were detected in regions that did not contain metal. CONCLUSIONS: NMAR, FSLIMAR and FSNMAR have the potential to improve image quality in patients with artefacts from metal hardware and to improve the diagnostic accuracy of CT of the organs of the pelvis. Although introducing some algorithm-related artefacts, FSNMAR most accurately displayed adjacent bone and tissue next to metal implants. KEY POINTS: • Orthopaedic metallic hardware often creates serious artefacts in computed tomography, hindering diagnosis. • The normalised metal artefact reduction (NMAR) algorithm was developed to suppress such artefacts. • NMAR improves CT assessment of pelvic organs in patients with orthopaedic hardware. • Addition of the frequency split technique (FSNMAR) helps assess tissue near metal hardware. • NMAR and FSNMAR are robust and computationally effective sinogram interpolation algorithms.

[Current strategies for dosage reduction in computed tomography]. / Aktuelle Strategien zur Dosisreduktion in der Computertomographie.

The potential risks of radiation exposure associated with computed tomography (CT) imaging are reason for ongoing concern for both medical staff and patients. Radiation dose reduction is, according to the as low as reasonably achievable principle, an important issue in clinical routine, research and development. The complex interaction of preparation, examination and post-processing provides a high potential for optimization on the one hand but on the other a high risk for errors. The radiologist is responsible for the quality of the CT examination which requires specialized and up-to-date knowledge. Most of the techniques for radiation dose reduction are independent of the system and manufacturer. The basic principle should be radiation dose optimization without loss of diagnostic image quality rather than just reduction.

Dual source multidetector CT-angiography before Transcatheter Aortic Valve Implantation (TAVI) using a high-pitch spiral acquisition mode.

OBJECTIVES: Transcatheter Aortic Valve Implantation (TAVI) is an alternative to surgical valve replacement in high risk patients. Angiography of the aortic root, aorta and iliac arteries is required to select suitable candidates, but contrast agents can be harmful due to impaired renal function. We evaluated ECG-triggered high-pitch spiral dual source Computed Tomography (CT) with minimized volume of contrast agent to assess aortic root anatomy and vascular access. METHODS: 42 patients (82 ± 6 years) scheduled for TAVI underwent dual source (DS) CT angiography (CTA) of the aorta using a prospectively ECG-triggered high-pitch spiral mode (pitch = 3.4) with 40 mL iodinated contrast agent. We analyzed aortic root/iliac dimensions, attenuation, contrast to noise ratio (CNR), image noise and radiation exposure. RESULTS: Aortic root/iliac dimensions and distance of coronary ostia from the annulus could be determined in all cases. Mean aortic and iliac artery attenuation was 320 ± 70 HU and 340 ± 77 HU. Aortic/iliac CNR was 21.7 ± 6.8 HU and 14.5 ± 5.4 HU using 100 kV (18.8 ± 4.1 HU and 8.7 ± 2.6 HU using 120 kV). Mean effective dose was 4.5 ± 1.2 mSv. CONCLUSIONS: High-pitch spiral DSCTA can be used to assess the entire aorta and iliac arteries in TAVI candidates with a low volume of contrast agent while preserving diagnostic image quality.

New drug development during and after a period of regulatory change: clinical research activity of major United States pharmaceutical firms, 1958 to 1979.

The 1962 drug amendments fundamentally changed the way in which U.S. pharmaceutical firms could test new drugs in man and receive New Drug Application (NDA) approval. Although it is well known that the amendments and associated events caused a profound decline in the annual number of new drugs receiving NDA approval, the amendments' effects on clinical research into new chemical entities (NCEs) have not been investigated because data were unavailable. To study this we requested drug development information dating back to 1958 from most major United States-owned pharmaceutical firms and obtained complete responses from nine. The results showed that the introduction rate of NCEs into human testing dropped sharply in the early 1960s and declined substantially thereafter. The number of NCEs entering human testing fell from a mean of 89 a year in 1958-1962, to 35 a year in 1963-1972 (a reduction of 61%), and to 17 a year in the last 5 years of the survey, 1975-1979--an overall reduction of 81%. The number of NDA approvals received by these firms fell sharply by 49% in the early 1960s and more slowly for 10 years thereafter, from the mid-1960s to the mid-1970s. In the case of self-originated NCEs, the size of this later fall was 71%. Causes of these changes in NCE flow include the amendments and the events that prompted them; changes in scientific philosophy, standards, and state of the art; and economic factors.

New drug development by United States pharmaceutical firms with analyses of trends in the acquisition and origin of drug candidates, 1963-1979.

The average number of self-originated new chemical entities (NCEs) first tested in man by 39 United States-owned pharmaceutical firms in the 3-year period from 1977 to 1979 was 26 a year, approximately half the number investigated annually in the previous decade. Investigational New Drug (IND) Exemption filings on self-originated NCEs, but not those on acquired NCEs, were also comparatively low. Consequently, the contribution of self-originated NCEs to total IND filings fell from 81% in 1963 through 1975 to 68% in 1976 through 1979. (There was a similar decline, from 78% to 61%, in the proportion of compounds synthesized in the United States.) The relative increase in IND filings on acquired NCEs was greatest for smaller firms. By the late 1970s acquired NCEs accounted for almost 50% of the INDs filed by smaller firms, but only 10% to 25% of those filed by large and medium-sized firms. The importance of NCEs acquired from abroad has increased since the mid-1970s. The number of INDs filed on Japanese-originated NCEs rose from approximately one a year in 1963 through 1975 to an average of 3.5 a year in 1976 through 1979. Initial clinical testing of self-originated drugs abroad, which increased sharply in the early 1970s to reach a peak of 36% in 1976, declined to approximately 21% in 1977 through 1979. Self-originated drugs approved in 1977-1979 spent an average of 6 years in United States clinical testing and 2 in regulatory review, a total of 8 years from IND filing to NDA approval. The percentage of IND filings on self-originated NCEs that received New Drug Application (NDA) approval after 8 years or more was 9% overall, although ultimate success rates will be higher. There was a higher success rate for anti-infective drugs (17%) than for other pharmacologic categories (7%). For acquired NCEs, the overall approval rate was much larger (28%).

In vivo methylation by Escherichia coli K-12 mec+ deoxyribonucleic acid-cytosine methylase protects against in vitro cleavage by the RII restriction endonuclease (R. Eco RII).

We have analyzed the susceptibility of the deoxyribonucleic acid (DNA) of phage fd replicative form (RF) and of Escherichia coli to in vitro cleavage by purified RII restriction endonuclease (R. Eco RII). The results are summarized as follows: (i) fd, mec- RFI, isolated from infected E. coli K-12 mec- bacteria (a mutant strain lacking DNA-cytosine methylase activity), is cleaved into at least two fragments, whereas fd. mec+ RFI, isolated from the parental mec+ strain, is not cleaved. (ii) E. coli mec- DNA is extensively degraded, whereas mec+ DNA-cytosine methylase acts as an RII modification enzyme.

Analysis of bacteriophage deoxyribonucleic acid sequences methylated by host- and R-factor-controlled enzymes.

Phages lambda and fd were propagated in Escherichia coli strains that have either host K-12 or the N-3 R-factor deoxyribonucleic acid-cytosine methylase activity. Pyrimidine tracts containing 3H-labeled 5-methylcytosine (MeC) were analyzed; in all cases, the major methylated sequence was 5' ... C-MeC-T ... 3'.

Deoxyribonucleic acid-cytosine methylation by host- and plasmid-controlled enzymes.

Deoxyribonucleic acid (DNA)-cytosine methylation specified by the wild-type Escherichia coli K 12 mec+ gene and by the N-3 drug resistance (R) factor was studied in vivo and in vitro. Phage lambda and fd were propagated in the presence of L-[methyl-3H]methionine in various host bacteria. The in vivo labeled DNA was isolated from purified phage and depurinated by formic acid-diphenylamine treatment. The resulting pyrimidine oligonucleotide tracts were separated according to size and base composition by chromatography on diethylaminoethyl-cellulose in 7 M urea at pH 5.5 and 3.5, respectively. The distribution of labeled 5-methylcytosine in DNA pyrimidine tracts was identical for phage grown in mec+ and mec minus (N-3) cells. For phage lambda the major 5-methylcytosine containing tract was the tripyrimidine, C2T; for both fd-mec minus (N-3) DNA and fd-mec+DNA, C2T was the sole 5-methylcytosine-containing tract. When various lambda DNAs were methylated to saturation in vitro by crude extracts from mec+ and mec minus (N-3) cells, the extent of cytosine methylation was the same. This is in contrast to in vivo methylation where lambda-mec minus (N-3) DNA contains twice as many 5-methylcytosines per genome as lambda-mec+ DNA. Therefore, we suggest that the K12 met+ cytosine methylase and the N-3 plasmid modification methylase are capable of recognizing the same nucleotide sequences, but that the in vivo methylation rate is lower in mec+ cells.