Regioselective enzymatic aminoacylation of lobucavir to give an intermediate for lobucavir prodrug.

Synthesis of lobucavir prodrug, L-valine, [(1S,2R,3R)-3-(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)-2-(hydroxymethyl) cyclobutyl]methyl ester monohydrochloride (BMS 233866), requires regioselective coupling of one of the two hydroxyl groups of lobucavir (BMS 180194) with valine. Either hydroxyl group of lobucavir could be selectively aminoacylated with valine by using enzymatic reactions. N-[(Phenylmethoxy)carbonyl]-L-valine, [(1R,2R,4S)-2-(2-amino-6-oxo-1H-purin-9-yl)-4-(hydroxymethyl)cyclobutyl]methyl ester (3, 82.5% yield), was obtained by selective hydrolysis of N,N'-bis[(phenylmethoxy)carbonyl]bis[L-valine], O,O'-[(1S,2R,3R)-3-(2-amino-6-oxo-1H-purin-9-yl)cyclobuta-1,2-diyl]methyl ester (1) with lipase M, and L-valine, [(1R,2R,4S)-2-(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)-4-(hydroxymethyl)cyclobutyl]methyl ester monohydrochloride (4, 87% yield) was obtained by hydrolysis of bis[L-valine], O,O'-[(1S,2R,3R)-3-(2-amino-6-oxo-1H-purin-9-yl)cyclobuta-1,2-diyl]methyl ester, dihydrochloride (2), with lipase from Candida cylindracea. The final intermediate for lobucavir prodrug, N-[(phenylmethoxy)carbonyl]-L-valine, [(1S,2R,4R)-3-(2-amino-6-oxo-1H-purin-9-yl)-2-(hydroxymethyl)cyclobutyl]methyl ester (5), could be obtained by transesterification of lobucavir using ChiroCLEC BL (61% yield), or more selectively by using immobilized lipase from Pseudomonas cepacia (84% yield).

Duplex sonography accurately assesses portacaval shunt patency.

Among 42 patients who had undergone portacaval shunt (PCS) to treat bleeding esophageal varices, shunt patency was assessed with duplex sonography 1 month to 5 years postoperatively. Patency was confirmed in all patients (100%). Correlative angiograms confirming the sonographic findings were obtained in 24 patients. Duplex scanning showed hepatofugal or stagnant flow in the distal portal vein in all 42 patients. Very low rates of liver-failure-related mortality (6%) and morbidity (6% incidence of encephaloparthy) in this series despite loss of portal perfusion of the liver in patients incriminate factors other than magnitude and direction of portal vein flow as the cause of complications occurring after PCS. Duplex sonography offers accurate and relevant clinical and physiologic data about shunt hemodynamics in patients who have undergone PCS.

Ultrasonography of the knee.

Sonography is a useful modality in the diagnosis of a wide variety of knee disorders, including lesions of the articular cartilage, tendons and ligaments, menisci, synovial space, and adjacent vessels and muscles. Sonography is noninvasive, rapidly performed, widely available, readily accepted by patients, uses no ionizing radiation, and is relatively inexpensive compared to other conventional imaging studies of the menisci, making it a potentially attractive screening examination for knee injuries. Although it is difficult to state the exact place of sonography in the diagnostic workup of knee disorders, we feel that sonography is vastly underutilized. With additional refinements in ultrasound technology and scanning techniques, we expect further expansion of its role in the evaluation of the knee.

Sonographic diagnosis of neutropenic typhlitis.

Five immunosuppressed patients with neutropenic typhlitis were studied with sonography. In four, sonography was the imaging technique that first suggested the diagnosis. In each case, sonography showed thickening of the right colon wall (1-2.5 cm) with low- or high-level echoes. Serial sonograms were used to monitor the daily progress of the disease in two patients. Sonography appears to be a useful tool not only to detect typhlitis in patients with symptoms suggestive of the disease, but also to follow their clinical course.

CT of sacral injury.

Eighty-eight patients with 188 sacral fractures were examined with computed tomography (CT) and conventional radiography. Four main patterns of sacral injury were defined: sacroiliac diastasis (39%), sacral and/or iliac lip fractures (25%), vertical shear fractures (25%), and comminuted fractures (5%). Initial interpretation of plain radiographs failed to define 29% of the sacroiliac joint diastases, 57% of the lip fractures, 34% of the vertical shear fractures, and 25% of the comminuted fractures. The extent of injury was better delineated with CT, and a more certain diagnosis of sacral injury was possible with CT than with radiography. Because of the higher detection rate and improved imaging of fracture configuration, CT should be performed in all patients with sacral injury.

Changing appearance of the normal uterus during the menstrual cycle: MR studies.

The authors obtained sagittal magnetic resonance (MR) images twice a week from six healthy women during one full menstrual cycle to establish the changes depicted in the uterine layers. Parallel endocrine and ultrasound studies were used to establish the day of ovulation precisely. Consistent changes in the thickness and intensity of the endometrium and myometrium wer noted in all subjects during the menstrual cycle. Both myometrial thickness and endometrial area increased linearly during the follicular (preovulatory) phase of the cycle; the rate of increase dropped significantly during the luteal phase. Two myometrial layers were observed; the best contrast between the layers was demonstrated during the first half of the cycle.

Intraoperative US as an aid to intraoperative electron beam radiation therapy.

Intraoperative electron-beam radiation therapy (IRT) is being used to treat certain abdominal malignancies. Accurate determination of tumor size, depth, and extent is necessary to select a treatment cone of appropriate size and appropriate electron beam energy for the treatment portal. Fourteen patients undergoing evaluation for this treatment were examined with intraoperative ultrasonography (IUS) to aid therapy planning. IUS study required little additional time and readily delineated tumor size, depth, and relationship to adjacent structures. In two patients, the US and operative findings provided information that precluded use of IRT. The traditional method of tumor evaluation by intraoperative palpation and inspection was consistently enhanced by the use of IUS findings. IUS is a valuable adjunct that improves the accuracy of therapy planning for IRT.

High resolution sonography of the menisci of the knee.

High-resolution real-time ultrasonography (5, 7.5, and 10 MHz) was used to examine the menisci of the knee in ten normal volunteers and in ten patients with knee injuries. The posterior horns of the medial and lateral menisci were easily demonstrated. Normal anatomy and pathologic changes could be imaged in the menisci, capsular ligaments, and articular cartilage. While the menisci were seen in all subjects, the weight-bearing portion of the femoral articular cartilage could not be seen in several of the symptomatic patients who could not flex their knees. Ultrasound promises to be a useful, noninvasive adjunct to conventional techniques in evaluating the injured knee--especially in assessing the posterior horns of the menisci, an area difficult to assess with arthroscopy.

Pancreatic insufficiency: role of CT evaluation.

The medical records of all patients discharged over a 3-year period with a diagnosis of pancreatic insufficiency were reviewed. In some patients, abdominal radiographs or sonograms provided adequate information. However, computed tomography (CT) was a key diagnostic tool in understanding the cause of pancreatic insufficiency in 11 of the 13 patients in whom it was performed. CT study detected previously undiagnosed carcinoma in one patient, enabled diagnosis of chronic pancreatitis in five, confirmed complete surgical removal of the pancreas in two, and--despite optimal use of contrast material and 5-mm contiguous sections--was unable to detect any pancreatic tissue in three patients, suggesting complete idiopathic atrophy. Pancreatic insufficiency is a difficult clinical diagnostic problem. CT scanning should be employed early if abdominal radiographs or sonograms do not detect an abnormality.

Nutrient canals of the ilium: a normal variant simulating disease on computed tomography.

The nutrient canals of the ilium are a frequent finding on computed tomography (CT), and were seen in 8 of 8 consecutive examinations of the pelvis. CT sections through these canals could be misinterpreted as fractures or metastases, especially if there is a history of pelvic trauma or malignancy elsewhere.