Synthesis and structure--activity analysis of novel dihydropyridine derivatives to overcome multidrug resistance.

The structure activity relationships were studied on newly synthesized 1,4-dihydropyridine derivatives possessing a 1-pentyl group at the 4-position, and 3-pyridylpropylester was found to be one of the effective fragments for overcoming P-glycoprotein mediated multidrug-resistance (MDR) in cultured human cancer cells, in vitro. 3-Pyridylpropylester was also found to be one of the effective fragments for increasing the life span of P-glycoprotein overexpressing MDR P388 leukemia-bearing mice, in vivo. All compounds had weak calcium antagonistic activities, but there appeared no relationship between MDR reversing effect and calcium antagonistic activity.

Ultrasound-guided core needle biopsy for breast cancer: preliminary report.

BACKGROUND: Ultrasound-guided automated percutaneous core needle biopsy (US-CNB) for breast tumors has been introduced into clinical practice, but it has not yet been used routinely. We evaluated its usefulness, especially in terms of histological accuracy. METHODS: Thirty-one consecutive patients underwent mammography followed by breast biopsy with the automated core needle biopsy device. RESULTS: Mammography was highly suggestive of malignancy or suspicious abnormalities in 17 cases whose histological findings from US-CNB specimens were invasive ductal carcinoma without exception. The other 14 cases with benign or probably benign mammography findings showed no malignancy histologically in the US-CNB specimens. In cases of malignancy, the accuracy rates of histological findings for the specimens obtained by US-CNB were 94.1% in histological type, 100% in direct infiltration, 82.4% in lymphatic infiltration, 82.4% in venous infiltration, 94.1% in histological grading and 82.4% in intraductal spread. CONCLUSION: US-CNB was useful for making reliable preoperative histopathological diagnosis and may substitute fine needle aspiration biopsy and surgical biopsy.

Newly synthesized dihydropyridine derivatives as modulators of P-glycoprotein-mediated multidrug resistance.

Newly synthesized 1,4-dihydropyridine derivatives possessing alkyl chains at the 4-position screened whether they could overcome P-glycoprotein-mediated multidrug resistance in cultured cancer cells and also leukemia-bearing animals. Of these derivatives, some could overcome drug resistance to doxorubicin and vincristine in multidrug resistant human cancer cell lines. Combined administration of vincristine and some of the derivatives significantly increased the life span of P-glycoprotein overexpressing multidrug-resistant P388 leukemia-bearing mice. The calcium antagonistic activities, an undesirable effects, were weaker than that of verapamil. These results suggested that the introduction of alkyl groups at the 4-position were effective for both overcoming multidrug resistance and reducing the calcium antagonistic activity.

Aberrant left gastric vein demonstrated by helical CT.

PURPOSE: Our goal was to describe the CT findings of aberrant left gastric vein (ALGV) and to evaluate the clinical significance of this vein. METHOD: Four patients in whom ALGVs were demonstrated by helical CT were examined. Each patient had either intrahepatic cholangiocarcinoma, cirrhosis with gastric varices, chronic hepatitis, or nonspecific abdominal pain. All patients underwent two phase helical CT, and the patient with cholangiocarcinoma underwent CT during arterial portography, and 3D images of the abdominal veins were obtained. RESULTS: In all patients, the ALGVs ran along the hepatogastric ligament and were directly connected with the left portal branch. In the patient with cholangiocarcinoma, the portal vein had severe stenosis by tumor invasion, and both the ALGV and the aberrant right gastric vein functioned as a collateral pathway of the portal flow into the liver. In the patient with cirrhosis, dilated ALGV with hepatofugal flow caused gastric varices. CONCLUSION: The ALGV is directly connected with the left portal branch and may play an important role in the collateral pathway of the portal system.

Differential diagnosis of early homogeneously enhancing hepatocellular carcinoma and hemangioma by two-phase CT.

PURPOSE: Our goal was to differentiate between early homogeneously enhancing hepatocellular carcinoma (HCC) and hemangioma by two-phase CT. METHOD: Two phase images of 51 HCCs and 28 hemangiomas showing homogeneous high attenuation in the first series (arterial dominant phase) were reviewed. Enhancement patterns of the lesions in the second series (parenchymal phase) were classified as homogeneous high, peripheral high, iso-, and low attenuation. The attenuation values of all and the enhancement values of some (21 HCCs and 18 hemangiomas) in the first series were calculated. RESULTS: Although low and peripheral high attenuation patterns were seen during the second series only in HCCs (n = 35), which could be used to correctly diagnose HCC, other nonspecific patterns were demonstrated in both HCCs (n = 16) and hemangiomas (n = 28). The attenuation values of 49 of the 51 HCCs and 5 of the 28 hemangiomas were below 130 HU on the first series. The enhancement values of all 21 HCCs and 3 of 18 hemangiomas were below 70 HU. Combining the enhancement patterns with a borderline attenuation value of 130 HU or borderline enhancement value of 70 HU yielded overall accuracies of 94 and 92%, respectively. CONCLUSION: The combined criteria (enhancement pattern plus attenuation or enhancement value) were useful for differentiating between early homogeneously enhancing HCCs and hemangiomas.

Segmental anatomy of the liver under the right diaphragmatic dome: evaluation with axial CT.

PURPOSE: To evaluate the segmental anatomy of the liver under the right side of the diaphragm with axial computed tomography (CT). MATERIALS AND METHODS: Forty-six patients underwent CT arteriography with selective catheterization of the right hepatic artery in 25 cases, the left hepatic artery in 12, the anterior branch of the right hepatic artery in six, the posterior branch of the right hepatic artery in five, the superior anterior branch of the right hepatic artery in 10, and the superior posterior branch of the right hepatic artery in eight. RESULTS: The boundary between the right and left lobes shifted by 16.2 degrees +/- 16.8 anteriorly, and the boundary between the anterior and posterior segments shifted by 43.9 degrees +/- 14.0 posteriorly to the line through the middle or right hepatic vein from the inferior vena cava. The top of the liver consisted of both lobes in 22 patients, only the right lobe in 17, and only the left lobe in two. Participation of segment 7 in the top was not demonstrated. CONCLUSION: The line that extends beyond the middle or right hepatic vein from the inferior vena cava does not coincide with the main or right longitudinal scissura on axial images of the upper portion of the liver.

Hepatic pseudolesion in the left lobe around the falciform ligament at helical CT.

PURPOSE: To determine the prevalence and possible cause of pseudolesions in the left hepatic lobe around the falciform ligament at hepatic helical computed tomography (CT). MATERIALS AND METHODS: Portal venous-dominant CT scans of 472 consecutive patients were reviewed. CT of the left hepatic lobe was performed after injection of contrast material into the portal vein in 73 patients, the hepatic artery in 32, and the internal thoracic artery in four. The scans were compared with those obtained at helical CT, and the findings were analyzed. RESULTS: Pseudolesions were seen on 64 (14%) of 472 helical CT scans and correlated well (accuracy, 96%) with portal perfusion defects. They were not more enhanced than the surrounding liver parenchyma at CT arteriography with hepatic artery injection but were enhanced in two patients at CT arteriography with internal thoracic artery injection. CONCLUSION: Pseudolesions are caused by portal perfusion defects and may receive an aberrant blood supply.

Vasoconstriction by angiographic contrast media in isolated canine arteries.

To study the mechanism of the pain produced by contrast media (CM) in peripheral arteriography, we examined the direct effects of low concentrations (1.85-100 mg I/ml) of CM (diatrizoate, iopamidol, ioxaglate, and iotrolan) on helically cut strips of canine blood vessels taken from six different regions. We found that: (a) low concentrations of CM induced vasoconstriction. (b) This occurred immediately after the application of CM and produced sustained constriction. (c) The constriction produced in arteries was dose-dependent. (d) The production and intensity of constriction in the arterial strips differed as follows: cranial mesenteric artery > renal artery > femoral artery > common carotid artery > thoracic aorta > coronary artery. The effects of the CM were, in order of magnitude: diatrizoate > iopamidol > ioxaglate > iotrolan. Differences between CM corresponded with the differences in osmolality of the CM solutions. (e) Low concentrations of meglumine and mannitol also produced vasoconstriction. (f) Constriction caused by all drug samples used was reversible, but the process of relaxation to the original tension was much slower in CM-treated arterial strips than in the other strips. From these results, we confirmed that the incidence and degree of vasoconstriction produced by all drug samples used in this experiment depended on solution osmolality, rather than on chemotoxicity or ionicity. We discuss the physiological mechanism of these results and stress the importance of CM hyperosmolality in vasoconstriction and vascular pain production.

Ultrasonographic appearance of dermoid and epidermoid cysts in the head and neck.

The ultrasonographic features of 6 histologically proven dermoid and epidermoid cysts in the head and neck are reported. All 6 cysts had internal echoes, with a solid appearance. Five of the 6 were echogenic, with only slight or no posterior echo enhancement. Amorphous keratinous debris from keratinizing stratified squamous epithelium filled the lumen of each cyst, producing the internal echoes. Most of the true solid tumors examined were generally of lower echogenicity, and could be differentiated from dermoid and epidermoid cysts ultrasonographically, although lipomas were indistinguishable from these cysts.

CT features in second cancers of the maxillary sinus.

Five patients with a second maxillary cancer (squamous cell carcinoma), which developed 6 to 17 years after initial treatment for the first cancer on the opposite side, were compared with 21 control cases with a primary cancer on the basis of computed tomography (CT) findings. Generally, the second cancer was found at an earlier stage. The specific CT findings of early sinus carcinoma were uneven soft tissue distribution in the antrum and tumor permeation with bone fragments remaining at the original tumor site. These findings may be helpful for distinguishing this cancer from benign chronic sinusitis and/or other malignant sinus disease. The pterygoid process, medial bony wall, and ethmoid sinus had a tendency to be spared in most of the 5 patients with second maxillary cancer compared to the 21 control cases.