[Sonographic appearance of benign subcutaneous nodules--including color Doppler sonography].

OBJECTIVE: Color Doppler sonography is used to distinguish malignant from benign subcutaneous nodules because many malignant tumors show an increased number of vessels. But benign lesions, such as inflammatory epidermal cysts, pilomatricomas, palmoplantar fibromatoses show vascular flow signals. We analyze diagnostic factors for subcutaneous nodules on the basis of ultrasonographic appearance including color Doppler sonography. METHODS: We evaluated with sonography 79 subcutaneous nodules in histopathologically proven cases. RESULTS AND DISCUSSION: The diagnostic findings for 28 epidermal cysts were increased posterior echo(sensitivity 77%, specificity 90%). Vascular flow signals were seen in 7 cases(25%). The signals were seen from periphery to adjacent zone of the mass. They were accompanied by inflammatory granulation tissues histologically. The percentage of blood flow may be related to the percentage of "ruptured" epidermal cysts. Pilomatricomas (n = 9) had internal echogenic foci or Doppler flow signals, and no posterior enhancement (sensitivity 89%, specificity 78%). Seven pilomatricomas showed Doppler flow signals in the mass. The percentage of flow signals is explained by the degree of internal echogenic foci because remarkable calcium deposits producing posterior acoustic shadowing prevent us from flow signals. Palmoplantar fibromatoses (n = 5) were ill-defined margins and showed internal vascularity with no posterior enhancement (sensitivity 80%, specificity 94%). CONCLUSION: More benign lesions showed vascular flow signals than reported previously. We have to diagnose subcutaneous nodules referring to not only color Doppler but also gray scale sonography.

Analysis of the plasma concentration of tacrolimus: a useful method for distinguishing falsely elevated tacrolimus concentrations reported by the ACMIA.

UNLABELLED: Tacrolimus monitoring is essential because tacrolimus has a narrow therapeutic dose range. A 35-year-old male after kidney transplantation showed unusually high tacrolimus concentrations in the affinity column mediated immunoassay (ACMIA). METHODS: His whole blood tacrolimus concentrations were measured by the ACMIA, microparticle enzyme immunoassay (MEIA), enzyme-linked immunosorbent assay (ELISA), and the enzyme multiplied immunoassay technique (EMIT). Since the findings were discrepant, the possible causes were investigated. To screen for endogenous beta-galactosidase, the cyclosporin A concentration of the patient's sample was measured by ACMIA. To determine whether the false increase was attributable to his plasma, tacrolimus concentrations were measured in the whole blood and plasma of the patient in question and 3 other patients. To eliminate heterophilic antibodies, the patient's plasma was treated with heterophilic blocking tube. To eliminate immunoglobulin interference, the patient's plasma was incubated with Protein A or G. RESULTS AND DISCUSSION: The patient's tacrolimus concentration was found to be 16.4, 3.7, 3.2, and 3.0 microg/L by the ACMIA, MEIA, ELISA, and EMIT, respectively. In the cyclosporin assay, the absorbance did not increase; therefore, beta-galactosidase participation was ruled out. Tacrolimus is mainly sequestered in erythrocytes; however, this patient's plasma and whole blood showed similar tacrolimus levels. Heterophilic blocking tube did not affect the patient's tacrolimus level. His tacrolimus concentration was reduced after incubation with Protein A, indicating that immunoglobulins trapped by Protein A had non-specifically interfered with the assay system. CONCLUSION: When the tacrolimus level indicated by the ACMIA is unexpectedly high, the patient's plasma should be assayed. If the tacrolimus plasma level is subsequently found to be high, the original result might be incorrect, and it is recommended that another method be used.

Effect of rapamycin on hepatocyte function and proliferation induced by growth factors.

BACKGROUND: Rapamycin is a specific inhibitor of the mammalian target of rapamycin (mTOR). The effect of rapamycin on proliferation and cellular function was studied in hepatocytes stimulated by hepatocyte growth factor (HGF) or transforming growth factor-alpha (TGFalpha). METHODS AND RESULTS: When isolated rat hepatocytes were cultured at low density, the addition of HGF or TGFalpha increased DNA synthesis but did not affect albumin or fibrinogen concentrations in the medium. In contrast, in hepatocytes cultured at high density, the albumin and fibrinogen concentrations, but not DNA synthesis, were increased by HGF or TGFalpha. The HGF- or TGFalpha-induced increase in DNA synthesis and in albumin or fibrinogen concentrations was suppressed by the addition of rapamycin, as well as wortmannin, a phosphatidylinositol-3 kinase inhibitor. CONCLUSION: HGF and TGFalpha stimulate proliferation and function of hepatocytes depending upon the conditions, and rapamycin inhibited these stimulatory effects, possibly by inhibiting the mTOR-dependent signaling pathway.