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A unique acquisition method is proposed for quantitative, high-sensitivity (19)F MR spectroscopic imaging for the study of drug distribution aiming at nmol-level metabolite information in mice. The use of fast spin echo (FSE) at 9.4T allowed us to obtain whole-body images with minimal effect of magnetic susceptibility and to acquire several metabolite signals simultaneously by the method of interleaved multifrequency selection. Modified 2-shot FSE was designed for simultaneous, high-sensitivity (19)F imaging and T(2) mapping. A time course study including all the main metabolites at 10-minute resolution was attained with an oral dose of 1-2 mmol 5-fluorouracil (5-FU) (130-260 mg)/kg in mice. With acquisition parameters optimized for in vivo T(2) of 40 ms, images of F-nucleotides/-sides, effective anabolites of the anticancer drug 5-FU, were obtained at the level of 200 nmol in the tumor for all the mice studied with a linear correlation (R = 0.96) between image intensity and the quantity determined in the excised tissue. The method exhibits potential capability of molecular imaging with a variety of (19)F-labeled compounds and drug evaluation., ((c) 2009 Wiley-Liss, Inc.)

The problems of Mrs. A's children are the initial focus of professional work. Her depression receives professional attention in the course of treatment of the children. Mrs. A is most likely working individually with an eclectic therapist, with increasing her awareness and insight as treatment goals. Developing a good working relationship with the client is of prime importance to the therapist. Projective as well as objective psychological tests may be used. Her psychiatrist prescribes antidepressant and sleep-inducing medications. Mrs. A's family may not be involved in her treatment; group therapy and self-help resources are also unlikely to be used. I argue that to understand psychotherapy in Japan, the context of psychotherapy practice as well as cultural influence needs to be considered., ((c) 2007 Wiley Periodicals, Inc.)

Caffeine-assisted chemotherapy for bone and soft tissue tumours is very effective. However, high serum caffeine concentrations cause severe side effects, so monitoring of the serum level during therapy is important. For this purpose, a rapid determination method was established by high-performance liquid chromatography after solid-phase extraction. This method can measure caffeine and its three major metabolites in serum samples within 8 min. The mean serum caffeine concentrations of patients were 34.6+/-7.8, 54.5+/-11.9 and 73.0+/-12.8 microg/ml at 24, 48 and 72 h, respectively, after the start of a 1500 mg/m2/day continuous infusion for 72 h. The distribution volume of caffeine was 0.65+/-0.23 l/kg, and the total body clearance was 0.025+/-0.011 l/h/kg, which was one-third of the reported low dose clearance. The appropriate infusion rate was calculated to avoid severe side effects in the final phase of the infusion by using a one-compartment constant infusion model based on the serum levels measured at 24 and 48 h. Caffeine clearance did not correlate with the metabolite/caffeine ratio in serum at any time. It is concluded that individual monitoring with this method for the purpose of dose adjustment is useful for avoiding the side effects of caffeine-assisted chemotherapy., (Copyright 2004 John Wiley & Sons, Ltd.)

In vivo quantitative metabolic mapping is an ideal tool for pharmacokinetic studies. Oral 5-fluorouracil (5-FU) and its metabolites in mice were imaged simultaneously by the (19)F fast spin echo (FSE) sequence using interleaved frequency selection at 9.4T. However, 5-FU images in the small intestine have never been obtained regardless of concentration. The reason for the discrepancy between image intensity and concentration was T(2). At a pH above 6, a dramatic decrease in T(2) of a (19)F 5-FU signal in an aqueous solution was found; T(2) was shorter in the small intestine (14 ms) than in the stomach (52 ms). The (19)F CSI sequence in FID sampling mode was employed for detecting short T(2) signals. With a 13-min resolution time, the detection of the 5-FU signals in the region of the small intestine (0.6 mmol/kg) was successful with a 5 x 5 mm(2) in-plane resolution. Furthermore, two signals separated by 2 ppm were clearly distinguishable, but failed to be separately detectable with the (19)F FSE sequence. For quantitative simultaneous monitoring of 5-FU and its metabolites of varying T(2), the (19)F CSI sequence in FID sampling mode was found to be superior to the (19)F FSE sequence., (Copyright 2001 Wiley-Liss, Inc.)

Some methacrylates are known to be strong contact sensitizers. To determine the effect of side-chain length on sensitizing potential, we examined 11 derivatives with linear side chains from C1 to C18 in an experimental sensitization test in guinea pigs. The results showed an increase in the sensitizing potential with increasing length of the alkyl side chain from C1 to C12. The C12 derivative, lauryl methacrylate, showed the strongest sensitizing potential. Further elongation of the alkyl side chain of methacrylates resulted in a decrease in the potential. With respect to the side-chain-length-dependent sensitizing potential, the present results correspond well with the findings obtained with other compounds like primin, catechols, phenols, hydroquinones, and gallates.

A well-known radiopharmaceutical 2-deoxy-2-fluoro-D-glucose widely used for positron emission tomography diagnosis in terms of glucose utilization, was re-evaluated here as a nuclear magnetic resonance pharmaceutical for cancer detection. The uptake and metabolism of FDG in the experimental tumor, MH134, transplanted to the peritoneum of C3H mice as an ascitic tumor was studied extensively by ex vivo 19F NMR. Prolonged retention of FDG and its metabolites over 2 days was confirmed in the tumor cells as well as in the heart. In these tissues, the 6-phosphate of the injected compound was converted reversibly to its epimer 2-deoxy-2-fluoro-D-mannose and further to their NDP bound forms. The metabolites were almost cleared within a day from the other healthy organs where the formation of NDP-2-deoxy-2-fluoro-D-mannose was low. Thus, the 19F NMR signal of NDP-FDM detected 1 day after the FDG injection could be used as a target signal for tumor detection. Through the use of in vivo 19F NMR spectra and 19F chemical shift images, the feasibility of this proposal was demonstrated. It was concluded that FDG-NMR has a potential for tumor diagnosis in animals.

The effect of anesthesia on the epimerization of 2-deoxy-2-fluoro-D-glucose(-6-phosphate) to 2-deoxy-2-fluoro-D-mannose(-6-phosphate) in mice was demonstrated with 19F NMR spectroscopy of excised tissue specimens from heart, muscle, and brain. Spectra from each of six excised organs confirmed that pretreatment with an anesthetic suppressed the conversion ratio, FDM/(FDG + FDM), in brain at 3 h from 52 +/- 5 to 30 +/- 6% under the dose of 100 mg/kg. We propose potential applications for NMR monitoring of FDG-FDM conversion, including the assessment of regional brain metabolism and the evaluation of various pharmacologic agents.

A case of hyperamylasemia with lung cancer is described. Macroamylasemia was excluded by a normal amylase/creatinine clearance ratio and by a sedimentation constant obtained by sucrose density gradient centrifugation. Positive immunofluorescent staining of tumor cells with a specific antibody against human salivary amylase and significant amylase activity in the primary tumor and metastases support the hypothesis of independent production of amylase by the lung tumor. Cellulose--acetate membrane electrophoresis demonstrated three bands of amylase activity. The major component corresponded to normal salivary amylase in electrophoretic mobility, isoelectric point and molecular size. The minor bands, one of which occupied about 10% of the total amylase activity in serum, urine and tissue homogenates, demonstrated a lower electrophoretic mobility and a more acidic isoelectric point. Gel filtration and electrophoresis disclosed that these minor bands were derived from an amylase isozyme with a larger molecular size than that of normal salivary amylase. The results suggest ectopic tumor production of heterogenous amylase isozymes, with the larger form being secreted into the circulation.

A case of multiple endocrine neoplasia type I (MEN I) consisting of Cushing's disease, primary hyperparathyroidism, and insulin-glucagonoma is described. This condition was treated successfully by transsphenoidal pituitary adenomectomy, subtotal parathyroidectomy, and enucleation of pancreatic tumors. Histologic features showed a basophilic adenoma in the pituitary, chief cell hyperplasia in the parathyroid, and islet cell adenomas in the pancreas. The rarity of multiple endocrine hyperfunctioning states and the pathophysiology created by the combination of these three diseases in this patient are of interest.