Hepatic conversion of 1-(tetrahydro-2-furanyl)-5-fluorouracil into 5-fluorouracil in patients with hepatocellular carcinoma

The pharmacokinetics of 1-(tetrahydro-2-furanyl)-5-fluorouracil (FT) and its conversion into 5-fluorouracil (FUra) in liver tissue were studied in ten patients with hepatocellular carcinoma (HCC). The plasma concentration of FT after its intravenous injection (dosage: 800 mg) was computerfitted to a bi-exponential function (C = Ae-alpha t + Be-beta t), indicating a two-compartment disposition. The pharmacokinetic parameters did not significantly differ between the five patients with, and the five without cirrhosis of the liver. The plasma concentrations of FUra likewise showed no significant difference between the two groups. The rates of FT degradation in the liver tissue homogenate were similar for four of the patients with cirrhosis (0.10 +/- 0.05 mumol/g liver protein/30 min) and four of those without it (0.13 +/- 0.05). The rates of cytochrome P-450-dependent FUra formation in the microsomal fraction of liver tissue from two patients (1.1 and 1.3 nmol/mg microsomal protein/30 min) were dramatically reduced to less than half of those of two control subjects (2.4 and 2.7). The estimated rates of FUra formation in the soluble fraction (105,000 X g supernatant fraction) from the two patients (0.1 and 0.13 nmol/mg protein/30 min) were almost identical to those from the controls (0.12 and 0.14), suggesting that the rate in the soluble fraction from HCC patients may not be as strongly affected as the rate in the microsomal fraction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Recovery functions of somatosensory vertex potentials in man: interaction of evoked responses from right and left fingers.

Somatosensory vertex potentials (SVPs) were examined in 12 healthy subjects in response to painful electrical stimulation of the finger. SVPs consisted of N1, P1, and N2. The average latencies of the 3 peaks were 150, 225, and 350 msec, respectively. The latency and amplitude of each potential were reproducible for each subject. Recovery functions of the SVPs were analyzed in 10 subjects. A pair of stimuli were delivered to the right or left finger with interstimulus intervals (ISIs) of 50, 100, 150, 200, 350, 500 and 650 msec. SVPs partially recovered with the shortest ISI (50 msec). Full recovery could not be obtained even with the longest ISI (650 msec). Differences in recoveries within 650 msec of ISI were not observed between right and left stimulations. To examine the interaction between SVPs evoked by right and left finger stimulation, recovery functions from prior contralateral finger stimulation were analyzed with the same ISIs. SVP recoveries for right after left or left after right patterns of stimulus delivery were nearly the same as those for ipsilateral ones. It is suggested that SVPs are generated at nearly the same site in the sensory pathway regardless of the side stimulated.     

Comparative study of the bacterial flora in both uterocervical and uterine regions

The relationship between indigenous bacterial floras in the lower genitals and the uterocervical region is of importance due to a barrier-like role against ascending infections through the mechanism of the localized protection at a boundary of the uterocervical region. Therefore, bacterial flora in the uterocervical and uterine regions was studied in cases for which gynecological operations were performed (n = 77). 1. Ratios of incidences of the detection of bacteria on the uterocervical and in the uterine regions were 50/77 (64.9%) and 6/77 (7.8%), respectively. When different age groups are compared, the detection ratio from the uterocervical region was high among patients in the 40 s, and all the cases in which bacteria were detected from the uterine region were in the 40 s. 2. Gram-positive bacteria were detected at a high ratio, and anaerobic bacteria were noted in the uterocervical region, and ratios of detection of Staphylococcus epidermidis, Lactobacillus sp. and Propionibacterium acnes were high. Six strains of Gram-positive bacteria and 1 strain of Candida sp. were noted in the uterine region. 3. When cefmetazole (CMZ) was administered for the prevention of the infections after these panhysterectomy cases examined here, no postoperative infectious diseases nor adverse reactions were noted.     

Resected cases of middle lobe primary cancer

Of 200 lung cancer lesions resected in our hospital, there were 15 cases (7.5%) with middle lobe origin. The histological types were adenocarcinoma in 13 patients (4 patients with alveolar cell carcinoma), squamous cell carcinoma in one and large cell carcinoma in one. These patients were classified into two groups according to the type of operation they received and each group was evaluated. Group I (resection of the middle lobe) included 8 patients. Each one of Stage IIIB and Stage IV received the operation to improve their symptoms. The six patients of Stage I received only middle lobectomy as absolute curable cases. Group II (resection of the middle and lower lobes) included 7 patients, who had preoperative diagnosis of stage III. Two of them were postoperatively found to be cases of Stage I and Stage II. Although it was still short-term, the follow-up evaluation proved that these patients survived without local recurrence and distant metastasis, except for two with pleural dissemination and one with cerebral metastasis, who had received lobectomy as palliative operation. No difference was observed between the two groups receiving different types of operation.     

The kapurimycins, new antitumor antibiotics produced by Streptomyces. Physico-chemical properties and structure determination

The kapurimycins A1, A2 and A3 were revealed to be new antitumor antibiotics with molecular formula of C27H26O9, C26H24O9 and C27H24O9, respectively. The structures of the kapurimycins were determined by NMR spectroscopic analysis. The kapurimycins are new class of polycyclic microbial metabolites having the tetrahydroanthra-gamma-pyrone skeleton and the beta, gamma-unsaturated delta-keto carboxylic acid structure. The individual components of the kapurimycins differ from one another in the side chain at the pyrone ring of the molecule.     

Multiple neurinoma of the spinal cord: case report

The patient, a 72-year-old female, was admitted with an 11-year history of progressive dysesthesia in the left leg. Neurological findings on admission revealed weakness in the bilateral legs, hyperreflexia of left leg, hypalgesia and hypesthesia under the Th 8 level, and urinary incontinence. Plain lumber X-ray showed enlargement of the intervertebral foramen of L 1/2. Myelography disclosed block age at the level of Th 9 and filling defect at the level of Th 10/11 and L1/2. CT myelography revealed a cord swelling and partially exophytic tumor from Th 8 to Th 9, another tumor located posterior-laterally at the level of Th 11, and another tumor located extra and intradural at the level of L1/2. Laminectomy was performed from Th 8 to L 3. A tumor of the Th 9 was located intramedullary, another tumor of the Th 11 was located intradural extramedullary, and another tumor of the L1/2 was located in the epidural space (so-called dumb-bell type tumor). These tumors were removed completely except the extra-canal part of L1/2 tumor. Histopathological examination revealed typical Antoni type A schwannoma in all tumors. This case was considered multiple neurinomas of the spine in which tumors were located in three separate anatomical sites, intramedullary, intradural extramedullary, and epidural sites. This patient did not show café-au-lait spot, and neurofibroma in her body. The authors considered the patient might be a case of central neurofibromatosis. The authors stressed that multiple neurinomas of the spine is not rare, so careful study of the whole spine is necessary including its intramedullar space.     

Effect of repeated transcatheter arterial embolization on the survival time in patients with hepatocellular carcinoma. An analysis by the Cox proportional hazard model.

One hundred fifty-eight patients with hepatocellular carcinoma (HCC) were treated by transcatheter arterial embolization (TAE) as repeatedly as possible. Survival rates at the end of the first, second, and third year were 76.5%, 54.5%, and 41.1%, respectively. In 142 patients with repeated TAE, a significantly increased number of patients with complete necrosis of tumor was observed after repetition of the therapy. Adjusting the imbalance in prognostic factors among patients by using Cox proportional hazard model, it proved that the best response during the repeated therapy, rather than the first response, was significantly associated with survival period of the patients. Aside from the factor of response to the treatment, tumor size was the worst prognostic factor at the time when diagnosis was made. Other significant factors were portal vein invasion by HCC and bilirubin. The survival period of patients with HCC treated by repeated TAE was, therefore, affected by cancer factors, liver cirrhosis factors, and therapy-responsiveness factors. It is concluded that even if complete necrosis of tumor is not obtained after the first trial, repetition of TAE is an effective measure for prolonging of survival time in patients with HCC.     

Gene polymorphism of myospryn (cardiomyopathy-associated 5) is associated with left ventricular wall thickness in patients with hypertension.

We examined a gene polymorphism of a novel Z-disc-related protein, myospryn (cardiomyopathy-associated 5). We focused on one haplotype block associated with a tag single nucleotide polymorphism (SNP) that covered 16 of 27 coding SNPs with linkage disequilibrium (minor allele frequency 0.413). Screening a myospryn polymorphism (K2906N) in a general health check-up of a rural Japanese population revealed an association with cardiac diseases (p=0.0082). In further analysis of the interaction between K2906N and cardiac function in patients, K2906N was associated with the anteroseptal wall thickness of the left ventricle in a recessive model (p=0.0324) and with the ratio of the peak velocity of the early diastolic filling wave to the peak velocity of atrial filling (A/E) (p=0.0278). In an association study based on left ventricular wall thickness, we found a significant difference in the K2906N genotype between controls and patients with cardiac hypertrophy. These results suggest that the K2906N polymorphism could be clinically associated with left ventricular hypertrophy and diastolic dysfunction independent of known parameters. Although the precise mechanism underlying this association remains to be elucidated, treatment with angiotensin II induced an increase in heart myospryn mRNA level in vitro and in vivo. Our results suggest that the polymorphism of myospryn is associated with left ventricular hypertrophy, and an association between a Z-disc protein and cardiac adaptation in response to pressure overload.