A case report--a patient with gingiva carcinoma showing complete remission after combination chemotherapy with nedaplatin and 5-fluorouracil

We report a patient showing a complete remission after combination chemotherapy with nedaplatin and 5-fluorouracil (5-FU). A 63-year-old man was admitted to our hospital for advanced carcinoma of gingiva. 5-FU was administered at a dose of 1,000 mg/body (700 mg/m2) by continuous infusion for 120 hours on days 1 to 5. Nedaplatin was administered at a dose of 140 mg/body (90 mg/m2) by drip infusion for 120 minutes on day 5. This combination chemotherapy resulted in a complete remission of the tumor after 2 weeks. There has been no sign of recurrence for 6 months after the chemotherapy.     

Functional analysis of single nucleotide polymorphisms of hepatic organic anion transporter OATP1B1 (OATP-C)

OBJECTIVE: Two kinds of single nucleotide polymorphism (SNP; Asn130Asp and Val174Ala) are frequently observed in the liver specific transporter, organic anion transporting polypeptide 1B1 (OATP1B1/OATP-C) gene. Although these two SNPs occur independently in European-Americans, Val174Ala is mostly associated with Asn130Asp in Japanese. Our previous in-vivo studies in Japanese subjects indicated that the non-renal clearance of pravastatin was decreased to 13% of that in wild-type subjects (Nishizato et al. Clin Pharmacol Ther 2003;73(6):554-564). The purpose of the present study is to characterize the function of SNPs variants of OATP1B1 in cDNA transfected cells. METHODS: The localization and transport activity were analyzed in HEK293 cells stably expressing wild-type OATP1B1 (OATP1B1*1a), OATP1B1*1b (Asn130Asp), OATP1B1*5 (Val174Ala) and OATP1B1*15 (Asn130Asp and Val174Ala). To characterize the intrinsic Vmax, observed Vmax in uptake study were normalized by the expression level estimated from Western blotting. RESULTS: All SNP variants are predominantly located on the cell surface. No significant alteration was observed in Km values for the transport of 17beta-estradiol 17beta-d-glucuronide (E217betaG), a typical substrate of OATP1B1, among these SNP variants. However, the normalized Vmax value for OATP1B1*15 was drastically decreased to less than 30% compared with OATP1B1*1a. In contrast, the transport activity of OATP1B1*1b (Asn130Asp) and OATP1B1*5 (Val 174Ala) was similar to that of OATP1B1*1a. CONCLUSIONS: These results are consistent with the results of our previous clinical studies. It is thus suggested that in-vivo disposition may be predicted from in-vitro results using recombinant transporters.     

Increased excess deaths in urban areas: quantification of geographical variation in mortality in Japan, 1973-1998

To quantify the magnitude of geographical health inequality by sex and age group, and to observe the change in regional distribution of health disadvantage, this study estimated excess deaths attributable to the mortality variation among municipalities across Japan from 1973 through 1998. The municipalities (N = 3340 in 1995) were divided into quintiles according to standardized mortality ratio (SMR). Using the mortality of the lowest SMR quintile as the standard, the number of excess deaths (ED) and its ratio to observed deaths (EDR) were estimated by sex, age group (total population and under 65-year population) and regional block in 1973-1977, 1978-1982, 1983-1987, 1988-1992 and 1993-1998. Total annual ED in 1993-1998 was estimated as 47,124 for males and 46,562 for females, representing EDR of 9.9 and 11.6%, respectively. The under 65-year population had a higher EDR than the total population. Rural regions showed a marked decrease in EDR in contrast to the increase in urban regions over time. The present study suggests that the reduction of a large number of deaths, especially premature deaths, is expected by elimination of geographical health inequality, and that health policies for urban residents are prioritized.     

Inhibitory effects of prior low-dose X-ray irradiation on carbon tetrachloride-induced hepatopathy in acatalasemic mice

The catalase activities in blood and organs of the acatalasemic (C3H/AnLCs(b)Cs(b)) mouse of C3H strain are lower than those of the normal (C3H/AnLCs (a)Cs(a)) mouse. We examined the effects of prior low-dose (0.5 Gy) X-ray irradiation, which reduced the oxidative damage under carbon tetrachloride-induced hepatopathy in the acatalasemic or normal mice. The acatalasemic mice showed a significantly lower catalase activity and a significantly higher glutathione peroxidase activity compared with those in the normal mice. Moreover, low-dose irradiation increased the catalase activity in the acatalasemic mouse liver to a level similar to that of the normal mouse liver. Pathological examinations and analyses of blood glutamic oxaloacetic and glutamic pyruvic transaminase activity and lipid peroxide levels showed that carbon tetrachloride induced hepatopathy was inhibited by low-dose irradiation. These findings may indicate that the free radical reaction induced by the lack of catalase and the administration of carbon tetrachloride is more properly neutralized by high glutathione peroxidase activity and low-dose irradiation in the acatalasemic mouse liver.     

A combination of serum low albumin and above-average cholesterol level was associated with excess mortality

BACKGROUND: There is no population-based prospective study concerning the relation between serum albumin and mortality in a non-Western population, and few previous studies included the subgroup analysis stratified by serum cholesterol level. METHODS: A 13.7-year cohort study was conducted on 6,957 males and females aged 30-59 years from 300 randomly selected areas throughout Japan, who participated in the National Survey on Circulatory Disorders in 1980. RESULTS: In the group with median and above of total cholesterol, one standard deviation (SD) increment of serum albumin (2.6 g/L for males and 2.4 g/L for females) was inversely associated with all-cause mortality for both males and females (relative risk RR = 0.68 and 0.81: 95% confidence interval CI = 0.53-0.87 and 0.68-0.98), and with cancer mortality for females (RR = 0.74; 95% Cl = 0.57-0.96);and the lowest category of serum albumin (< or = 43 g/L) showed the highest cardiovascular mortality for males (RR = 5.04; 95% CI = 1.04-24.5) among the three albumin categories. These relationships were not evident in the group with total cholesterol level below median. CONCLUSION: A combination of a low albumin level and above average cholesterol level, even both within the clinical normal range,is associated with excess mortality in the Japanese general population.     

Volumetric localization of somatosensory cortex in children using synthetic aperture magnetometry

BACKGROUND: Magnetic signal from the human brain can be measured noninvasively by using magnetoencephalography (MEG). OBJECTIVE: This study was designed to localize and reconstruct the neuromagnetic activity in the somatosensory cortex in children. MATERIALS AND METHODS: Twenty children were studied using a 151-channel MEG system with electrical stimulation applied to median nerves. Data were analyzed using synthetic aperture magnetometry (SAM). RESULTS: A clear deflection (M1) was clearly identified in 18 children (90%, 18/20). Two frequency bands, 30-60 Hz and 60-120 Hz, were found to be related to somatosensory cortex. Magnetic activity was localized in the posterior bank of the central sulcus in 16 children. The extent of the reconstructed neuromagnetic activity of the left hemisphere was significantly larger than that of the right hemisphere ( P<0.01). CONCLUSION: Somatosensory cortex was accurately localized by using SAM. The extent of the reconstructed neuromagnetic activity suggested that the left hemisphere was the dominant side in the somatosensory system in children. We postulate that the volumetric characteristics of the reconstructed neuromagnetic activity are able to indicate the functionality of the brain.     

Basal metabolic rate in hyperemesis gravidarum: comparison to normal pregnancy and response to treatment

OBJECTIVE: The aim of the study was to measure resting minute ventilation and oxygen consumption in patients with hyperemesis gravidarum before and after treatment and to compare the results with those of normal pregnant women. STUDY DESIGN: Baseline evaluation was performed with the use of an open-circuit ventilatory system in 17 hospitalized patients with hyperemesis gravidarum and was repeated 1 week after treatment. Thirty-seven normal pregnant women served as control subjects. RESULTS: Resting minute ventilation and oxygen consumption were decreased by 20% and 15% (P <.001), respectively, in patients with hyperemesis compared with control subjects. The decrease occurred despite a measurable increase of free thyroxine compared with normal pregnancy. Treatment resulted in a 10% increase in oxygen consumption in those patients with increased thyroid stimulation, but not otherwise. CONCLUSION: Resting oxygen consumption is reduced significantly in patients with hyperemesis gravidarum that is consistent with a state of partial starvation rather than increased in parallel with increases of thyroid axis activity.     

Association analysis of an (AC)n repeat polymorphism in the GABA(B) receptor gene and schizophrenia

The human gamma-aminobutyric acid type B (GABA(B)) receptor gene is a candidate gene for schizophrenia due to its chromosomal location and neurobiologic roles. In the present study, association analyses of genetic polymorphisms of the GABA(B) receptor gene with schizophrenia were carried out in 102 unrelated schizophrenic patients and 100 healthy controls, using a polymerase chain reaction-based, single-strand conformational polymorphism analysis. Although the Ala20Val and Gly489Ser mutations were not found in our samples, we found a novel polymorphism of (AC)n dinucleotide repeats located approximately 1.6 kb upstream from the translational start site. No significant difference in allele frequencies was found between controls and patients with schizophrenia (P = 0.0587) using the Monte Carlo method. Significant differences were found between controls and patients with continuous-course schizophrenia (P = 0.0019), and between controls and patients with a positive family history of psychoses (P = 0.0015). These differences, however, were not significant after Bonferroni correction. These data did not support our hypothesis that polymorphisms of the GABA(B) receptor gene may confer vulnerability for schizophrenia.     

Trigeminal neuralgia: evaluation of neuralgic manifestation and site of neurovascular compression with 3D CISS MR imaging and MR angiography

PURPOSE: To evaluate three-dimensional (3D) constructive interference in steady-state (CISS) magnetic resonance (MR) imaging and MR angiography with multiplanar reconstruction (MPR) for detection of neurovascular compression (NVC) in patients with trigeminal neuralgia and to evaluate the relationship between clinical symptoms related to trigeminal branches and those related to the site of trigeminal nerve compression. MATERIALS AND METHODS: Fifty-four consecutive patients with trigeminal neuralgia were examined at 3D CISS imaging and MR angiography with a 1.5-T MR system. Original transverse and four reformatted images were used for image interpretation. Vascular contact with the trigeminal nerve at the root entry zone (REZ) was determined, and the nature of the involved vessels was identified. The position of the blood vessel compressing the nerve was classified into cranial, caudal, medial, or lateral sites. Statistical analysis was performed with the chi2 test or the Fisher exact test between two groups and with the chi2 test among more than two groups. RESULTS: In 12 of 15 patients who underwent surgery, the artery that was considered a responsible vessel at 3D CISS imaging and MR angiography was confirmed as such. In the other three patients, the vein was the responsible vessel, which was detected only at 3D CISS imaging. Sixteen (89%) of 18 patients with symptoms related to the maxillary division had NVC at the medial site of the REZ, while 16 (76%) of 21 patients with symptoms related to the mandibular division had NVC at the lateral site (P <.001, chi2 test). CONCLUSION: 3D CISS MR imaging with MPR is useful in the detection of NVC in patients with trigeminal neuralgia, compared with MR angiography. A close relationship was found between the region of neuralgic manifestation and the site of trigeminal nerve compression.