Simple and rapid analysis of endocrine disruptors in liquid medicines and intravenous injection solutions by automated in-tube solid-phase microextraction/high performance liquid chromatography

A simple and rapid method was developed for analyzing contamination of endocrine disruptors in liquid medicines and intravenous injection solutions. Endocrine disrupting compounds such as bisphenol A (BPA), alkylphenols and phthalates were quantitated by on-line in-tube solid-phase microextraction coupled with high performance liquid chromatography (in-tube SPME/HPLC) with UV detection. The liquid medicines and intravenous injection solutions could be used directly without any pretreatment, and the BPA, alkylphenols and phthalates in these solutions were automatically analyzed. The limits of quantification for these compounds were 1-10 ng/ml. Recoveries of these compounds spiked to the intravenous injection solutions was over 80%, except for some phthalates. Di-n-butyl phthalate (DBP) was detected at a concentration of 7-60 ng/ml in most intravenous injection solutions in plastic containers, but it was not detected in solutions in glass bottles. Diethyl phthalate, di-n-propyl phthalate, DBP and di-2-ethylhexyl phthalate (DEHP) were also detected in syrup, lotion and eye drops in plastic containers. On the other hand, BPA and alkylphenols were not detected at all in these solutions. DEHP contamination from an administration set increased when total vitamin formulation was added to the infusion solution. DEHP was easily leached from polyvinyl chloride tubing by polysorbate 80. The in-tube SPME/HPLC method is simple, rapid and automatic, and it provides a useful tool for the screening and determination of endocrine disruptor contamination in liquid medicines and intravenous injection solutions.     

Suppressive effect of taurine on platelet-derived growth factor (PDGF) BB-induced c-fos and c-jun mRNA expressions through extracellular signal-regulated kinase (ERK) in mesenchymal cell lines

Platelet-derived growth factor (PDGF) plays an important role in the pathogenic course of atherosclerosis, pulmonary fibrosis, and glomerulonephritis, and increased activity of the PDGF signaling pathway has been implicated as a contributing factor in the progression of the diseases. Taurine may be a prophylactic amino acid for atherosclerosis not only by decreasing plasma cholesterol level, but also by inhibiting the cell proliferation-signaling pathway. To elucidate how taurine affects the signaling pathway, we investigated the effect of taurine on the expression of immediate-early genes and activation of mitogen-activated protein kinases (MAPKs) in NIH/3T3 cells as standard mesenchymal cells. Taurine inhibited PDGF-BB-induced c-fos and c-jun mRNA expressions dose-dependently, although structural analogues of taurine did not. Taurine decreased the PDGF-induced p44/p42 ERK (extracellular signal-regulated kinase) phosphorylation state dose-dependently, although no phosphorylation was observed on JNK/SAPK (c-Jun N-terminal kinase/stress-activated protein kinase) and p38 MAPK. Further, PDGF-BB-induced tyrosine phosphorylation of the PDGF-beta receptor was not influenced by treatment with taurine, indicating that taurine never affects ligand-receptor interaction, and may act downstream of the PDGF receptor. Thus, the inhibitory mechanism of taurine on PDGF-induced c-fos and c-jun mRNA expressions may depend on the p44/p42 ERK pathway, but not on PDGF-beta receptor tyrosine phosphorylation, JNK/SAPK or p38 MAPK pathway. These results suggest that taurine may suppress the cell proliferation-signaling pathway through the inhibition of ERK activity and immediate-early gene expression.     

Doxorubicin cardiotoxicity: Prevention of congestive heart failure with serial cardiac function monitoring with equilibrium radionuclide angiocardiography in the current era

BACKGROUND: Congestive heart failure (CHF) is among the most serious toxicities of doxorubicin, a potent cancer chemotherapeutic agent. Serial left ventricular ejection fraction (LVEF) monitoring during doxorubicin therapy for preventing CHF was proposed over 20 years ago. The current utility and cost-effectiveness of this approach in the present era are not known. METHODS AND RESULTS: Clinical and follow-up data of 265 patients with cancer (age, 53 +/- 14 years; 76% women) undergoing doxorubicin chemotherapy with serial equilibrium radionuclide angiocardiography (ERNA) monitoring (> or =2 studies) were analyzed retrospectively. Patients with a normal baseline LVEF (> or =50%) and a 10% or greater point fall in LVEF to a final value of less than 50% during doxorubicin therapy were considered "at risk" for CHF (n = 41). Over 679 +/- 426 days of follow-up, 7 patients (2.6%) had CHF develop and 90 (34%) died (all cancer-related deaths, with none due to CHF). A comparison of "at-risk" (n = 41 [15%]) and "low-risk" (n = 224 [85%]) groups showed a higher incidence of CHF (12% vs 0.9%, P <.0001), lower baseline LVEF (58% +/- 8% vs 64% +/- 8%, P <.0001), lower value for the lowest LVEF (42% +/- 8% vs 57% +/- 7%, P <.0001), and higher rate of cancer-related deaths (59% vs 29%, P =.0003) in the former despite similar cumulative doxorubicin dose (304 +/- 124 mg/m(2) vs 284 +/- 110 mg/m(2), P = not significant). There were no differences in age, gender, cancer type, and co-morbidity. Cost analysis showed the overall cost of ERNA studies to be lower than the 1-year cost of caring for additional cases of CHF that would potentially be prevented by routine LVEF monitoring. CONCLUSIONS: An incipient fall in LVEF detected on serial ERNA during doxorubicin therapy provides an appropriate and cost-effective approach for predicting and preventing impending CHF. Use of this approach was associated with a low incidence of CHF (2.6%) and no CHF-related mortality in this study.     

Expression of multidrug resistance protein 4 and 5 in the porcine coronary and pulmonary arteries

Guanosine 3',5'-cyclic monophosphate (cGMP) has an important role in regulating vascular smooth muscle tone. We examined whether mRNA for multidrug resistance protein (MRP) 4 and MRP5, which were recently identified as ATP-dependent export pumps for cyclic nucleotides, is expressed in the porcine coronary and pulmonary arteries. The results showed that both arteries express mRNA for MRP4 and MRP5, and thus these proteins may be novel targets for the prevention and/or treatment of various cardiovascular diseases.     

A clinical study of 104 patients with tongue cancer and the relationship between DNA ploidy and prognosis in 41 cases

One-hundred and four patients with previously untreated tongue cancer seen in our department between 1986 and 1998 were enrolled in a clinical study. The DNA ploidy patterns observed in fresh frozen specimens obtained from 41 patients were analyzed, and prognostic factors were investigated. According to the TNM classification (UICC 1997), 43 patients had stage I tumors, 29 had stage II tumors, 17 had stage III tumors, and 15 had stage IV tumors. The 5-year cause-specific survival rates for each stage were 94.7%, 64.4%, 50.0% and 45.7%, respectively. The most frequent cause of death associated with the original disease was the recurrence of the disease in cervical lymph nodes (19/27, 70.4%). The occurrence of late cervical metastasis was high among patients with a T2N0 disease. Patients with stage II disease should undergo elective neck dissection or be carefully monitored using ultrasonography. Among the 41 cases in which the DNA ploidy pattern was analyzed, diploid patterns were found in 30 cases and aneuploid patterns were found in 11. The 5-year cause-specific survival rate and the 5-year locoregional control rate were significantly lower for the aneuploid cases (18.2%, 38.9%) than for the diploid cases (66.5%, 69.8%) (p = 0.0003, p = 0.0339). The incidence of distant metastasis was significantly higher among the aneuploid cases (6/11, 54.5%) than among the diploid cases (3/30, 10.0%) (p = 0.0058). The ploidy pattern, as determined by flow cytometric DNA analysis, may reflect the malignancy grade of tongue cancers.     

Ulnar bursa distention following volar subluxation of the distal radioulnar joint after distal radial fracture: a rare cause of carpal tunnel syndrome

This report describes an eighty-four-year-old woman with persistent carpal tunnel syndrome attributable to an ulnar bursa distention associated with the subluxation of the distal radioulnar joint after distal radial fracture. During surgery, when the forearm was placed in supination, the ulna head with a sharp osteophyte was found to be displaced into the carpal tunnel through a defect of the ruptured capsule of the wrist joint. This volar subluxation of the ulnar head had caused distention of the ulnar bursa, causing compression of the median nerve, which resulted in carpal tunnel syndrome. In addition to reduce displaced fractured segment to obtain anatomic articular surface, original radial length and tilt, the anatomic restoration of the distal radioulnar joint is essential to maintain better long-term function after fracture of the distal radius.     

Argyrophilic grain disease mimicking temporal Pick's disease: a clinical, radiological, and pathological study of an autopsy case with a clinical course of 15 years

This report concerns an autopsy case of argyrophilic grain disease (AGD) mimicking temporal Pick's disease. The patient was a Japanese woman without hereditary burden who was 89 years old at the time of death. She developed memory impairment and began wandering at the age of 74, followed by prominent character changes about 6 years after disease onset. A neurological examination 5 months before her death revealed poor rapport, unconcern, severe dementia, and double incontinence, without aphasia or muscle rigidity. Serial neuroradiological examination revealed progressive enlargement of the bilateral inferior horns of the lateral ventricle, reflecting progressive atrophy of the medial temporal lobes. Macroscopically, neuropathological examination showed circumscribed atrophy of the bilateral amygdalae, hippocampi, parahippocampal gyri, and lateral occipitotemporal gyri. Histologically, there was neuronal loss in the areas mentioned above, the caudate nucleus, putamen, thalamus, substantia nigra, and locus ceruleus, with ballooned neurons in the cerebral cortex and amygdala. Numerous argyrophilic grains with coiled bodies were present not only in the limbic system, but also in the affected cerebrum. Rare neurofibrillary changes were present in the limbic areas, consistent with Braak stage II, with no senile plaques. Based on these findings and a review of the literature, we note that AGD is clinicopathologically similar not only to mesolimbocortical dementia, but also to atypical senile dementia of Alzheimer type. This report may contribute to the elucidation of the clinicopathological hallmarks of AGD.     

Mastoid pneumatization of the patulous eustachian tube

The pathophysiology of the patulous eustachian tube (PET) remains unclear. The degree of mastoid cell pneumatization is considered an indicator of chronic inflammation of the middle ear. We used the mastoid cell area to investigate the relationship between past chronic inflammation of the middle ear cavity and a PET in 84 patients (20 to 83 years old). The mastoid cell size was calculated from radiographs and analyzed relative to the history of otitis media (OM). The controls were 100 normal ears. The patients' mastoid cell size was significantly suppressed versus that of the controls, in both 31 PET cases with and 53 PET cases without past OM. We surmise the possibility that the PET ears had experienced inflammation even when the patients had no history of OM and the tympanic membrane showed no OM sequelae. This study indicates the existence of some relationship between a history of chronic inflammation of the middle ear cavity and a PET.     

Treatment strategy for cervical node metastasis from squamous cell carcinoma of the oropharynx

The purpose of this study is to ascertain the role of neck surgery and radiation therapy for cervical lymph node metastasis in oropharyngeal cancer patients. We reviewed 217 previously untreated patients with squamous cell carcinoma of the oropharynx who were treated at the Cancer Institute Hospital in Tokyo between 1971 and 1995. The N stage distribution was; N0: 83(38.2%), N1: 42(19.4%), N2a: 23(10.6%), N2b: 27(12.4%), N2c: 33(15.2%), and N3: 9(4.2%). A predominance of cervical node metastases in level II and III was revealed and there were no skip metastases outside of level II and III. The control rate of cervical metastasis for each N stage was; N0: 96.9%, N1: 90.0%, N2a: 76.5%, N2b: 62.5%, N2c: 50.0%, and N3: 0%. Definitive irradiation provided sufficient treatment for small nodes, when the primary tumor growth was well controlled by radiation therapy. Neck dissection was necessary for more advanced neck metastases. Selective limited neck dissection (level II and III) is recommended for N0 and N1 patients, and modified or classical RND is considered to be better for most cases with N2 and N3.