Paclitaxel, ifosfamide, nedaplatin (TIN) for patients with metastatic urothelial cancer

TIN (ifosfamide 1.5 g/m2 daily for 3 days, paclitaxel 175 mg/m2, and nedaplatin 70 mg/m2 on day 1) was administered to patients with metastatic urothelial cancer previously treated by platinum-based chemotherapy and repeated every 4 weeks. Four patients received maintenance therapy, which consisted of 5'-DFUR 800 mg/day orally for 12 weeks and 1 subsequent course of TIN. This therapy regimen was repeated for 2 years from initiation of TIN. Eleven of 12 patients (91.6%) demonstrated a major response (3 complete responses, 8 partial responses), with durations of response ranging from 3 to 20 months. Progression-free survival time was from 0 to 20 months (median 8 months). One-year progression-free survival rate was 45.8%. Overall survival time was from 2 to 20 months (median 10.5 months). One-year overall survival rate was 53.5%. Grade 3/4 hematologic toxicity involved neutropenia in 100% and thrombocytopenia in 33.3%. Febrile neutropenia was observed in 5 patients (41.6%). Grade 3 nonhematologic toxicity involved malaise in 15.3%. No patient discontinued this therapy because of complications. TIN is a potent, well-tolerated regimen for previously treated patients with urothelial cancer.     

Duration of untreated psychosis and pathways to psychiatric services in first-episode schizophrenia

The aim of the present study was to examine the duration of untreated psychosis (DUP) in first-episode schizophrenia patients in Japan and to investigate the available pathways to psychiatric services. Eighty-three patients who visited Keio University Hospital (n = 54) or Oizumi Mental Hospital (n = 29) were evaluated retrospectively with regard to their DUP, living situation, social participation level, referral pathway, reason for seeking treatment, and their global assessment of functioning (GAF) score. The mean DUP was 13.7 months (median, 5.0 months) overall. No significant difference in DUP was found between subjects living alone and those living with others; however, employed patients had a significantly shorter DUP (8.1 months) than unemployed patients (18.7 months). Pathways to psychiatric services were totally different between the two institutions. Fifty-two subjects (62.7%) came to the services directly: 40 patients (74.1%) came to the university hospital and 12 patients (41.4%) came to the mental hospital. At the mental hospital, nine patients (31.0%) had been admitted because of a legal obligation, and six (20.7%) had been referred through public health centers. None of the patients had been referred to either of the services by general practitioners. The main reason for seeking treatment was psychiatric symptom aggravation (59.3%) at the university hospital and acting out (64.3%) at the mental hospital. Some universal psychosocial factors appear to influence the DUP but the characteristics of specific psychiatric services may also affect treatment delays.     

Pulmonary nodules at chest CT: effect of computer-aided diagnosis on radiologists' detection performance

PURPOSE: To evaluate the effect of computer-aided diagnosis (CAD) on radiologists' detection of pulmonary nodules. MATERIALS AND METHODS: Fifty chest computed tomographic (CT) examination cases were used. The mean nodule size was 0.81 cm +/- 0.60 (SD) (range, 0.3-2.9 cm). Alternative free-response receiver operating characteristic (ROC) analysis with a continuous rating scale was used to compare the observers' performance in detecting nodules with and without use of CAD. Five board-certified radiologists and five radiology residents participated in an observer performance study. First they were asked to rate the probability of nodule presence without using CAD; then they were asked to rate the probability of nodule presence by using CAD. RESULTS: For all radiologists, the mean areas under the best-fit alternative free-response ROC curves (Az) without and with CAD were 0.64 +/- 0.08 and 0.67 +/- 0.09, respectively, indicating a significant difference (P <.01). For the five board-certified radiologists, the mean Az values without and with CAD were 0.63 +/- 0.08 and 0.66 +/- 0.09, respectively, indicating a significant difference (P <.01). For the five resident radiologists, the mean Az values without and with CAD were 0.66 +/- 0.04 and 0.68 +/- 0.04, respectively, indicating a significant difference (P =.02). At observer performance analyses, there were no significant differences in Az values obtained either without (P =.61) or with (P =.88) CAD between the board-certified radiologists and the residents. For all radiologists, in the detection of pulmonary nodules 1.0 cm in diameter or smaller, the mean Az values without and with CAD were 0.60 +/- 0.11 and 0.64 +/- 0.11, respectively, indicating a significant difference (P <.01). CONCLUSION: Use of the CAD system improved the board-certified radiologists' and residents' detection of pulmonary nodules at chest CT.     

Distribution and disposition of benzalkonium chloride following various routes of administration in rats

Benzalkonium chloride (BZK) is a cationic surfactant used widely as a disinfectant, preservative and sanitizer in hospitals, at home and many public places. The toxicity of BZK is not well established although several human fatalities have been reported over the years. In this study, distribution and disposition of BZK following oral administration (PO) and intravascular (jugular vein (JV), femoral artery (FA), femoral vein (FV) and jugular artery (JA)) administration in rats were investigated along with pathological examinations. Toxic doses of 250 and 15 mg/kg of BZK were used for PO and intravascular administration, respectively. The fatal effects of BZK appeared soon in JV-, FV- or JA-rats, but took hours in PO or FA-rats. No rat receiving BZK via FA survived longer than 1 day. The PO-rats that aspirated BZK into their lungs had some systemic symptoms and higher blood and tissue concentrations of BZK. The blood BZK levels and kinetics were similar among the different routes of intravascular administration, but the lung and kidney levels were higher in JV-rats. Pathological examinations confirmed severe congestion and edema in the lungs and kidneys. These results suggest that (1) the toxic effects of BZK varied depending on the route of administration, (2) the degree of toxicity correlated with peak blood and tissue concentrations in orally dosed rats, (3) different toxicological progressions and manifestations were observed in FA- and JV-dosed rats even though these groups had similar blood concentration profiles, and (4) lung and kidney are reservoirs for BZK and considered to be the target organs of BZK.     

Design and its application of the f(n)-zeta chart capable of direct readout of the highest frequency indicating the limit of obtaining distortion-free waveforms

We have already reported that the highest frequency (f(h)) could serve as an index for evaluating the fidelity of pressure waveform derived via a catheter manometer system and be read off by the f(n)-zeta chart. Fh is determined by the natural frequency (f(n)) and damping coefficient ( zeta ) in the frequency characteristics of the system. Inversely, f(h) determines two pairs of f(n) and zeta in the f(n)-zeta chart, one in the case of zeta < 0.7 and the another zeta > 0.7. Then, each pair of f(n) and zeta determines respectively the resonant frequency (f(r)) and its amplitude (Ar) ( zeta < 0.7), or the corner frequency (f(c)) and its amplitude (Ac) ( zeta > 0.7) in the frequency characteristics. Thus, the point (f(r), Ar) or (f(c), Ac) represents the position of f(h) projected in the frequency characteristics. Repeating the same operation for other f(n) and zeta corresponding to the same f(h), yields the curve of f(h) in the frequency characteristics. Calculations for other f(h)'s provide a group of curves. Frequency characteristics of pulmonary artery catheters were measured and overwritten thereupon, resulting in f(h)'s to be from 1.2 to 3.2 Hz. These results were in agreement with that calculated by the conventional method.     

Airway management during the laryngoscopic surgery for the benign laryngeal obstructive disease

The airway management and anesthesia maintenance during the laryngoscopic surgery is essential for a safe operation. For the benign laryngeal obstructive disease such as a large mass or a foreign body of the upper airway, it is difficult to secure the airway. Sometimes they might be hazardous and potentially lethal. We present two cases of a large laryngeal polyp and a laryngeal foreign body of pressthrough-package (PTP). They were successfully operated on with laryngomicrosurgery under neuroleptanalgesia (NLA) without intubation. The choice of the operation and airway management were discussed.     

Effects of a novel anti-hyperlipidemic agent, S-2E, on blood lipid levels in rats with fructose-induced hypertriglyceridemia

Using rats with fructose-induced hypertriglyceridemia, an animal model of human hypertriglyceridemia, we investigated whether (+)-(S)-p-[1-(p-tert-butylphenyl)-2-oxo-4-pyrrolidinyl]-methoxybenzoic acid (S-2E), a novel anti-hyperlipidemic agent, reduced the elevated levels of triglyceride (TG) and non-high-density lipoprotein cholesterol (non-HDL-C), and then whether it elevated HDL-C levels. At doses of 3-30 mg/kg, S-2E reduced elevated TG levels and non-HDL-C levels simultaneously in a dose-dependent manner after a week. Furthermore, S-2E treatment at 10 mg/kg for 4 weeks showed similar effects, while the elongation of intervals between feeding periods led to further increases in these levels. Interestingly, S-2E increased blood HDL-C levels after 4 weeks of treatment. It is therefore reasonable to assume that S-2E may be useful to improve dyslipidemia such as hypertriglyceridemia and low levels of HDL-C.     

Fluctuation of 6Ckine expression in human endometrium during the menstrual cycle

OBJECTIVE: To clarify the expression of 6Ckine, a potential chemoattractant for endometrial natural killer (NK) cells, in the human endometrium. DESIGN: Experimental study. SETTING: Department of obstetrics and gynecology at a medical university. PATIENT(S): Fifty-seven fertile women 25 to 52 years of age who had regular menstrual cycles and normal endometrium and were undergoing hysterectomy. INTERVENTION(S): Endometrium was obtained from operative samples. MAIN OUTCOME MEASURE(S): Tissue was immunostained to determine the localization of 6Ckine in the endometrium throughout the menstrual cycle. The number of NK cells was counted in 10 nonoverlapping stromal areas. The concentration of 6Ckine in homogenized endometrium was determined by enzyme-linked immunosorbent assay. RESULT(S): Endometrial surface, glandular epithelial cells, and perivascular stromal cells were immunoreactive for 6Ckine throughout the menstrual cycle with some fluctuation. In addition, some T cells, NK cells, and macrophages in the stroma were immunoreactive for 6Ckine. The 6Ckine concentration was low in the proliferative phase but elevated in the secretory phase. It showed a moderate positive correlation with the number of endometrial NK cells. CONCLUSION(S): 6Ckine may be a potential chemoattractant for endometrial NK cells.     

Resorbability and solubility of zinc-containing tricalcium phosphate

Using zinc-containing tricalcium phosphate (ZnTCP) as the zinc carrier for zinc-releasing calcium phosphate ceramic implants promoted bone formation around the implants. Because no quantitative information was available on the equilibrium solubility and resorbability of ZnTCP, in vitro equilibrium solubility and in vivo resorbability of ZnTCP were determined and compared quantitatively in this study. The solubility of ZnTCP decreased with increasing zinc content. The negative logarithm of the solubility product (K(sp)) of ZnTCP was expressed as pK(sp) = 28.686 + 1.7414C - 0.42239C(2) + 0.063911C(3) - 0.0051037C(4) + 0.0001595C(5) in air, where C is the zinc content in ZnTCP (mol %). The solubility of ZnTCP containing a nontoxic level of zinc (<0.63 wt %) decreased to 52-92% of the solubility of pure tricalcium phosphate (TCP) in the pH range 5.0-7.4. However, the in vivo resorbed volume of ZnTCP containing the same amount of zinc was much lower than that expected from the in vitro solubility, becoming as low as 26-20% of that of TCP. Cellular resorption of TCP is substantially a process of dissolution in a fluid with an acidic pH that is maintained by the activities of cells. Therefore, the reduction of the resorbability of ZnTCP could be attributable principally to its lowered cellular activation property relative to that associated with pure TCP.     

Accuracy of flow and sensors of indirect calorimetry for neonates and infants: using mass spectrometry and a pneumotachogram

1. The accuracy of measurements of flow rate and concentrations of O2 and CO2 in expiratory gas by indirect calorimetry (IC) using paediatric and adult circuits were assessed by mass spectrometry and a pneumotachogram, which have been proven as the most reliable instruments for these purposes. 2. In the paediatric circuit, all measurements were demonstrated to be reliable: error rates for flow rate, O2 concentration and CO2 concentration were +3.13, +2.66 and -6.63%, respectively. All were within the 10%, which is acceptable as a biological error. 3. However, in the adult circuit of IC, all measurements were reliable except for measurements of CO2 concentration: error rates for flow rate, O2 concentration and CO2 concentration were +2.82, +1.64 and +11.42%, respectively. 4. A fluctuation phenomenon of expiratory gas concentration was observed only in IC. Mass spectrometry did not show this phenomenon. This phenomenon seems to be derived from the IC machine itself.