Factors affecting total and "respirable" dose delivered by a salbutamol metered dose inhaler.

BACKGROUND--Many factors contribute to the high variability of doses delivered to the lungs of patients using metered dose inhalers (MDIs). Relatively little attention has been paid to the contribution to this variability of the way in which the MDI is handled before the inhalation manoeuvre. Instruction leaflets often recommend procedures at odds with those used for in vitro testing of the device. The standard protocol for in vitro assessment of salbutamol MDIs involves shaking the MDI vigorously for 30 seconds and wasting the first two actuations. Subsequent actuations are introduced into the testing device at five second intervals. Patient instructions do not include a recommendation to waste the first two actuations and recommend a delay of one minute between actuations. A series of experiments was performed to determine whether such differences might be important. METHODS--The total and "respirable" doses delivered by a salbutamol MDI (Ventolin, Allen & Hanburys) under various conditions were assessed with a multistage liquid impinger. The quantity of drug deposited on each stage was measured by an ultraviolet spectrophotometric method. The effect on the delivered dose of not shaking the canister, not wasting the first two doses, waiting 30 seconds between actuations, and using multiple rapid actuations was assessed by comparing the results with those obtained using the standard in vitro testing protocol. RESULTS--Compared with a standard protocol, it was found that not shaking the MDI before use reduced the total and "respirable" dose by 25.5% and 35.7%, respectively. The dose delivered when actuating the MDI at 30 second intervals was no different from that when intervals was no different from that when intervals of five seconds were used. Two actuations separated by one second had no effect on the total dose but reduced the "respirable" dose by 15.8%, while four rapid actuations reduced the total and "respirable" doses by 8.2% and 18.2%, respectively. Storing the MDI stem down reduced the total and "respirable" dose delivered in the first actuation by 25.0% and 23.3% despite shaking the MDI before use. CONCLUSIONS--MDIs containing drug in suspension must be shaken before use to resuspend the drug contained in the MDI, but shaking does not alter the composition of the suspension in the metering chamber and hence the dose in the first actuation remains low. Very rapid actuations can reduce the dose delivered per actuation, but salbutamol MDIs can be actuated immediately after a 10 second breath holding pause without affecting the dose delivered.     

脾切除后血小板聚集及ATP释放增高机制的探讨

测定了32例脾切除患者血小板聚集(PAg),其中包括16例同步测定PAg及ATP释放(ATP-R)的结果。脾切除组由ADP、Coll及ADR所致5分钟内最大聚集率(M~1)及ATP-R的均值较脾切除前组及正常对照组均有一定程度升高,其中以肝硬化代偿期脾切除组升高最明显(P<0.05～0.001)。其发生机制与血小板数增多、凝血因子增加、抗凝活性减低、继发性纤溶活性增加及血小板代谢活性指标TXB_2增高等因素有关,提示脾切除患者PAg及ATP-R升高与临床存在的高凝状态有关。     

Pancreaticobiliary maljunction: pathophysiological and clinical aspects and the impact on biliary carcinogenesis

BACKGROUND: Pancreaticobiliary maljunction (PBM) is frequently associated with congenital choledochal cyst (CCBD), but differs in embryonic cause and clinical features. It is thought to develop as a misarrangement of the embryonic connections in the pancreaticobiliary ductal system, with the terminal bile duct joined to one of the ducts of the ventral pancreas. Clinical aspects are intermittent abdominal pain, relapsing acute pancreatitis, jaundice, cholangitis, and gallbladder cancer. In patients with PBM and CCBD, primary bile duct stones, acute cholangitis, and bile duct cancer are considered to result from cholestasis, regurgitation of pancreatic juice, and reciprocal reflux of bile and pancreatic juice. The mixture of bile and pancreatic juice due to recipocal reflex very likely plays an important role in biliary carcinogenesis. PATIENTS AND METHODS: We reviewed the pathophysiological and clinical aspects and biliary carcinogenesis in 250 PBM patients (169 with benign hepatobiliary and pancreatic disease, 81 with malignancy). RESULTS: PBM patients show elevated cellular proliferation activity in the gallbladder epithelia. A number of oncogenes and tumor suppressor genes have been identified and implicated in carcinogenesis, particularly the K- ras oncogene and the p53 suppressor gene. Some K- ras mutations do not appear essential for hyperplasia but may be an early event in carcinogenesis. The p53 mutations are involved in carcinogenesis in the biliary epithelium in PBM patients.     

Two cases of atraumatic iliopsoas hematoma

We report two cases of atraumatic iliopsoas hematoma. First patient was a 76-year-old man admitted to our hospital from appetite loss. Blood transfusion did not improve his anemia. Five days after admission, suddenly he went into shock. CT scan revealed ileopsoas hematoma. He died from hemorrhagic shock in spite of conservative therapy. Second patient was a 70-year-old man admitted because of acute heart failure. Continuous hemodiafiltration was required to relieve anuria. The next day, he developed left leg and hip pain. CT scan revealed ileopsoas hematoma and he received CT guided aspiration drainage for decompression, but almost 7 days were needed to achieve successful pain control. In a case of iliopsoas hematoma, early diagnosis and adequate choise of therapy are necessary to improve prognosis of patients.     

Precancerous mucosal changes in the gallbladder of patients with occult pancreatobiliary reflux

BACKGROUND: Pancreatobiliary reflux can occur even if the pancreaticobiliary junction is normal (occult pancreatobiliary reflux), and it may be associated with gallbladder carcinoma. The aim of the present study was to examine precancerous mucosal changes in the gallbladder from patients with occult pancreatobiliary reflux. METHODS: The mucosa of the gallbladder from 13 patients who underwent cholecystectomy was examined histopathologically. These patients had an anatomically normal pancreatobiliary junction and a biliary amylase concentration greater than 10,000 IU/L. The gallbladder of patients without carcinoma was further examined by using immunohistochemical techniques to detect Ki-67, and the results were compared with those from control patients. RESULTS: Of the 13 patients, 5 (38%) had gallbladder carcinoma and 8 (62%) did not. Of the 8 patients without carcinoma, 4 (50%) had dysplasia accompanied by hyperplasia, and 2 (25%) had hyperplasia alone of the gallbladder mucosa. The Ki-67 labeling index was significantly higher in hyperplastic and dysplastic mucosa than in control gallbladder mucosa (p < 0.0004). CONCLUSIONS: Occult pancreatobiliary reflux could be associated with precancerous mucosal changes in the gallbladder, such as hyperplasia and dysplasia with increased cellular proliferation, and could be a possible risk factor for gallbladder carcinoma.     

Antidepressant effects of the sleep/wake cycle phase advance. Preliminary report

Five patients with endogenous depression were asked to participate in a phase-advance procedure consisting in advancing by 5 h the time schedule of the major external synchronizers such as light/dark, sleep/wake, meal time and social activity cycles. Clinical and biological parameters were observed throughout this 2-week process which followed one night of partial sleep deprivation. All patients improved with partial sleep deprivation and four of the five showed continuing remission during the phase-advance process. The antidepressant effects of the phase-advance process are discussed in light of different chronobiological models for depression.     

Interplay between long- and short-range interactions drives neuritogenesis on stiff surfaces

Substrate factors such as surface energy distribution can affect cell functions, such as neuronal differentiation of PC12 cells. However, the surface effects that trigger such cell responses need to be clarified and analyzed. Here we show that the total surface tension is not a critical parameter. Self-assembled monolayers of alkylsiloxanes on glass were used as culture substrates. By changing the nanoscale structure and ordering of the monolayer, we designed surfaces with a range of dispersive (γ(d) ) and nondispersive (γ(nd) ) potentials, but with a similar value for total free-energy (50 ≤ γ(d) + γ(nd) ≤ 55 mN m?1). When seeded on surfaces displaying γ(d) /γ(nd) ≤ 3.7, PC12 cells underwent low level of neuritogenesis. On surfaces exhibiting γ(d) /γ(nd) ≥ 5.4, neurite outgrowth was greatly enhanced and apparent by only 24 h of culture in absence of nerve growth-factor treatment. These data indicate how the spatial distribution of surface potentials may control neuritogenesis, thus providing a new criterion to address nerve regeneration issues on rigid biocompatible surfaces.