Malignant transformatin of human bronchial epithelial cells by radon-simulated {alpha}-particles

Epidemiological studies have shown that inhalation of radonis associated with an increased risk for bronchogenic carcinomain uranium miners. These     

A comparative study of tamoxifen metabolism in female rat, mouse and human liver microsomes

The metabolisms of tamoxifen in female rat, mouse and humanliver microsomal preparations were compared. Rat, mouse andhuman liver microsomes were incubated with tamoxifen in thepresence of NADPH and MgCl₂ and the metabolites formed wereanalysed by on-line HPLC electrospray ionization MS. The majormetabolites formed by rat liver microsomes were 4-hydroxytamoxifen,4'-hydroxytamoxifen, N-desmethyltamoxifen and tamoxifen N-oxide.In addition, two epoxide metabolites, 3,4-epoxytamoxifen and3',4'-epoxytamoxifen, and their hydrolysed derivatives, 3,4-dihydrodihydroxytamoxifenand 3',4'-dihydrodihydroxytamoxifen, have been identified. Thepattern of the main metabolites obtained with human liver microsomesresembles qualitatively that of rat liver microsomes. The majordifferences between rat and human liver microsomes were thatthe amount of hydroxylated metabolites were much lower in humanand only traces of 3,4-epoxytamoxifen and the correspondingdihydrodihydroxy derivative were detected. No 3',4'-epoxytamoxifendetected in human liver microsomes. The four major metaboliteswere also formed in much larger amounts and with faster ratesof formation by mouse liver microsomes, though tamoxifen N-oxideclearly predominated in this species. Polar metabolites, 3,4-dihydroxytamoxifenand 4-hydroxytamoxifen N-oxide, which were undetectable in ratand human, were formed in significant amounts in mouse microsomes.As in human microsomes, there was only one epoxide metabolite,3,4-epoxytamoxifen, produced by mouse liver microsomes at levelslower than that found in rat. The faster rate of metabolismand the production of polar metabolites may indicate the abilityof mouse to detoxify tamoxifen by rapid elimination comparedwith rat and human. The production of a larger amount of potentiallyreactive epoxide metabolites in rat may be responsible for theliver carcinogenesis in this species.     

Beneficial impact of a clinical care pathway in patients with testicular cancer undergoing retroperitoneal lymph node dissection

PURPOSE: Since 1997, we have used a clinical collaborative care pathway for patients undergoing retroperitoneal lymph node dissection. We examined its impact on perioperative care and outcome. MATERIALS AND METHODS: We examined the records of all patients with germ cell carcinoma who underwent retroperitoneal lymph node dissection from July 1990 to July 2001. Variables examined included clinical/pathological stage, hospital stay, postoperative care and the complication rate. RESULTS: A total of 118 patients underwent retroperitoneal lymph node dissection for germ cell carcinoma during this period, including 46 (39%) before pathway implementation in 1997 and 72 patients (61%) after pathway implementation. Of the 118 patients 40 (34%) underwent the procedure after chemotherapy. This rate remained fairly constant in the period before and after pathway initiation (31% and 36%, respectively). After pathway implementation fewer patients received a nasogastric tube (94% versus 5%, p <0.001) and had complications (26% versus 16%, p = 0.036). Mean hospital stay decreased after pathway implementation in all primary and post-chemotherapy retroperitoneal lymph node dissection cases (4.2 versus 6.4 days, p <0.005). Although patients who underwent the procedure after chemotherapy were more likely to have complications than those who underwent a primary procedure, the difference was not statistically significant (p = 0.09). CONCLUSIONS: Our collaborative clinical care pathway safely and efficiently outlines routine postoperative care and significantly decreased hospital stay.     

Bronchoscopic findings in children with non-cystic fibrosis chronic suppurative lung disease

BACKGROUND: Published data on the frequency and types of flexible bronchoscopic airway appearances in children with non-cystic fibrosis bronchiectasis and chronic suppurative lung disease are unavailable. The aims of this study were to describe airway appearances and frequency of airway abnormalities and to relate these airway abnormalities to chest high resolution computed tomography (cHRCT) findings in a cohort of children with non-cystic fibrosis chronic suppurative lung disease (CSLD). METHODS: Indigenous children with non-cystic fibrosis CSLD (>4 months moist and/or productive cough) were prospectively identified and collected over a 2.5 year period at two paediatric centres. Their medical charts and bronchoscopic notes were retrospectively reviewed. RESULTS: In all but one child the aetiology of the bronchiectasis was presumed to be following a respiratory infection. Thirty three of the 65 children with CSLD underwent bronchoscopy and five major types of airway findings were identified (mucosal abnormality/inflammation only, bronchomalacia, obliterative-like lesion, malacia/obliterative-like combination, and no macroscopic abnormality). The obliterative-like lesion, previously undescribed, was present in 16.7% of bronchiectatic lobes. Structural airway lesions (bronchomalacia and/or obliterative-like lesion) were present in 39.7% of children. These lesions, when present, corresponded to the site of abnormality on the cHRCT scan. CONCLUSIONS: Structural airway abnormality is commonly found in children with post-infectious bronchiectasis and a new bronchoscopic finding has been described. Airway abnormalities, when present, related to the same lobe abnormality on the cHRCT scan. How these airway abnormalities relate to aetiology, management strategy, and prognosis is unknown.     

Cryopreservation and mycophenolate therapy are detrimental to hematopoietic progenitor cells

BACKGROUND: The aim of the present study was to determine whether certain components of nonmyeloablative regimens for hematopoietic cell transplantation might compromise the growth of hematopoietic progenitors. METHODS: Porcine peripheral blood progenitor cells (PBPC) were cytokine-mobilized, collected by leukapheresis, and cryopreserved using 5% dimethyl sulfoxide and 6% hydroxyethyl starch. The influence of cryopreservation on PBPC was tested in vitro by enumeration of colony-forming units (CFUs) in methylcellulose and cobblestone area-forming cell (CAFC) subsets in stromal-associated long-term cultures on fresh and frozen PBPC. The effects of mycophenolate mofetil (MMF) on porcine PBPC and baboon and human bone marrow (BM) were tested in vitro by adding varying doses of MMF to the CFU assays. One baboon was treated with increasing doses of MMF (100-500 mg/kg per day continuously intravenous), and sequential BM aspirations were tested for CFU content. RESULTS: Fresh cytokine-mobilized PBPC had similar frequencies of progenitor cells when compared with porcine BM. Freezing-thawing of PBPC had no effect on porcine CFUs but reduced the recovery of CAFCs by more than 90%. In vitro, MMF completely inhibited the development of porcine and human CFUs at a concentration of 1 microg/mL and of baboon CFUs at levels between 10 and 100 microg/mL. Plasma-free mycophenolic acid levels of 10 to 30 microg/mL were associated with decreased CFUs in the BM. CONCLUSIONS: Cryopreservation and MMF potentially prevent engraftment of porcine PBPC by reducing the content or development of progenitor cells. These results indicate that the use of fresh PBPC might improve the induction of mixed hematopoietic chimerism and raise the possibility that use of high doses of MMF in the poststem cell transplant may compromise engraftment.     

Prediction of Caesarean Section from Ultrasound and Clinical Assessment of Fetal Size

EDITORIAL COMMENT: We accepted this paper for publication because the authors have explored the possible value of ultrasound versus clinical assessment of fetal size to see whether they can predict the need for Caesarean section when the baby is large. In this study both the ultrasound and the clinical assessment were impressively accurate and fetal femur length was the most accurate of the ultrasound parameters in assessing fetal weight in predicting the need for Caesarean section. However, as the authors indicate, none of these methods of assessment of fetal size are recommended as an absolute indication for Caesarean section. Every obstetrician uses clinical assessment of the fetus when evaluating management of the patient but the need for clinical judgment remains.
Summary: One hundred and five women with singleton pregnancies and cephalic presentation were assessed. Fundal height and a clinical estimate of fetal weight were recorded. The fetal biparietal diameter, abdominal circumference and femur length were measured with ultrasound. Ultrasound estimated fetal weight was calculated using 3 different formulas (Shepard, Campbell and CUHK). The liquor volume was assessed using the amniotic fluid index.
Ultrasound was able to predict Caesarean section with more reliability than clinical assessment of fetal size or weight. The biparietal diameter, fundal height and amniotic fluid index were poor predictors of mode of delivery. The measurements which best predicted the mode of delivery were the fetal femur length and abdominal circumference. Femur length, but not abdominal circumference, was a statistically better predictor of Caesarean section than clinical estimation of fetal weight. There was no improvement in prediction using ultrasound estimated fetal weight.     

Epidemiology and clinical significance of chronic hepatitis-related viruses infection in hemodialysis patients from Taiwan

BACKGROUND/AIMS: A novel DNA virus which was designated TT virus (TTV) in 1997 was considered a possible hepatitis-related virus, like hepatitis C (HCV), hepatitis B (HBV) and GB virus C/hepatitis G viruses (GBV-C/HGV). In the present study, the molecular epidemiology and clinical significance of TTV, GBV-C/HGV and HCV infection in hemodialysis patients from Taiwan are investigated. METHODS: Sera of 85 patients on maintenance hemodialysis were tested for alanine aminotransferase (ALT), hepatitis B surface antigen (HBsAg), second-generation HCV antibody (anti-HCV), anti-envelope protein 2 antibody (anti-E2) and RNA of GBV-C/HGV, HCV RNA and TTV DNA. Sera of patients with positive TTV DNA, GBV-C/HGV RNA or HCV RNA were tested for viruses 2 years later. RESULTS: Seven (8.2%) 29 (34.1%), 21 (24.7%), 12 (14.1%) and 9 (10.6%) hemodialysis patients were positive for HBsAg, Anti-HCV, HCV RNA, GBV-C/HGV RNA and anti-E2, respectively. TTV DNA was positive in 46 (54.1%) patients. Neither clinical nor virological factors were associated with TTV viremia. The ALT level was significantly elevated in HCV RNA-positive individuals than -negative ones (34.5 vs. 12.5%, p < 0.05). TTV DNA, GBV-C/HGV RNA and HCV RNA remained detectable in sera of 31 (86.1%), 6 (50%) and 21 (100%) patients collected 2 years after first diagnosis of viremia. CONCLUSION: Among Taiwanese hemodialysis patients, TTV infection is highly prevalent. No clinical or virological factor was observed to be significantly associated with TTV infection. The ALT abnormality was mainly attributable to HCV but not TTV infection in Taiwanese hemodialysis patients.     

Acute interstitial nephritis due to nicergoline (Sermion)

We report a case of acute interstitial nephritis (AIN) due to nicergoline (Sermion). A 50-year-old patient admitted to our hospital for fever and acute renal failure. Before admission, he had been taking nicergoline and bendazac lysine due to retinal vein occlusion at ophthalmologic department. Thereafter, he experienced intermittent fever and skin rash. On admission, clinical symptoms (i.e. arthralgia and fever) and laboratory findings (i.e. eosinophilia and renal failure) suggested AIN, and which was confirmed by pathologic findings on renal biopsy. A lymphocyte transformation test demonstrated a positive result against nicergoline. Treatment was consisted of withdrawal of nicergoline and intravenous methylprednisolone, and his renal function was completely recovered. To our knowledge, this is the first report of nicergoline-associated AIN.     

Case studies in contact burns caused by exhaust pipes of motorcycles

Contact burns caused by the exhaust pipe of motorcycles are rarely reported. We performed retrospective studies of such cases in 78 patients with complete records. The majority of victims were unmarried (75.7%), young (<25 years, 70.5%), and female (69.3%), dressed mostly in short pants or mini skirts (75.7%). The burn accident occurred mostly in late spring and early summer (52.7%), during rush hours (57.7%), and during parking the motorcycles (65.4%). The burn wounds located mostly on the lateral aspect (46.2%) of the lower leg, usually took 3-4 weeks for complete healing. Continuous monitoring of the exhaust pipe and its outside cover on moving motorcycles showed that the temperature reached 170-250 and 40-60 degrees C, respectively.For the prevention of these injuries, our suggestions include well-designed external shield with adequate separation from the exhaust pipe, motorcycle parking lots of adequate width (>120cm), the wearing of trousers by motorcyclists, decrease of the density of motorcycle traffic, and development of the electric assisted cycle in place of the fuel-driven motorcycle.     

Working memory after traumatic brain injury in children

To investigate the effects of traumatic brain injury on working memory in children, we administered semantic (letter identity) and phonological (letter rhyme) N-back tasks to children who were on average 5 years post-mild (n = 54) or -severe (n = 26) traumatic brain injury and 44 typically developing children who were comparable in age. The correct detection of targets and false alarms were measured for each task. Memory load (which varied from 0 to 3 letters back) and age significantly affected the detection of targets and false alarms in both tasks. The severity of traumatic brain injury affected the correct detection of letters on the identity task and false alarms on the rhyme task. Traumatic brain injury severity also interacted with memory load in its effect on false alarms on the rhyme task. Traumatic brain injury results in impaired working memory and diminished inhibition in children. The N-back working memory task is feasible for administration to brain-injured children and potentially could be useful for studying brain activation associated with working memory and effects of drug therapy in this group of patients.