Discovery of distinct protein profiles specific for lung tumors and pre-malignant lung lesions by SELDI mass spectrometry

Objectives: Early lung cancer detection and treatment remain a challenge. The efficacy of surface-enhanced laser desorption/ionization (SELDI) technology in lung cancer detection, has not been defined. This study identifies specific protein peak patterns in malignant lung tumors, and in pre-malignant airways epithelium showing neoplastic transformation. Methods: Lung tumor specimens taken from patients participating in a lung cancer screening study (H. Lee Moffitt Cancer Center, Tampa, FL) were laser capture microdissected to obtain pure cell populations from frozen sections of normal lung, atypical adenomatous hyperplasia (AAH) and malignant tumors. SELDI mass spectrometry was used to generate protein profiles in each epithelial cell type. Results: SELDI mass spectroscopy is highly reproducible in detecting lung tumor-specific protein profiles. Three peaks at 17–23 kDa mass range from tumor cells showed markedly increased compared with normal cells. The peak at 17 250 Da was not detected in any of the normal cells. This peak appeared to be present at low levels in the atypical cell samples. Conclusions: This study demonstrates the feasibility of detecting “malignant” protein signatures from lung tumor and pre-malignant pulmonary epithelium using SELDI mass spectrometry. Although additional study is necessary to validate these patterns as unique diagnostic tools, these “malignant” protein signatures lend themselves to identification of populations at high-risk for lung cancer and for monitoring response to lung cancer chemopreventive agents.     

Uptake of meta-iodobenzylguanidine in neuroendocrine tumours is mediated by vesicular monoamine transporters

The radio-iodinated noradrenaline analogue meta-iodobenzylguanidine (MIBG) can be used for scintigraphy and radiation therapy of neuroendocrine (NE). The aim of the present study was to study the importance of vesicular monoamine transporters (VMATs) for the uptake of (123)I-MIBG in NE tumours. In nude mice, bearing the human transplantable midgut carcinoid GOT1, all organs and xenografted tumours accumulated (123)I after i.v. injection of (123)I-MIBG. A high concentration of (123)I was maintained in GOT1 tumours and adrenals, which expressed VMATs, but rapidly decreased in all other tissues. In the VMAT-expressing NE tumour cell lines GOT1 and BON and in VMAT-expressing primary NE tumour cell cultures (carcinoids, n=4 and pheochromocytomas, n=4), reserpine significantly reduced the uptake of (123)I-MIBG. The membrane pump inhibitor clomipramine had no effect on the uptake of (123)I-MIBG in GOT1 and BON cells, but inhibited the uptake in one out of four primary carcinoid cell cultures and three out of four primary pheochromocytoma cell cultures. In conclusion, VMATs and secretory granules are of importance for the uptake and retention of (123)I-MIBG in NE tumours. Information about the type and degree of expression of VMATs in NE tumours may be helpful in future to select patients suitable for radiation therapy with radio-iodinated MIBG.     

Sex differences in the toxicokinetics of inhaled solvent vapors in humans 2. 2-propanol

The aim of this study was to evaluate possible sex differences in the inhalation toxicokinetics of 2-propanol vapor. Nine women and eight men were exposed on different occasions for 2 h during light physical exercise (50 W) to 2-propanol (350 mg/m3) and to clean air (control exposure). The level corresponds to the Swedish occupational exposure limit. 2-Propanol and its metabolite acetone were monitored up to 24 h after exposure in exhaled air, blood, saliva, and urine by headspace gas chromatography. Body fat and lean body mass were estimated from sex-specific equations using bioelectrical impedance, body weight, height, and age. Genotypes were determined by PCR-based assays for alcohol dehydrogenase and cytochrome P450 2E1 (CYP2E1). The CYP2E1 phenotype was assessed by the 2-h plasma 6-hydroxychlorzoxazone/chlorzoxazone metabolic ratio in vivo. The toxicokinetic profile in blood was analyzed using a one-compartment population model. The following sex differences were significant at the p = 0.05 level (Student's t test). The respiratory uptake was lower and the volume of distribution smaller in females. The women had a slightly shorter half-time of 2-propanol in blood and a higher apparent total clearance when corrected for body composition. However, women reached approximately four times higher 2-propanol levels in exhaled air at 10-min postexposure and onward. Acetone in blood was markedly higher in females than in males in the control experiment and slightly higher following exposure to 2-propanol. A marked sex difference was that of a 10-fold higher in vivo blood:breath ratio in men, suggesting sex differences in the lung metabolism of 2-propanol. The most marked sex difference was that of salivary acetone, for which an approximately 100-fold increase was seen in women, but no increase in men, after exposure to 2-propanol compared to clean air. The toxicokinetic analysis revealed no significant differences in toxicokinetics between subjects of different metabolic genotypes or phenotypes. In conclusion, the study indicates several sex differences in the inhalation toxicokinetics of 2-propanol. Most of these differences are consistent with anatomical differences between women and men. However, body build can not explain the sex differences in 2-propanol levels in expired air and acetone in saliva.     

A randomised controlled trial of epidural compared with non-epidural analgesia in labour

Objectives To investigate possible short and long term side effects of epidural analgesia, compared with non-epidural analgesia for pain relief in labour.
Design Randomised controlled study, with long term follow up by questionnaire. Analysis by intention-to-treat.
Setting Busy maternity unit within a district general hospital in England.
Participants Three hundred and sixty nine primigravid women in labour were included (randomised allocation: epidural   n = 184  , non-epidural   n = 185  ).
Main outcome measures Backache at three and twelve months after delivery, instrumental delivery rates and maternal opinion of pain relief in labour.
Results No significant differences were found in the reported incidence of backache between the groups at three months: middle backache [  22% vs 20%, χ ²= 0.057, P = 0.81; odds ratio (95% CI) 1.4(0.9-2.3)  ]; low backache [  35% vs 34%, χ ²= 0.009, P = 0.92  ; odds ratio  (95% CI) 1.0(0.6-1.6)  ]. Nor were there significant differences at 12 months: [middle backache 16% vs 16%,   χ ²= 0.013, P = 0.91; odds ratio (95% CI) 1.0(0.5-1.8)  ]; or low backache [  35% vs 27%, χ ²= 1.91, P = 0.17; odds ratio (95% CI) 1.4(0.9-2.3)  ]. The incidence of instrumental delivery was somewhat higher in the epidural group [30% vs 19%, odds ratio (95% CI) 1.77 (1.09-2.86)]. Maternal satisfaction was not significantly different between the groups.
Conclusions This study provided no evidence to support the suggestion of a direct association between the use of epidural anaesthesia in labour and the incidence of long term backache. Despite a significant proportion of women in each group not receiving their allocated analgesia, a significant difference in terms of instrumental delivery rates remained. Satisfaction in both groups of women was high.     

Obscure gastrointestinal bleeding

This is one of a series of statements discussing the utilization of GI endoscopy in common clinical situations. The Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy prepared this text. In preparing this guideline, a MEDLINE literature search was performed, and additional references were obtained from the bibliographies of the identified articles and from recommendations of expert consultants. When little or no data exist from well-designed prospective trials, emphasis is given to results from large series and reports from recognized experts. Guidelines for appropriate utilization of endoscopy are based on a critical review of the available data and expert consensus. Further controlled clinical studies are needed to clarify aspects of this statement, and revision may be necessary as new data appear. Clinical consideration may justify a course of action at variance to these recommendations.     

Development of the ETOC: a European test of olfactory capabilities

A number of smell tests designed to evaluate human olfactory capabilities have been published, but none have been validated cross-culturally. The aim of this study was therefore to develop a reliable and quick olfactory test that could be used to evaluate efficiently the olfactory abilities of a European population. This test, named ETOC and based on a combination of a supra-threshold detection task and an identification task, was designed to be a cross-cultural tool that would measure the decline in olfactory performance with ageing. Two versions of the ETOC, one easy and one less easy, were used to test the olfactory performance of European citizens in three countries (France, Sweden and the Netherlands). The results indicated that neither version of the ETOC is culture-dependent, and that both give scores that well reflect the decrease in olfactory abilities with increasing age. A retest session showed that the less easy (and final) version of the ETOC is also highly reliable.     

Reducing risk by improving standards of intrapartum fetal care

Confidential Enquiries into Stillbirths and Deaths in Infancy (CESDI) have pointed to a high frequency of suboptimal intrapartum fetal care of a kind that, in the event of an adverse outcome, is hard to defend in court. In an effort to minimize liability, various strategies were applied in a district hospital labour ward--guidelines, cyclical audit, monthly feedback meetings and training sessions in cardiotocography (CTG). The effects of these interventions on quality of care was assessed by use of the CESDI system in all babies born with an Apgar score of 4 or less at 1 min and/or 7 or less at 5 min. 540 babies (4.3%) had low Apgar scores, and neither the percentage nor gestational age differed significantly between audit periods. In the baseline audit, care was judged suboptimal (grade II/III) in 14 (74%) of 19 cases, and in the next four periods it was 23%, 27%, 27% and 32%. In the latest audit period, after further educational interventions, it was 9%. Many of the failures to recognize or act on abnormal events were related to CTG interpretation. After the interventions there was a significant increase in cord blood pH measurement. There were no differences between audit periods in the proportion of babies with cord pH < 7.2. These results indicate that substantial improvements in quality of intrapartum care can be achieved by a programme of clinical risk management.     

Reducing maternal mortality from eclampsia, using magnesium sulphate

Since the introduction of low dose magnesium sulphate to treat eclamptic patients at Dhaka Medical College, mortality rates have fallen from 16% to 8%. Personal communications from other centres in Bangladesh show similar findings.     

Nursing law violations. A threat to competent and safe nursing practice

Nurse Practice Act violations pose threats to consumers of nursing services and lead to disciplinary actions against nurses by boards of nursing. To analyze nursing law violations, the actions and decisions of boards of nursing, and evaluate trends in negligent and unsafe nursing practice, the authors reviewed nursing law violations as well as rates of recidivism among nurses who received actions against their nursing licenses in Kentucky. The authors discuss how their findings can assist nurse administrators in investigating nurse care givers before employment and in initiating safeguards against nurse violations that affect client safety.