Bilateral Ureterovaginal Fistulas and Vesicovaginal Fistula in Setting of Retained Pessary.

Urogenital fistulas in the setting of foreign body are rare. Isolated vesicovaginal fistula is the most common and has been reported in the setting of retained intraureterine device,1,2 neglected pessary3,4 and atypical insertions related mostly to sexual activity or underlying psychiatric disorders.5-7 Combined vesicovaginal and ureterovaginal fistulas related to foreign body are extremely rare. To our knowledge, we present the first reported case of bilateral ureterovaginal fistula and concurrent vesicovaginal fistula in the setting of retained pessary.

Src inhibitors, PP2 and dasatinib, increase retinoic acid-induced association of Lyn and c-Raf (S259) and enhance MAPK-dependent differentiation of myeloid leukemia cells.

All-trans-retinoic-acid (ATRA)-induced differentiation of human myeloid leukemia cells is characterized by persistent mitogen-activated protein kinase (MAPK) signaling. Fragmentary data suggests Src family kinase (SFK) inhibitors enhance differentiation, and thus have potential therapeutic value. The present study shows that SFK inhibitors PP2 and dasatinib enhance aspects of MAPK signaling and regulate a panel of differentiation markers, including CD11b and p47(phox). HL-60 and NB4 myeloid leukemia cells show accelerated ATRA-induced G1/0 arrest/differentiation with inhibitor co-treatment. We also identified components of a Lyn- and c-Raf-containing MAPK signaling complex augmented by the inhibitors. PP2 and dasatinib increased the ATRA-induced expression of Lyn and c-Raf (total and c-RafpS259) and their interaction. The Lyn-associated serine/threonine kinase, casein kinase II (CK2), also complexed with c-Raf and c-RafpS259, and the kinase suppressor of Ras 1 (KSR1) scaffold protein bound c-Raf, Lyn and extracellular signal-regulated kinase (ERK). c-Raf/ERK association was increased by the inhibitors, which is significant as ERK may cause c-Raf C-terminal domain (CTD) phosphorylation in a putative feedback mechanism. Consistent with this, inhibitor treatment caused more CTD phosphorylation. Lyn knockdown decreased c-Raf CTD and S259 phosphorylation. This is the first evidence suggesting SFK inhibitors enhance ATRA-induced differentiation through a possible feedback loop involving KSR1-scaffolded c-Raf and ERK complexed with Lyn and CK2.

Investigation and management of lung cancer in older adults.

BACKGROUND: The average age of patients with lung cancer is increasing, but there is little data of the management and outcomes of this common cancer in the elderly. METHODS: Data were collected from our hospital lung cancer database, medical, radiology and pathology records, for all patients with a new diagnosis of lung cancer from Jan 2002 to Dec 2004. The investigation, treatment and outcomes of these patients were analysed, and the younger (<75 years old) and elderly (75 years+) populations were compared. RESULTS: Data on 367 were analysed. Median age at diagnosis was 72 years and median survival was 5.2 months. Elderly patients were less likely to be fully investigated i.e. have histological confirmation (88.2% vs. 66.4%; p<0.001), stage recorded (88.6% vs. 78.1%; p=0.001) and performance status recorded (88.6% vs. 75.3%; p=0.003). They had poorer performance status. The older patients were less likely to receive active treatment (surgery 11.6% vs. 6.4%; p<0.001, chemotherapy or radiotherapy 50.9% vs. 26.2% p<0.001). Improved survival was independently associated with younger age (p<0.001), better performance status (p<0.001), early stage (p<0.001) and active treatment (p=0.005). Hazard ratios for death for poor PS vs. good PS was 1.88 (p<0.001), for late stage vs. early stage was 2.01 (p=0.011), for BSC vs. active treatment was 1.46 (p=0.005) and for 75 years+ patients vs. under 75 years was 1.36 (p=0.069). When comparing elderly with younger patients, median survival remained better in patients who were actively treated, had good PS and early stage (p<0.001). CONCLUSIONS: Elderly patients are less likely to be fully investigated and actively treated than younger patients with lung cancer. The causes of this difference are unclear but may include patient and clinicians' more conservative approach in the elderly. Predictors of improved outcome are the same in older and younger populations, and the elderly derive a similar survival advantage if actively treated. These data show that elderly patients are managed differently to younger patients, though the clinical basis for this is not clear. SUMMARY: Lung cancer is common in the older population and has a poor prognosis. We reviewed the investigation, treatment and survival of all patients with a new diagnosis of lung cancer over a three-year period. We compared the management of our younger (under 75 years) population with those aged 75 years or older. In our population, people over 75 years with lung cancer are less completely investigated. They were less likely to have full staging investigations, a histological or cytological diagnosis, or have their performance status recorded. Our over 75-year olds are less likely to receive active treatment (chemotherapy, radiotherapy or surgery) for lung cancer. Our older patients who received active treatment for lung cancer had similar survival advantages to younger patients.

Effect of dietary alpha-tocopherol + ascorbic acid, selenium, and iron on oxidative stress in sub-yearling Chinook salmon (Oncorhynchus tshawytscha Walbaum).

A three-variable central composite design coupled with surface-response analysis was used to examine the effects of dietary alpha-tocopherol + ascorbic acid (TOCAA), selenium (Se), and iron (Fe) on indices of oxidative stress in juvenile spring Chinook salmon. Each dietary factor was tested at five levels for a total of fifteen dietary combinations (diets). Oxidative damage in liver and kidney (lipid peroxidation, protein carbonyls) and erythrocytes (erythrocyte resistance to peroxidative lysis, ERPL) was determined after feeding experimental diets for 16 (early December) and 28 (early March) weeks. Only TOCAA influenced oxidative stress in this study, with most measures of oxidative damage decreasing (liver lipid peroxidation in December and March; ERPL in December; liver protein carbonyl in March) with increasing levels of TOCAA. We also observed a TOCAA-stimulated increase in susceptibility of erythrocytes to peroxidative lysis in March at the highest levels of TOCAA. The data suggest that under most circumstances a progressive decrease in oxidative stress occurs as dietary TOCAA increases, but higher TOCAA concentrations can stimulate oxidative damage in some situations. Higher levels of TOCAA in the diet were required in March than in December to achieve comparable levels of protection against oxidative damage, which may have been due to physiological changes associated with the parr-smolt transformation. Erythrocytes appeared to be more sensitive to variation in dietary levels of TOCAA than liver and kidney tissues. Using the March ERPL assay results as a baseline, a TOCAA level of approximately 350-600 mg/kg diet would provide adequate protection against lipid peroxidation under most circumstances in juvenile Chinook salmon.

Preliminary examination of oxidative stress in juvenile spring Chinook salmon Oncorhynchus tshawytscha of wild origin sampled from transport barges.

Migrating juvenile wild Chinook salmon Oncorhynchus tshawytscha, collected and loaded onto transport barges at Lower Granite Dam on the Snake River, were sampled from barges at John Day Dam, 348 km downstream, at 5 day intervals beginning in late April and ending in late May. An increase in lipid peroxidation and decrease in vitamin E in liver were observed from early to late in the barge transportation season. These changes seemed unrelated to changes in plasma cortisol or corresponding glucose levels, which declined from early to late in the season, or the concentration of n-3 highly unsaturated fatty acid (HUFA) concentrations in tissue but may be related to water temperature, which increased during the transport season, or other changes associated with the parr-smolt transformation.

The influence of supporting the Oxylog instrument on estimated maximal aerobic capacity during a step test and heart rate in a lifting test.

This study investigated the influence of wearing, an Oxylog mask and heart rate monitor while the Oxylog instrument was supported in a stand versus that of wearing the Oxylog mask, heart rate monitor, and the Oxylog instrument, on oxygen consumption (VO2) and heart rate response during a graduated submaximal step test protocol. Also, the predicted maximal aerobic capacities ( VO2max) produced by the two graduated step tests were compared. In addition, differences in the working heart rates in a submaximal lifting test were analyzed in two lifting tests, one with the participant wearing the Oxylog mask, heart rate monitor, and Oxylog instrument and the other required the participant to only wear a heart monitor. Seventeen experienced male manual materials handlers participated in the study, and each treatment was seen by each participant in a randomized Latin Square design. Results from the two investigations indicate that there was no significant difference in the estimated maximal oxygen consumption (p = 0.1384) and no significant difference in the heart rate between the two lift tests. The analysis did show that the 4th stage (participants reaching their physiological limits) of the step tests indicated a statistically significant difference (p = 0.0259 for oxygen consumption, and p = 0.0465 for heart rate).

Influence of an anaesthetist on nurse-led, computer-based, pre-operative assessment.

Trained nurses using a rule-based computer program can successfully carry out pre-anaesthesia screening. All medical problems and abnormal laboratory results need to be reviewed by an experienced anaesthetist. Following the introduction of this system, there was a reduction in the frequency of cancellations of patients from elective orthopaedic operating lists from 4.8% to 1.8%, a difference that was statistically significant (p = 0.03, CI = [0.6%, 5.5%]). To minimise cancellations from booked operating lists, a booked admissions policy is essential, so that the anaesthetist who will eventually be responsible for patients with medical problems can be identified. Cancellations cannot be avoided completely because some abnormal conditions arise or deteriorate after completion of the screening process. The anaesthetist responsible for the patient's anaesthetic may have different views of the risks involved from those of the anaesthetist undertaking the screening process.

The pulmonary cachexia syndrome: aspects of energy balance.

The present paper reviews current knowledge of the pulmonary cachexia syndrome with reference to chronic obstructive pulmonary disease (COPD). Aspects of incidence, aetiology and management are discussed. Malnutrition occurs in approximately one-quarter to one-third of patients with moderate to severe COPD. Both fat mass and fat-free mass become depleted. Loss of fat-free mass is the more important and appears to be due to a depression of protein synthesis. Weight loss is an independent prognostic indicator of mortality, and is associated with increased morbidity and decreased health-related quality of life. The aetiology of malnutrition in COPD is not well understood. Reduced food intake does not seem to be the primary cause. Resting energy expenditure (REE) is elevated in a proportion of patients and probably contributes to negative energy balance. Measurement of actual REE is helpful when considering the adequacy of nutritional supplementation. The underlying reason for a hypermetabolic state is not known. Although weight-losing COPD patients are not catabolic, nutritional supplementation alone does not appear to reverse the loss of fat-free mass. Strategies involving nutritional supplementation in combination with a second intervention are being explored, and there are some encouraging results using anabolic hormones.

Factors affecting minimum push and pull forces of manual carts.

The minimum forces needed to manually push or pull a 4-wheel cart of differing weights with similar wheel sizes from a stationary state were measured on four floor materials under different conditions of wheel width, diameter, and orientation. Cart load was increased from 0 to 181.4 kg in increments of 36.3 kg. The floor materials were smooth concrete, tile, asphalt, and industrial carpet. Two wheel widths were tested: 25 and 38 mm. Wheel diameters were 51, 102, and 153 mm. Wheel orientation was tested at four levels: F0R0 (all four wheels aligned in the forward direction), F0R90 (the two front wheels, the wheels furthest from the cart handle, aligned in the forward direction and the two rear wheels, the wheels closest to the cart handle, aligned at 90 degrees to the forward direction), F90R0 (the two front wheels aligned at 90 degrees to the forward direction and the two rear wheels aligned in the forward direction), and F90R90 (all four wheels aligned at 90 degrees to the forward direction). Wheel width did not have a significant effect on the minimum push/pull forces. The minimum push/pull forces were linearly proportional to cart weight, and inversely proportional to wheel diameter. The coefficients of rolling friction were estimated as 2.2, 2.4, 3.3, and 4.5 mm for hard rubber wheels rolling on smooth concrete, tile, asphalt, and industrial carpet floors, respectively. The effect of wheel orientation was not consistent over the tested conditions, but, in general, the smallest minimum push/pull forces were measured with all four wheels aligned in the forward direction, whereas the largest minimum push/pull forces were measured when all four wheels were aligned at 90 degrees to the forward direction. There was no significant difference between the push and pull forces when all four wheels were aligned in the forward direction.

Microwave emissions from police radar.

This study evaluated police officers' exposures to microwaves emitted by traffic radar units. Exposure measurements were taken at approximated ocular and testicular levels of officers seated in patrol vehicles. Comparisons were made of the radar manufacturers' published maximum power density specifications and actual measured power densities taken at the antenna faces of those units. Four speed-enforcement agencies and one transportation research institute provided 54 radar units for evaluation; 17 different models, encompassing 4 frequency bands and 3 antenna configurations, were included. Four of the 986 measurements taken exceeded the 5 mW/cm2 limit accepted by the International Radiation Protection Association and the National Council on Radiation Protection and Measurement, though none exceeded the American Conference of Governmental Industrial Hygienists, American National Standards Institute, Institute of Electrical and Electronic Engineers, or Occupational Safety and Health Administration standard of 10 mW/cm2. The four high measurements were maximum power density readings taken directly in front of the radar. Of the 812 measurements taken at the officers' seated ocular and testicular positions, none exceeded 0.04 mW/cm2; the highest of these (0.034 mW/cm2) was less than 1% of the most conservative current safety standards. High exposures in the limited region directly in front of the radar aperture are easily avoided with proper training. Results of this study indicate that police officer exposure to microwave radiation is apparently minimal. However, because of uncertainty in the medical and scientific communities concerning nonionizing radiation, it is recommended that law enforcement agencies implement a policy of prudent avoidance, including purchasing units with the lowest published maximum power densities, purchasing dash/rear deck-mounted units with antennae mounted outside the patrol vehicle, and training police officers to use the "stand-by" mode when not actually using radar.

Recurrence of recipient Langerhans' cell histiocytosis following bilateral lung transplantation.

Langerhans' cell histiocytosis may cause irreversible respiratory failure due to progressive destruction of lung parenchyma and widespread cystic change. Transplantation offers a therapeutic option. A case is described of recurrence of Langerhans' cell histiocytosis which was associated with deterioration in lung function four years following bilateral lung transplantation. Patients transplanted for Langerhans' cell histiocytosis should be followed up with this complication in mind.

Do Nottingham Health Profile scores change over time in cystic fibrosis?

We have previously shown that the Nottingham Health Profile (NHP) shows good correlation with physiological scores in an adult cystic fibrosis (CF) population when assessing health status (HS). The aim of this study was to determine whether the NHP can detect change in HS over time. Patients attending an adult CF clinic were studied at the time of their 'annual review' appointment. HS was assessed by the NHP and an 'in house' CF-specific score was used. FEV1% predicted, FVC% predicted, FEV1/FVC ratio, and body mass index (BMI) were calculated. The patients were then studied at subsequent annual review appointments. Change over time was calculated for each parameter and the relationship between change in HS and change in physiological parameters was examined using Spearman's rank correlation. Initial (t1), NHP scores were obtained from 204 patients, median age 26 years (range 16-56 years). Follow-up scores were obtained from 152 patients (t2). The mean rate of change in FEV1 was -8.6 (261) ml yr-1 or -0.2 (6.9)% predicted yr-1. The only dimension of the NHP which showed a significant change over time was emotion, which showed a small improvement in score (score at t1 = 11.3, score at t2 = 8.1, P = 0.02). There was a significant deterioration in the CF-specific total score (t1 = 4.4, t2 = 4.7, P = 0.008). There were no significant correlations between change in physiology and change in NHP scores. There was no overall difference in change in NHP scores between the patients whose FEV1 declined at > 4% predicted yr-1 and those who did not. In conclusion, although the NHP correlates well with one-off physiological parameters, there is poor correlation between change in NHP scores and change in physiological parameters over time.

Effect of regular use of high-dose nebulized beta2-agonists on resting energy expenditure, weight, and handgrip strength in patients with chronic airflow limitation.

STUDY OBJECTIVES: A proportion of patients with chronic airflow limitation (CAL) have a raised resting energy expenditure (REE). The mechanism underlying this is not known. The question of whether the increased REE seen in some patients with CAL is due to beta2-agonist therapy has arisen, and the aim of this study was to examine REE, body composition, and peripheral muscle strength in patients before and after the use of regular high-dose beta2-agonists administered by nebulizer. DESIGN: Prospective observational study. SETTING: Respiratory outpatient clinic. PARTICIPANTS: Twenty outpatients with CAL being considered for a home nebulizer prescription. INTERVENTIONS: REE was measured by indirect calorimetry. Fat-free mass and handgrip strength were measured. Quality of life was assessed by the St. George's Hospital Respiratory Questionnaire. All subjects were assessed independently of this study for provision of a home nebulizer using a standard protocol. Based on the assessment, either standard-dose salbutamol therapy was continued or a nebulizer was provided with a prescription for high-dose salbutamol (5 mg qd). A mean of 8.1 months later (range, 3 to 16 months), 16 patients were restudied. MEASUREMENTS AND RESULTS: Eight patients had been taking regular high-dose nebulized salbutamol, and eight had continued taking standard-dose salbutamol by metered dose inhaler. There was no difference in baseline measures between the group who were later prescribed high-dose salbutamol and the group who were not. There were no changes in REE, anthropometric measures, or handgrip strength over time in either of the groups. CONCLUSIONS: The long-term use of high-dose nebulized beta2-agonists in patients with chronic airflow limitation has no effect on baseline REE, handgrip strength, weight, or body composition.

Correlation of injury occurrence data with estimated maximal aerobic capacity and body composition in a high-frequency manual materials handling task.

This article evaluates the correlation between injury occurrence, step test estimated maximal aerobic capacity (VO2max), and body composition in a high-frequency manual materials handling task. The study used 212 highly trained male manual material handlers working for a major materials handling company. Three locations across the United States (western, midwestern, and southeastern) were chosen based on similarity of size and function. An estimated maximal aerobic capacity was obtained for each participant using a submaximal bench step protocol. Also, a percentage body fat estimation was randomly obtained for approximately 25% of the participants. The correlation between injury occurrences, absolute VO2max, relative VO2max, and percentage body fat were analyzed. Also, the relationship between both VO2max estimations and percentage body fat was analyzed. Finally, the correlation between location VO2max and percentage body fat was studied. Results indicated no significant difference between absolute VO2max, injury, or percentage body fat. Relative VO2max suggested a significant relationship with injury occurrences and body composition. Body composition also indicated a significant correlation with injury occurrences. Finally, location played a significant factor in injury occurrence, step test estimated VO2max, and estimated body composition. This investigation demonstrates significant evidence of the predictability of employee injury occurrence and the fitness estimation methods used. In a high-frequency manual materials handling task, high occurrences of injury were significantly correlated with low estimated relative maximal aerobic capacity and high estimated percentage body fat.

Three-dimensional computed tomography bronchoscopy using clinical datasets: a comparison with fibreoptic bronchoscopy.

OBJECTIVE: To assess three-dimensional computed tomography 'bronchoscopic' (3-DCTB) reconstruction of routine CT data as a non-invasive method of airway visualization, and compare it with fibreoptic bronchoscopy (FOB). METHODS: Fourteen datasets were acquired from 13 patients undergoing both FOB and CT examination of the chest. Standard continuous volume CT using 6 mm collimation and clinical FOB techniques were employed. Images were obtained from 3-DCTB reconstructions by segmentation and surface recognition algorithms generating surface rendered 'bronchoscopic views'. These were scored for technical quality and anatomical detail. The most distal bronchi seen in left upper and right lower lobes were recorded for FOB and 3-DCTB. RESULTS: On FOB, the subsegmental bronchi were seen in right lower and in left upper lobe in 10/14 cases and 4/14 cases, respectively. Visualization of the subsegmental airways was not achieved with 3-DCTB, as they could not be identified with confidence. 3-DCTB never achieved a more distal view than obtained by FOB. Using 3-DCT, the right, lower lobe segmental bronchi were seen in 10/14 cases, and lobar bronchus in 14/14 cases (two occluded). In the left upper lobe, 3-DCT showed segmental bronchi in 6/14 cases, lobar bronchus in 11/14 cases (one occluded) and the left main bronchus appeared occluded in 3/14 cases. Overall, technical quality and anatomical detail scores of the carina and proximal bronchi ranked significantly higher than views of segmental bronchi. CONCLUSIONS: 3-DCTB cannot routinely replace FOB for inspection of major and segmental bronchi. Subsegmental bronchi cannot be adequately demonstrated by 3-DCTB using 6 mm collimation datasets.

Resting energy expenditure in cryptogenic fibrosing alveolitis.

A proportion of patients with chronic airflow limitation appear to have a raised resting energy expenditure (REE). This has been suggested as the reason for weight loss which may occur in these patients. A previous study found an increased REE in patients with interstitial lung disease of mixed aetiology. We were interested in studying REE in a more homogeneous group, with cryptogenic fibrosing alveolitis (CFA). Twenty patients with CFA were studied. They were compared with 18 controls matched for age, sex, weight and height. REE was measured by indirect calorimetry. Fat-free mass (FFM), was estimated by anthropometry. Patients had respiratory function tests performed, disability related to breathlessness was assessed by the activity section of the St George's Respiratory Questionnaire. Mean REE in the CFA group was not different from the control group: 5.20 (0.56) versus 5.12 (0.51) kj x h(-1) x kgFFM(-1). REE was elevated to greater than 110% of the value predicted by the Harris-Benedict equation in one CFA patient and in no control subjects. There was no correlation of REE with weight, pulmonary function tests, arterial oxygen saturation or activity score. The prevalence of a raised resting energy expenditure in cryptogenic fibrosing alveolitis patients with low transfer factor and relatively preserved vital capacity is low, and is less than that reported previously in a group of patients with interstitial lung disease of mixed aetiology.