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Amniotic fluid Clara cell protein concentration in normal pregnancy, a marker of fetal airway growth or fetal lung maturation?

OBJECTIVE: To evaluate the relationship of Clara cell protein (CCP) in amniotic fluid (AF) with the lecithin/sphingomyelin (L/S) ratio, and the concentrations of saturated phosphatidylcholine (Sat PC) and surfactant protein A (SP-A). STUDY DESIGN: AF samples were obtained by amniocentesis from 98 pregnancies without conditions known to influence fetal lung maturation between 25 and 41 weeks of gestation. These samples were used for determinations of CCP, L/S ratio, Sat PC, and SP-A. Simple and multiple linear regressions were used to analyze the data. RESULTS: CCP in AF increased logarithmically with gestational age (R(2)=0.51, p=0.006). The L/S ratio (R(2)=0.41, p<0.001), and the concentrations of Sat PC (R(2)=0.26, p<0.001) and SP-A (R(2)=0.52, p<0.001) also increased with advancing gestation. Weak correlations of CCP with the L/S ratio (R(2)=0.22, p=0.009) and Sat PC (R(2)=0.12, p=0.004), but not with SP-A (R(2)=0.07, p=0.10), were found. Using multiple linear regressions, gestational age was the only predictor of CCP (F=10.9, R(2)=0.13, p=0.015). Conversely, gestational age, Sat PC, and SP-A accounted for most of the variation of the L/S ratio (F=34.7, R(2)=0.61, p=0.0001). CONCLUSION: CCP correlated very poorly with known and widely accepted indices of fetal lung maturation. The increasing concentration of CCP in AF throughout gestation probably reflects growth and development of the fetal airways.

Amniotic Fluid↗

Influences on quality of life in GH deficient adults and their effect on response to treatment.

OBJECTIVE: Studies of the effect of GH on quality of life (QOL) in growth hormone deficient (GHD) adults have reported conflicting results. Recently, however, we have demonstrated that by selecting only those patients with impaired QOL the efficacy of GH replacement on QOL can be greatly improved. The improvement in QOL was observed to correlate significantly with that recorded before commencing GH therapy. This study aims to assess if demographic variables affect QOL in untreated GHD adults or the improvement in QOL following GH therapy. DESIGN: An open study of GH replacement, initiating treatment with a dose of 0.8 IU/day and titrating the dose by 0.4 IU increments to normalize the IGF-I SDS between - 2.0 and + 2.0 SD of the age related normal range. PATIENTS: 65 severely GHD patients (peak GH < 9 mU/l to provocative testing), mean age 38.7 (range 17-72) years. Inclusion criterion was that of subjectively poor quality of life on clinical interview. MEASUREMENTS: Blood was taken for insulin-like growth factor 1 (IGF-I). The Psychological General Well-Being Schedule (PGWB) and Adult Growth Hormone Deficiency Assessment (AGHDA) self-rating questionnaires were used to assess quality of life at baseline, three and eight months after commencing GH. RESULTS: The patients were subgrouped on the basis of gender, age of onset of GHD, pathology and presence of additional pituitary hormone deficits. The cohort consisted of 40 females and 25 males, 45 of adult-onset (AO) and 20 of childhood-onset (CO). GH deficiency resulted from a hypothalamo-pituitary pathology, or treatment thereof, in 36 patients and as a result of cranial irradiation for a primary brain tumour or prophylaxis in acute lymphoblastic leukaemia in 29 patients. Isolated GH deficiency (IGHD) was present in 25 patients, and 32 patients were demonstrated to have at least two additional pituitary hormone deficits (MPHD). No significant difference was detected between baseline PGWB scores of the subgroups. Multiple linear regression analysis revealed the age of onset of GHD to be a significant determinant of both the baseline PGWB (P = 0.05) and AGHDA (P = 0.025) scores, AO patients perceiving the greater distress. A significant improvement, from baseline, in both QOL scores was observed in all subgroups at three months, and in all subgroups at eight months except IGHD, where a trend towards improvement in the AGHDA score was observed but failed to reach significance. The mean improvement in the PGWB following GH therapy was not significantly different between subgroups. Multiple linear regression analysis confirmed baseline PGWB and AGHDA scores to be the most important variable in prediction of the level of improvement in respective scores following GH therapy. Age of onset was also observed to be a significant determinant of the PGWB scores following GH therapy (P = 0.02), the CO cohort experiencing the greater improvement. A similar relationship between age of onset and AGHDA scores was not observed (P = 0.22). CONCLUSIONS: Baseline QOL as assessed by self-rating questionnaires is influenced by the age of onset of the GH deficiency, adult onset patients expressing the greater distress. Improvements in QOL scores are influenced by both baseline score and to a lesser extent the age of onset of GHD, the greater improvement being observed in childhood onset patients. The degree of improvement was observed to be independent of gender, pathology and number of pituitary hormone deficits. In a cohort selected by subjectively impaired QOL, we have demonstrated childhood onset GHD patients perceive themselves to have less impairment of QOL pretreatment. In contrast to previous data in unselected cohorts, however, we have shown that those childhood onset GHD patients in whom QOL is significantly reduced, show a capacity for improvement that is equal to, if not greater, than that seen in adult onset-GHD patients.

Adolescent↗

Evaluation of a proposed standard reporting system for preoperative angiograms in infrainguinal bypass procedures: angiographic correlates of measured runoff resistance.

Preoperative angiography is widely used to estimate runoff before peripheral vascular bypass surgery. The Ad Hoc Committee on Reporting Standards for the Society for Vascular Surgery and the International Society for Cardiovascular Surgery recently proposed an angiographic scoring system that grades the quality of vessels distal to the proposed bypass site and calculates an overall runoff score after adjusting each vessel score by an arbitrary weighting factor. We compared this score with intraoperatively measured runoff resistance in 67 patients undergoing infrainguinal bypass. Correlation between overall runoff score and measured resistance varied with the distal bypass site and was reasonably predictive for femoropopliteal above-knee bypasses (r = 0.67, p = 0.004, N = 17) and femoroposterior tibial bypasses (r = 0.73, p = 0.03, N = 9), but not for femoropopliteal below-knee (r = 0.05, p = 0.76, N = 34) or femoroperoneal (r = 0.57, p = 0.18, N = 7) bypasses. When multiple linear regression was used to calculate the weighting factors (rather than using arbitrarily assigned factors), the correlation between overall angiogram score and measured resistance improved substantially for femoropopliteal above-knee (r = 0.85, p = 0.00006), femoropopliteal below-knee (r = 0.50, p = 0.03) and femoroperoneal (r = 0.83, p = 0.02) bypasses. Correlation for the entire group of 67 patients improved from r = 0.30 (p = 0.02) to r = 0.64 (p = 0.0001). We conclude that the committee's scoring system correlates with measured runoff resistance but can be improved by the use of multiple linear regression to calculate weighting factors for each vessel in the outflow tract.

Anastomosis, Surgical↗

Audiometric analyses confirm a cochlear component, disproportional to age, in stapedial otosclerosis.

OBJECTIVE: To report the preoperative audiometric profile of surgically confirmed otosclerosis. STUDY DESIGN: Retrospective, multicenter study. SETTING: Four tertiary referral centers. PATIENTS: One thousand sixty-four surgically confirmed patients with otosclerosis. INTERVENTIONS: Therapeutic ear surgery for hearing improvement. MAIN OUTCOME MEASURES: Preoperative audiometric air conduction (AC) and bone conduction (BC) hearing thresholds were obtained retrospectively for 1064 patients with otosclerosis. A cross-sectional multiple linear regression analysis was performed on audiometric data of affected ears. Influences of age and sex were analyzed and age-related typical audiograms were created. Bone conduction thresholds were corrected for Carhart effect and presbyacusis; in addition, we tested to see if separate cochlear otosclerosis component existed. Corrected thresholds were than analyzed separately for progression of cochlear otosclerosis. RESULTS: The study population consisted of 35% men and 65% women (mean age, 44 yr). The mean pure-tone average at 0.5, 1, and 2 kHz was 57 dB hearing level. Multiple linear regression analysis showed significant progression for all measured AC and BC thresholds. The average annual threshold deterioration for AC was 0.45 dB/yr and the annual threshold deterioration for BC was 0.37 dB/yr. The average annual gap expansion was 0.08 dB/year. The corrected BC thresholds for Carhart effect and presbyacusis remained significantly different from zero, but only showed progression at 2 kHz. CONCLUSION: The preoperative audiological profile of otosclerosis is described. There is a significant sensorineural component in patients with otosclerosis planned for stapedotomy, which is worse than age-related hearing loss by itself. Deterioration rates of AC and BC thresholds have been reported, which can be helpful in clinical practice and might also guide the characterization of allegedly different phenotypes for familial and sporadic otosclerosis.

Adult↗

Demographic predictors of resource utilization for bleeding peptic ulcer disease: the Ontario GI Bleed Study.

Peptic ulcer disease (PUD) and its complications impose a substantial burden on health care resources. To help identify subpopulations in which preventative measures might achieve maximal cost savings, the authors studied the variation in resource utilization and cost for management of bleeding PUD among demographic subgroups. Resource utilization profiles and direct medical cost estimates were generated for consecutive admissions for bleeding PUD at four hospitals in southern Ontario via chart review and adaptation of an administrative cost database. Multiple linear regression models were developed to identify independent demographic predictors of direct medical case cost and hospital length of stay (LOS). Among 158 admissions, the average LOS and case costs were 5.73 days and $2,953 (Canadian) respectively. Age, comorbid illness, nonsteroidal anti-inflammatory drug use, and the absence of prior PUD or upper gastrointestinal hemorrhage were associated with higher cost in univariate analysis, whereas increasing age and comorbidity predicted LOS. Only age and absence of prior PUD persisted as independent predictors of direct medical cost and LOS in a stepwise multiple linear regression. Costs for managing bleeding PUD vary substantially among demographic subgroups. More careful stratification of treatment costs is needed when economic models of interventions to prevent or to treat PUD are applied to specific subpopulations.

Adult↗

Continuous representation of human portraits and natural scenery in human ventral temporal cortex: evidence from functional magnetic resonance imaging.

BACKGROUND: Functional magnetic resonance imaging (fMRI) has become a powerful tool for tracking human brain activity in vivo. This technique is mainly based on blood oxygenation level dependence (BOLD) contrast. In the present study, we employed this newly developed technique to characterize the neural representations of human portraits and natural sceneries in the human brain. METHODS: Nine subjects were scanned with a 1.5 T magnetic resonance imaging (MRI) scanner using gradient-recalled echo and echo-planar imaging (GRE-EPI) pulse sequence while they were visually presented with 3 types of white-black photographs: natural scenery, human portraits, and scrambled nonsense pictures. Multiple linear regression was used to identify brain regions responding preferentially to each type of stimulus and common regions for both human portraits and natural scenery. The relative contributions of each type of stimulus to activation in these regions were examined using linear combinations of a general linear test. RESULTS: Multiple linear regression analysis revealed two distinct but adjacent regions in both sides of the ventral temporal cortex. The medial region preferentially responded to natural scenery, whereas the lateral one preferentially responded to the human portraits. The general linear test further revealed a distribution gradient such that a change from portraits to scenes shifted areas of activation from lateral to medial. CONCLUSIONS: The boundary between portrait-associated and scenery-associated areas is not as clear as previously demonstrated. The representations of portraits and scenes in ventral temporal cortex appear to be continuous and overlap.

Adult↗

Early leukocytosis in trauma patients: what difference does it make?

OBJECTIVE: To determine the association of the admission white blood cell count in trauma patients with demographics, severity and mechanism of injury, and need for therapeutic intervention. METHODS: Evaluation of prospectively collected registry data (admissions to a Level I trauma center in 2001). Differences in mean white blood cell count on admission were evaluated with t tests. Multiple linear regressions were performed with forward stepwise selection of variables. RESULTS: Of the 882 patients admitted for greater than 24 hours, white blood cell count was available for 786. Variations in white blood cell count were noted on bivariate analysis among different races, injury mechanisms and severities, Glasgow Coma Scores, blood pressures, and between patients requiring early transfusions versus those who did not. No difference was noted between patients who went to the operating room in the first 24 hours versus those who did not, or for patients who died in the hospital. On multiple linear regression analyses, only ISS greater than 15, GCS less than or equal to 8, and white race were associated with increases in white blood cell count. Leukocytosis was found not to be associated with mechanism of injury, specific organ injury, shock on admission, or the need for transfusion or surgery. CONCLUSION: Variations in white blood cell count in trauma patients are associated with race and injury severity, but they are not beneficial in predicting the need for volume resuscitation, transfusion, or surgery.

Female↗

Increased risk of breast cancer in splenectomized patients undergoing radiation therapy for Hodgkin's disease.

PURPOSE: Second malignancies have been reported among patients who were treated by radiation therapy or chemotherapy alone or in combination. Studies have implied an increased risk of breast cancer in women who received radiotherapy as part of their treatment for Hodgkin's disease. This review was performed to determine if there is an association between splenectomy and subsequent breast cancer. METHODS AND MATERIALS: One hundred and thirty-six female patients with histologically proven Hodgkin's disease were seen in the Division of Radiation Oncology between 1962 and 1985. All patients received mantle or mediastinal irradiation as part of their therapy. The risk of breast cancer was assessed and multiple linear regression analysis was performed on the following variables: patient age, stage, dose and extent of radiation field, time after completing radiation therapy, splenectomy, and chemotherapy. RESULTS: Breast cancer was observed in 11 of 74 splenectomized patients and in none of 62 patients not splenectomized. The mean follow-up was 13 years in splenectomized patients and 16 years, 7 months in nonsplenectomized patients. Nine patients developed invasive breast cancer and two developed ductal carcinoma in situ. Splenectomy was the only variable independently associated with an increased risk of breast cancer (p < 0.005) in multiple linear regression analysis; age, latency, and splenectomy considered together were also associated with an increased risk of breast cancer (p < 0.01). CONCLUSION: Our data show an increased risk of breast cancer in splenectomized patients who had treatment for Hodgkin's disease. A multiinstitutional survey may better define the influence of splenectomy relative to developing breast cancer in patients treated for Hodgkin's disease. The risk of breast cancer should be considered when recommending staging laparotomy, and we recommend close follow-up examination including routine mammograms for female patients successfully treated for Hodgkin's disease.

Adolescent↗

A QSPR study of the 31P NMR chemical shifts of phosphines.

Quantitative structure-property relationships (QSPR) on a large set of descriptors are developed for the 31P NMR chemical shifts of a large set of phosphines. The data set was composed of 291 primary, secondary, and tertiary phosphines, PH3-nRn, including substituents with different steric and electronic characteristics. Multiple linear regression and computational neural networks (CNN) were employed to create the models best suited for the prediction of 31P NMR chemical shifts. A correlation equation including seven descriptors (R2 = 0.8619) is reported. A 7-5-1 CNN was developed that produced a root-mean-error of 9.6 ppm (R2 = 0.9513) for the training set, of 11.7 ppm (R2 = 0.8986) for the cross-validation set, and of 11.3 ppm (R2 = 0.9527) for an external prediction set. The CNN methods give significantly better predictions of 31P NMR chemical shifts for phosphines than the multiple linear regression approach.

Journal Article↗

Gastric emptying characteristics of a novel (13)C-octanoate-labeled muffin meal.

GOALS: Determine the gastric emptying characteristics of a novel, 350-kcal test meal consisting of two muffins, using scintigraphy and the 13C-octanoate breath test (OBT). STUDY: Healthy volunteers underwent three studies on separate days within a 1-week period. On day 1, we measured emptying of the 350-kcal muffin test meal labeled simultaneously with 99mTc sulfur colloid and 13C-octanoate. On day 2, reproducibility of the OBT using a single-labeled 350-kcal test meal was assessed. On day 3, the effect of erythromycin on the 350-kcal OBT was determined. RESULTS: The mean (+/-SD) half-emptying time (T1/2) as measured by scintigraphy was 104 +/- 24 minutes, versus 212 +/- 52 minutes by OBT. There was a strong correlation between T1/2 determined by scintigraphy and the breath test (r = 0.83). Multiple linear regression analysis identified a significant relationship between T1/2 determined by scintigraphy and the 90-and 180-minute breath samples. There was a strong correlation (r = 0.830, slope = 0.732 +/- 0.120 [SE], intercept = 26.4 +/- 12.7) between the T1/2 obtained using the regression equation and the actual T1/2 obtained by scintigraphy. The mean T1/2 (+/-SD) for replicate determinations using the OBT was 209 +/- 52 minutes, compared with 196 +/- 42 minutes on days 1 and 2, respectively (not significant, p = 0.28, paired Student t test). Treatment with erythromycin on day 3 produced a significant decrease in T1/2 (155 +/- 49 minutes, p = 0.002). CONCLUSIONS: The 350-kcal muffin meal OBT provides a convenient, nonscintigraphic way of measuring solid-phase gastric emptying. Multiple linear regression appears promising as a method of analyzing OBT data and may allow for an abbreviated breath test protocol.

Adult↗

Functional indices for sciatic, peroneal, and posterior tibial nerve lesions in the mouse.

The sciatic functional index previously described in rats has proven to be a reliable index of functional recovery following sciatic nerve injury and repair. A similar functional assay of sciatic, peroneal, and posterior tibial nerve lesions was developed in a mouse model. Forty-eight C57/BL6 mice were randomly divided into 4 groups: sham surgery, sciatic nerve transection, peroneal nerve transection, and posterior tibial nerve transection. Preoperative and postoperative (48 hours) walking tracks were obtained. The pawprints were analyzed in a blinded fashion for measurements of print length (PL), toe spread (TS), intermediate toe spread (IT), and the orthogonal distance from the toe of one paw to the hind pad of the opposite paw (TOF). Multiple linear regression analysis was performed using these measurements to determine their significance and appropriate weighted contribution to the index formula for each nerve lesion. For the sciatic functional index, changes in the PL (P = 0.0092) and TS (P = 0.0008) were significant, resulting in an R2 value of 0.88. For the peroneal functional index, only TS (P < 0.0001) was significant with R2 = 0.83. For the posterior tibial index, only PL (P < 0.0001) was significant with R2 = 0.89. Formulas for a sciatic, peroneal, and posterior tibial functional index were created based on the coefficients derived from the multiple linear regression analysis. The indices that were developed will allow investigators to assess functional recovery following specific nerve lesions in mice.

Animals↗

Impaired ventilatory function and elevated insulin levels in nondiabetic males: the Normative Aging Study.

Lower levels of baseline ventilatory function have consistently been associated with increased risk of cardiovascular mortality in prospective studies, but the underlying mechanisms are not known. Increased risk of coronary heart disease is associated with higher serum insulin levels. This report examines the relationship between ventilatory function and indirect measures of insulin resistance. Cross-sectional data from 922 nondiabetic participants in the Normative Aging Study were analysed using multiple linear regression models with adjustment for potential confounders. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were examined in relation to indicators of insulin resistance, i.e. fasting insulin and the fasting insulin resistance index (FIRI). Diabetics were excluded because impaired insulin secretion interferes with the validity of these as measures of insulin resistance. Fasting insulin and FIRI were negatively correlated with FVC and FEV1 (all p< 0.001). These associations persisted after adjusting for potential confounders including age, height, body mass index, waist to hip circumference ratio, physical activity, alcohol intake and smoking in separate multiple linear regression models, for both insulin (all p< or =0.0008) and FIRI (all p< or =0.0001). Negative cross-sectional associations between ventilatory function and indirect measures of insulin resistance were found in nondiabetic males. Insulin resistance may contribute to the previously unexplained association between ventilatory function impairment and cardiovascular mortality. Mechanisms underlying the relationship between insulin resistance and decreased ventilatory function remain to be elucidated.

Adult↗

Analysis of tidal breathing profiles in cystic fibrosis and COPD.

STUDY OBJECTIVES: To explore the flow and time domain characteristics of resting tidal airflow profiles in the presence of obstructive airway disease. METHODS: Spirometry was performed on 81 adults and 46 juveniles in the lung function laboratory. All the juveniles had cystic fibrosis (CF), as did some of the adults (n = 25), with the remainder having either healthy lungs or COPD. Resting breathing profiles were recorded using a pneumotachograph. Thirteen flow and time domain parameters were extracted from each profile. Two new indexes were derived that are influenced by the shape of the post-peak expiratory flow portion of the expirogram. In this expirogram, the first index (change in post-peak expiratory flow at time 20% [TPPEF(20)]) describes early changes in post-peak flow, while the second index (change in post-peak expiratory flow at time 80% [TPPEF(80)]) describes later changes in flow. Multiple linear regression techniques were used to define the relationship between body size, flow and time domain parameters, and FEV(1), a measure of obstructive airway disease. RESULTS: In juvenile subjects with CF, body weight and the time to reach peak expiratory flow are the main correlates with FEV(1) (adjusted r(2) = 0.74). The adult CF group are different with the expiratory flow index (TPPEF(20)) being the major correlate with FEV(1) (adjusted r(2) = 0.77). In the COPD group, the second expiratory flow index (TPPEF(80)) is the major correlate instead (adjusted r(2) = 0.6). CONCLUSIONS: Using multiple linear regression techniques has allowed the description of the interrelationships between body size, age, and tidal breathing profile in obstructive airway disease. The relationship between the flow indexes TPPEF(20) and TPPEF(80) show that in adults with CF, the loss of expiratory flow braking is an important adaptation to disease, while in COPD pulmonary hyperinflation is the predominant factor.

Adolescent↗

Determinants of parental authorization for involvement of newborn infants in clinical trials.

OBJECTIVE: Parents have the right to decide on behalf of their infants whether to enroll them in controlled clinical trials. We determined the degree to which such parental decisions are influenced by risk and benefit considerations compared with other factors. DESIGN: Cross-sectional survey. PARTICIPANTS: Parents who had recently given or declined consent to one of three controlled trials in the neonatal intensive care unit. INTERVENTION: Parents were asked to complete a questionnaire that consisted of 15 sociodemographic items and 13 scaled responses to statements assessing the probability and magnitude of risk and benefit as well as perceived illness severity, attitudes toward research, and the consent process. ANALYSIS: Responses were subjected to factor analysis to identify underlying constructs. The sample was then randomly split, and multiple regression was performed on each half. RESULTS: The response rate was 83% (103 of 124) for those who had consented and 86% (37 of 43) for those who had declined. Factor analysis yielded three factors: (1) illness severity, (2) perceptions of risk or benefit and attitudes to research, and (3) sociodemographic characteristics. Multiple linear regression showed a significant multiple correlation of consent decision (r = .502), but only the second factor contributed. The analyses on split halves of the sample were comparable. Thirty-two percent of all parents agreed with the statement, "I would prefer to have the doctors advise me whether my baby should be in the study, rather than asking me to decide." CONCLUSIONS: In making consent decisions on behalf of their newborn infants, parents are influenced by risk and benefit assessments, attitudes toward research, and the integrity of the consent process. Illness severity or sociodemographic characteristics do not seem to be of similar importance. Rather than making the decision alone, a significant minority of parents would prefer to have the physicians advise them whether to volunteer their infants for a clinical trial.

Attitude to Health↗

In vivo elongation of the palmar and dorsal scapholunate interosseous ligament.

PURPOSE: To investigate the elongation of the palmar and dorsal subregions of the scapholunate interosseous ligament (SLIL) in healthy human subjects throughout a complete range of wrist motion. METHODS: The 3-dimensional in vivo kinematics of the scaphoid and lunate were determined in both wrists of 13 female and 13 male volunteers from computed tomography volume images. For each wrist the palmar and dorsal insertions of the SLIL were identified on reconstructed surface models of the scaphoid and lunate. The interbone distances between the palmar and dorsal sites were calculated for the neutral wrist position. Elongations were then calculated after applying the 3-dimensional kinematics to the scaphoid and lunate. A multiple linear regression model was used to determine if elongations varied significantly as a function of wrist flexion/extension and radioulnar deviation. RESULTS: From pure wrist extension to pure wrist flexion, the fibers of the SLIL at the palmar insertion site increased significantly, from 29% shortening to 27% elongation, and the dorsal insertion decreased from 26% to 4% shortening with respect to the fiber lengths in the neutral position. From pure radial deviation to pure ulnar deviation, the elongation of the palmar insertion significantly decreased from 9% elongation to 21% shortening. There was no notable change in dorsal elongation with wrist radioulnar deviation. The multiple linear regression model predicted that there would be minimal elongation of the palmar and dorsal fibers at the wrist position along the dart thrower's path from radial extension to ulnar flexion. CONCLUSIONS: In vivo elongation of the palmar and dorsal fibers of the SLIL varied with wrist position. The palmar fibers lengthened and the dorsal fibers shortened with wrist flexion and the opposite occurred with wrist extension. Scapholunate interosseous ligament elongation was minimal as the wrist was positioned along the dart thrower's path.

Adult↗

Polyamine biosynthesis in relation to K-ras and p-53 mutations in colorectal carcinoma.

BACKGROUND: Polyamines are important polycations found in high concentrations in gastrointestinal neoplasms, and ornithine decarboxylase is the key enzyme in their biosynthesis. Also genes with oncogenic potential (e.g. K-ras and p53) contribute to neoplastic transformation by modifying normal cellular proliferation and differentiation. Our aim was to evaluate the ornithine decarboxylase activity and polyamine levels in samples of colorectal carcinoma and uninvolved surrounding mucosa from 86 patients (52 men and 34 women) showing different patterns of K-ras/p53 mutations. METHODS: Polyamines were evaluated by high performance liquid chromatography. Ornithine decarboxylase activity was determined using the radiometric method. K-ras and p53 mutations were investigated by PCR followed by restriction fragment length polymorphism (PCR-RFLP) and single strand conformational polymorphism (PCR-SSCP), respectively. Multiple linear regression analysis was used to analyse relationships among polyamine biosynthesis, clinical-pathological variables and K-ras/p53 mutations. RESULTS: ODC activity and polyamine levels were significantly higher in neoplastic samples than in normal surrounding mucosa. K-ras codon 12 mutation was found in 25/86 patients (29.1%) and p53 gene mutation in 41/86 (47.7%). Polyamine biosynthesis was significantly higher in cancers showing K-ras mutation, either with or without p53 mutation [K-ras(+)/p53(-) and K-ras(+)/p53(+)], compared to samples with K-ras wild type [K-ras(-)/p53(-) and K-ras(-)/p53(+)]. Multiple linear regression analysis confirmed this finding. CONCLUSIONS: The present study provides evidence of a close relationship between K-ras mutation and polyamine biosynthesis in human colorectal carcinoma in a way that is largely p53 independent. In addition, our data support the hypothesis of different pathways in colorectal tumorigenesis reflecting different combinations of biochemical parameters and genetic alterations.

Adenocarcinoma↗

Black clouds. Work load, sleep, and resident reputation.

OBJECTIVE: Although it is assumed that residents in a specific training program will have comparable experiences, residents commonly perceive that some have consistently more difficult times on call. Such residents in our program are said to have "black clouds." We sought to determine if these perceptions were related to differences in real work load. METHODS: We collected data about the on-call experiences of our first-year pediatric residents (PL-1s) for 358 days (1355 on-call experiences) during the 1984-1985 academic year. Every PL-1 (n = 19) reported the following data the morning after each night on call: hours of sleep, number of admissions, total number of patients, number of deaths, number of transfers to the pediatric intensive care unit, number of delivery room trips, and a subjective assessment of work load, using a three-point scale. The reputation of each house officer was determined by asking all residents in the program (PL-1s, PL-2s, and PL-3s) to rate each other three times during the year regarding how hard they worked on call. RESULTS: There were significant differences among PL-1s in how difficult they perceived their work load to be and in how much they slept (P < .001 using analysis of variance). However, actual work load (as measured by the number of either admissions or patients) did not vary significantly among the residents. There was a strong negative association between self-perception of work load and hours of sleep (r = -.75; 95% confidence interval, -0.73 to -0.76). Sleep was the major predictor of perceived work load (multiple R2 = .563 using multiple linear regression analysis). The absence of an association between perceived and actual work load is attributed to large differences in the residents' working styles. This is evidenced by a wide range of correlations among PL-1s between the number of admissions and hours of sleep (range of r values, -.66 to -.16). A reputation for difficult on-call experiences was strongly associated with few hours of sleep (r = -.77; 95% confidence interval, -0.49 to -0.91), but not with actual work load measured by the number of admissions, patients, deaths, or other variables. Sleep was the major predictor of reputation (multiple R2 = .567 using multiple linear regression analysis). CONCLUSIONS: Some residents did have a black cloud; they slept less, perceived that they worked harder than average, and had a reputation for having difficult on-call experiences. Residents with a black cloud function differently from their colleagues; for example, some may be inefficient, while others may create extra work for themselves. Residency program directors must recognize these functional differences to effectively evaluate and counsel house officers.

Analysis of Variance↗

Biochemical markers for the prediction of spontaneous pre-term birth.

OBJECTIVES: The aim of this study was to identify predictive biochemical markers for preterm labor. METHODS: In this prospective study we included 225 asymptomatic Caucasian women consecutively enrolled at 24 weeks of gestation. The following data were collected only once at 24 weeks of gestation: vaginal pH, vaginal fFN, cervical and serum concentration of IL-6, IL-8 and TNFalpha, maternal blood serum, ferritin. Student's t-test, the chi(2)-test and multiple linear regression were used as statistical methods. RESULTS: There were no differences between the age of patients, parity and gestational age at sampling between women who delivered at term and those who delivered pre-term (<37 weeks' gestation). There was a significant increase of cervical IL-6 (pre-term 608+/-1595 pg/l vs. at term 58.9+/-112 pg/l) and serum ferritin (pre-term microg/l 74.4+/-1.1 vs. at term 26.3+/-56.5 microg/l) in pregnant women who delivered pre-term (P<0.05). No differences in cervical IL-8 and cervical TNFalpha between pre-term and term deliveries were found. Multiple linear regression confirmed that the vaginal pH value and cervical fFN test were the best predictive biochemical markers of pre-term birth (standardized coefficient Beta=0.33 and 0.22, respectively). CONCLUSIONS: In order to evaluate pregnancies for pre-term labor, the presence of pH>4.5 and a positive fFN test seems to be predictive of subsequent pre-term delivery.

Adult↗