The effect of increased chewing strokes on the DeMeester score.

Saliva is known to be protective for esophageal mucosa. Increased chewing strokes result in a quantitative and qualitative enhancement of saliva. Reduction in the amount of saliva produced results in an increased incidence of gastroesophageal reflux disease (GERD), which can be objectively measured by the DeMeester score. The impact of increased chewing strokes on the DeMeester score remains largely unknown, thus this study aimed to find out their impact on the value of the DeMeester score and its individual components.The effect of increased chewing strokes on the DeMeester score was investigated in 12 subjects (5 male and 7 female) who were diagnosed with GERD. All subjects underwent a 48-hour pH monitoring using the Bravo® pH capsule. All the patients chewed their food 20 times more on Day 2 as compared to Day 1. The data were analyzed for change in the DeMeester score and its individual components in 2 days.In patients with GERD (DeMeester score > 14.72 on Day 1), the number of long refluxes (>5 minutes) on Day 2 (mean = 3.2, SD = 2.3) was significantly lower than on Day 1 (mean = 6.4, SD = 2.7); Z = -2.032, p = 0.04. Though, the DeMeester score and its other individual parameters decreased on Day 2, they were not statistically significant.In patients with GERD, increased chewing strokes lead to a decrease in the number of long reflux episodes. Though there is a decrease in the DeMeester score and its other individual components, larger randomized controlled studies are required to reach statistical significance.

Racial disparities in the treatment of endometrial intraepithelial neoplasia in postmenopausal women.

Disparities in endometrial cancer has increased during the past decade with Black women more likely to be diagnosed at a later stage and have higher mortality. The majority of research has been focused on cultural barriers, socioeconomic status, lack of access to care, comorbidities, and tumor histology to explain these disparities. Limited studies have been conducted on the disparity in the treatment of endometrial intraepithelial neoplasia(EIN). We sought to analyze the differences in treatment used in the management of postmenopausal women with EIN to evaluate whether race/ethnicity is a contributing factor. An IRB approved retrospective study was conducted amongst women at a single institution diagnosed with EIN. Ethnicity/race was defined as non-Hispanic White, non-Hispanic Black, Hispanic, and Asian. Demographic and clinical data was extracted. Multivariable logistic regression was used to examine the association between ethnicity/race and treatment, adjusted for age, BMI, and underlying medical conditions such as cardiovascular disease and diabetes. In total, 254 patients were analyzed. A significant association between ethnicity/race and treatment with non-Hispanic Black women less likely to be treated with surgical management compared to non-Hispanic White women (OR = 0.326, 95 %CI 0.129-0.827, p = 0.026). Importantly, after adjusting for clinical risk factors(age, BMI, CVD, diabetes), non-Hispanic Black women remained at an increased risk of not undergoing surgical intervention (OR = 0.333, 95 % CI 0.125-0.882, p = 0.027). Future research is imperative to evaluate the root cause of this disparity in the healthcare system.

Gender Differences and Their Effects on Survival Outcomes in Lung Cancer Patients Treated With PD-1/PD-L1 Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.

AIMS: Programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) immune checkpoint inhibitors have had a major impact on the approach to care of patients with lung cancer. An important issue that is not known is whether they benefit men and women the same. We conducted a meta-analysis of all randomised controlled trials evaluating PD-1/PD-L1 inhibition in patients with non-small cell lung cancer (NSCLC) to determine if clinical response and survival are influenced by gender. MATERIALS AND METHODS: A PubMed search was carried out to identify all randomised controlled trials evaluating PD-1/PD-L1 inhibitors compared with conventional chemotherapy in NSCLC. Random-effects meta-analysis and meta-regression were performed to assess overall survival and progression-free survival (PFS) and whether there were differences in these outcomes between men and women. RESULTS: In total, 12 studies with data for overall survival and 11 studies with data for PFS were included. Immunotherapy showed a statistically significant benefit over chemotherapy for overall survival (pooled hazard ratio = 0.72, 95% confidence interval = 0.65-0.81, P < 0.001) and progression-free survival (pooled hazard ratio = 0.62, 95% confidence interval = 0.54-0.72, P < 0.001). We did not find a statistically significant difference between men and women in terms of overall survival (males versus females: pooled hazard ratio = 0.74, 95% confidence interval = 0.66-0.83 versus pooled hazard ratio = 0.72, 95% confidence interval = 0.63-0.82, P = 0.709) or progression-free survival (males versus females: pooled hazard ratio = 0.63, 95% confidence interval = 0.53-0.75 versus pooled hazard ratio = 0.72, 95% confidence interval = 0.58-0.88, P = 0.372). CONCLUSION: This is the first systematic review and meta-analysis investigating the effect of gender and response to PD-1/PD-L1 checkpoint inhibitors in patients solely with NSCLC. We examined 9270 and 6193 patients in terms of overall survival and PFS, respectively. Although there are significant biological differences between men's and women's immune responses, we have shown that these drugs offer the same survival benefit in patients with NSCLC regardless of gender.

Metabolic and hormonal effects of oral DHEA in premenopausal women with HIV infection: a randomized, prospective, placebo-controlled pilot study.

Women with HIV infection use dehydroepiandrosterone (DHEA) because of its potential effects on mood and energy. We examined the effects of DHEA on the hypothalamic-pituitary-adrenal and gonadal axes and on insulin sensitivity. Fifteen HIV-positive women were randomized to receive placebo (6 subjects) or oral DHEA (9 subjects). ACTH-, CRF-, and GnRH-stimulation tests were performed before and after 8 weeks of treatment. DHEA, DHEA-S, dihydrotestosterone, total testosterone, free testosterone, sex hormone-binding globulin, estrone, estradiol, cortisol, insulin, IGF-1, IGFBP-1, IGFBP-3, and adiponectin in plasma or serum were measured. There was a significant increase in DHEA (p<0.004), DHEA-S (p<0.008), total testosterone (p<0.008), dihydrotestosterone (p<0.004), androstenedione (p<0.04), and estrone (p<0.03) from baseline within the DHEA group but not within the placebo group. There was a significant increase in DHEA (p<0.0006), DHEA-S (p<0.032), total testosterone (p<0.01), and dihydrotestosterone (p<0.005) in the DHEA group compared with the placebo group. Oral DHEA produces significant increases in circulating DHEA, DHEA-S, testosterone, DHT, and, possibly, androstenedione and estrone levels in premenopausal women with HIV infection. In the current pilot study these hormone changes did not affect the pituitary or adrenal axis or insulin/IGF indices. Long-term studies with larger groups of patients are needed to confirm these data and to determine their clinical significance.

Adjunctive nadolol in the treatment of acutely aggressive schizophrenic patients.

BACKGROUND: This study assessed the safety and efficacy of nadolol 120 mg/day compared with placebo, when administered adjunctively to neuroleptic in a group of acutely aggressive schizophrenic patients. METHOD: Thirty-four male patients enrolled in this double-blind, placebo-controlled trial. The subjects were evaluated with the Brief Psychiatric Rating Scale (BPRS) and the Simpson Angus Neurologic Rating Scale for extrapyramidal effects. The total BPRS score as well as three factors, thought disturbance, hostility, and activation, was analyzed. RESULTS: Compared with those who received placebo, the patients taking nadolol showed significant improvement on total BPRS score, particularly on the thought disturbance and activation factors, after the first treatment week (p = .05). By the end of the second treatment week, the patients taking placebo also began to show improvement, and the group differences were no longer significant. The patients treated with nadolol showed significantly more improvement on Simpson-Angus scores than those who received placebo (p = .03). However, there was no significant correlation between BPRS and Simpson-Angus changes. In the nadolol group, patients with and without akathisia showed no significant difference in their BPRS scores. CONCLUSION: These findings suggest that adjunctive nadolol may be useful in the treatment of acutely aggressive schizophrenic patients by inducing a more rapid and consistent decrease of overall psychiatric symptoms and by reducing the extrapyramidal effects. Our results raise the possibility that the mechanism of action of nadolol on psychiatric symptoms in schizophrenic patients may be different from the mechanism of improvement of neuroleptic-induced extrapyramidal symptoms and akathisia. Nadolol may be a helpful adjunctive treatment for schizophrenic patients in general and not just for those with a high hostility level.

Prophylactic ureteral catheterization in gynecologic surgery.

OBJECTIVES: To examine the frequency of ureteral catheter usage, its efficacy in preventing injury, and related complications, because the preoperative routine placement of ureteral catheters as a prophylactic measure to prevent ureteral injury is controversial. METHODS: All major gynecologic operations performed between January 1992 and December 1994 were identified. All gynecologic procedures that were preceded by ureteral catheter placement were also identified. A data base maintained by the Department of Quality Management allowed identification of all urinary tract complications and ureteral injuries. Four categories of surgery were analyzed: exploratory laparotomy with catheters, exploratory laparotomy without catheters, operative laparoscopy with catheters, and operative laparoscopy without catheters. The medical records of all patients with urinary tract complications were reviewed. RESULTS: Bilateral prophylactic ureteral catheterization was performed in 469 (15.3%) of 3071 patients. A ureteral injury occurred in 4 (0.13%) of 3071 patients. All four ureteral injuries (0.17%) occurred among 2338 patients who underwent exploratory laparotomy. None of the 733 patients who underwent operative laparoscopy suffered ureteral injury. The incidence of ureteral injury in patients who had ureteral catheters placed before exploratory laparotomy was 2 (0.62%) of 322. Two (0.10%) of 2016 patients who did not have prophylactic ureteral catheters suffered a ureteral injury. There was no statistically significant difference in the incidence of ureteral injury between patients who did and patients who did not undergo ureteral catheterization (P=0.094). CONCLUSIONS: The use of prophylactic ureteral catheters did not affect the rate of ureteral injury in our patients. The very low incidence of ureteral injury among our patients is attributed mainly to meticulous surgical technique.

Effects of inhaled nitric oxide and surfactant treatment on lung function and pulmonary hemodynamics in bronchoalveolar-lavage-induced respiratory failure.

Our aim was to study whether inhaled nitric oxide (iNO) moderates respiratory failure induced by bronchoalveolar lavage (BAL) without severe pulmonary hypertension. The following successive treatments, interrupted by 20-30-min rest periods, were given to piglets: iNO (20 ppm for 20 min), exogenous surfactant, iNO, Nomega-nitro-L-arginine methyl ester (L-NAME), and iNO. The controls inhaled NO first after L-NAME. Lung mechanics and hemodynamics were measured serially. The pulmonary to systemic arterial pressure ratio decreased during iNO and tended to increase after its discontinuation. In contrast, the iNO-induced decreases in severity of respiratory failure were not reversible during the rest periods. In a second experiment, iNO/placebo and surfactant containing (3)H-labeled dipalmitoyl phosphatidylcholine were given to rabbits. The surfactant aggregates and the surface activity from postmortem BAL, and extravascular lung water, were studied. Inhaled NO improved the surface activity and increased the large surfactant aggregates. There was no detectable decrease in extravascular lung water. The results suggest that a low dose of iNO has a beneficial effect on the gas exchange that is in part unrelated to its effect on the pulmonary vasculature.

Respiratory burst activity in bronchopulmonary dysplasia and changes with dexamethasone.

The first objective of this study was to evaluate longitudinal changes in respiratory burst activity in circulating neutrophils and monocytes in infants of less than 30 weeks of gestation with respiratory distress syndrome (RDS), and to examine differences in neonates who subsequently developed bronchopulmonary dysplasia (BPD) compared with those neonates who did not. The second objective was to investigate the effects of dexamethasone on respiratory burst activity in neutrophils and monocytes. We measured burst activity on neutrophils and monocytes in fresh heparinized blood in response to E. coli, N-formyl-met-leu-phe (fMLP), and phorbol 12-myristate 13-acetate stimulation on days 3, 7, 14, and 21 of life, before and 2-3 days after initiating a 6-day course of dexamethasone treatment. Infants with RDS participating in the study were followed until discharge, and were classified as non-BPD and either 1) BPD d28, reflecting their oxygen requirement at day of life 28, or 2) BPD 36 weeks, reflecting oxygen dependence at 36 weeks' corrected gestational age. The diagnosis of BPD was supported by radiological changes of BPD. The percentage of activated neutrophils producing a respiratory burst increased in all premature infants with increasing postnatal days during the first 28 days of life, when the physiological stimulus E. coli was used as an activator (P < 0.02). There was no significant difference in respiratory burst activity measured either as percent activation or as mean fluorescence intensity between non-BPD and BPD infants after adjusting for the difference in weight and gestational age between the two groups. The treatment of premature infants with dexamethasone was associated with decreased activation of neutrophils (P < 0.005) when E. coli was used as a stimulus. In conclusion, a significant increase in neutrophil respiratory burst activity occurs during the first month of life in very low birth weight infants. Greater pulmonary damage in BPD cannot be attributed to reduced burst activity in either neutrophils or monocytes. Dexamethasone treatment was associated with decreased neutrophil respiratory burst activity.

Tenascin patterns of expression in duct carcinoma in situ of the breast.

Immunohistochemical methods were used to study tenascin (TN) expression in duct carcinoma in situ (DCIS) of the breast of different histologic types. We evaluated 82 lumpectomy specimens of DCIS. There were 5 cases of comedo type, 19 cases of noncomedo type, and 58 cases of mixed comedo and noncomedo type. In 44 cases, the intraductal carcinomas were associated with infiltrating (invasive) duct carcinoma. TN expression was studied by immunohistochemical methods using monoclonal mouse anti-human tenascin (DAKO-TN2M636; 1:50 dilution). Positivity was recorded on a scale of 0 to 2+ for presence of TN staining around tumor ducts and thickness of TN-stained fibrous bands. TN showed positive correlation between thick bands around comedo DCIS and thin bands around noncomedo DCIS. The TN score had statistically significant positive association with high nuclear grade (p 0.004), periductal inflammatory infiltrate of DCIS (p 0.0006), associated extensive central necrosis of DCIS (p 0.0005), and comedo DCIS (p 0.0004). TN expression in the stroma was positively associated with tumor size (p 0.00002), extensive central necrosis (p 0.02), comedo DCIS (p 0.0005), and associated invasive carcinoma (p 0.006). The TN score did not correlate with duct size, multicentric carcinoma, or associated microcalcification. These results demonstrate the different biological nature of DCIS comedo type and suggest its preinvasive potential.

Effects of hypnosis and imagery training on naming behavior in aphasia.

The effects of hypnosis and imagery training on the naming behavior of three subjects with Broca's aphasia were investigated using a multiple baseline design across subjects. Treatment consisted of the induction of hypnosis, followed by guided imagery focused on the physical and functional attributes of stimulus objects. Measures of naming ability on both trained and untrained items were taken at baseline, after every training session, and a few hours after training each day. Measures were also taken of imagery ability, hypnotic susceptibility, and psychological state. Results indicated that treatment facilitated improvement in naming ability, over baseline level, for two subjects. In the case of the third subject, the verbal label was incorporated into the imagery procedure following 10 training sessions. Subsequently, this subject's naming behavior improved over baseline level. The results are discussed in terms of current theory and research in neuropsychology and cognitive psychology.

Carcass composition of "bob" and "special-fed" veal and its prediction.

Percentage of lean, fat, and bone were determined in 18 bob veal (BV) and 28 special-fed veal (SFV) carcasses. Carcasses were subjected to a set of visual conformation scores and a variety of physical measurements. No significant differences were found regarding carcass percentage of lean, fat, and bone within the three BV weight groups (P > .05). On average, SFV were 12% fatter than BV and did not have a greater percentage of lean (P > .05), except for SFV carcasses weighing 88.2 to 97.7 kg. Bob veal had less fat (internal, external, and intermuscular) and a higher bone percentage than SFV (P < .05). The round and shoulder primals had the greatest proportion of lean in both the BV and SFV carcasses. Bob veal carcasses had an average conformation score of average Good and SFV carcasses had an average conformation score of average Choice. In addition, a parsimonious subset of variables was identified for predicting total percentage of lean (TPLEAN) for both BV and SFV separately, using "stepwise" regression model building procedures. For BV, all four identified predictor variables were subjective conformation scores (i.e., muscling, appearance, leg thickness, loin-back plumpness) (R = .73, P < .03). For SFV, four predictor variables were also identified: kidney and pelvic fat, fat thickness, carcass length, and lateral thickness (R = .61, P < .03). Although both regression equations were significant predictors of TPLEAN, confidence limits for predicting future TPLEAN value were wide relative to the variation in the actual TPLEAN values. Thus, the practical utility of the regression equations is limited.

Reproducibility of a glycemic response to mixed meals in type 2 diabetes mellitus.

OBJECTIVE: To evaluate the inter-patient and intra-patient reproducibility of the glycemic response to a mixed meal in individuals with type 2 diabetes mellitus (DM). SUBJECTS/SETTING: Six individuals with DM were admitted to the General Clinical Research Center for 6 days. INTERVENTION: Subjects consumed 3 different meal plans consisting of 4 meals daily (breakfast, lunch, dinner and snack) on 2 separate occasions. Serum insulin and glucose levels were sampled at 19 time points every day. The glycemic response (GR) to a meal was calculated as the area under the glucose response curve after consumption of a given meal. In addition, the incremental area under the curve (IGR) was calculated assuming a pre-prandial (baseline) glucose value before each meal as zero. RESULTS: Intra-patient correlation coefficients (R) of GR for meals in subjects with DM were quite good, ranging 0.69-0.94. The range of the inter-patient coefficients of variation (CV) for the same meals was 21.5-30.4%. For IGR, the R values ranged from 0.64 to 0.91 for 8 out of 12 meals, confirming good intra-patient reproducibility for these meals. CV for IGR ranged from 31% to 113%. CONCLUSIONS: For patients with DM, the GR of individual meals exhibits excellent intra-patient reproducibility, allowing prediction of the glycemic response to a given meal in an individual subject. However, significant inter-patient variability of the GR precludes its use for the prediction of post-prandial glucose concentrations in groups of patients with diabetes.

Effect of relative risk and cluster configuration on the power of the one-dimensional scan statistic.

The scan test for clustering in time is based on the maximum number of events in an interval (window) of width w as the window moves across the entire time frame. Power estimates of the scan statistic are simulated for a variety of epidemiologically motivated situations. Two cluster configurations are used: a rectangular pulse, and a triangular pulse designed to emulate environmental contamination. For a rectangular pulse, the relative risk R of disease in the cluster region is R-fold as high as it is for the background region. The power is strongly influenced by the sample size, the relative risk, and the width or duration of the cluster region, whereas the effect of the cluster configuration is small. Using a 5 per cent significance level, a relative risk of 4, a standardized cluster duration of 0.10, a relative window width of 1.5, and a (non-random) sample size of 50, the simulated power is approximately 80 per cent, indicating that the minimum sample size in the cluster region for adequate power is in the 12-32 range for values of the parameters used in this study.

Neuropsychological testing in adult attention deficit hyperactivity disorder: a pilot study.

Diagnosing adult ADHD is frequently problematic because behavioral information from the patient's childhood, and multiple informants who can delineate the patient's current behavior, are often unavailable. This preliminary study was designed to explore whether objective neuropsychological testing may be a useful adjunct in the diagnosis of adult ADHD. Nineteen adults diagnosed with ADHD according to DSM-IV criteria, along with 10 controls, were assessed using a neuropsychological battery which comprised tests assessing linguistic, visual-spatial perceptual, academic, attentional and inhibitory control, mnestic and executive functions. Following preliminary analyses, designed to determine which variables best discriminated the groups, receiver operating characteristic (ROC) curves were constructed to determine the sensitivity and specificity of the best measures both alone and in combination. Only three measures significantly (p < 0.01) distinguished the groups; Digits Backwards from the WAIS-R and two reaction time measures from a computerized task modeled after Luria's Competing Motor Programs. ROC curve analyses indicated that in combination these measures had greater than 90% accuracy for classifying ADHD and non-ADHD patients. While further research is necessary these preliminary findings suggest that neuropsychological testing may be a useful adjunct in the differential diagnosis of adult ADHD.

Clinical and acoustic measures of the negative syndrome.

We studied 12 male schizophrenia patients in a 6-week treatment trial comparing two neuroleptics and placebo. Efficacy in regard to negative symptoms was of interest, and Alphs' Negative Symptom Assessment (NSA) was included. The NSA includes behaviorally anchored ratings such as "prolonged time to response" and "restricted speech output." Audio recordings of interviews with the patients were analyzed acoustically. In general, the behavioral anchors did not prevent the ratings from being influenced by global impressions. There was a strong correlation between each item and the total of other items, but a modest correlation with the relevant behavioral measure. Results suggest that, even with specific and behaviorally anchored items, the clinician's assessment is confounded by global impressions. Treatment effects were greater for the acoustic measures than for the clinical measures.

Constricted expressiveness and psychophysiological reactivity in schizophrenia.

The present study investigated flat affect in schizophrenia within a multicomponent model of emotions in which affects were identified with the expression or display of feelings. Display, as well as other components of emotion, such as subjective experience and psychophysiological reactivity, were examined as 24 schizophrenic inpatients (12 with flat affect) and 12 depressed inpatients were guided through imagery of personal emotional experiences. It was hypothesized that display variables would show a relationship with flat affect, whereas physiological and subjective variables would not. Increased flatness of affect was associated with longer pauses and reduced dyadic interaction and less zygomatic (cheek) electromyogram activity. The flat affect patients unexpectedly showed more corrugator (brow) electromyogram activity compared with the depressed group, which perhaps reflects difficulty in self-expression. The flat affect group had faster heart rates at baseline. The groups did not, however, differ in self-report of the intensity of experienced emotion. These results support the view that flat affect patients show a reduction in emotional display, whereas other subsystems of emotion processing appear normally engaged.

The relationship between negative symptoms of schizophrenia and extrapyramidal side effects with haloperidol and olanzapine.

Atypical neuroleptics present a unique opportunity to examine confounding by neuroleptic-induced extrapyramidal symptoms (EPS) in the assessment of negative signs of schizophrenia. EPS, such as facial bradykinesia and akinesia, involve some of the same response systems and phenomena as emotional display channels. EPS are attributed to the blockade of dopamine receptors in the striatum by traditional neuroleptics. Newer atypical neuroleptics target primarily mesolimbic and mesocortical areas, and receptors for other transmitters such as serotonin. Olanzapine has been reported as less likely to cause EPS and may improve some negative signs. We investigated the relationship between measures of EPS and negative symptoms in patients with schizophrenia treated with haloperidol or olanzapine. Patients were rated with the Positive and Negative Syndrome Scale (PANSS) and the Simpson-Angus Scale EPS scale. Results show that the two agents have comparable efficacy but different safety outcomes. A positive correlation between EPS and PANSS negative score was detected in the haloperidol group only. Stepwise multiple regression analysis shows that a big proportion of variability in PANSS negative symptoms is predicted by EPS in the haloperidol group, but not in the olanzapine group, even though EPS increased in patients treated with haloperidol but not in olanzapine patients.

The resurgence of congenital syphilis: a cocaine-related problem.

The relationship of maternal illicit drug use to congenital syphilis was studied in a population of newborn infants (N = 1012) who were screened for intrauterine exposure to illicit drugs by meconium analysis and whose mothers were screened for syphilis by the rapid plasmin reagin fluorescent treponemal antibody, absorbed (RPR/FTA-ABS) test. The result of the meconium drug screening was positive in 449 (44.3%) infants: 401 (39.6%) screening results were positive for cocaine, 71 (7%) positive for opiate, and 31 (3.1%) positive for cannabinoid. The maternal RPR/FTA-ABS result was positive in 72 (7.1%) women, and congenital syphilis was diagnosed in 46 (4.5%) infants on the basis of Centers for Disease Control and Prevention definitions. The incidence of positive RPR/FTA-ABS result (10.5% vs 4.4%) and congenital syphilis (7% vs 2.5%) was significantly higher (p < 0.01) among infants with positive results compared with those with negative drug screening results. Similarly, the incidence of positive RPR/FTA-ABS (11% vs 4.6%) and congenital syphilis (8% vs 2.3%) was significantly (p < 0.01) higher among infants with cocaine-positive results compared with those with cocaine-negative results. We conclude that maternal illicit drug use, specifically cocaine, is significantly related to the resurgence of congenital syphilis among newborn infants.