Macromolecular interstitial clearance, tumour vascularity, other prognostic factors and breast cancer survival

Background: Clearance of large molecules from the interstitialspace is an important function of lymphatics andis affected by local pathologic changes.Objective: To determine if the clearance rate ofinterstitially injected albumin is correlated to tumour characteristicsand outcome in women with invasive breast cancer.Method: In a consecutive series of women comingto biopsy for suspected breast cancer, technetium-tagged albuminwas injected into the tissue adjacent to thepalpable mass. The isotope disappearance rate was measuredover two hours. Also assessed were the maximumvessel density (MVD – using Factor VIII polyclonalantisera), the proliferation rate (using Ki-67 antisera), nodestatus, tumour size, histologic and nuclear grade, mitoticrate, and p53 and c-erbB-2 oncoproteins. All patientswere followed until relapse and for a minimumof 10 years.Results: In multivariate analysis, an association between relapse-freesurvival and isotope clearance rate was suggested (p= 0.024). The best outcome was seen inpatients with the least isotope clearance. Node status,size, histologic and nuclear grade, and mitotic ratecorrelated with survival. MVD did not correlate withsurvival and was inversely related to the isotopeclearance rate. Tumour proliferation rate, and the c-erbB-2and p53 oncoproteins did not relate to outcome.Conclusion: The role of lymphatics in breast canceris difficult to study. Measurement of interstitial clearancemay be a useful technique and could bea prognostic factor.     

Laparoscopy in infants and children: a prospective study on feasibility and the impact on routine surgery

BACKGROUND/PURPOSE: The feasibility of laparoscopy in children and its impact on routine pediatric surgery are not well established. The purpose of this study was to determine the role of laparoscopy in a university department of pediatric surgery. METHODS: All children undergoing laparoscopy during the period of 1 year were included in a prospective trial. Data on patients, the operation, technical problems, intraoperative events, and the postoperative course were documented using standardized questionnaires. All patients underwent at least 1 follow-up assessment 2 weeks after the operation. All conventional abdominal operations performed during the same period were analyzed for comparison purposes. RESULTS: Of 244 abdominal operations performed during the study period, 147 (60.2%) were laparoscopies. One hundred twenty-three (83.7%) of these included a laparoscopic operation, and 24 (16.3%) were diagnostic procedures. Of 26 types of laparoscopic operations 3 were performed more than 15 times (fundoplication, appendectomy, pyloromyotomy), and 9 types were performed once. Problems with instruments and devices led to a mean time loss of 15.1 minutes in 15.6% of the procedures. The conversion rate was 10.1% mainly because of complicated appendicitis. Fifty-six children (38.1%) weighed less than 10 kg, and the conversion rate did not correlate with the body weight. There was 1 (0.07%) intraoperative event. A small bowel perforation was identified immediately and resolved with an uneventful course. Postoperative complications included an incisional hernia in 3 children and an incisional leakage of liquor in 1 child with a ventriculoperitoneal drain. There was a reprolaps after laparoscopic correction of an ileostomy in 1 child and fever in another. In 3 newborns the diagnosis was missed during laparoscopy and had to be established by laparotomy later with an uneventful course. Primary conventional operations were mainly restricted to bowel resection and anastomosis performed in 52 of 97 laparotomies. CONCLUSIONS: The authors showed that 60% of abdominal operations in children can be performed via laparoscopy. Most types of laparoscopic operations are not performed frequently, but the feasibility of the technique in routine use is excellent. However, the performance of instruments should be improved further, and laparoscopy for establishing the diagnosis in newborns remains difficult.     

Evidence of Normal Cerebellar Control of the Vestibulo-Ocular Reflex (VOR) in Children with High-Functioning Autism

The effect of tilt-suppression on post-rotatory vestibular nystagmus was investigated to assess the function of the caudal cerebellar vermis (lobules IX and X, or nodulus and uvula) in 13 school-age children with high-functioning autism (HFA) and 10 normal controls. Tilt-suppression of the vestibulo-ocular reflex (VOR) refers to the decreasing of the duration of post-rotatory vestibular nystagmus that occurs when the head is moved out of the plane in which it was located during the previous sustained constant-velocity rotation. The participant is rotated in a vestibular chair with the head upright and then the head is tilted forward just after the chair stops rotating. Such tilt-suppression is impaired with lesions of the cerebellar nodulus and portions of the uvula. Results show that children with HFA have normal post-rotatory nystasmus with the head upright and normal attenuation of post-rotatory nystagmus induced by head tilt. These behavioral findings suggest that lobules IX and X of the cerebellum are spared in high-functioning autism.     

Being circadian or not: vasopressin release in cultured SCN mirrors behavior in adult voles

We studied vasopressin (AVP) release patterns from organotypic suprachiasmatic nucleus (SCN) cultures obtained from circadian rhythmic and non-rhythmic voles. All eight SCN cultures made from non-rhythmic voles did not produce any circadian pattern in AVP release, while five out of six SCN cultures of rhythmic voles produced significant (circadian) peak values. The total amount of AVP released was 2-fold higher in SCN cultures from rhythmic vole. These data confirm our previously formulated AVP release deficit hypothesis for nonrhythmic voles, and suggest that AVP in the vole SCN plays an important role in mediating output of its circadian clock, regulating circadian organization of locomotor behavior.     

Quantitative measurement of post-irradiation neck fibrosis based on the young modulus: description of a new method and clinical results

BACKGROUND: Postirradiation fibrosis is one of the most common late effects of radiation therapy for patients with head and neck carcinoma. An objective and quantitative method for its measurement is much desired, but the criteria currently used to score fibrosis are mostly semiquantitative and partially subjective. METHODS: The Young Modulus (YM) is a physical parameter that characterizes the deformability of material to stress. The authors measured the YM in soft tissues of the neck, at defined reference points, using an ultrasound probe and computer algorithm that quantified the indentation (deformation) on tissue due to a measured, applied force. One hundred five patients who had received previous radiation therapy to the entire neck were assessed, and the results were compared with the hand palpation scores and with a functional parameter represented by the range of neck rotation, and all results were correlated with symptoms. RESULTS: The YM was obtained successfully in all patients examined. It had a significant positive correlation with the palpation score and a significant negative correlation with the range of neck rotation. The YM was significantly higher on the side of the neck that received a boost dose of radiation, although the corresponding palpation scores were similar. The results of all three measurement methods were correlated with symptoms. CONCLUSIONS: Postirradiation neck fibrosis can be measured in absolute units based on the YM. The results showed a significant correlation with hand palpation scores, with restriction of neck rotation, and with symptoms. Compared with the palpation method, the YM is more quantitative, objective, focused on small subregions, and better discriminates regions subject to differential radiation dose levels. Its inclusion in the Analytic category of the Late Effects of Normal Tissues-SOMA system should be considered to facilitate comparative studies.     

Topoisomerase I and II activity in human breast,cervix, lung and colon cancer

The identification of human DNA topoisomerases as cellular targets for active anti-cancer drugs has stimulated further interest in topoisomerase function in tumour biology. Topoisom-erase I and II catalytic activity is detectable in many normal and malignant tissues. However, little is known about the expression of topoisomerases in most human solid tumours. The present study evaluated topoisomerase I and II activity in biopsy samples from 86 patients with breast, lung, cervix or colon cancers. Significant intra- and inter-tumour variation in topoisomerase expression was observed. Topoisomerase I activity was relatively high in cervix and colon tumours in comparison to lung and breast cancers. Topoisomerase II activity was high in cervix, colon and lung cancers relative to breast cancer. Topoisomerase I and II activity co-segregated in individual colon tumour samples, but no correlation was observed in cervix, lung or breast tumours. The large heterogeneity in both topoisomerase I and II activity within a tumour type suggests a mechanism for variable response to topoisomerase-directed therapy. The differences in activity between tumour groups suggest that the potential efficacy of inhibitors of topoisomerase I in colon and cervical tumours may be greater than in lung and breast tumours. Future in vivo evaluation is required to establish the clinical relevance of the observed heterogeneity in topoisomerase activity.     

Racial and Ethnic Differences in Eating Duration and Meal Timing: Findings from NHANES 2011–2018

Background: In addition to quantity and quality, meal timing and eating duration are additional dietary characteristics that impact cardiometabolic health. Given that cardiometabolic health disparities exist among racial and ethnic groups, we examined whether meal timing and eating duration are additional diet-related differences among racial and ethnic groups. Methods: Participants (n = 13,084) were adults (≥20 years) from the National Health and Nutrition Examination (NHANES, 2011–2018) Survey. Times of first and last meal and the interval between them (eating duration) were derived from two 24-h dietary recalls. Multiple linear regression analyses compared these variables among race and ethnicity after adjusting for potential confounders. Results: Compared to non-Hispanic White adults, the first mealtime was significantly later for Mexican American (23 min), Non-Hispanic Asian (15 min), Non-Hispanic Black (46 min), and Other Hispanic (20 min) and Other Racial (14 min) adults (all p < 0.05). Mexican American and Non-Hispanic Asian adults had a significantly different last mealtime by 13 min earlier and 25 min later, respectively, compared to Non-Hispanic White adults. Compared to Non-Hispanic White adults, the mean eating duration was shorter for other Hispanic (20 min), Mexican American (36 min), and Non-Hispanic Black (49 min) adults. Conclusions: Meal timing and eating duration are additional dietary characteristics that vary significantly among racial and ethnic groups.     

Bronchoscopic management of airway obstruction in pediatric endobronchial tuberculosis

The present report describes a case of severe airway obstruction caused by endobronchial tuberculosis in an 11-year-old girl who was successfully treated by bronchoscopic balloon dilation. This case illustrates the insidious presentation and the increasingly important role of bronchoscopic intervention in the management of endobronchial tuberculosis. In addition, a brief literature review of the condition in the pediatric age group is included.     

Endogenous protein phosphorylation by resting and activated human neutrophils

NADPH oxidase is an enzyme in the plasma membrane of the neutrophil that catalyzes the production of O2-, a species central to the oxygen- dependent killing mechanisms of this cell. The oxidase is dormant in resting cells and is activated upon the addition of a stimulus. Neutrophils of patients with chronic granulomatous disease (CGD) manifest no oxidase activity when stimulated. The possible role of protein phosphorylation in the activation of NADPH oxidase was examined in normal and CGD neutrophils by measuring the incorporation of 32Pi into proteins as determined by gel electrophoresis followed by autoradiography. Resting neutrophils from normal subjects exhibit at least 40 distinct phosphoprotein bands. The level of phosphorylation of these bands was examined after the addition of phorbol myristate acetate (PMA), opsonized zymosan, digitonin, N-formyl-methionyl- phenylalanine (FMLP), or NaF. PMA and opsonized zymosan increased the phosphorylation of a set of 6 protein bands. Digitonin and FMLP consistently caused the phosphorylation of 4 of these protein bands, while NaF failed to induce increased phosphorylation of any protein band. All activators tested caused the dephosphorylation of one specific protein band. The time course of phosphorylation (dephosphorylation) was examined using PMA as the activating agent. Increased phosphorylation of one protein band was evident by 12 sec after the addition of PMA. The most slowly phosphorylated protein band did not slow evidence of change until 5 min after the addition of PMA. Three of the phosphoproteins examined were phosphorylated either earlier than or concomitant with the activation of NADPH oxidase. CGD neutrophils were compared with normal cells for their ability to phosphorylate proteins in response to PMA. The phosphoprotein banding patterns of CGD neutrophils were identical with those of normal neutrophils in both the resting and activated states. The evidence presented shows that the phosphorylation of proteins is a prominent feature of neutrophil metabolism. The striking similarity of phosphorylation changes induced by the various activators tested suggests that protein phosphorylation may play a role in some aspects of neutrophil activation. Evidence was not obtained, however, regarding a link between protein phosphorylation and activation of NADPH oxidase.