Significant Increase In Mean Number Research Articles

2624. The Usual Suspects: A Retrospective Analysis of Pediatric Respiratory Viral Testing During the Pandemic

Abstract Background Contention measures implemented during the pandemic drastically changed the epidemiology of viral respiratory infections. Some reports have shown a sharp decrease in Emergency department visits for respiratory illnesses in the first months of the pandemic with an increase in Respiratory Syncytial Virus (RSV) and Enterovirus (EV) in subsequent months. The concern caused by COVID-19 during the beginning of the pandemic may have led healthcare professionals to underdiagnose other respiratory viral infections. The aim of this study is to evaluate the behavior of viral infection through the pandemic. Methods A retrospective analysis was conducted to determine temporal changes in respiratory panel use and viral epidemiology in the pediatric ED from 2018 to 2022. Medical records were used to determine ICU admission and mortality in those with a positive respiratory panel. Results During the study period, a total of 10,000 respiratory PCR panels were performed in the pediatric ED. There was a significant increase in mean number of panels performed per year during the pandemic period compared to two years prior (2899 vs 198 panels/year). However, the Positivity rate decreased considerably during the pandemic (38.27% vs. 63.54%). Of the 10,000 panels performed, COVID-19 was identified in in 993 cases (9.93%), while other respiratory viruses were identified in 31.27% of cases. The most prevalent virus identified were EV (n=1411, 14.9%) and RSV (n=483, 5.1%). These viruses also had the highest rate of ICU admission and mortality. Patients that tested positive for COVID-19 had a lower rate of ICU admission compared to those infected by other viruses (RR=0.88; CI95%=0.78-0.99). Additionally, the mortality rate associated with COVID-19 was significantly lower than that of other viruses (RR=0.62; CI95%=0.49-0.79). PCR Panel Positivity Rate and Viral Infections in Pediatrics ED from 2018-2022 PCR viral panel tests performed, positive tests, and viral isolates from 2018 to 2022 Conclusion The pandemic increased the use of PCR testing for respiratory illnesses, providing a better picture of seasonal epidemiology of viral infections. Although COVID-19 infection in children was a major of concern, this report shows that throughout the pandemic other viruses were more prevalent and significantly more severe. This study serves as a reminder than even in times of emerging infections, healthcare professionals shouldn’t forget the usual causes of infection. Disclosures All Authors: No reported disclosures

The role of accelerated growth plate fusion in the absence of SOCS2 on osteoarthritis vulnerability.

AimsOsteoarthritis (OA) is the most prevalent systemic musculoskeletal disorder, characterized by articular cartilage degeneration and subchondral bone (SCB) sclerosis. Here, we sought to examine the contribution of accelerated growth to OA development using a murine model of excessive longitudinal growth. Suppressor of cytokine signalling 2 (SOCS2) is a negative regulator of growth hormone (GH) signalling, thus mice deficient in SOCS2 (Socs2 -/-) display accelerated bone growth.MethodsWe examined vulnerability of Socs2 -/- mice to OA following surgical induction of disease (destabilization of the medial meniscus (DMM)), and with ageing, by histology and micro-CT.ResultsWe observed a significant increase in mean number (wild-type (WT) DMM: 532 (SD 56); WT sham: 495 (SD 45); knockout (KO) DMM: 169 (SD 49); KO sham: 187 (SD 56); p < 0.001) and density (WT DMM: 2.2 (SD 0.9); WT sham: 1.2 (SD 0.5); KO DMM: 13.0 (SD 0.5); KO sham: 14.4 (SD 0.7)) of growth plate bridges in Socs2 -/- in comparison with WT. Histological examination of WT and Socs2 -/- knees revealed articular cartilage damage with DMM in comparison to sham. Articular cartilage lesion severity scores (mean and maximum) were similar in WT and Socs2 -/- mice with either DMM, or with ageing. Micro-CT analysis revealed significant decreases in SCB thickness, epiphyseal trabecular number, and thickness in the medial compartment of Socs2 -/-, in comparison with WT (p < 0.001). DMM had no effect on the SCB thickness in comparison with sham in either genotype.ConclusionTogether, these data suggest that enhanced GH signalling through SOCS2 deletion accelerates growth plate fusion, however this has no effect on OA vulnerability in this model.Cite this article: Bone Joint Res 2022;11(3):162–170.

Ameliorative Effect of Ginger Extract and Selenium in theThyroid Gland Toxicity Induced by Chlorpyrifos in Male Albino Rats

Background: Chlorpyrifos CPF is one of the organophosphate insecticides that were interfered with the body’s hormones. Thyroid hormones are necessary to maintained normal metabolism, growth and development and the disturbance of their levels leads to adverse medical conditions. Ginger extract and selenium are effective anti- oxidants. Aim of the work: This study examined effect of CPF on the thyroid gland structure and function and the ameliorative effect of ginger extract and selenium. Material and Methods: forty rats were categorized into four groups. Control group I, group II: rats were given CPF at a dose of 6.7 mg/kg orally five days / week for six weeks, group III: rats were given CPF and ginger extract at a dose of 750 mg/kg orally, five days / week for six weeks. Group IV: rats were given CPF and sodium selenite 10 µg/Kg orally five days / week for six weeks, blood samples were taken for hormonal essay. Thyroid gland specimens were prepared for the histological and immunohistochemical studies. Results: chlorpyrifos induced functional toxic effect and destruction of the thyroid gland histological structures. There was a significant decrease in area % of the colloid and a significant increase in mean number of PCNA positive nuclei in comparison with the control group. Ginger extract and selenium eliminated the damage effect of CPF on the thyroid gland function and histological structure. Conclusion: CPF had adverse effects on the thyroid structure and function that could be eliminated by administration of ginger and selenium.

Ophthalmic photographer virtual clinics in medical retina

To determine whether ophthalmic photographers (OPs) can conduct virtual clinics (VCs) in medical retina appropriately and whether this increases clinic capacity. Three OPs underwent a training programme to learn how to assess and manage macular edema secondary to diabetes or retinal vein occlusion. The 300 consecutive patients over a 7-month observation period in 2018 were assessed in VCs by both OPs and medical retina consultants. The degree of agreement in treatment decisions between doctors and photographers, as well as adverse events, was recorded. The change in number of patients seen in VCs over two years was also measured. There was 100% agreement in management decisions between doctors and photographers during the 300-patient observation period. No adverse events were recorded. In 2017, 572 patients were seen in VCs by doctors. After OP clinics were introduced in 2018, this number increased by 24% to 709 patients seen by both photographers and doctors. There was a significant increase in mean number of patients seen per month between 2017 (47.7±11.7) and 2018 (59.1±14.4; P=0.045, 95%CI -22.5 to -0.296). OPs can manage certain medical retina patients in VCs appropriately and can increase clinic capacity significantly for particular conditions.

Nematicidal Effect of Some Botanical Extracts for the Management of Meloidogyne incognita and on Growth of Tomato

Tomato (Solanum lycopersicum L.) is an important and widely grown vegetable crop all over the world. Although tomato is nutritionally and economically important, its production is constrained by biotic and abiotic constraints leading to poor marketable quantity and quality worldwide. Root-knot nematodes are one of the major pests affecting tomato production worldwide, especially, in the tropical and sub-tropical regions. Green house experiments were laid out in Complete Block Design (CBD) with a 3x7 factorial arrangement replicated three times carried out at the Department of Crop and Environmental Protection, University of Agriculture. The soil was sterilized before the experiment. Fresh leaves and seeds of Moringa oleifera, Ricinus communis and Jatropha curcas were washed with tap water, 15 g from each of leaves and seeds of the different botanicals was macerated separately in an electric blender at high speed for 4 minutes in 100 ml distilled water. The mixtures were passed through a Whatman filter paper number 1; the filtrates of the leaves/seeds were then collected. Three tomato varieties viz: Roma Vf, Rio Grande and UC82B were inoculated with approximately 5,000 freshly hatched second stage juvenile of Meloidogyne incognita, two weeks after transplanting. Thirty percent aqueous extract each of Castor, Moringa and Jatropha leaves and seeds was used, while double distilled water (0%) served as the control. Thirty ml of each leaf and seed aqueous extract was applied, 48 hours after inoculation as soil drench. Application was done at 1 weeks intervals thereafter for a period of 16 weeks. Data collected include number of fruits per plant, root gall index, nematode reproductive factor, and final nematode population. The results showed that various Moringa oleifera, Ricinus communis and Jatropha curcas leaves and seed extracts significantly (P&lt;0.05) reduced root gall index, final population of M. incognita in the soil and nematode reproductive factor than the control. Application of the various treatments Moringa oleifera, Ricinus communis and Jatropha curcas led to significant increase in mean number of fruits and mean fruit weight yield of all the three tomato varieties. Therefore, the application of leaf and seed aqueous extracts of Moringa, Jatropha and Castor will serve as good alternative for the management of root knot nematode Meloidogyne incognita.

Smoking behaviour and patterns among university students during the Syrian crisis

The ongoing Syrian war has resulted in many changes in the social and economic life of Syrians. To date, no study has documented the relationship between smoking behaviour and the war. To determine the prevalence of cigarette smoking among university students during the crisis in Damascus, Syrian Arab Republic, and the impact of the war on smoking behaviour. We conducted an anonymous online cross-sectional survey of 1027 undergraduate students from all years and colleges at Damascus University. The overall prevalence of tobacco smoking was 24.73% for cigarettes and 30.4% for waterpipe. Prevalence of cigarette smoking was significantly higher in men, non-health profession students, and in students living away from their families. There was no significant difference in prevalence of smoking cigarettes when comparing students according to their origin (urban vs rural), year of study, and change of residence due to war. War was associated with a significant increase in mean number of cigarettes smoked daily, and 53.1% of smokers reported that the number of cigarettes consumed per day had increased since the beginning of the war. Increased smoking is an additional health concern in areas of conflict and may require special consideration and efforts by public health authorities.

Prominence of scientific publications towards peri-implant complications in implantology: A bibliometric analysis using the H-classics method.

Current bibliometric analyses of the evolving trends in research scope category across different time periods using the H-classics method in implantology are considerably limited. The purpose of this study was to identify the classic articles in implantology to analyse bibliometric characteristics and associated factors in implantology for the past four decades. H-Classics in implantology were identified within four time periods between 1977 and 2016, based on the h-index from the Scopus® database. For each article, the principal bibliometric parameters of authorship, geographic origin, country origin, and institute origin, collaboration, centralisation, article type, scope of study and other associated factors were analysed in four time periods. A significant increase in mean numbers of authors per H-Classics was found across time. Both Europe and North America were the most productive region/country and steadily dominated this field in each time period. Collaborations of author, internationally and inter-institutionally had significantly increased across time. A significant decentralisation in authorships, institutes and journals was noted in past four decades. The journal of Clinical Oral Implant Researches has raised its importance for almost 30years (1987-2016). Research on Complications, peri-implant infection/pathology/therapy had been increasing in production throughout each period. This is the first study to evaluate research trends in implantology in the past 40years using the H-classics method, which through analysing via principle bibliometric characteristics reflected a historical perspective on evolutionary mainstream in the field. Prominence of research regarding complications may forecast innovative advancements in future.

Evaluating the impact of a resident research program in general surgery

Programs of resident research have been found to improve research productivity. However, evidence of the success of these programs is lacking in a Canadian context. The objective of this study was to evaluate the impact of the introduction of a formal program of resident research at a single Canadian academic centre. Resident research activities were tracked over a 10-year period (Resident Research Day (RRD) presentations, abstract presentations, published articles). Activities were divided into pre (2002-2007) and post (2007-2012) resident research program implementation time frames. Differences in research productivity were compared between time frames. Surveys of resident attitudes towards research were administered prior to the program's implementation in 2007, and following introduction of the resident research program in 2009 and 2015. Overall, research productivity (abstracts, publications, and RRD presentations) increased between pre and post resident research program time periods, with a statistically significant increase in mean number of published abstracts. Resident attitudes towards research changed somewhat over time, with fewer residents supporting mandatory research in recent years. Implementation of a resident program of research resulted in a significant increase in research productivity. The setting of clear, modifiable, and achievable goals, as well as providing tools for research success, have contributed to the success of this program.

PTU-127 Efficacy of Linaclotide in Constipation-Predominant Irritable Bowel Syndrome in Routine Clinical Practice: A Multicentre Experience

<h3>Introduction</h3> Constipation-predominant irritable bowel syndrome (IBS-C) is a common and difficult disorder to manage. Linaclotide is licensed in the UK for symptomatic treatment of moderate to severe IBS-C. Data from randomised, controlled trials demonstrate that the drug improves symptoms in patients with IBS-C, but real-world data are lacking. <h3>Methods</h3> We treated adult patients with IBS-C (Rome III Criteria), attending outpatient clinics in three UK hospitals, with linaclotide 290 mcg once daily. IBS symptoms were assessed at baseline, 4 weeks, and 12 weeks after commencing therapy using the validated IBS symptom severity scale (IBS-SSS). Responders were defined as those patients with a decrease in total IBS-SSS score of &gt;75. <h3>Results</h3> A total of 108 patients (mean age 43.2; range 17–84 years; 94 (87.0%) female) received linaclotide. In total, 4 week IBS-SSS scores were available for 72 (66.7%) patients, and 12 weeks scores in 26 (24.1%) patients. Effect of linaclotide on individual components of the IBS-SSS, as well as total IBS-SSS score, at 4 and 12 weeks are detailed in Table 1. There were 49 (45.4%) patients who responded to linaclotide, with a reduction in IBS-SSS of &gt;75 at 4 weeks. The drug also led to a significant reduction in straining (3.9 at baseline vs. 2.0 at 4 weeks, P &lt; 0.001), and increase in mean number of stools per week (3.8 at baseline vs. 8.9 at 4 weeks, P &lt; 0.001). At 4 weeks, 61 (56.5%) patients continued the drug and 47 (43.5%) discontinued, 24 (22.2%) due to lack of efficacy or losses to follow-up, and 23 (21.3%) due to adverse events (AEs). Among the 61 patients continuing linaclotide, 22 (36.1%) were responders at 12 weeks. AEs occurred in 43 (39.8%) patients overall, which lead to discontinuation of the drug in 23 (21.3%) patients either before or at their 4 week assessment. These included diarrhoea in 28 (25.9%) (15 discontinued), abdominal pain in 6 (5.6%) (5 discontinued), nausea in 3 (2.8%) (1 discontinued), flatulence in 2 (1 discontinued), headaches in 2 (0 discontinued), faecal incontinence in 1 (1 discontinued), and urgency in 1 (0 discontinued). <h3>Conclusion</h3> Linaclotide was effective in IBS-C patients in a real-world setting, with significant reductions in IBS-SSS scores and straining, and a significant increase in mean number of stools per week. Responder rates at 4 and 12 weeks were 45% and 36% respectively. 40% of patients reported AEs, with diarrhoea the commonest, occurring in 26% of patients. Previous literature has reported a lower frequency of AEs, which infrequently led to withdrawal of linaclotide. However, in our study the occurrence of AEs led to discontinuation in 21% of patients. <h3>Disclosure of Interest</h3> None Declared

Mo1635 Efficacy of Linaclotide in Constipation-Predominant Irritable Bowel Syndrome in Routine Clinical Practice: A Multicentre Experience

Introduction Constipation-predominant irritable bowel syndrome (IBS-C) is a common and difficult disorder to manage. Linaclotide is licensed in the UK for symptomatic treatment of moderate to severe IBS-C. Data from randomised, controlled trials demonstrate that the drug improves symptoms in patients with IBS-C, but real-world data are lacking. Methods We treated adult patients with IBS-C (Rome III Criteria), attending outpatient clinics in three UK hospitals, with linaclotide 290 mcg once daily. IBS symptoms were assessed at baseline, 4 weeks, and 12 weeks after commencing therapy using the validated IBS symptom severity scale (IBS-SSS). Responders were defined as those patients with a decrease in total IBS-SSS score of >75. Results A total of 108 patients (mean age 43.2; range 17–84 years; 94 (87.0%) female) received linaclotide. In total, 4 week IBS-SSS scores were available for 72 (66.7%) patients, and 12 weeks scores in 26 (24.1%) patients. Effect of linaclotide on individual components of the IBS-SSS, as well as total IBS-SSS score, at 4 and 12 weeks are detailed in Table 1. There were 49 (45.4%) patients who responded to linaclotide, with a reduction in IBS-SSS of >75 at 4 weeks. The drug also led to a significant reduction in straining (3.9 at baseline vs. 2.0 at 4 weeks, P Conclusion Linaclotide was effective in IBS-C patients in a real-world setting, with significant reductions in IBS-SSS scores and straining, and a significant increase in mean number of stools per week. Responder rates at 4 and 12 weeks were 45% and 36% respectively. 40% of patients reported AEs, with diarrhoea the commonest, occurring in 26% of patients. Previous literature has reported a lower frequency of AEs, which infrequently led to withdrawal of linaclotide. However, in our study the occurrence of AEs led to discontinuation in 21% of patients. Disclosure of Interest None Declared

Polypharmacy among inpatients aged 70 years or older in Australia.

To investigate medication changes for older patients admitted to hospital and to explore associations between patient characteristics and polypharmacy. Prospective cohort study. Patients aged 70 years or older admitted to general medical units of 11 acute care hospitals in two Australian states between July 2005 and May 2010. All patients were assessed using the interRAI assessment system for acute care. Measures of physical, cognitive and psychosocial functioning; and number of regular prescribed medications categorised into three groups: non-polypharmacy (0-4 drugs), polypharmacy (5-9 drugs) and hyperpolypharmacy (≥10 drugs). Of 1220 patients who were recruited for the study, medication records at admission were available for 1216. Mean age was 81.3 years (SD, 6.8 years), and 659 patients (54.2%) were women. For the 1187 patients with complete medication records on admission and discharge, there was a small but statistically significant increase in mean number of regular medications per day between admission and discharge (7.1 v 7.6), while the prevalence of medications such as statins (459 [38.7%] v 457 [38.5%] patients), opioid analgesics (155 [13.1%] v 166 [14.0%] patients), antipsychotics (59 [5.0%] v 65 [5.5%] patients) and benzodiazepines (122 [10.3%] v 135 [11.4%] patients) did not change significantly. Being in a higher polypharmacy category was significantly associated with increase in comorbidities (odds ratio [OR], 1.27; 95% CI, 1.20-1.34), presence of pain (OR, 1.31; 1.05-1.64), dyspnoea (OR, 1.64; 1.30-2.07) and dependence in terms of instrumental activities of daily living (OR, 1.70; 1.20-2.41). Hyperpolypharmacy was observed in 290/1216 patients (23.8%) at admission and 336/1187 patients (28.3%) on discharge, and the proportion of preventive medication in the hyperpolypharmacy category at both points in time remained high (1209/3371 [35.9%] at admission v 1508/4117 [36.6%] at discharge). Polypharmacy is common among older people admitted to general medical units of Australian hospitals, with no clinically meaningful change to the number or classification (symptom control, prevention or both) of drugs made by treating physicians.

Role of dehydroepiandrosterone in improving oocyte and embryo quality in IVF cycles

The purpose of this study was to evaluate the role of dehydroepiandrosterone (DHEA) on the number and quality of oocytes and embryos in poor responders undergoing IVF cycles. A total of 50 patients with a history of poor ovarian response in the previous cycle(s) were enrolled in a prospective cohort study. They were treated with oral micronized DHEA 25mg three times a day for 4months. Oocyte and embryo number and quality were recorded before and after treatment. The results were analysed using Student’s paired t-test. After treatment with DHEA, a significant increase in number of mature follicles was seen in the post treatment period (⩽35years P<0.001; ⩾36years P=0.002). There were significant increases in numbers of oocytes retrieved, fertilization rates and, consequently, the total number of embryos available. More embryos were vitrified among patients ⩽35years (P<0.001) post treatment, and clinical pregnancy rate in this group was 26.7%. DHEA treatment resulted in a higher number of oocytes retrieved, oocytes fertilized, embryos overall and of grade-I embryos. It can help in increasing pregnancy rate in poor responders.This study was performed to evaluate the role of dehydroepiandrosterone (DHEA) treatment on the number and quality of oocytes and embryos in poor responders undergoing IVF cycles. Fifty patients with a history of poor ovarian response in the previous cycle(s) were enrolled in the study and a prospective cohort study was performed. Patients were prescribed oral micronized DHEA 25mg three times a day for 4months. Oocytes and embryos in terms of both number and quality were measured before and after treatment. A significant increase in mean number of mature follicles was seen in the post-treatment group. There was a significant increase in the number of oocytes retrieved, fertilization rates and, consequently, in the total number of embryos available after treatment with DHEA. More embryos were vitrified post treatment and the overall pregnancy rate was 20%. DHEA resulted in a significant improvement in the numbers of oocytes retrieved, oocytes fertilized, embryos and grade-I embryos. DHEA can help improve pregnancy rate in poor responders with history of previous failed IVF cycles.

Effect of CPP-ACP Paste on Dental Caries in Primary Teeth

This clinical trial tested the effect of daily application of 10% w/v calcium phosphopeptide-amorphous calcium phosphate (CPP-ACP) paste for 1 yr when added to regular toothbrushing with fluoridated toothpaste to prevent dental caries in pre-school children. High-caries-risk children aged 2½ to 3½ yrs in a suburban area of central Thailand were assigned to receive either CPP-ACP (n = 150) or a placebo control (n = 146) in addition to fluoridated toothpaste. The International Caries Detection and Assessment System (ICDAS) was recorded at baseline, 6 mos, and 1 yr. At 1 yr, a significant increase in mean numbers of enamel and dentin caries lesions, as well as dmfs, was found in both groups (p < 0.001). No significant difference was observed between groups on these 3 outcome measures (p = 0.23, 0.84, and 0.91, respectively). The odds of enamel caries lesion transitions to a state of regression or stability, compared with progression from baseline, was also not different between groups [OR = 1.00, 95% CI (0.86, 1.17)]. This trial found that daily application of 10% w/v CPP-ACP paste on school days for 1 yr, when added to regular toothbrushing with a fluoride toothpaste, had no significant added effect in preventing caries in the primary dentition of these pre-school children (ClinicalTrials.gov number CT01 604109).

The probiotic VSL#3 increases scbm and reduces symptom severity scores in patients with functional constipation

IntroductionThere is increasing evidence for the use of probiotic bacteria in the treatment of irritable bowel syndrome (IBS). Most reports to date have been in patients with diarrhoea or bloating....

Ventilation Defects Observed with Hyperpolarized3He Magnetic Resonance Imaging in a Mouse Model of Acute Lung Injury

Regions of diminished ventilation are often evident during functional pulmonary imaging studies, including hyperpolarized gas magnetic resonance imaging (MRI), positron emission tomography, and computed tomography (CT). The objective of this study was to characterize the hypointense regions observed via (3)He MRI in a murine model of acute lung injury. LPS at doses ranging from 15-50 μg was intratracheally administered to C57BL/6 mice under anesthesia. Four hours after exposure to either LPS or saline vehicle, mice were imaged via hyperpolarized (3)He MRI. All images were evaluated to identify regions of hypointense signals. Lungs were then characterized by conventional histology, or used to obtain tissue samples from regions of normal and hypointense (3)He signals and analyzed for cytokine content. The characterization of (3)He MRI images identified three distinct types of hypointense patterns: persistent defects, atelectatic defects, and dorsal lucencies. Persistent defects were associated with the administration of LPS. The number of persistent defects depended on the dose of LPS, with a significant increase in mean number of defects in 30-50-μg LPS-dosed mice versus saline-treated control mice. Atelectatic defects predominated in LPS-dosed mice under conditions of low-volume ventilation, and could be reversed with deep inspiration. Dorsal lucencies were present in nearly all mice studied, regardless of the experimental conditions, including control animals that did not receive LPS. A comparison of (3)He MRI with histopathology did not identify tissue abnormalities in regions of low (3)He signal, with the exception of a single region of atelectasis in one mouse. Furthermore, no statistically significant differences were evident in concentrations of IL-1β, IL-6, macrophage inflammatory protein (MIP)-1α, MIP-2, chemokine (C-X-C motif) ligand 1 (KC), TNFα, and monocyte chemotactic protein (MCP)-1 between hypointense and normally ventilated lung regions in LPS-dosed mice. Thus, this study defines the anatomic, functional, and biochemical characteristics of ventilation defects associated with the administration of LPS in a murine model of acute lung injury.

Brain Irradiation-Induced Lymphocytosis Predicts Response in Cancer Patients with Brain Metastases

Lymphocytopenia is one of the main toxicities of radiotherapy and its severity is related to the irradiation dose. The occurrence of lymphocytopenia depends on the body site of radiotherapy; it is most pronounced with pelvic irradiation, whereas the effect of brain irradiation on the lymphocyte count is to be elucidated. This preliminary study was performed to evaluate changes in lymphocyte number occurring during brain irradiation in cancer patients with brain metastases. The study included 50 patients who received brain radiotherapy for single or multiple brain metastases at a total dose of 30 Gy. Overall, no significant changes in mean lymphocyte number occurred during brain radiotherapy. However, when lymphocyte variations were assessed in relation to the clinical response of brain metastases, a significant increase in the mean number of lymphocytes was found in patients who achieved objective regression of brain metastases on brain irradiation. The mean lymphocyte number decreased in nonresponding patients, albeit without a statistically significant difference with respect to the pretreatment values. The results of this study show that the efficacy of radiotherapy in the treatment of brain metastases is associated with a significant increase in mean lymphocyte number. Therefore, evidence of brain irradiation-induced lymphocytosis may predict the efficacy of radiotherapy.

Brain irradiation-induced lymphocytosis predicts response in cancer patients with brain metastases

Lymphocytopenia is one of the main toxicities of radiotherapy and its severity is related to the irradiation dose. The occurrence of lymphocytopenia depends on the body site of radiotherapy; it is most pronounced with pelvic irradiation, whereas the effect of brain irradiation on the lymphocyte count is to be elucidated. This preliminary study was performed to evaluate changes in lymphocyte number occurring during brain irradiation in cancer patients with brain metastases. The study included 50 patients who received brain radiotherapy for single or multiple brain metastases at a total dose of 30 Gy. Overall, no significant changes in mean lymphocyte number occurred during brain radiotherapy. However, when lymphocyte variations were assessed in relation to the clinical response of brain metastases, a significant increase in the mean number of lymphocytes was found in patients who achieved objective regression of brain metastases on brain irradiation. The mean lymphocyte number decreased in nonresponding patients, albeit without a statistically significant difference with respect to the pretreatment values. The results of this study show that the efficacy of radiotherapy in the treatment of brain metastases is associated with a significant increase in mean lymphocyte number. Therefore, evidence of brain irradiation-induced lymphocytosis may predict the efficacy of radiotherapy.

New Treatment Options in Childhood Constipation?

To date, the worldwide prevalence of symptoms of constipation in children varies widely and is estimated to range between 0.3–28%. Childhood constipation is recognized by infrequent, hard stools and the involuntary loss of faeces in the underwear. It is a debilitating condition that is often associated with abdominal pain. It causes distress to the child and to the family and can result in severe emotional disturbance and family discord. Importantly, childhood constipation often continues into adulthood and it is suggested that longstanding faecal impaction from childhood-on may result in a more complex pathophysiological end-state later in life (1). This again emphasizes the significance of an effective therapeutic intervention in children. To date however, treatment modalities are mainly based on empiricism and have little evidence of long-term efficacy. Although many compounds have been tried, there are little data to support there use. Moreover, there is a huge lack of large double-blind randomised controlled trials in children with well defined outcome measures. As in many more other fields in the medical treatment of children only a minority of the drugs used to treat constipated children have been studied adequately in the population, have appropriate use information on the product label and the information regarding safety and efficacy for pediatric patients is insufficient or absent. Currently acute simple constipation is usually treated with a high fibre diet and sufficient fluid intake, filling out a diary and toilet training. Based on the American medical position statement the treatment of chronic constipation consists of 4 important phases: 1) education, 2) disimpaction, 3) prevention of re-accumulation of faeces and 4) follow up (2). In this paper firstly recent advances in the treatment of constipation in adults and children are discussed, such as the selective 5-HT4, agonist, tegaserod, preand probiotics and sacral nerve stimulation. The second part will cover the use of polyethylene glycol which has been described as an effective and welltolerated treatment choice for pediatric constipation, especially as an adjunct to education and behavioural training. PEG 3350 and PEG 4000 have been proved an option for children with constipation who have failed or are intolerant of other pharmacotherapies. Serotonin plays a key role in mediating peristalsis and stimulating intestinal secretion via 5-HT4 receptors in the gut wall. Tegaserod, a selective agonist that acts at 5-HT4 receptors and increases small bowel transit, stimulates intestinal secretion and inhibits visceral afferent responses has proven effective in the treatment of chronic constipation in adults (3,4). Two randomized placebo controlled trials including more than 3000 patients with constipation showed a significant increase in spontaneous bowel movements per week and a significant reduction in straining, abdominal bloating/distension, and abdominal pain/discomfort. The most common adverse events, headache and abdominal pain, were more frequent with placebo than with tegaserod. In children with hard stools, caused by excessive straining, 5-HT4 agonist might benefit children with constipation and tendency to form hard stools, scybala and large rectal masses. This seems to be present more frequently in children.The role of this promising new agent in pediatric constipation has to be established in future studies. National and international collaboration to evaluate the efficacy of Tegaserod in children is of imminent importance to match similar quality and valuable results as described in adults with constipation. Researchers claim a positive effect on intestinal transit and stool consistency of preand probiotics. Nondigestible oligosaccharides consist mainly of fructooligosaccharides (FOS). FOS is a soluble dietary fibre, which reduces faecal pH, increases the water/holding capacity of stool and faecal weight and decreases intestinal transit time. Furthermore, it has prebiotic effects by selectively stimulating the growth of probiotic bacteria, such as bifidobacteria. A double-blind randomized controlled study in healthy infants comparing a fructooligosaccharide-supplemented cereal (0.75 g FOS per cereal serving) with placebo showed a significant increase in mean numbers of stool per infant and softer stools (5). The FOS supplemented cereal was well tolerated. In another study in healthy women, the probiotic strain Bifidobacterium animalis shortened both the total colonic transit time and the rectosigmoid transit time (6). However, the number of stools per week did not significantly change between the Bifidobacterium and M. A. Benninga, MD, PhD (e-mail: m.a.benninga@amc.uva.nl). Journal of Pediatric Gastroenterology and Nutrition 41:S56–S57 September 2005 Lippincott Williams & Wilkins, Philadelphia

Influence of stress on gonadotrophin induced testicular recrudescence in the lizardMabuya Carinata

Administration (ip) of FSH (10 IU/0.1 ml distilled water (dw)/lizard/alternate days/30 days) to adult male lizards, Mabuya carinata, during the early recrudescence phase of the reproductive cycle caused activation of spermatogenic and steroidogenic activity of the testis, as shown by a significant increase in mean number of spermatogonia, primary spermatocytes and spermatids, and serum levels of testosterone, as compared to initial controls. In addition, there were abundant spermatozoa in the lumen of the seminiferous tubules. Interestingly, administration of a similar dosage of FSH to lizards exposed to stressors (handling, chasing, and noise randomly applied, five times a day for 30 days) resulted in a significant increase in mean number of spermatogonia and primary spermatocytes over initial control values, whereas the number of secondary spermatocytes and spermatids and serum levels of testosterone did not significantly differ from those of initial controls, and were significantly lower than FSH treated normal lizards. Further, spermatozoa were infrequently found in the seminiferous tubules of these lizards. Treatment controls (receiving 0.1 ml dw/lizard/alternate days for 30 days) did not show significant variation in mean number of spermatogonia, spermatocytes and spermatids, and serum levels of testosterone from initial controls. Another group of lizards was exposed to stressors and did not receive FSH. These lizards showed a significant decrease in mean number of secondary spermatocytes compared to treatment controls and all other parameters did not significantly differ from those of both control groups. The results reveal that gonadotrophin-induced spermatogonial proliferation occurs under stressful conditions, whereas progress of spermatogenesis beyond primary spermatocyte stage is impaired due to inhibition (under stress) of gonadotrophin induced steroidogenic activity in M. carinata.

Evaluating health-related wellbeing outcomes among outpatient adults with human immunodeficiency virus infection in the HAART era.

Quality of life (QoL) changes among 56 adult patients living with HIV/AID (PHA) were assessed following two years of care in which most had received highly active antiretroviral therapy (HAART). The sample was stratified by initial disease stage; subjects were classified 'asymptomatic' if they had no HIV-related constitutional symptoms, 'symptomatic' if they had at least one symptom, and 'AIDS' if symptomatic with a history of opportunistic infections and/or CD4 count less than 200 cells/ micro L. For the overall group, changes in mean QoL (Medical Outcomes Study Short-Form-36 [SF-36]) ratings were non-significant, irrespective of initial disease stage or prior HAART exposure. Although overall there were health status improvements over the two-year period, clinical changes were generally unrelated to changes in QoL ratings. Patients with better immunologic/virologic outcomes showed slight improvements in mean QoL ratings, while those with poorer clinical outcomes showed slight deterioration. These within-group changes over time were statistically non-significant. The corresponding between-group differences in changes in SF-36 social and psychological dimensions were significant. Statistically significant differences among the three disease stage groups on a number of subscales at baseline (Physical Function, Body Pain, Vitality, Role Limitations due to Physical Problems) became non-significant (i.e. nullified) at follow-up. Significant increases in mean number of symptoms for the asymptomatic and symptomatic groups were not associated with two-year changes in QoL ratings. Overall, wellbeing was moderately stable over the two-year follow-up period, although somewhat affected by symptom changes and immunologic/virologic outcome. The study results contrast with pre-HAART longitudinal research, in which deterioration in all areas of QoL occurred.