Variability in serotonin and enterochromaffin cells in patients with colonic inertia and idiopathic diarrhoea as compared to normal controls

Aim To evaluate differences in distribution, density and staining intensity of enterochromaffin cells (EC) and serotonin cells (SC) in the colonic mucosa of patients with colonic inertia (CI), idiopathic diarrhoea (ID) and a control group. Methods Three groups were studied: 19 patients' colons after subtotal colectomy for CI, and 17 patients' biopsies for diarrhoea (>3 bowel movements/day) with histological findings of normal mucosa (excluding microscopic, eosinophillic and collagenous colitis). The third group included 15 patients who underwent colonoscopy and biopsy for indications other than constipation, inflammatory bowel disease, diarrhoea or neoplasm (control group). Specimen blocks were obtained in each case from the right and left colon. Immunohistochemical staining for EC and SC were done on 4 µm sections from Hollandes fixed, paraffin embedded tissues with primary rabbit antibody against chromagranin A or serotonin, and biotynylated secondary antibody and enzyme labelled streptavidin. Results The number of EC in the mucosa of the left colon in patients with CI (16.8 ± 10.2) and ID (19.9 ± 9.7) were significantly higher than they were on the right side (CI: 9.4 ± 6.0, ID: 12.1 ± 5.3). However, there were no significant differences between the left and right sides in the control group (L: 10.3 ± 5.3; R: 13.4 ± 7.6). Although the quantity of EC in the left colon in both patients with CI (P < 0.05) and ID (P < 0.01) were significantly higher than in the controls, there was no significant difference between CI and ID. In both the right and left colon, the percentage of EC with low positive density was significantly higher (P < 0.01) while those cells with moderate or low staining intensity were significantly lower in patients with CI than in either patients with ID or control group. In patients with CI, the quantity of SC in the mucosa of the left colon (12.1 ± 6.4) was higher than in the right (CI: 7.9 ± 3.6; control 4.6 ± 3.3; ID 4.6 ± 2.9) (P = 0.0057). In contrast there was no significant difference in SC in either the ID or control groups. The quantity of SC in both sides of the colon was significantly higher both in patients with CI as compared to the control group (P < 0.01) and patients with CI vs. patients with ID (L = P < 0.01; R = P < 0.05). There was a significantly positive correlation between the numbers of EC and SC in patients with CI (L: r = 0.5425, P < 0.05; R: r = 0.745, P < 0.01). Conclusion In patients with CI, EC increases possibly due to an increase in SC. Conversely, in patients with ID, the EC increase results from peptides other than SC. Our results suggest that different aetiological factors contribute to ID and CI.     

Can central neuropeptides be implicated in carotid sinus reflex hypersensitivity?

Carotid sinus reflex hypersensitivity involves profound and intermittent changes in heart rate and blood pressure associated with symptoms of dizziness and syncope. This involves a reflex arc in which the main defect is believed to lie within the central nervous system. The discovery of classical and peptidergic neurotransmitters within the same neurone, and the presence of these peptides within the central nervous system raises the possibility that carotid sinus reflex hypersensitivity may be related to an abnormality of peptide distribution or function.     

Antigen dependent adjuvant activity of a polydispersed beta-(1,4)-linked acetylated mannan (acemannan).

The adjuvant properties of a polydispersed beta-(1,4)-linked acetylated mannan, acemannan (ACE-M), were evaluated. Day-old broiler chicks were randomly selected and allocated to four flocks (Vac 1-4). The Vac 1 flock was sham vaccinated with saline. The Vac 2 flock was vaccinated with an oil-based vaccine (Breedervac III; Newcastle disease virus (NDV), infectious bursal disease virus (IBDV) and infectious bronchitis virus). The Vac 3 flock was vaccinated with a vaccine-ACE-M mixture, and the Vac 4 flock was vaccinated with vaccine and ACE-M at separate anatomical sites. ELISA titres to NDV and IBDV were determined. The immune response to NDV at 21 days postvaccination (PV) was significantly enhanced (P less than or equal to 0.05) by the addition of ACE-M to the vaccine, compared with vaccination without ACE-M. Subsequently, the vaccine-ACE-M mixture appeared to suppress the immune response to NDV. However, at day 35 PV, 95% of the Vac 3 chicks compared with 90% of the Vac 2 and 89% of the Vac 4 chicks exhibited protective titres. The response to IBDV differed from that to NDV. At day 21 PV the immune response to IBDV was essentially the same for all flocks that received vaccine, i.e. addition of ACE-M to the vaccine did not significantly enhance the immune response; however, it did significantly (P less than or equal to 0.05) sustain the immune response at days 28 and 35. In addition to the observed effect on titres to NDV and IBDV, ACE-M also had an effect on flock immunity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Developing High-specificity Anti-hypertensive Alerts by Therapeutic State Analysis of Electronic Prescribing Records

Objective

This paper presents a model for analysis of chronic disease prescribing action over time in terms of transitions in status of therapy as indicated in electronic prescribing records. The quality of alerts derived from these therapeutic state transitions is assessed in the context of antihypertensive prescribing.

Design

A set of alert criteria is developed based on analysis of state-transition in past antihypertensive prescribing of a rural Australian General Practice. Thirty active patients coded as hypertensive with alerts on six months of previously un-reviewed prescribing, and 30 hypertensive patients without alerts, are randomly sampled and independently reviewed by the practice’s two main general practice physicians (GPs), each GP reviewing 20 alert and 20 non-alert cases (providing 10 alert and 10 non-alert cases for agreement assessment).

Measurements

GPs provide blind assessment of quality of hypertension management and retrospective assessment of alert relevance.

Results

Alerts were found on 66 of 611 cases with coded hypertension with 37 alerts on the 30 sampled alert cases. GPs assessed alerting sensitivity as 74% (CI 52% - 89%) and specificity as 61% (CI 45% - 74%) for the sample, which is estimated as 26% sensitivity and 93% specificity for the antihypertensive population. Agreement between the GPs on assessment of alert relevance was fair (kappa = 0.37).

Conclusions

Data-driven development of alerts from electronic prescribing records using analysis of therapeutic state transition shows promise for derivation of high-specificity alerts to improve the quality of chronic disease management activities.     

Assessment of Trace Metal and Metalloid Accumulation and Human Health Risk from Vegetables Consumption through Spinach and Coriander Specimens Irrigated with Wastewater

This study focused on evaluating the metal and metalloid contamination and associated risks in the two vegetables crops, coriander (Coriandrum sativum) and spinach (Spinacia oleracea) treated with three water regimes, canal water, groundwater and municipal wastewater. These vegetables are widely consumed by people and are also used in traditional medicine for treating various disorders. Metal and metalloid accumulation (Zn, Pb, Se, Cu, As, Mo, Fe, Ni) was found higher in vegetables treated with wastewater. Wastewater treated soil had high pollution load index. Fe, Zn, As and Pb had higher values in water, soil and vegetables as compared to other studied metals. Overall, metal correlation for soil and vegetables was significant and positive except for Fe and Cu in spinach. The highest value for daily metal intake was estimated for Fe while Se had the lowest value for the same index. It was thus concluded that trace metal and metalloid accumulation was a major health concern for the public consuming these vegetables.     

The Heartfile Lodhran CVD prevention project--end of project evaluation

Mainstream preventive interventions often fail to reach poor populations with a high risk of cardiovascular diseases (CVDs) in Pakistan. A community-based CVD primary prevention project aimed at developing approaches to reduce risk factors in such populations was established by Heartfile in collaboration with the National Rural Support Program in the district of Lodhran. The project implemented a range of activities integrated with existing social and health service mechanisms during a three year intervention period 2000/01-03/04. These were targeted in 4 key settings: community health education, mass media interventions, training of health professionals and health education through Lady Health Workers. The project received support from the Department for International Development, U.K. At the community level, a pre-test-post-test quasi-experimental design was used for examining project outcomes related to the community component of the intervention. Pre and post-intervention (training) evaluations were conducted involving all health care providers in randomly selected workshops in order to determine baseline levels of knowledge and the impact of training on knowledge level. In order to assess practices of physician and non-physician health care providers patient interviews, with control comparisons were conducted at each health care facility. Significant positive changes were observed in knowledge levels at a community level in the district of intervention compared with baseline knowledge levels particularly in relation to a heart healthy diet, beneficial level of physical activity, the causes of high blood pressure and heart attack and the effects of high blood pressure and active and passive smoking on health. Significant changes in behaviors at a practice level were not shown in the district of intervention. However the project played a critical role in spurring national action for the prevention and control of non-communicable diseases and introducing sustainable public health interventions for poor communities in Pakistan.     

The evaluation and physiologic assessment of hemorrhoidal disease: a review

The term hemorrhoids in generally used to describe “symptomatic hemorrhoids”. A Medline review of the literature on anatomy, physiology and post-hemorrhoidectomy changes was performed and summarized in this review. Received: 19 October 2001 / Accepted: 10 November 2001     

Telomere length is a novel predictive biomarker of sensitivity to anti-EGFR therapy in metastatic colorectal cancer

Background:

Telomeres are TTAGGG tandem repeats capping chromosomal ends and partially controlled by the telomerase enzyme. The EGFR pathway putatively regulates telomerase function, prompting an investigation of telomere length (TL) and its association with anti-epidermal growth factor receptor (EGFR) therapy in metastatic colorectal cancer (mCRC).

Methods:

Colorectal cancer cell lines were treated with multiple drugs and sensitivity determined. Clinical information was gathered from 75 patients who had received anti-EGFR drugs. Telomere length was measured using a validated qRT–PCR technique.

Results:

In CRC cell lines, TL independently predicted cetuximab sensitivity. Cells with shorter TL had growth inhibition of 18.6±3.41% as compared with 41.39±8.58% in longer TL (P=0.02). These in vitro findings were validated clinically, in a robust multivariate model. Among patients with KRas WT tumours, those with longer TL had a superior median progression-free survival (PFS) of 24.9 weeks than those with shorter TL; median 11.1 weeks, HR 0.31; P=0.048.

Conclusion:

Telomere length could be a potential unique biomarker predictive of clinical benefit (PFS) of mCRC patients treated with anti-EGFR therapy. This is the novel demonstration of a complex hitherto undescribed interaction, placing anti-EGFR therapy, EGFR pathway, and the telomerase complex within a clinical context.