Prevention of non-communicable diseases in Pakistan: an integrated partnership-based model

Development and implementation of non-communicable disease (NCD) prevention polices in the developing countries is a multidimensional challenge. This article highlights the evolution of a strategic approach in Pakistan. The model is evidence-based and encompasses a concerted and integrated approach to NCDs. It has been modelled to impact a set of indicators through the combination of a range of actions capitalizing on the strengths of a public-private partnership. The paper highlights the merits and limitations of this approach. The experience outlines a number of clear imperatives for fostering an enabling environment for integrated NCD prevention public health models, which involve roles played by a range of stakeholders. It also highlights the value that such partnership arrangements bring in facilitating the mission and mandates of ministries of health, international agencies with global health mandates, and the non-profit private sector. The experience is of relevance to developing countries that have NCD programs running and those that need to develop them. It provides an empirical basis for enhancing the performance of the health system by fostering partnerships within integrated evidence-based models and permits an analysis of health systems models built on shared responsibility for the purpose of providing sustainable health outcomes.     

Cathepsin D protein levels in colorectal tumors: divergent expression patterns suggest complex regulation and function

Cathepsin D protein patterns were analyzed in 59 colorectal tumors by Western blotting, glycosylation and immunohistochemical assays. Measurement of protein content by laser densitometry of tumor/normal pairs on Western blots revealed loss of cathepsin D protein in more than 50% of colorectal tumors. Independent loading controls and statistical estimates of reproducibility on duplicate assays confirmed frequent decreases in cathepsin D. For cases having a tumor/normal ratio (T/N) <1, the average T/N was 0.50+/-0.19, equivalent to the loss of one cathepsin D allele. However, 2-fold increases in cathepsin D protein levels were also observed in approximately 1/3 of tumors, supporting the concept that colorectal cancers develop via divergent molecular pathways and that cathepsin D may function differently in different cancers. Although normal cathepsin D expression was detected in some earlier stage tumors, protein levels became increasingly bimodal with progression such that cathepsin D levels were increased in 1/3 but decreased in 2/3 of stage III and IV cancers. Other laboratories have reported both significant loss and gain of chromosome 11 (site of the cathepsin D gene) in different colorectal tumors, providing a possible mechanism for our observations on cathepsin D. However, differential regulation of cathepsin D expression by mutant versus wild-type p53 may also contribute to variable cathepsin D levels in colorectal cancers. Immunohistochemical studies demonstrated a shift from a predominantly punctate distribution of cathepsin D protein in normal mucosa to a more diffuse cytoplasmic distribution in tumor tissues. Mutant forms of cathepsin D were not detected in tumors either as changes in electrophoretic mobility or altered glycosylation but minor changes in protein sequence could not be ruled out. Loss of cathepsin D protein may provide an advantage to colorectal tumors related to a loss of cathepsin D function in proapototic or antiangiogenic pathways while increased cathepsin D may promote cancer cell proliferation or invasion.     

Chitosan-DNA nanoparticles as non-viral vectors in gene therapy: strategies to improve transfection efficacy.

Currently, the major drawback of gene therapy is the gene transfection rate. The two main types of vectors that are used in gene therapy are based on viral or non-viral gene delivery systems. The viral gene delivery system shows a high transfection yield but it has many disadvantages, such as oncogenic effects and immunogenicity. However, cationic polymers, like chitosan, have potential for DNA complexation and may be useful as non-viral vectors for gene therapy applications. Chitosan is a natural non-toxic polysaccharide, it is biodegradable and biocompatible, and protects DNA against DNase degradation and leads to its condensation. The objective of this paper was to summarize the state of the art in gene therapy and particularly the use of chitosan to improve the transfection efficiency in vivo and in vitro.     

Buspirone in the management of refractory irritable bowel syndrome: A case report

Rationale:Irritable bowel syndrome (IBS) is a chronic and debilitating functional disorder of the gastrointestinal tract manifested by abdominal pain and bowel habit dysregulation. The pathophysiology is complex and management targets symptom resolution. Therapeutic interventions range from dietary modification, psychological interventions, exercise, to the use of antispasmodics, antibiotics, and antidepressants. Anecdotal reports have suggested that buspirone may be beneficial in the treatment of functional dyspepsia and IBS and its physiological effect of reducing gastric tone provides a rational for its benefit.Patient concerns:A 28-year-old man with unremarkable past medical and psychiatric history presented with worsening abdominal pain, bloating, and bowel movement dysregulation of over 6-year duration.Diagnoses:Physical examination revealed mild distension and discomfort on deep palpation. Thorough blood investigations, stool analysis and culture, and imaging were unremarkable except for the detection of mucus with stool. The patient was diagnosed with irritable bowel syndrome with mixed habits.Interventions:Dietary adjustment and a range of medications (mebeverine, simethicone, loperamide, rifaximin, sertraline and amitriptyline) yielded unsatisfactory response of were not tolerated. Buspirone was eventually introduced.Outcomes:Buspirone was associated with a significant and sustained improvement in IBS symptoms and quality of life.Lessons:This case suggests that buspirone was effective in treating refractory IBS. Further research is needed to assess the role of buspirone in IBS management.     

Presence of activated ras correlates with increased cysteine proteinase activities in human colorectal carcinomas

The metastatic potential of ras-transfected cells has been attributed in part to significant ras induction of proteinase expression. To determine whether primary cancers also demonstrate higher cysteine proteinase activities in the presence of activated ras genes or altered ras protein expression, we have analyzed 60 primary human colorectal carcinomas for ras gene or protein changes together with the expression of cathepsins B and L. Cancers containing K-ras mutations (47% of 60 carcinomas) demonstrated greater increases in cathepsin L activity than cancers without K-ras mutations (p = 0.029), with particularly significant correlations for earlier stage cancers (Dukes' A and B carcinomas, p = 0.006). Western blots used to characterize ras protein patterns in the same cancer/normal pairs have demonstrated that N-ras protein is more highly expressed in colon tissues than H- or K-ras proteins and that N-ras overexpression occurs in almost 70% of colorectal cancers, with or without a concurrent change in electrophoretic mobility of N-ras protein. Our current study has now shown that N-ras protein overexpression alone does not significantly induce cathepsin B or L activity levels in colon cancers. However, carcinomas demonstrating altered N-ras protein forms, in the absence of any K- or N-ras mutations, expressed significantly higher levels of cathepsin B and L activities compared with carcinomas with normal N-ras protein banding patterns. Our data suggest that colorectal carcinomas with either K-ras mutations or altered forms of N-ras protein may increase their tumorigenic potential via the induction of cathepsin L or B expression levels. Our results also confirm that ras oncogene up-regulation of cathepsin B and L activities, previously reported in cultured cells, is a frequent event in primary human colorectal carcinomas. Int. J. Cancer (Pred. Oncol.) 79:324–333, 1998. © 1998 Wiley-Liss, Inc.     

Tracheal inujry due to blunt chest trauma: a rare surgical emergency

Tracheal injury is a rare complication of blunt chest trauma. The patients usually present with signs of respiratory distress. Primary repair is the treatment of choice in case of large defects, while small tears can be managed conservatively. Immediate operation is recommended to improve deteriorating pulmonary function. The decrease in mortality and long-term morbidity depends on early diagnosis. We report a case of tracheal injury due to non-penetrating thoracic trauma which was successfully managed with surgery.     

Incremental value of Late Gadolinium Enhancement by Cardiac MRI in risk stratification of heart failure patients with moderate and severe LV dysfunction

ObjectiveThis is a prospective study of patients with LVEF ≤40%, with the objective of correlating CV events to LGE detected and quantified by CMRI.MethodsHeart Failure (HF) patients with LVEF <40% who underwent CMRI were included. LGE volume of ≥6% of the myocardial volume was considered significant. Data of appropriate ICD shocks, CV hospitalizations and mortality were recorded.ResultsThere were 133 HF (72 ICM & 62 NIDCM) patients with a mean age of 54 ± 12 years, mean LVEF of 34 ± 6% and a follow up of 24 ± 3 months. Totally 46 CV events were recorded in 30 patients, 44 in LGE +ve & 2 in LGE -ve groups (HR 17.8, 95% CI-8.03-39.3, P = 0.000095). All the 7 deaths were in LGE +ve group. CV events were 22 (30.5%) in ICM group and 8 (13.1%) in NIDCM group (p = 0.03). All the 22 ICM patients and 6 of the 8 NIDCM with CV events were LGE +ve. The distribution of CV events amongst LGE +ve and LGE -ve were 35 vs 0 (ICM) and 9 vs 2 (NIDCM); p < 0.005.CV events in LVEF ≤ 30% group, were seen in 19 (47.5%) vs 1 (5.8%) in LGE +ve vs LGE -ve and no of events were 29 vs 1 (p = 0.003). In those with LVEF >30% the corresponding figures were 9 (22.5%) vs 1 (2.8%) and 15 vs 1 respectively (p = 0.02).ConclusionDemonstration of significant LGE by CMRI indicates high risk occurrence of CV events (CV hospitalization, appropriate shocks and total mortality) in NIDCM & ICM patients with LVEF < 40%.