Mycobacterium tuberculosis (Mtb) is known to produce wax esters (WE) when subjected to stress. However, nothing is known about the enzymes involved in biosynthesis of WE and their role in mycobacterial dormancy. We report that two putative Mtb fatty acyl-CoA reductase genes (fcr) expressed in E. coli display catalytic reduction of fatty acyl-CoA to fatty aldehyde and fatty alcohol. Both enzymes (FCR1/Rv3391) and FCR2/Rv1543) showed a requirement for NADPH as the reductant, a preference for oleoyl-CoA over saturated fatty acyl-CoA and were inhibited by thiol-directed reagents. We generated Mtb gene-knockout mutants for each reductase. Metabolic incorporation of 14C-oleate into fatty alcohols and WE was severely diminished in the mutants under dormancy-inducing stress conditions that are thought to be encountered by the pathogen in the host. The fatty acyl-CoA reductase activity in cell lysates of the mutants under nitric oxide stress was significantly reduced when compared with the wild type. Complementation restored the lost activity completely in the Δfcr1 mutant and partially in the Δfcr2 mutant. WE synthesis was inhibited in both Δfcr mutants. The Δfcr mutants exhibited faster growth rates, an increased uptake of 14C-glycerol suggesting increased permeability of the cell wall, increased metabolic activity levels and impaired phenotypic antibiotic tolerance under dormancy-inducing combined multiple stress conditions. Complementation of the mutants did not restore the development of antibiotic tolerance to wild-type levels. Transcript analysis of Δfcr mutants showed upregulation of genes involved in energy generation and transcription, indicating the inability of the mutants to become dormant. Our results indicate that the fcr1 and fcr2 gene products are involved in WE synthesis under in vitro dormancy-inducing conditions and that WE play a critical role in reaching a dormant state. Drugs targeted against the Mtb reductases may inhibit its ability to go into dormancy and therefore increase susceptibility of Mtb to currently used antibiotics thereby enhancing clearance of the pathogen from patients.

Completion of recommended liver imaging and carcinoembryonic antigen testing falls well below guidelines in Manitoba, whereas colonoscopy is better provided. Addressing this gap should improve outcomes for colorectal cancer survivors.

Purpose:

Intensive surveillance after curative treatment of colorectal cancer (CRC) is associated with improved overall survival. This study examined concordance with the 2005 ASCO surveillance guidelines at the population level.

Methods:

A cohort of 250 patients diagnosed with stage II or III CRC in 2004 and alive 42 months after diagnosis was identified from health administrative data in Manitoba, Canada. Colonoscopy, liver imaging, and carcinoembryonic antigen (CEA) testing were assessed over 3 years. Guidelines were met if patients had at least one colonoscopy in 3 years and at least one liver imaging test and three CEA tests annually. Multivariate logistic regression assessed the effect of patient and physician characteristics and disease and treatment factors on guideline concordance.

Results:

Guidelines for colonoscopy, liver imaging, and CEA were met by 80.4%, 47.2%, and 22% of patients, respectively. Guideline concordance for colonoscopy was predicted by annual contact with a surgeon, higher income, and the diagnosis of colon (rather than rectal) cancer. Adherence was lower in those older than 70 years and with higher comorbidity. For liver imaging, significant predictors were annual contact with an oncologist, receipt of chemotherapy, and diagnosis of colon cancer. Concordance with CEA guidelines was higher with annual contact with an oncologist and high levels of family physician contact, and lower in urban residents, in those older than 70, and in those with stage II disease.

Conclusion:

Completion of recommended liver imaging and CEA testing fall well below guidelines in Manitoba, whereas colonoscopy is better provided. Addressing this gap should improve outcomes for CRC survivors.

BACKGROUND:

There are limited data regarding the use of sedation for colonoscopy and concomitant monitoring practices in different countries.

METHODS:

A survey was mailed to 445 clinician members of the Canadian Association of Gastroenterology and 80 members of the Canadian Society of Colon and Rectal Surgeons in May and June 2009.

RESULTS:

Sixty-five per cent of Canadian Association of Gastroenterology members and 69% of Canadian Society of Colon and Rectal Surgeons members responded with the full survey. Most endoscopists reported using sedation for more than 90% of colonoscopies. The most common sedation regimen was a combination of midazolam and fentanyl. Propofol, either alone or with another drug, was used in 12% of cases. A higher proportion (94%) of adult gastroenterologists who routinely used propofol were highly satisfied compared with those using other sedative agents (45%; P<0.001). Fifty per cent of adult gastroenterologists and 29% of surgeons who were not currently using propofol expressed interest in starting to use it for routine colonoscopies. Only a single nurse was present in the endoscopy room during colonoscopy performed by two-thirds of the endoscopists.

CONCLUSIONS:

Results of the present survey suggest that gastroenterologists in Canada use sedation for colonoscopy in more than 90% of their patients. There was higher satisfaction among gastroenterologists who used propofol routinely for all colonoscopies. Most endoscopy rooms were staffed by a single nurse, which may limit further increases in the use of propofol. Further studies are needed to determine optimal staffing of endoscopy units with and without the use of propofol. Sedation practices of general surgery endoscopists need to be evaluated.

The Canadian Association of Gastroenterology and the Canadian Digestive Health Foundation published guidelines on colon cancer screening in 2004. Subsequent to the publication of these guidelines, many advances have occurred, thereby necessitating a review of the existing guidelines in the context of new technologies and clinical knowledge. The assembled guideline panel recognized three recent American sets of guidelines and identified seven issues that required comment from a Canadian perspective. These issues included, among others, the role of program-based screening, flexible sigmoidoscopy, computed tomography colonography, barium enema and quality improvement. The panel also provided context for the selection of the fecal immunochemical test as the fecal occult blood test of choice, and the relative role of colonoscopy as a primary screening tool. Recommendations were also provided for an upper age limit for colon cancer screening, whether upper endoscopy should be performed following a negative colonoscopy for a positive fecal occult blood test and when colon cancer screening should resume following negative colonoscopy.

BACKGROUND:

There are limited data regarding complications associated with colonoscopy and flexible sigmoidoscopy in usual clinical practice in Canada.

OBJECTIVE:

To determine the risk factors for lower gastrointestinal (GI) endoscopy-associated complications in usual clinical practice.

METHODS:

All outpatient lower GI endoscopies performed in Winnipeg (Manitoba) between April 1, 2004 and March 31, 2006, were identified from the provincial physicians’ claims database. All subsequent hospital admissions within 30 days that documented potential complications associated with lower GI endoscopies were identified from the electronic hospital discharges database and reviewed. Multivariate generalized estimating equation regression analysis was performed to determine independent factors (patient, endoscopist and procedure) associated with the risk of developing complications.

RESULTS:

There were 29,990 outpatient lower GI endoscopies performed in Winnipeg during the years studied. Seventy-seven (0.26%) procedures were associated with complications requiring hospitalization within 30 days of the index procedure. Stricture dilation (rate ratio [RR] 23.14; 95% CI 6.70 to 76.51), polypectomy (RR 5.93; 95% CI 3.66 to 9.62), increasing patient age (for each year increase in age, RR 1.03; 95% CI 1.01 to 1.05) and performance of endoscopy by low-volume endoscopists (fewer than 200 procedures per year, RR 2.28; 95% CI 1.18 to 4.42) and family physicians (RR 2.23; 95% CI 1.39 to 3.58) were independently associated with complications.

CONCLUSIONS:

The results of the present study suggest that increasing patient age, complex procedures and performance of the index procedure by low-volume endoscopists are independent risk factors for lower GI endoscopy-associated complications in usual clinical practice. This suggests that it may be time to consider implementing minimum volume requirements for endoscopists performing non-screening lower GI endoscopies.

Nevirapine, a non-nucleoside reverse transcriptase inhibitor (NNRTI), is widely prescribed as a part of the combination therapy of human immunodeficiency virus (HIV) infection because of its efficacy and good tolerability. Here, we report a case of Stevens–Johnson syndrome (SJS) secondary to nevirapine. The patient had a diffuse, exfoliating exanthema with generalized bullous eruptions that involved the face, trunk and both extremities with elevated hepatic alanine aminotransferase and aspartate aminotransferase enzyme activities. The condition improved with stoppage of nevirapine-based highly active antiretroviral therapy (HAART) regimen, so we attributed this adverse event to nevirapine. A strict vigilance of adverse drug reaction is required in HAART.

BACKGROUND:

Assessment of current wait times for specialist health services in Canada is a key method that can assist government and health care providers to plan wisely for future health needs. These data are not readily available. A method to capture wait time data at the time of consultation or procedure has been developed, which should be applicable to other specialist groups and also allows for assessment of wait time trends over intervals of years.

METHODS:

In November 2008, gastroenterologists across Canada were asked to complete a questionnaire (online or by fax) that included personal demographics and data from one week on at least five consecutive new consultations and five consecutive procedure patients who had not previously undergone a procedure for the same indication. Wait times were collected for 18 primary indications and results were then compared with similar survey data collected in 2005.

RESULTS:

The longest wait times observed were for screening colonoscopy (201 days) and surveillance of previous colon cancer or polyps (272 days). The shortest wait times were for cancer-likely based on imaging or physical examination (82 days), severe or rapidly progressing dysphagia or odynophagia (83 days), documented iron-deficiency anemia (90 days) and dyspepsia with alarm symptoms (99 days). Compared with 2005 data, total wait times in 2008 were lengthened overall (127 days versus 155 days; P<0.05) and for most of the seven individual indications that permitted data comparison.

CONCLUSION:

Median wait times for gastroenterology services continue to exceed consensus conference recommended targets and have significantly worsened since 2005.

Objective:

To assess and evaluate the frequency, severity and classification of drug-related problems (DRP) resulting in hospitalization in an internal medicine department of a large tertiary care hospital and to identify any patient, prescriber, drug, and system factors associated with these events.

Materials and Methods:

A prospective and descriptive study carried out in Department of Medicine, Government Medical College, Jagdalpur. The DRP and relevant data were recorded on the personal record of every individual patient, filled during the course of treatment.

Result:

A total of 3560 patient’s records were analyzed. Among them118 admissions were due to DRP. The most common DRP noted was noncompliance in part of patient’s i.e 55 (46.6%). Statistically significant correlations were found in the number of prescribed drugs and over the counter drugs (OTC) used by patients.

Conclusion:

The DRP that attributed to hospital admission are mostly avoidable through proper patient education and strengthening the need of pharmacovigilance with little more vigilance in patient care.

Background/Objective:

Intervertebral disk herniation is relatively common. Migration usually occurs in the ventral epidural space; rarely, disks migrate to the dorsal epidural space due to the natural anatomical barriers of the thecal sac.

Design:

Case report.

Findings:

A 49-year-old man presented with 1 week of severe back pain with bilateral radiculopathy to the lateral aspect of his lower extremities and weakness of the ankle dorsiflexors and toe extensors. Lumbar spine magnetic resonance imaging with gadolinium revealed a peripheral enhancing dorsal epidural lesion with severe compression of the thecal sac. Initial differential diagnosis included spontaneous hematoma, synovial cyst, and epidural abscess. Posterior lumbar decompression was performed; intraoperatively, the lesion was identified as a large herniated disk fragment.

Conclusions:

Dorsal migration of a herniated intervertebral disk is rare and may be difficult to definitively diagnose preoperatively. Dorsal disk migration may present in a variety of clinical scenarios and, as in this case, may mimic other epidural lesions on magnetic resonance imaging.

Small bowel hemorrhage is responsible for approximately 4% of all cases of gastrointestinal bleeding. The etiology of bleeding from the small bowel is a tumour in approximately 10% of cases. Pyogenic granuloma is a common inflammatory vascular tumour of the dermis, which rarely occurs in the gastrointestinal tract. Pyogenic granuloma is a rare cause of overt or obscure small bowel bleeding. The present paper reports the first case of pyogenic granuloma presenting as a massive gastrointestinal bleed, and reviews the relevant literature to date regarding the clinical presentation, diagnosis and management of this rare gastrointestinal lesion.

Objective:

Hemoglobin F augmentation is another approach to treat sickle cell disease (SCD). This study evaluates the efficacy and impact of Hydroxyurea (HU) on fetal hemoglobin (HbF) and other hematological parameters, which result in decreasing the painful crisis and lower hospital admissions.

Materials and Methods:

A prospective study was carried out in the Department of Medicine, Government Medical College, Jagdalpur. Twenty-seven patients with SCD received HU at a mean dose of 22 mg/kg/d. The baseline results were analyzed and compared with the post treatment result, at the end of one year.

Statistics:

Student's t-test was used to determine the level of significance.

Results:

Twenty-four patients completed a one-year period successfully; a significant increase was noted in the mean HbF%, from 12.83 to 19.17, and the mean corpuscular volume (MCV) from 82.57 to 89.87 Fl. The mean hospital admission (numbers) in the last one year decreased from 4.75 to 2.25 and the mean number of SCD crisis for the last one year decreased significantly from 3.63 to 1.67.

Conclusion:

We found a significant reduction in hospital admissions, a reduction in the overall sickle cell crisis and an associated improvement in HbF% without any significant side effects in the patients with SCD, treated with HU.

Objective:

The primary objective was to study the epidemiology of Human Immunodeficiency Virus (HIV) positive tribal patients, and the secondary objective was to study the associated comorbidities in a tertiary care hospital in the tribal (Bastar) region of Chhattisgarh, India, between December 2006 and November 2008, and their relation to CD4 counts.

Materials and Methods:

In this study 90 tribal HIV positive subjects were enrolled. Information on demographics, that is, weight, height, age, educational status, sex, clinical finding, and laboratory parameters (CD4 counts) were noted.

Results:

Among 90 HIV patients, 54 (60%) were males and 36 (40%) were females. Among these, most patients, 37 (41.1%), were in the age group of 30 to 39 years. Among these patients, 79.56% belonged to the lower socioeconomic status, whereas, only 1.45% were from a high socioeconomic status. The largest group was made up of drivers (32.2%), with the second largest group being housewives (27.7%) and laborers (17.7%), respectively. A majority of the patients had a low education, 35.5% were educated only up to the fifth standard and 31.8% up to high school, while 18.8% were illiterate. The predominant mode of transmission was heterosexual contact (78.8%), only one patient (1.1%) was infected through transfusion of infected blood, five (5.5%) patients acquired infection via vertical (mother to child) transmission, and in 13 patients the transmission history was not clear.

Conclusion:

There was a high frequency of behavioral risk factors, together with unawareness, and very little health infrastructure, thus creating an impending risk for the rapid spread of HIV/AIDS (acquired immunodeficiency syndrome).

Background:

Cutaneous disorders during HIV infection are numerous and skin is often the first and only organ affected during most of the course of HIV disease. Some Cutaneous disorders reflect the progression of HIV disease; though the relation is still controversial.

Aims:

The objective of this study, conducted at a tertiary care centre in Bastar, Jagdalpur, is to estimate the status of cutaneous manifestation in HIV-infected patients and its relationship with CD4 cell counts.

Methods:

We enrolled 137 HIV positive subjects. Demographic information such as age, gender, weight, height, socioeconomic status, and educational status were recorded. Laboratory parameter (CD4 counts) and treatment regimen were noted. Patients were examined for skin disorders by a dermatologist. Data were analyzed using chi-square test for categorical variables.

Results:

Majority of the patients were from rural area (65.69%) and belonged to a low socioeconomic and educational status. 30.65% of the patients were housewives, 23.35% drivers, and 16.78% labourers. Predominant mode of transmission was heterosexual contact (94.16%). Most common HIV-related dermatological manifestations were seborrheic dermatitis (74.16%), xerosis (52.5%), generalized skin hyperpigmentation 56 (46.67%), onychomycosis 53 (44.16%), pruritic papular eruption 27 (22.5%), oral candidiasis 21 (17.5%), photo dermatitis 21 (17.5%), and scabies 4 (3.33%). Significant correlation with low CD4+ cell counts was found for oral candidiasis (P < 0.0001) and Kaposi's sarcoma (P = 0.03), while other disorders such as seborrheic dermatitis (P = 0.22), xerosis (P = 0.25), and onychomycosis (P = 0.08) were not statistically significant.

Conclusion:

This study showed high prevalence of dermatological manifestations in HIV-infected subjects, and they occur more frequently with progression of HIV and decline in immune functions. Therefore, early diagnosis and management of skin disorders can improve the quality of life of HIV-infected subjects.

Objective:

To assess the adverse effects of antiretroviral therapy (HAART) and its adherence in HIV-infected patients, in remote and tribal area with restricted resources.

Materials and Methods:

This was a prospective, observational study carried out at Department of Medicine, Government Medical College, Jagdalpur. A set of questions were asked and adverse drug reactions (ADRs) were recorded for every patient.

Results:

79 HIV positive patients were analyzed. Among them, 68 (86%) had at least one ADR. The mean ADR per patient was 1.64 (±1.09). The most common ADR in our study was peripheral neuropathy (20.83%), followed by skin rashes (15.83%). Twenty-one patients (26.58%) had severe (grade-3 and grade-4) ADRs. Female patients had more ADRs (45.71%) than males (11.36%); severe ADRs had a statistically significant positive correlation with sex and CD4 cell count of the patients.

Conclusion:

In spite of high ADRs, HAART is the only answer to HIV/AIDS; thus, management requires a highly precise balance between benefits of durable HIV suppression and the risks of drug toxicity to achieve the therapeutic goals, with conventional drugs or with newer less toxic agents.

Over the past decade, multiple clinical reports have demonstrated that the use of propofol sedation for gastrointestinal endoscopy by gastroenterologists and trained endoscopy nurses is safe and effective in appropriately selected patients. Proposed benefits of propofol sedation include rapid onset of action, improved patient comfort and rapid clearance, as well as prompt recovery and discharge from the endoscopy unit. As a result of medical evidence, a number of international professional societies have endorsed the use of propofol in gastrointestinal endoscopy. In Canada, no formal guidelines currently exist. In the present article, the Clinical Affairs Committee of the Canadian Association of Gastroenterology presents a position statement, incorporating updated information on the use of propofol sedation for endoscopy in adult patients.

BACKGROUND:

Over the past several years, colonic stenting has been advocated as an alternative to the traditional surgical approach for relieving acute malignant left-sided colonic obstruction. The aim of the present study was to determine the most cost-effective strategy in a Canadian setting.

PATIENTS AND METHODS:

A decision analytical model was developed to compare three competing strategies: CS – emergent colonic stenting followed by elective resective surgery and reanastomosis; RS – emergent resective surgery followed by creation of either a diverting colostomy or primary reanastomosis; and DC – emergent diverting colostomy followed by elective resective surgery and reanastomosis. The costs were estimated from the perspective of the Manitoba provincial health plan.

RESULTS:

The use of CS resulted in fewer total operative procedures per patient (mean CS 1.03, RS 1.32, DC 1.9), lower mortality rate (CS 5%, RS 11%, DC 13%) and lower likelihood of requiring a permanent stoma (CS 7%, RS 14%, DC 14%). CS is slightly more expensive than DC, but less costly than RS (DC $11,851, CS $13,164, RS $13,820). The incremental cost-effectiveness ratio associated with the use of CS versus DC is $1,415 to prevent a temporary stoma, $1,516 to prevent an additional operation and $15,734 to prevent an additional death.

CONCLUSIONS:

Colonic stenting for patients with acute colonic obstruction secondary to a resectable colonic tumour is comparable in cost with surgical options, and reduces the likelihood of requiring both temporary and permanent stomas. Colonic stenting should be offered as the initial therapeutic modality for Canadian colorectal cancer patients presenting with acute obstruction as a bridge to definitive RS.

• Background and Aims Determining the mode of action of allelochemicals is one of the challenging aspects in allelopathic studies. Recently, allelochemicals have been proposed to cause oxidative stress in target tissue and induce an antioxidant mechanism. α-Pinene, one of the common monoterpenoids emitted from several aromatic plants including forest trees, is known for its growth-inhibitory activity. However, its mechanism of action remains unexplored. The aim of the present study was to determine the inhibitory effect of α-pinene on root growth and generation of reactive oxygen species, as indicators of oxidative stress and changes in activities of antioxidant enzymes.

• Methods Effects of α-pinene on early root growth were studied in five test species, Cassia occidentalis, Amaranthus viridis, Triticum aestivum, Pisum sativum and Cicer arietinum. Electrolyte leakage, lipid peroxidation, hydrogen peroxide generation, proline accumulation, and activities of the enzymes superoxide dismutase (SOD), ascorbate peroxidase (APX), guaiacol peroxidase (GPX), catalase (CAT) and glutathione reductase (GR) were studied in roots of C. occidentalis.

• Key Results α-Pinene inhibited the radicle growth of all the test species. Exposure of C. occidentalis roots to α-pinene enhanced solute leakage, and increased levels of malondialdehyde, proline and hydrogen peroxide, indicating lipid peroxidation and induction of oxidative stress. Activities of the antioxidant enzymes SOD, CAT, GPX, APX and GR were significantly elevated, thereby indicating the enhanced generation of reactive oxygen species (ROS) upon α-pinene exposure. Increased levels of scavenging enzymes indicates their induction as a secondary defence mechanism in response to α-pinene.

• Conclusions It is concluded that α-pinene inhibits early root growth and causes oxidative damage in root tissue through enhanced generation of ROS, as indicated by increased lipid peroxidation, disruption of membrane integrity and elevated antioxidant enzyme levels.

OBJECTIVE:

Nutrition education is a required part of gastrointestinal training programs. The involvement of gastroenterologists in clinical nutrition once their training has been completed is unknown. The aim of the present study was to determine the practice pattern of gastroenterologists in clinical nutrition and their perceived adequacy of nutrition training during their gastroenterology (GI) fellowship.

METHODS:

The Canadian Association of Gastroenterology mailed a survey to all of its 463 Canadian clinician members and 88 trainee members. Components of the survey included knowledge of nutritional assessment and total parenteral nutrition, involvement in a nutrition support service, physician involvement in nutritional assessment and nutrition support teams, obesity management, insertion of gastrostomy (G) tubes and management of tube-related complications, and adequacy of training in clinical nutrition.

RESULTS:

Sixty per cent (n=279) of the Canadian Association of Gastroenterology clinicians and 38% (n=33) of the fellows responded. Of the clinicians, 80% were practicing adult gastroenterologists with the following demographics: those practicing full time in academic centres (42%), community practice (45%), completed training in the last 10 years (32%) and those that completed training in the United States (14%). Although only 6% had a primary focus of nutrition in their GI practices, 65% were involved in nutrition support (including total parenteral nutrition), 74% placed G tubes and 68% managed at least one of the major complications of G tube insertion. Respondents felt a gastroenterologist should be the physician’s consultant on nutrition support services (89%). Areas of potential inadequate training included nutritional assessment, indications for nutrition support, management of obesity and management of G tube-related complications. The majority of clinicians (67%) and trainees (73%) felt that nutrition training in their GI fellowship was underemphasized.

CONCLUSIONS:

The majority of Canadian gastroenterologists are involved in nutrition support. However, this survey demonstrated that nutritional training is underemphasized in most training programs. It is important for GI fellowship programs to develop standardized nutrition training that prepares trainees for their practice.

Vibrio cholerae WO7 (serogroup O1) isolated from patients with diarrhea produces an extracellular toxin despite the absence of ctx, zot, and ace genes from its genome. The toxin elongates Chinese hamster ovary cells, produces fluid accumulation in ligated rabbit ileal loops, and agglutinates freshly isolated rabbit erythrocytes. Maximal production of this toxin (WO7 toxin) was seen in AKI medium with the pH adjusted to 8.5 at 37°C under shaking conditions. We purified this toxin to homogeneity by sequential ammonium sulfate precipitation, affinity chromatography using a fetuin-Sepharose CL-4B column, and gel filtration chromatography, which increased the specific activity of the toxin by 1.6 × 106-fold. The toxin is heat labile and sensitive to proteases and has a subunit structure consisting of two subunits with molecular masses of about 58 and 40 kDa as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Agglutination of GM1-coated sheep erythrocytes by toxin suggests that GM1 might be the physiologic receptor for WO7 toxin on the enterocytes. An immunodiffusion test between the antiserum raised against the purified WO7 toxin and the purified toxin gave a well-defined precipitation band. In the immunoblot assay, two bands were observed in the 58- and 40-kDa region. At the same time, antiserum against WO7 toxin failed to show any cross-reactivity with cholera toxin or Escherichia coli heat-labile toxin (LT1) in an immunodiffusion test or immunoblot assay. The enterotoxic activity of WO7 toxin could be inhibited by antiserum against purified WO7 toxin. Our results indicate that WO7 toxin is structurally and functionally distinct from other cholera toxins and that the enterotoxic activities expressed by WO7 toxin appear to contribute to the pathogenesis of disease associated with V. cholerae O1 strains.