Role of enteric fever in ileal perforations: an overstated problem in tropics?

PURPOSE: To determine the role of enteric fever in ileal perforations. METHODS: A prospective cohort of 47 patients of ileal perforation was subjected to clinical examination and investigations for APACHE II scoring. Blood, ulcer edge biopsy, mesenteric lymph node and peritoneal aspirate were subjected to culture to determine the predominant aerobic bacterial isolate and its antibiogram. RESULTS: Seven patients (14.9%) required intensive care and seven (14.9%) developed septicaemia. Mortality was 17%. Highest isolation rate was seen in ulcer edge (70.2%) followed by lymph node (66%) culture. The bacterial spectrum was Escherichia coli (23.4%), Enterococcus faecalis (21.3%), Salmonella enterica serovar Typhi (6.3%), Salmonella enterica serovar Paratyphi A (4.2%), etc. CONCLUSIONS: Enteric fever organisms are not the predominant causative agents of ileal perforations. Culture of ulcer edge biopsy, lymph node is crucial for aetiological diagnosis. The use of APACHE II triaging and prescription of antimicrobials based on the local pattern of susceptibility profile of the aetiological agent is recommended.

Antioxidant-statin combination for the management of intraperitoneal sepsis in rats

There is a good evidence that endotoxemia, sepsis, and septic shock are associated with the generation and release of reactive oxygen species [ROS], indicating that oxygen-derived free radicals play an important role in the pathogenesis of septic shock. Inhibitors of HMG-CoA reductase in addition to lowering serum cholesterol levels, exert many pleiotropic effects as antioxidant and anti-inflammatory action. The present study was designed to investigate the possible modulatory effect, if any, of atorvastatin alone or in combination with N-acetylcysteine in cecal ligaiton and perforation [CLP] model of sepsis in rats. Sixty four male albino rats weighing 150-200 g were used in the present study. Rats were randomly divided into eight groups, each of eight rats. Group I, sham operated group. Group II, non treated CLP control group. Group HI, vehicle-treated CLP control group, received saline SC and 2% gum acacia orally. Group IV, CLP group, treated by ceftriaxone plus gentamicin IM every six hours immediately after resuscitation. Group V, CLP group, treated by atorvastatin orally suspended in 2% gum acacia after resuscitation. Group VI, CLP group, treated by N-acetylcysteine [NAC] SC every 6 hours starting after resuscitation. Group VII, CLP group, treated by both atorvastatin and NAC in the same doses and routes of groups V and VI respectively. Group VIII, CLP group, treated by ceftriaxone-gentamicin combination as in group IV in addition to atorvastatin-NAC combination as in group VII. Twelve hours after CLP, malondialdehyde [MDA] levels, my eloperoxidase [MPO], superoxide dismutase [SOD], and catalase activities in heart, liver, and kidney were significantly elevated. Early treatment of CLP rats with ceftriaxone-gentamicin combination, atorvastatin and/or NAC caused a significant reduction in the aforementioned parameters. The concomitant administration of atorvastatin-NAC combination with ceftriaxone -gentamicin combined therapy nearly normalized the studied parameters. The results of the present work demonstrated that ROS plays an important role in CLP model of sepsis in rats. Furthermore, atorvastatin proved to have a protective effect in CLP rats which could be due to an antioxidant effect in addition to a possible anti-inflammatory action. These beneficial effects are augmented by the co-administration of NAC. Nevertheless, it is not advisable to use antioxidants alone for the management of sepsis, so it is recommended to use atorvastatin-NAC combination with optimum chemotherapeutic agents. Future human studies are indicated to assess the clinical relevance of the results of the present work in patients with septic shock

Early effect of Mycobacterium tuberculosis infection on Mac-1 and ICAM-1 expression on mouse peritoneal macrophages

Effect of M. tuberculosis infection was studied on the expression of intercellular adhesion molocule-1 (ICAM-1) and Mac-1 markers on murine peritoneal macrophages. Intraperitoneal administration of M. tuberculosis resulted in a marked increase in the proportion of Mac-1+ cells whereas the proportion of ICAM-1+ cells declined sharply 4 h post infection. Absolute numbers of Mac-1+ and ICAM-1+ cells however increased at all time points after the infection. Comparison of kinetics of changes observed in Mac-1+ and ICAM-1+ cell populations with differential leukocyte counts in peritoneal cells indicated that these alterations could be due to cellular influx, especially that of neutrophils, or up regulation of these markers on macrophages and other peritoneal cells. In adherent peritoneal macrophages infected in vitro with M. tuberculosis, proportion of Mac-1+ and ICAM-1+ cells increased markedly within 24 h of infection. Mean expression of these markers on per cell basis also increased significantly. Similar results were obtained by using RAW 264.7 mouse macrophage cell line, suggesting that the enhanced expression of Mac-1 and ICAM-1 markers was a direct effect of M. tuberculosis infection and not mediated by contaminating cell types present in adherent macrophage preparations. Mac- 1 and ICAM-1 expression was further studied on macrophages that had actually engulfed M. tuberculosis and compared with bystander macrophages without intracellular M. tuberculosis. For this purpose M. tuberculosis pre-stained with DilC18 fluorescent dye were used for infecting adherent peritoneal macrophages. Mac-1 and ICAM-1 expression on gated DilC18 positive and negative cell populations was analyzed. Our results indicate that the expression of Mac-1 and ICAM- 1 markers was significantly enhanced on all macrophages incubated with M. tuberculosis but was more pronounced on macrophages with internalized mycobacteria. Taken together, our results suggest that the expression of Mac-1 and ICAM-1 markers is significantly up regulated

Mycobacterium Leprae in Cultured Mouse Peritoneal Macrophages: In vivo Infection In vitro Cultivation

To grow Mycobacterium leprae in cultured mouse peritoneal macrophages, studies were made on 1) the purification of M. leprae from lepromatous nodules by trypsinization, 2) growth experiment of purified M. leprae in cu1tured macrophages by in vivo infection-in vitro cultivation technique and 3) the observation of pathological changes in sp1eens of mice induced by intraperitoneal inoculation of purified M. leprae. Results are summarized as follows. 1. A simple and effective procedure is described for purification of M. leprae from biopsied nodules of lepromatous leprosy patients by trypsinization and high speed centrifugation. The procedure resulted in a good yie1d of homogeneous preparation of M. leprae with a negligible contamination of tissue debris. 2. Significant decreases were observed in the numbers of acid-fast bacilli in cultured macrophages and of macrophages harboring acid-fast bacilli by the length of intervals between the time of intraperitoneal inoculation of purified M. leprae and the time of initiation of macrophage cultures. 3. Microscopic examination of stained preparations of macrophages cultured by in vivo infection-in vitro cultivation technique indicated that an apparent increase in the number of acid-fast bacilli in the macrophages occurred when the cultures made at 24 hours and 1 week after inoculation were maintained in vitro up to 2 months or more. 4. Pathological changes in the spleens of mice inoculated with purified M. leprae were of mainly degenerative nature in the red pulp. No multiplication of M. leprae was observed in the spleens of mice up to 5 months after inoculation.