Dengue haemorrhagic fever outbreak in Karachi, Pakistan, 1994.
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Adolescent↗
Biomedical subjects
J Khan
Publications and source records attributed to J Khan.
Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response.
BACKGROUND: Interleukin-5 (IL-5) is essential for the formation of eosinophils, which are thought to have a major role in the pathogenesis of asthma and other allergic diseases. We aimed to assess the effects of monoclonal antibody to IL-5 on blood and sputum eosinophils, airway hyper-responsiveness, and the late asthmatic reaction to inhaled allergen in patients with mild asthma. METHODS: We did a double-blind randomised placebo-controlled trial, in which a single intravenous infusion of humanised (IgG-K) monoclonal antibody to IL-5 (SB-240563) was given at doses of 2.5 mg/kg (n=8) or 10.0 mg/kg (n=8). The effects of treatment on responses to inhaled allergen challenge, sputum eosinophils, and airway hyper-responsiveness to histamine were measured at weeks 1 and 4 with monitoring of blood eosinophil counts for up to 16 weeks. FINDINGS: Monoclonal antibody against IL-5 lowered the mean blood eosinophil count at day 29 from 0.25x10(9)/L (95% CI 0.16-0.34) in the placebo group to 0.04x10(9)/L (0.00-0.07) in the 10 mg/kg group (p<0.0001), and prevented the blood eosinophilia that follows allergen challenge. After inhaled allergen challenge, 9 days after treatment, the percentage sputum eosinophils were 12.2% in the placebo group and lowered to 0.9% (-1.2 to 3.0; p=0.0076) in the 10 mg/kg group, and this effect persisted at day 30 after the dose. There was no significant effect of monoclonal antibody to IL-5 on the late asthmatic response or on airway hyper-responsiveness to histamine. INTERPRETATION: A single dose of monoclonal antibody to IL-5 decreased blood eosinophils for up to 16 weeks and sputum eosinophils at 4 weeks, which has considerable therapeutic potential for asthma and allergy. However, our findings question the role of eosinophils in mediating the late asthmatic response and causing airway hyper-responsiveness.
Adult↗
Effects of recombinant human interleukin-12 on eosinophils, airway hyper-responsiveness, and the late asthmatic response.
BACKGROUND: Interleukin-12 (IL-12) is a macrophage-derived cytokine that modulates T lymphocyte responses and has the capacity to suppress allergic and eosinophilic inflammation. METHODS: We carried out a double-blind, randomised, parallel group clinical study, in which patients with mild allergic asthma were given subcutaneous recombinant human IL-12 at increasing weekly injections of 0.1, 0.25, 0.5 microg/kg (n=19), or placebo (n=20). We compared responses to inhaled allergen challenge 24 h before the first injection and 24 h after the final injection. Airways hyper-responsiveness and concentrations of peripheral blood eosinophils and sputum eosinophils were also assessed. FINDINGS: IL-12 caused a significant decrease from baseline in the main peripheral blood eosinophil count 24 h after the fourth injection compared with placebo (p=0.0001). Sputum eosinophils were also significantly decreased 24 h after allergen challenge when treated with IL-12 compared with placebo (p=0.024). IL-12 caused a non-significant trend towards improvement in airway hyper-responsiveness to histamine, but had no significant effect on the late asthmatic reaction after inhaled allergen challenge. After administration of IL-12, four of 19 patients withdrew prematurely; two with cardiac arrhythmias, one with abnormal liver function, and a single patient with severe flu-like symptoms. INTERPRETATION: We have shown that IL-12 lowers numbers of blood and sputum eosinophils, but without any significant effects on airway hyper-responsiveness or the late asthmatic reaction. This questions the role of eosinophils in mediating these reactions, and has important implications for development of new anti-inflammatory treatments.
Adjuvants, Immunologic↗
A new technique for placement of central venous catheters in small infants.
The delivery of total parenteral nutrition to premature infants has been a major advance in neonatal intensive care. Ideally, total parenteral nutrition fluids should be given through a central venous catheter, but insertion of such a catheter may be a very difficult procedure in small neonates. We describe a new technique that improves the success rate of central venous catheterization in premature infants.
Catheterization, Central Venous↗
Adhesive mucous gel layer and mucus release as intestinal barrier in rats.
BACKGROUND: Although it has been reported that total parenteral nutrition induces an increased intestinal permeability and a decreased mucous gel layer covering the intestinal epithelium, the role of mucous gel on intestinal permeability has not been well understood. We examined the in vivo effects of N-acetyl cysteine (NAC) as mucolytic agent and colchicine as suppressant of the mucus production on the intestinal transmission of fluorescein isothiocyanate dextran 70,000 (FITC-dextran). METHODS: Rats were divided into four groups. In each group, FITC-dextran (750 mg/kg) with or without NAC (3000 mg/kg) was injected into the small intestinal lumen 3 hours after intraperitoneal injection of saline or colchicine (Col, 10 mg/kg). Thirty minutes after injection of FITC-dextran, blood samples were taken from portal vein to analyze plasma fluorescein concentration by fluorescence spectrometry. Samples of small intestine were sectioned in a cryostat for fluorescence microscopy, and the identical sections were stained by periodic acid-Schiff reaction. RESULTS: Plasma FITC-dextran level in NAC group was higher than that in control group (p < .01), that in Col + NAC group was higher than that in Col group (p < .01) and that in Col + NAC group was higher than that in NAC group (p < .05). The spaces between villi were filled with mucous gel in the control and Col groups, whereas those were not entirely filled with mucous gel in NAC and Col + NAC groups. FITC-dextran and mucous gel showed complementary distribution in all rats. The villous interstitial edema was recognized in NAC group and the villi were disrupted in Col + NAC group. CONCLUSIONS: These results suggest that intestinal permeability is possibly affected not only by the mucous gel covering the intestinal epithelium but also by mucus release from goblet cells of the small intestine.
Acetylcysteine↗
Developmental changes in distribution of the mucous gel layer and intestinal permeability in rat small intestine.
BACKGROUND: From the developmental aspects, the distribution of fluorescein isothiocyanate dextran 70,000 (FTTC-dextran) and mucous gel across the lumen of small intestine was observed as an investigation into the role of mucous gel on intestinal permeability. Furthermore, the effect of N-acetyl cysteine (NAC), a mucolytic agent, on intestinal permeability was examined. METHODS: In suckling and weaned rats, FTTC-dextran (750 mg/kg body wt) was gavage-fed. After 3 hours, blood samples were taken by cardiac puncture to analyze plasma FTTC-dextran by fluorescence spectrometry. Samples of small intestine with luminal contents were frozen and sectioned in a cryostat for fluorescence microscopy; the same sections were placed in a 0.2% celloidin solution to preserve mucous gel and were stained by periodic acid-Schiff reaction for light microscopy. In weaned rats, intestinal permeability was examined with different concentrations of intraluminally instilled NAC. RESULTS: The plasma level of FTTC-dextran showed a significant increase (p < .01) in suckling rats compared with the weaned rats. Morphologic findings were similar in both the jejunum and ileum: The spaces between villi were not entirely filled with mucus but filled with FTTC-dextran in suckling rats, whereas the spaces were filled with mucus and not filled with FTTC-dextran in weaned rats. Intestinal permeability in groups with NAC were significantly higher (p < .01) than that in group without NAC. CONCLUSIONS: These results suggest that an increase in the mucous gel layer that coats the epithelial lining according to the maturation of the gastrointestinal tract is one of the most important factors for a restriction in intestinal permeability.
Acetylcysteine↗
Total parenteral nutrition increases uptake of latex beads by Peyer's patches.
BACKGROUND: Dysfunction of the intestinal barrier, as evidenced by increased intestinal permeability and bacterial translocation, has been reported under total parenteral nutrition (TPN). However, the role of Peyer's patches on the intestinal barrier in TPN is not well understood. We investigated whether TPN alters the uptake of microparticles by the follicle-associated epithelium of Peyer's patches. METHODS: Twenty rats were divided into two groups, a control group and a TPN group. Fluorescent polystyrene latex beads, 3.2 +/- 0.2 microns in diameter, were used as a probe for measuring the uptake by Peyer's patches. After 1 week of consuming either the control or TPN diet, rats were killed. On the day of killing, 0.1 mL of latex beads solution was injected into a 1-cm length of ileal loop, within 10 cm of the ileocecal valve. Samples were taken after 30 minutes of injection, sectioned by cryostat, and then viewed under a fluorescent microscope. Follicle-associated epithelial length and particles were counted using a confocal laser scanning microscope. The number of particles within each compartment was standardized per unit length of epithelium of Peyer's patches. RESULTS: Particle numbers within Peyer's patch dome of the TPN group were significantly increased compared with those of the control group (p < .01). CONCLUSIONS: These data suggest that dysfunction of the intestinal barrier in TPN might be associated with a change of uptake by Peyer's patches.
Animals↗
Role of intestinal mucus on the uptake of latex beads by Peyer's patches and on their transport to mesenteric lymph nodes in rats.
BACKGROUND: The effects of N-acetylcysteine (NAC) as a mucolytic agent on the uptake of fluorescent polystyrene microparticles by Peyer's patches, on intestinal permeability, and on subsequent transport to mesenteric lymph nodes (MLNs) were investigated to establish the role of mucus gel layer in this process. METHODS: Twenty rats were divided into two groups: control (n = 10) and NAC (n = 10). Fluorescent polystyrene latex beads of 3.2+/-0.2 microm in diameter were used as a probe for measuring the previously mentioned parameters. The solution of latex beads (0.1 mL) was injected into a 2-cm length of ileal loop containing Peyer's patches, with 0.1 mL of saline (control group) or with 0.1 mL of NAC solution (NAC group) within 10 cm proximal from the ileocaecal valve. Intestinal loops, portal blood, and neighboring MLNs were taken within 1 hour of injection. Intestinal sections were stained by periodic acid-Schiff reagent. Peyer's patches and MLNs were analyzed for the count of particles by image analysis using a confocal laser scanning microscope. RESULTS: Morphologically, periodic acid-Schiff positive uniform mucus gel was present in front of Peyer's patches of the control group, and mucus gel layer was disrupted and noncontinuous in the NAC group. The number of particles within Peyer's patches and MLNs in the NAC group was significantly higher than that in the control group (p<.001). Intestinal permeability of latex beads in the NAC group was significantly higher than that in the control group (p<.001). CONCLUSIONS: These data suggest that the mucus gel layer located in front of Peyer's patches is one of the important factors for the uptake of noxious macromolecules, and this in turn plays a major role on small intestinal permeability and subsequent translocation to MLNs.
Acetylcysteine↗
Alanyl-glutamine-supplemented parenteral nutrition increases luminal mucus gel and decreases permeability in the rat small intestine.
BACKGROUND: Effect of supplemental alanyl-glutamine in standard TPN (S-TPN) on luminal mucus gel and small intestinal permeability was investigated. METHODS: Thirty Sprague-Dawley rats were divided into group I (n = 10), receiving standard rat diet; group II (n = 10), receiving S-TPN; and group III (n = 10), receiving alanyl-glutamine-supplemented TPN for 1 week. After 1 week, fluorescein isothiocyanate (FITC)-dextran was injected into the small intestine of the rats, and they were killed. A small intestinal sample and portal blood were obtained for morphologic and functional analysis of mucus gel and intestinal permeability. RESULTS: In group II, thickness and optical density of mucus gel per millimeter serosal length of intestine were significantly lower than group I (p<.001) and were significantly higher in group III than in group II (p<.001). The number of goblet cells in the villi and in the crypt of the small intestine was significantly lower in group II than in group I (p<.001) and was significantly higher in group III than in group II (p<.001), with the exception of the villi of jejunum. Villous and crypt surface area per millimeter serosal length of intestine was significantly lower in group II than in group I (p<.001) and was significantly higher in group III than in group II (p<.001). Small intestinal permeability to FITC-dextran was significantly higher in group II than in group I (p<.001) and was significantly lower in group III than in group II (p<.001). Glucosamine synthetase level was significantly higher in group III than in group I and ileum of group II (p<.001). CONCLUSIONS: Alanyl-glutamine-supplemented TPN prevents a decrease in mucus gel and an increase in small intestinal permeability associated with S-TPN.
Animals↗
Tumor lysis syndrome complicating treatment of widespread metastatic abdominal rhabdomyosarcoma.
In this paper we describe a 9-year-old girl with abdominal embryonal rhabdomyosarcoma. She had ascites and widespread metastatic disease at presentation and was oliguric but had a normal creatinine. Following the start of chemotherapy she developed acute renal failure secondary to the tumor lysis syndrome, requiring hemodialysis, and had considerable myelotoxicity.
Abdominal Neoplasms↗
The incidence of non ulcer dyspepsia and its response to treatment.
BACKGROUND: This study was undertaken to identify Non Ulcer Dyspepsia (NUD) in young patients presenting with peptic ulcer like symptoms. Their response to treatment was also determined. METHODS: 100 patients between the ages of 20-40 of both sexes were included in the study. Investigations done were Chest X-ray Plain Abdominal X-ray, ECG, ESR, LFTs Amylase Abdominal Ultrasound and upper GI endoscopy. All patients then received 6-week therapy with Omeprazole and Helicobacter Pylori eradication with Clarithromycin and Tinidazole. RESULTS: NUD was by far the most common cause (59%) in both the sexes. Response to therapy was unsatisfactory. CONCLUSIONS: This relatively newly discovered clinical entity should be kept in mind while dealing with patients presenting with refractory dyspeptic symptoms.
Anti-Bacterial Agents↗
Household composition in Sind, Pakistan: has it changed or persisted?
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Asia↗