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Biomedical subjects

S Rafi

Publications and source records attributed to S Rafi.

At least 19 recordsLinked to original sources

Efficacy of bronchial wash cytology and its correlation with biopsy in lung tumours.

OBJECTIVE: To evaluate bronchial wash cytology with histology in our set up. METHODS: Seventy three specimens were obtained by flexible fiberoptic bronchoscope at pulmonology department of Military Hospital Rawalpindi. All the preserved samples were processed under standard conditions. The slides were stained with Papanicolaou and Haematoxylin and Eosin stains. RESULTS: A total of 73 patients were studied. The age range was 21 to 80 years. Male to female ratio was 8:1. Complete cytological and biopsy consensus was found in 55 (77.4%) cases. Cytology revealed 24 cases as malignant and nine as atypical/suspicious. Benign and inadequate were 29 and 2 respectively. Histopathology of these cases confirmed 24 (32.9%) as malignant and 29 (39.8%) as benign. True positive alongwith suspicious/atypical were 33 and true negative cases were 29. False positive was one case only whereas false negative cases were eight. The bronchial wash cytology showed sensitivity (80.5%), specificity (96.6%) and accuracy (87.3%). Positive predictive value and negative predictive value were 97% and 78.4% respectively. The commonest types of tumours were squamous cell carcinoma and small cell carcinoma. CONCLUSION: It is concluded that bronchial wash cytology is a valuable tool and yields almost same information as biopsy. It is useful in patients with evidence of obstruction or risk of haemorrhage.

Adult↗

Fluroquinolone resistance in typhoidal Salmonella and its detection by nalidixic acid disc diffusion.

OBJECTIVE: To determine the presence of fluoroquinolone resistance in Typhoidal salmonellae at Rawalpindi and the role of nalidixic acid in predicting the resistance against fluoroquinolones in Microbiology Laboratory, Department of Pathology, Army Medical College, Rawalpindi. METHODS: One hundred consecutive clinical isolates of Typhoidal salmonellae isolated from blood culture samples were studied. The organisms were identified biochemically and serologically by standard technique. Sensitivity testing was carried out against nalidixic acid and ciprofloxacin by modified Kirby bauer disc diffusion method and minimum inhibitory concentration (MICs) were determined by E-test. RESULTS: Seventeen percent of the isolates were resistant to nalidixic acid. Nalidixic acid disc diffusion and MIC estimation by E-test were 100% comparable. All isolates were sensitive to ciprofloxacin but the isolates which were resistant to nalidixic acid had raised MIC values against ciprofloxacin. CONCLUSION: Typhoidal salmonellae have not shown an overt in vitro resistance against fluoroquinolones in our set up but a significant population has emerged with raised MIC values. Nalidixic acid susceptibility test can be used an indirect evidence of resistance to quinolones.

Anti-Infective Agents↗

An evaluation of topical and local anesthesia in phacoemulsification.

OBJECTIVE: To assess the comparative efficacy of topical and local anesthesia in phacoemulsification. MATERIAL AND METHODS: The medical records of 186 men and women between the ages of 45-85 years, who underwent elective cataract surgery by phacoemulsification technique, under the care of one surgeon, over a period of one year, from March 1999-March 2000 were reviewed. RESULTS: Of 186 patients who underwent small incision, self-healing phacoemulsification cataract surgery, 124 received topical and 62 local anesthesia. The most common cataract types were nuclear sclerosis. The duration of surgery with topical anesthesia was shorter. Sutures and eye padding were more frequently applied for procedures done under local anesthesia. Uncorrected visual acuity in the first post-op week was between 20/20-20/50 for 53.6% of the cases done under topical compared to 30.9% in local anesthesia. A similar trend was noted in the visual acuity one month post operatively. CONCLUSION: The uncorrected visual acuity improves faster and the duration of surgery is shorter when topical anesthesia is used.

Administration, Topical↗

Frequency of Campylobacter jejuni in diarrhoea/dysentery in children in Rawalpindi and Islamabad.

OBJECTIVE: To determine the frequency of Campylobacter jejuni infection in children suffering from diarrhoea/dysentery in the Department of Microbiology, Army Medical College and Military Hospital, Rawalpindi, from 29 August 2002 to 29 November 2002. METHODS: The study was carried out on one hundred stool samples of children up to the age of twelve years admitted with diarrhoea/dysentery in Military hospital, Rawalpindi. The samples were collected in clean polypropylene containers containing Cary Blair medium. These were transported to the Microbiology Department, Army Medical College, Rawalpindi within 1-2 hours. The samples were inoculated on Modified Preston (Oxoid) and Karmali media (Oxoid) beside other routine stool culture media. The cultures were incubated at 42 degrees C under microaerophilic conditions. The growth after 48 hours was provisionally identified by colonial morphology, oxidase test, Gram staining and motility. The organisms were identified to species level by hippurate hydrolysis, urease test, nitrate reduction, catalase test, H2S production and resistance to cephalothin. RESULTS: Eighteen percent of samples yielded the growth of Campylobacter jejuni. Mean age of children with Campylobacter jejuni infection was 18 months with peak incidence from 12 to 21 months. Male female ratio was 1.7:1. All the children had loose motions. Seven out 18 (39%) had a combination of symptoms of loose motions, vomiting and pain abdomen. Those having fever with or without other complaints constituted 11 out of 18 (61.11%) i.e. more than 50% of all the children yielding C. jejuni had fever. About 90% of diarrhoeal stools had blood and fifty percent also had mucous. There was either history of chicken meat consumption or contact with cattle and pets in most of the cases and both in some of them. CONCLUSION: Campylobacter jejuni is a frequent cause of diarrhoea/dysentery in children in our set up. In children it is often related to pets keeping and chicken meat consumption. In the remaining, untreated drinking water may be the source. Campylobacter jejuni frequently presents with blood and mucous in stools with sporadic cases presenting with watery diarrhoea.

Campylobacter Infections↗

2, 4-diamino-6- hydroxy pyrimidine inhibits NSAIDs induced nitrosyl-complex EPR signals and ulcer in rat jejunum.

BACKGROUND: It has been suggested that one aspect of non-steroidal anti-inflammatory drugs induced intestinal damage is due to either uncoupling of mitochondrial oxidative phosphorylation or inhibition of electron transport. We investigated the latter possibility using electron paramagnetic resonance spectroscopy. RESULTS: Electron paramagnetic studies of NSAIDS on sub-mitochondrial particles revealed that indomethacin, but not with nabumetone, bound to a site near to Complex I and ubiquinone to generate a radical species. Normal rats exhibited prominent [3Fe-4S]ox signals (g approximately 2.01) at 20 K. One hour after indomethacin there was a prominent, intense and broad absorption pattern at (g approximately 2.07) suggesting, appearance of radical species overlapping [3Fe-4S]ox and was unaffected by pretreatment with 2,4 diamino -6-hydroxy pyrimidine. At 24 hrs, when macroscopic ulcers were seen, there was a new signal due to a nitric oxide radical (NO*). In contrast, nabumetone and 2,4 diamino-6-hydroxy pyrimidine pre-treated animals receiving indomethacin exhibited electron paramagnetic resonance spectra identical to those of controls at 24 hrs and neither was associated with small intestinal ulcers. Indomethacin and 2,4 diamino hydroxy pyrimidine pre-treated rats, but not nabumetone, had increased intestinal permeability. CONCLUSION: The results suggest that the in vivo effects of indomethacin modulate the mitochondrial respiratory chain directly at 1 h and 24 h through formation of nitric oxide. NO* appears to play an important role in the late pathogenic stages of NSAID enteropathy and may be the site for targeted treatment to reduce their toxicity.

Animals↗

A study of the effects of indometacin on liver mitochondria from rats, mice and humans.

BACKGROUND: A part of the mechanism of the gastrointestinal toxicity exhibited by non-steroidal anti-inflammatory drugs is believed to involve the uncoupling of mitochondrial oxidative phosphorylation. Most previous uncoupling studies have used rat liver mitochondria. There is little information on the effects of the drugs on mitochondria from other species. AIM: To study the effect of indometacin on isolated liver mitochondria from rats, mice and humans. METHODS: We studied the effects of indometacin on respiration and adenosine triphosphate synthesis by isolated liver mitochondria from rats, mice and humans. Its effects were compared with those of dinitrophenol, a classical uncoupler. RESULTS: Indometacin uncoupled oxidative phosphorylation at low concentrations (P < 0.05) and inhibited respiration at high concentrations (P < 0.01) in all three species. Adenosine triphosphate synthesis was, however, more sensitive to dinitrophenol or indometacin at lower concentrations in mouse and human compared to rat liver mitochondria (P < 0.05). CONCLUSIONS: The current study shows that indometacin acts as an inhibitory uncoupler in human mitochondria. It also demonstrates that the responses of rat, mouse and human mitochondria to indometacin are broadly similar.

Adenosine Triphosphate↗

Uncoupling of intestinal mitochondrial oxidative phosphorylation and inhibition of cyclooxygenase are required for the development of NSAID-enteropathy in the rat.

BACKGROUND: The pathogenesis of NSAID-induced gastrointestinal damage is believed to involve a nonprostaglandin dependent effect as well as prostaglandin dependent effects. One suggestion is that the nonprostaglandin mechanism involves uncoupling of mitochondrial oxidative phosphorylation. AIMS: To assess the role of uncoupling of mitochondrial oxidative phosphorylation in the pathogenesis of small intestinal damage in the rat. METHODS: We compared key pathophysiologic events in the small bowel following (i) dinitrophenol, an uncoupling agent (ii) parenteral aspirin, to inhibit cyclooxygenase without causing a 'topical' effect and (iii) the two together, using (iv) indomethacin as a positive control. RESULTS: Dinitrophenol altered intestinal mitochondrial morphology, increased intestinal permeability and caused inflammation without affecting gastric permeability or intestinal prostanoid levels. Parenteral aspirin decreased mucosal prostanoids without affecting intestinal mitochondria in vivo, gastric or intestinal permeability. Aspirin caused no inflammation or ulcers. When dinitrophenol and aspirin were given together the changes in intestinal mitochondrial morphology, permeability, inflammation and prostanoid levels and the macro- and microscopic appearances of intestinal ulcers were similar to indomethacin. CONCLUSIONS: These studies allow dissociation of the contribution and consequences of uncoupling of mitochondrial oxidative phosphorylation and cyclooxygenase inhibition in the pathophysiology of NSAID enteropathy. While uncoupling of enterocyte mitochondrial oxidative phosphorylation leads to increased intestinal permeability and low grade inflammation, concurrent decreases in mucosal prostanoids appear to be important in the development of ulcers.

Animals↗

Co-activation of Gi and Gq proteins exerts synergistic effect on human platelet aggregation through activation of phospholipase C and Ca2+ signalling pathways.

Our previous studies have shown that subthreshold concentrations of two platelet agonists exert synergistic effects on platelet aggregation. Here we studied the mechanism of synergistic interaction of 5-hydroxytryptamine (5-HT) and epinephrine mediated platelet aggregation. We show that 5-HT had no or little effect on aggregation but it did potentiate the aggregation response of epinephrine. The synergistic interaction of 5-HT (1-5 microM) and epinephrine (0.5-2 microM) was inhibited by alpha2-adrenoceptor blocker (yohimbine; IC50= 0.4 microM), calcium channel blockers (verapamil and diltiazem with IC50 of 10 and 48 mM, respectively), PLC inhibitor (U73122; IC50=6 microM) and nitric oxide (NO) donor, SNAP (IC50=1.6 microM)). The data suggest that synergistic effects of platelet agonists are receptor-mediated and occur through multiple signalling pathways including the activation PLC/Ca2+ signalling cascades.

Blotting, Western↗

Drug resistance in Mycobacterium tuberculosis: a four years experience.

OBJECTIVE: To assess the prevalence of drug resistance amongst the clinical isolates of M. tuberculosis. SETTING: Armed Forces Institute of Pathology, Rawalpindi. METHOD: Four first line anti-tuberculosis drugs, isoniazid (INH), rifampicin (RIF), ethambutol (ETH) and streptomycin (STR) were tested on 300 isolates from clinical samples, by agar dilution method on Lowenstein Jensen medium. The sensitivities were interpreted by the resistance ratio method. RESULTS: One hundred and fifty eight (52.66%) isolates were found resistant to one drug at least. Among the resistant isolates, 79 (26.33%) were resistant to INH, 72 (24.0%) to RIF, 84 (28.0%) to STR and 70 (23.33%) to ETH with or without resistance to other drugs. Multi-drug resistance (MDR) was found in 41 isolates (13.66%). CONCLUSION: To overcome this problem there is a need to establish centres at a number of places all over the country with professionals trained to handle the emerging problem of MDR. Each centre must be equipped with adequate facilities for susceptibility testing so that the resistance pattern can be ascertained and treatment regimens tailored accordingly.

Drug Resistance, Microbial↗

Comparison of indomethacin and nimesulide, a selective cyclooxygenase-2 inhibitor, on key pathophysiologic steps in the pathogenesis of nonsteroidal anti-inflammatory drug enteropathy in the rat.

BACKGROUND: The predicted gastrointestinal tolerability of specific cyclooxygenase-2 inhibitors could be due to either a lack of 'topical' irritation and/or lack of effect on cyclooxygenase-1. METHODS: Key pathophysiologic steps (in vitro and in vivo uncoupling, intestinal prostanoid levels (prostaglandin E, thromboxane B2, and 6-keto-prostaglandin F1alpha), intestinal permeability (51Cr-ethylenediaminetetraacetic acid), inflammation (faecal excretion of a granulocyte marker protein), and ulcer counts) in enteropathy induced by nonsteroidal anti-inflammatory drugs were assessed after administration of indomethacin, 10 mg/kg, and 15 (roughly equipotent), 30, and 60 mg/kg of the preferential cyclooxygenase-2 inhibitor nimesulide. RESULTS: Indomethacin uncoupled oxidative phosphorylation at lower concentrations than nimesulide in vitro. Indomethacin was associated with electron microscopy changes suggestive of uncoupling in 60%-70% of enterocytes examined, whereas nimesulide affected 10%-30% of enterocytes, depending on the dose. Indomethacin increased intestinal permeability and caused inflammation and ulcers with 71%-96% reductions in prostanoid levels. Nimesulide at 15 mg/kg caused no damage, whereas 30 and 60 mg/kg nimesulide were associated with significant decreases in mucosal prostanoids (46%-75%), but only the 60-mg/kg dose caused a transient increase in intestinal permeability. However, at none of the doses did nimesulide cause intestinal inflammation or ulcers. CONCLUSIONS: These results endorse the idea that selective cyclooxygenase-2 inhibitors may be associated with some gastrointestinal tolerance due to their selectivity for cyclooxygenase-2, inhibiting cyclooxygenase-1 at only very high doses, and reduced topical irritation.

Animals↗

Enantiomers of flurbiprofen can distinguish key pathophysiological steps of NSAID enteropathy in the rat.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) cause gastrointestinal damage by a non-prostaglandin (PG) dependent "topical" action and by inhibiting cyclooxygenase. AIMS: To discriminate between these two effects by studying some key pathophysiological steps in NSAID enteropathy following administration of (R)- and (S)-flurbiprofen, the racemic mixture, and an uncoupler, dinitrophenol. METHODS: The effects of dinitrophenol, racemic, (R)-, and (S)-flurbiprofen on mitochondria were assessed in vitro and on key pathophysiological features of small intestinal damage in vivo (ultrastructure by electron microscopy, mucosal prostanoid concentrations, intestinal permeability, inflammation, and ulcer count) in rats. RESULTS: All the drugs uncoupled mitochondrial oxidative phosphorylation in vitro, caused mitochondrial damage in vivo, and increased intestinal permeability. Dinitrophenol and (R)-flurbiprofen caused no significant decreases in mucosal prostanoid concentrations (apart from a decrease in thromboxane (TX) B2 concentrations following (R)-flurbiprofen) while racemic and (S)- flurbiprofen reduced mucosal prostanoids significantly (PGE, TXB2, and 6-keto-PGF1alpha concentrations by 73-95%). Intestinal inflammation was significantly greater following administration of (S)-flurbiprofen and racemate than with dinitrophenol and (R)-flurbiprofen. No small intestinal ulcers were found following dinitrophenol or (R)-flurbiprofen while both racemic and (S)-flurbiprofen caused numerous ulcers. CONCLUSIONS: Dinitrophenol and (R)-flurbiprofen show similarities in their actions to uncouple mitochondrial oxidative phosphorylation in vitro, alter mitochondrial morphology in vivo, increase intestinal permeability, and cause mild inflammation without ulcers. Concurrent severe decreases in mucosal prostanoids seem to be the driving force for the development of severe inflammation and ulcers.

Animals↗

CODBLAM IV chemotherapy for large cell lymphoma: sequential use of infusional vincristine and bleomycin and "high dose" consolidation.

BACKGROUND: Based on prior results in large cell lymphoma (LCL) with COPBLAM (Cyclophosphamide, Oncovin, Prednisone, Bleomycin, Adriamycin, Matulane) I and COPBLAM III, CODBLAM (Cyclophosphamide, Oncovin, Dexamethasone, Bleomycin, Adriamycin, Matulane) IV was developed to intensify treatment further by utilizing four sequential cycles of infusional chemotherapy followed by high-dose chemotherapy and cycle active agents. METHODS: Sixty-one patients with LCL, mostly B-cell lymphoma, with 54% >60 years of age, were treated with daily continuous infusion of vincristine 1.0 mg/m2 days 1-2, bleomycin 4 mg/m2 i.v. push x 1 only followed by daily infusion 4 mg/m2 days 1-5, dexamethasone 10 mg/m2 days 1-5, procarbazine 100 mg/m2 orally days 1-5, doxorubicin 35 mg/m2 i.v. push day 1 (escalated), and cyclophosphamide 350 mg/m2 i.v. push day 1 (escalated), all given every 3 weeks for four cycles. After infusions, patients were restaged and treated with single courses of doxorubicin 90 mg/ m2 i.v. push followed at 3 weeks with cyclophosphamide 1500 mg/m2 i.v. push (both with concomitant vincristine 1 mg/m2 i.v. push and dexamethasone 10 mg/m2 p.o. daily for 5 days). Remaining treatment consisted of methotrexate 120 mg/m2 i.v. push with citrovorum rescue, cytarabine 250 mg/m2 i.v. push, and etoposide 100 mg/m2 i.v. infusion over 1 h, all given every 10 days for six cycles. RESULTS: The overall complete response (CR) rate was 88%. Of all patients, 36 (59%) are sustained disease free at a median follow-up time of 55 months. In patients age < or = 60 years, 89% achieved CR and 85% of patients age >60 years attained CR. CR was achieved in 83% of patients with constitutional B-type symptoms, 69% of patients with bulky adenopathy, and 86% of patients with immunoblastic histology. Toxicity was primarily pulmonary, occuring in 15% of patients. One toxic death was observed. CONCLUSIONS: Infusional CODBLAM IV may represent an effective and unique treatment for LCL.

Adult↗

Intestinal tolerability of nitroxybutyl-flurbiprofen in rats.

BACKGROUND: Nitric oxide derivatives of non-steroidal anti-inflammatory drugs (NSAIDs) are thought to be much less ulcerogenic than their parent compounds. AIM: To compare the effect and potency of flurbiprofen and nitroxybutyl-flurbiprofen to uncouple mitochondrial oxidative phosphorylation (an early pathogenic event in NSAID enteropathy), increase intestinal permeability (transitional stage), and cause macroscopic small intestinal damage. METHODS: In vitro uncoupling potency was assessed using isolated coupled rat liver mitochondria and in vivo by electron microscopy of rat small intestinal mucosa (two hours after the drugs). A dose-response study with flurbiprofen (single doses of 5, 10, 20, and 40 mg/kg) and equimolar doses of nitroxybutyl-flurbiprofen was performed; assessing their effect on intestinal permeability (at 18-20 hours), with 51Cr EDTA, and the number of pointed (< 5 mm) and longitudinal (> 5 mm) small intestinal ulcers at 24 hours. RESULTS: Flurbiprofen, but not nitroxybutyl-flurbiprofen, stimulated coupled respiration in vitro. Both drugs, however, uncoupled in vivo; in the case of nitroxybutyl-flurbiprofen possibly because hydrolysis of its ester bond released free flurbiprofen. Intestinal permeability was uniformly and equally increased with both drugs compared with controls. The number of small intestinal ulcers, pointed and longitudinal, was significantly reduced with nitroxybutyl-flurbiprofen apart from the number of longitudinal ulcers with the highest dose. CONCLUSIONS: These studies show that nitroxybutyl-flurbiprofen is associated with significantly less macroscopic damage in the small intestine than flurbiprofen but was associated with mitochondrial damage in vivo and caused similar increases in permeability of the small intestine, suggesting that its beneficial effect is on the later pathogenic stages of the damage.

Animals↗

Mitochondrial damage: a possible mechanism of the "topical" phase of NSAID induced injury to the rat intestine.

BACKGROUND: The "topical" effect of non-steroidal anti-inflammatory drugs (NSAIDs) seems to be an important cause of NSAID induced gastrointestinal damage. AIM: To examine the possible mechanism of the "topical" phase of damage in the small intestine. METHODS: Electron microscopy and subcellular organelle marker enzyme studies were done in rat small intestine after oral administration of indomethacin (doses varied between 5 and 30 mg/kg). The effect of conventional and non-acidic NSAIDs on rat liver mitochondrial respiration was measured in vitro in a Clarke-type oxygen electrode. RESULTS: The subcellular organelle marker enzymes showed mitochondrial and brush border involvement within an hour of indomethacin administration. Electron microscopy showed dose dependent mitochondrial changes following indomethacin administration consistent with uncoupling of oxidative phosphorylation (or inhibition of electron transport) which were indistinguishable from those seen with the uncoupler dinitrophenol. Parenteral indomethacin caused similar changes, but not in rats with ligated bile ducts. A range of NSAIDs, but not paracetamol or non-acidic NSAIDs which have a favourable gastrointestinal tolerability profile, uncoupled oxidative phosphorylation in vitro at micromolar concentrations and inhibited respiration at higher concentrations. In vivo studies with nabumetone and aspirin further suggested that uncoupling or inhibition of electron transport underlies the "topical" phase of NSAID induced damage. CONCLUSION: Collectively, these studies suggest that NSAID induced changes in mitochondrial energy production may be an important component of the "topical" phase of damage induction.

Acetaminophen↗

Efficacy and safety of mebendazole in children with worm infestation.

Children aged between 2-16 years, were screened for worm infestation. Fifty-five children fulfilling the inclusion criteria were included in the study. They were treated with mebendazole 100 mg twice daily for three consecutive days and followed-up for 15 days to assess cure rate and side effects. Fifty children completed the study with their stools being tested by direct smear and concentration methods and blood CBC done before treatment and at the end of the study. The cure rate for ascaris was 100% and for trichuris 75%. The drug was well tolerated and apart from mild diarrhoea occurring in 22% children, no untoward effects were reported. Nemazole (mebendazole) has shown promise and seems useful in treating children with worm infestation.

Adolescent↗

Expanded programme of immunization in Karachi.

Immunization status of children and their mothers and reasons for their failure to be immunized were studied. The study lasted for two months, i.e., August and September, 1993 at the Paediatric Outpatient Department of Civil Hospital, Karachi. Three groups of patients were targeted. Six hundred and twenty-four children under 1 year of age, 955 children between the ages of 1 to 5 years and 1579 mothers were registered. These women were questioned regarding their immunization status and that of their children. In the group below 1 year of age, BCG, DPT and polio (3 doses) and measles were given to 75%, 35% and 23% respectively. Tetanus toxoid (2 doses) was given to 47% of their mothers. In the group of children between 1-5 years, BCG, DPT and polio 3 doses and measles were given to 84%, 63% and 58% respectively. Tetanus toxoid (2 doses) were given to 64% of their mothers. The main reasons for not vaccinating were lack of information and lack of motivation.

Adult↗

A change of Plasmodium species infecting children in Karachi over the last decade.

Febrile children of both sexes, aged between 0-15 years coming to the Civil Hospital over the last 12 years had their blood tested for malarial parasite. Five hundred and twenty-six slides positive for Plasmodium were analysed for species and stage identification. Of the total 59.3% children with malaria were between 5-15 years of age. Applying the test of proportion, Plasmodium vivax was the predominant species (P < 0.01) between 1981-1985 and plasmodium falciparum between 1986-1990. This trend persisted upto 1992. As malaria due to Plasmodium falciparum is more severe with multiple complications accurate and easier methods of its diagnosis are needed at primary health care level.

Adolescent↗