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Biomedical subjects

S Akram

Publications and source records attributed to S Akram.

14 recordsLinked to original sources

Reactive oxygen species-mediated regulation of the Na+-H+ exchanger 1 gene expression connects intracellular redox status with cells' sensitivity to death triggers.

We have previously demonstrated that a slight increase in intracellular superoxide (O2*-) anion confers resistance to death stimuli. Using pharmacological and molecular approaches to manipulate intracellular O2*-, here we report that an increase in intracellular O2*- anion induces Na+/H+ exchanger 1 (NHE-1) gene promoter activity resulting in increased NHE-1 protein expression, which strongly correlates with the resistance of cells to death stimuli. In contrast, exposure to exogenous hydrogen peroxide suppressed NHE-1 promoter activity and gene expression, and increased cell sensitivity to death triggers. Furthermore, the increase in cell sensitivity to death upon downregulation of NHE-1 gene expression correlates with reduced capacity of cells to recover from an acid load, while survival upon overexpression of NHE-1 appears independent of its pump activity. These findings indicate that NHE-1 is a redox-regulated gene, and provide a novel intracellular target for the redox control of cell death sensitivity.

Animals↗

Febrile seizures: factors affecting risk of recurrence in Pakistani children presenting at the Aga Khan University Hospital.

OBJECTIVES: To (a) describe the effect of temperature rise on seizure recurrence in the ER (b) investigate the effect of age, gender, family and developmental history, type, duration and multiple seizures, past history and number of seizures and treatment given (either late or early) on seizure recurrence in the ER and (c) explore prognostic indicators for seizure recurrence. METHODS: Data from 352 children [ages 3-84 months; 220 males (62.5%) 132 females (37.5%)] was taken using chart reviews for the years January 1998-August 2000 inclusive, from the Pediatric department of the Aga Khan University Hospital. Descriptive statistics, Chi-square, and Discriminant Analysis were used. RESULTS: Of the 52 (16%) cases that had seizure recurrence in the ER, majority (36.5%) occurred in > 38.5 degrees < or = 39.5 degrees C temperature range. The percentage declined to 15% at higher temperatures. Bivariate tests showed that age, family and developmental history, type of seizure and treatment given did not affect seizure recurrence in the ER. Past history number of seizures (p = .006), duration of seizure (p < 0.001), past history of seizures (p = 0.004) and multiple seizure (p = 0.024) were factors significantly associated with seizure recurrence in the ER at the bivariate level of analysis. Duration of seizure was the most important prognostic indicator for FS recurrence in the ER at the multivariate level with beta = .79. CONCLUSION: Duration of seizure (> 5 minutes) was the most important prognostic factor for FS recurrence. Early treatment did not affect recurrence,suggesting timely anti-pyretic vs. anti-leptic medication use.

Age Distribution↗

Randomized controlled trial of clarithromycin and ethambutol in the treatment of Crohn's disease.

BACKGROUND: A mycobacterial infection may be the cause of Crohn's disease in some patients. Measurement of intestinal permeability may identify Crohn's disease patients with a high likelihood of relapse and may quantify the severity of intestinal injury. AIM: To assess the effect of 3 months of clarithromycin and ethambutol on the disease activity and intestinal permeability in patients with Crohn's disease at high risk of relapse. METHODS: Patients with Crohn's disease, with a lactulose-mannitol permeability test above 0.03, were randomly assigned to receive either clarithromycin, 500 mg twice daily, and ethambutol, 15 mg/kg daily, or identically appearing placebo for 3 months in addition to their regular therapy. The Harvey-Bradshaw index and the lactulose-mannitol test were assessed in a blind fashion every 3 months for 12 months. RESULTS: Thirty-one patients were randomized to receive either drugs (n=15) or placebo (n=16). The groups were similar in age, sex, duration of disease, location of disease, past complications and disease severity. Specifically, there was no difference between the drug or placebo groups in the mean Harvey-Bradshaw index (4.8 vs. 4.4), number with active disease (33% vs. 44%) and mean lactulose-mannitol test (0.06 vs. 0.10). During the 12-month follow-up period, there were no consistent, statistically significant differences in the mean Harvey-Bradshaw index or lactulose-mannitol test between treatment and placebo groups. Individual patients showed either improvement or worsening of these indices, but these were not related to study medication. Specifically, no 'cures' were noted with anti-mycobacterial treatment. CONCLUSIONS: Three months of treatment with clarithromycin and ethambutol does not benefit Crohn's disease patients who are receiving standard medical therapy.

Adult↗

Placenta percreta with bladder invasion as a cause of life threatening hemorrhage.

PURPOSE: Abnormal placental penetration through the myometrium with bladder invasion is a rare obstetric complication with potential for massive blood loss. Urologists are usually consulted after a life threatening emergency has already arisen. Their familiarity with this condition is crucial for effective management. We describe 2 cases of placenta percreta with bladder invasion to highlight the catastrophic nature of this clinical entity, and review the literature on current diagnostic and management strategies. MATERIALS AND METHODS: Between 1986 and 1998, 250 cases of adherent placenta (0.9%) were identified in 25,254 births at our institution, including 2 (0.008%) of placenta percreta with bladder invasion. We treated these 2 multiparous women who were 33 and 30 years old, respectively. Each had undergone 2 previous cesarean sections. RESULTS: Presenting symptoms were severe hematuria in 1 patient and prepartum hemorrhage with shock in the other. Ultrasound showed complete placenta previa in each with evidence of bladder invasion in 1 patient. Hysterectomy, bladder wall resection and repair, and bilateral internal iliac artery ligation were required to control massive intraoperative hemorrhage. The patients received 22 and 15 units of packed red blood cells, respectively. Fetal death occurred in each case. Convalescence was complicated by disseminated intravascular coagulation in patient 1 but subsequent recovery was uneventful. CONCLUSIONS: A high index of suspicion for placenta percreta with bladder invasion is required when evaluating pregnant women with a history of cesarean delivery and placenta previa who present with hematuria and lower urinary tract symptoms. Ultrasonography and magnetic resonance imaging may assist in establishing the diagnosis preoperatively. With proper planning and a multidisciplinary approach fetal and maternal morbidity and mortality may be decreased.

Adult↗

Assessment of intestinal permeability with a two-hour urine collection.

The differential urinary excretion of orally administered lactulose and mannitol is used to evaluate intestinal permeability. This test usually involves a 5- to 6-hr urine collection. We hypothesized that a shorter collection time would give an equivalent result. Forty-three patients with a variety of gastrointestinal symptoms and diagnoses (group 1) and 42 patients with Crohn's disease (group 2) had a standard lactulose/mannitol permeability test. The lactulose and mannitol urinary excretion was calculated using the first urine (group 1) or the 1-hr and 2-hr urine (group 2) and was compared to the values calculated from the routine 5- or 6-hr collection. Lactulose excretion kinetics, expressed as the percent of the total urinary excretion within a given time period, were as follows: 21% in first hour (group 2), 29% in second hour (group 2), and 46% in first 2.5 hr (group 1). Mannitol urinary excretion kinetics were 16%, 31%, and 44%, respectively. The lactulose/mannitol ratio based on a standard urine collection correlated well with the ratio based on just the first urine produced by the patient (R2 = 0.94; P < 0.001; group 1) and the 2-hr urine (R2 = 0.464; P < 0.001; group 2). Future use of the lactulose/mannitol ratio to assess intestinal permeability may be able to be simplified by shortening the urine collection time.

Administration, Oral↗

de Lange syndrome.

Explore the source record for details and available documents.

De Lange Syndrome↗

Decreased susceptibility to imipenem among penicillin-resistant Streptococcus pneumoniae.

We assessed the antimicrobial susceptibilities of 59 penicillin-intermediate or penicillin-resistant pneumococci. All strains were susceptible to vancomycin and rifampicin. The frequency of strains with decreased susceptibility to cefotaxime, chloramphenicol, imipenem and meropenem was 15, 31, 47 and 49% respectively. The high percentage of penicillin-intermediate or penicillin-resistant Streptococcus pneumoniae with decreased susceptibility to third-generation cephalosporins, chloramphenicol and carbapenems limits the therapeutic options for the treatment of invasive pneumococcal infections and particularly of meningitis.

Anti-Bacterial Agents↗

Penicillin-resistant pneumococci from pediatric patients in the Washington, DC, area.

OBJECTIVE: To assess the prevalence and antimicrobial susceptibility of penicillin-resistant pneumococci (PRP) isolated from patients in a pediatric hospital. METHODS: All (108) isolates of Streptococcus pneumoniae recovered from usually sterile body sites between June 1, 1992, and May 31, 1993, were screened for susceptibility to penicillin by the E-test method. Minimum inhibitory concentrations of penicillin and other antibiotics were also determined by an agar dilution method for 10 PRP and 22 penicillin-susceptible strains. RESULTS: Fourteen isolates (12.9%) were PRP by the E-test; nine of these (8.3%) were intermediately resistant and five (4.6%) were highly resistant. All strains were sensitive to rifampin and vancomycin. Increased frequency of resistance to oral and parenteral cephalosporins and carbapenems was found among PRP; for most of these antibiotics, resistance exceeded 40% of the PRP. In addition, 20% of the PRP were resistant to macrolides and all penicillin-susceptible and PRP were resistant to a combination of trimethoprim and sulfamethoxazole. CONCLUSIONS: The decreased susceptibility to oral and parenteral cephalosporins, macrolides, a combination of trimethoprim and sulfamethoxazole, and carbapenems creates a significant problem in the treatment of pneumococcal infections in both ambulatory and hospitalized patients.

Adolescent↗

Streptococcus pneumoniae resistant to penicillin: incidence and potential therapeutic options.

Streptococcus pneumoniae was recovered from 12 (50%) samples of middle ear fluid of 24 consecutive patients with AOME and in mixed culture of middle ear pathogens from one (4%) additional specimen. Two (15.3%) isolates had intermediate resistance to penicillin (minimal inhibitory concentration (MIC) 0.125 and 1.0 micrograms/mL). The antimicrobial susceptibility to various antimicrobials of 30 S pneumoniae strains recovered from patients seen in the last 12 months was also determined. One of the patients with AOME developed bacteremia that resolved uneventfully, whereas the other developed meningitis. MIC90 was determined from penicillin (2 micrograms/mL), erythromycin (> 32 micrograms/mL), cefaclor (32 micrograms/mL), loracarbef (> or = 64 micrograms/mL), cefixime (16 micrograms/mL), ceftibuten (> 64 micrograms/mL), chloramphenicol (16 micrograms/mL), cefpodoxime (4 micrograms/mL), ciprofloxacin (2 micrograms/mL), cephalexin (> or = micrograms/mL), augmentin (2 micrograms/mL), cefprozil (8 micrograms/mL), clindamycin (64 micrograms/mL), TMP-SXT (> 64 micrograms/mL), clarithromycin (32 micrograms/mL), rifampin (0.06 micrograms/mL), cefuroxime (2 micrograms/mL), cefotaxime (0.25 micrograms/mL), vancomycin (0.25 micrograms/mL), and imipenem (0.5 micrograms/mL). Cefprozil, vancomycin, and rifampin inhibited all strains, whereas cefpodoxime, cefuroxime, clindamycin, and clarithromycin exhibited very good activity.

Anti-Bacterial Agents↗

Urinary N-acetyl-beta-glucosaminidase and beta-2-microglobulin in the diagnosis of urinary tract infection in febrile infants.

Urinary N-acetyl-beta-glucosaminidase (NAG) and beta-2-microglobulin (B2M) concentrations were measured in 24 pediatric patients with febrile urinary tract infection (UTI) and compared with the technetium-99m-labeled dimercaptosuccinic acid (DMSA) renal scan results, in order to evaluate a noninvasive means to localize the site of UTI. Increased urinary B2M and NAG were not associated with renal inflammation (pyelonephritis), as defined by positive dimercaptosuccinic acid scan. Median NAG concentrations were 114.2 mumol/hour/mg creatinine (CR) (range, 5.7 to 305.4) in 17 febrile UTI patients vs. 13.8 (range, 3.4 to 104.3) in 17 age and sex-matched febrile controls with negative urine cultures, P = 0.0001. The sensitivity and specificity of NAG > or = 40 mumol/hour/mg of CR in predicting UTI in febrile patients, regardless of the site of infection, were 88 and 88%, respectively. Increased urinary NAG is associated with UTI in febrile patients regardless of the level of infection (scan status), and may be an informative indicator of UTI.

Acetylglucosaminidase↗

Cefixime vs. cefaclor in the treatment of acute otitis media in children: a randomized, comparative study.

The efficacy of cefixime was compared with that of cefaclor in the treatment of 63 patients with acute otitis media. Patients received either a single dose of cefixime (8 mg/kg/day) or 3 divided doses of cefaclor (40 mg/kg/day). On the basis of otoscopic and tympanometric results at 10 to 14 days after the start of treatment, 28 (97%) of 29 cefixime-treated patients and 25 (78%) of 32 cefaclor-treated patients had resolution of acute otitis media. The clinical cure rate associated with all organisms was 94% for cefixime (16 of 17 isolates) and 68% (13 of 19 isolates) for cefaclor. The cure rate for Streptococcus pneumoniae was 12 of 12 (100%) for cefixime and 7 of 7 (100%) for cefaclor; the cure rate for Haemophilus influenzae (which includes 2 patients with mixed infections) was 3 of 4 (75%) for cefixime and 2 of 7 (29%) for cefaclor. One clinical relapse occurred among 29 cefixime-treated patients; however, at 28 days 9 recurrences were observed. Three of 25 (9%) cefaclor-treated patients failed and 4 (13%) relapsed at 10 to 14 days, an additional 2 (10%) experienced recurrence by Day 28. Eight (28%) cefixime-treated patients experienced adverse events (7 gastrointestinal and 1 diarrhea and rash); 8 (25%) cefaclor-treated patients experienced adverse events (all gastrointestinal). Our data suggest that both at end of therapy and for 14 days thereafter, cefixime given once a day for acute otitis media is clinically equivalent to cefaclor given 3 times a day.

Acute Disease↗

Quick responses save mothers' lives.

The maternal mortality rate in the city of Faisalabad, Pakistan, has been reduced to a level significantly below the national average. How this has been achieved is explained below.

Emergency Medical Services↗

Treatment of Pseudomonas meningitis with ceftazidime with or without concurrent therapy.

In ongoing studies in Europe and the United States, 10 pediatric patients with bacterial meningitis caused by Pseudomonas species were treated with ceftazidime. Pseudomonas aeruginosa was isolated from the CSF of 7 patients and other Pseudomonas species from the remaining 3. Eight of the 10 patients had received previous antimicrobial treatment which included aminoglycosides in 6, along with ticarcillin and ureidopenicillins in 3. Ceftazidime was administered 10 to 42 days in dosages ranging from 109 to 300 mg/kg/day. Seven of the 10 patients received ceftazidime only for 10 to 42 days. The other 3 patients received amikacin in 2 and gentamicin and tobramycin in the other. Seven patients were cured clinically and 3 died; 9 were cured bacteriologically and one who was presumed cured on the basis of clinical response subsequently died. Sterilization of the cerebrospinal fluid occurred at 48 hours to 12 days. Ceftazidime appears useful in treating bacterial meningitis caused by Pseudomonas species.

Adolescent↗