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Biomedical subjects

M M Mustafa

Publications and source records attributed to M M Mustafa.

At least 37 records · Page 2Linked to original sources

Aerosolized pentamidine for the prevention of Pneumocystis carinii pneumonia in children with cancer intolerant or allergic to trimethoprim/sulfamethoxazole.

PURPOSE: Trimethoprim/sulfamethoxazole (TMP/SMX) is the drug of choice for Pneumocystis carinii pneumonia (PCP) prophylaxis in immunocompromised patients. In children with malignancy, TMP/SMX is well tolerated, but adverse reactions that necessitate discontinuation can occur. We evaluated the safety and efficacy of aerosolized pentamidine (AP) as an alternative prophylaxis modality in children with malignancy who are intolerant of or allergic to TMP/SMX. PATIENTS AND METHODS: AP (200 mg/m2 every 4 weeks) was administered to 60 children with malignancy receiving chemotherapy who had experienced severe adverse reactions to TMP/SMX. Seven hundred twenty doses of AP have been administered during a 3 1/2-year period (21,600 patient-days), with 30 patients treated for > or = 12 months (range, 12 to 25). RESULTS: Adverse reactions occurred during 79 (10%) of the 720 treatments and included bronchospasm in 23, cough in 40, vomiting in 10, and nausea in six. Only two patients had severe bronchospasm. AP was discontinued due to toxicity in three patients (5%). None of the patients (upper 95% confidence limit, 0.049) have developed PCP. CONCLUSION: AP appears to be well tolerated and effective in the prevention of PCP in children with malignancy.

Adolescent↗

Gram-negative enteric bacillary meningitis: a twenty-one-year experience.

We reviewed our experience with gram-negative enteric bacillary meningitis in neonates and infants from 1969 through 1989. Ninety-eight patients were identified. Their ages were from 1 day to 2 years with a median of 10 days. In 25 patients (26%), predisposing factors were identified, the most common of which were neural tube defects and urinary tract anomalies. The causative agents were Escherichia coli (53%), Klebsiella-Enterobacter species (16%), Citrobacter diversus (9%), Salmonella species (9%), Proteus mirabilis (4%), Serratia marcescens (3%), Bacteroides fragilis (3%), and Aeromonas species (2%). At the time of diagnosis, Gram-stained smears of cerebrospinal fluid revealed gram-negative bacilli in 61% of patients. The causative organism was cultured from blood obtained from 55% of patients, and 21% had positive urine culture results. The cerebrospinal fluid leukocyte counts ranged from 0 to 80,600 cells/mm3, and the cerebrospinal fluid/serum glucose concentration ratio was less than 0.5 in 72% of patients. Antimicrobial regimens varied greatly. After initiation of antibiotic therapy, an average of 3 days was needed for eradication of bacteria from cerebrospinal fluid. The case-fatality rate was 17%, and 61% of survivors had long-term sequelae that included seizure disorders, hydrocephalus, physical disability, developmental delay, and hearing loss.

Anti-Bacterial Agents↗

Subacute measles encephalitis in the young immunocompromised host: report of two cases diagnosed by polymerase chain reaction and treated with ribavirin and review of the literature.

Two young patients with subacute measles encephalitis are described: a 20-year-old male hemophiliac infected with human immunodeficiency virus (HIV) and a 4-year-old girl with acute leukemia. Both patients were afebrile and had persistent focal seizures and slurred speech beginning 2 and 7 months, respectively, after the onset of uncomplicated acute measles. The diagnosis of subacute measles encephalitis was established by demonstration of paramyxovirus nucleocapsid on electron microscopy of brain tissue in one case and by detection of measles virus genome with the polymerase chain reaction in both. Treatment of the HIV-infected man with intravenous ribavirin was begun when the patient lost consciousness after several weeks of seizures; he died. The girl with leukemia was treated early after the onset of symptoms and recovered after a 15-week course. Review of 31 previously published cases revealed a typical clinical presentation. Cerebrospinal fluid (CSF) analysis, electroencephalography, measurement of measles antibody in serum and CSF, and computed tomography of the brain were not helpful in the diagnosis of subacute measles encephalitis. In contrast, histologic examination of brain tissue proved useful in establishing the diagnosis. On the basis of our experience and our literature review, we conclude that histologic and polymerase chain reaction studies of brain tissue are required for the early diagnosis of subacute measles encephalitis and that therapy with intravenous ribavirin is effective when administered early.

Adult↗

Cytomegalovirus-induced hemorrhagic cystitis following bone marrow transplantation.

Cytomegalovirus (CMV) is a common cause of morbidity and mortality following bone marrow transplantation but has not been demonstrated to cause hemorrhagic cystitis in this setting. We describe a patient who developed gross hematuria and lower abdominal pain 47 days after bone marrow transplantation was performed. Subsequently, CMV was detected in bladder endothelial cells with use of monoclonal antibody staining that was specific for the virus. No other cause for the patient's hemorrhagic cystitis was discovered. The gross hematuria and pain persisted until the patient received intravenous ganciclovir. This case demonstrates that CMV-induced hemorrhagic cystitis can occur following bone marrow transplantation and may respond to antiviral therapy.

Adolescent↗

Value of C-reactive protein determination in the initial diagnostic evaluation of the febrile, neutropenic child with cancer.

We studied prospectively the value of administration C-reactive protein (CRP) in the diagnostic evaluation of the child with cancer hospitalized for fever and neutropenia. During a 7-month period 74 patients with malignant disease had 122 hospital admissions because of fever and neutropenia. All patients had a serum CRP obtained 8 to 24 hours after the onset of fever as part of their initial evaluation. There was a borderline correlation between serum CRP concentration and temperature at admission (P = 0.06). Patients with fever without an identifiable source had significantly lower CRP concentrations compared with those having focal or microbiologically documented infection (34.9 +/- 6 vs. 70.2 +/- 12 mg/liter; P = 0.0005). Twelve patients had positive blood cultures, 5 of which were coagulase-negative staphylococci considered to be central venous catheter-related infection or colonization. CRP concentrations were significantly lower in these 5 patients compared with the 7 patients with septicemia caused by other organisms (21 +/- 9 vs. 113 +/- 23 mg/liter; P = 0.01). In distinguishing between septicemic and nonsepticemic children, serum CRP was found to have excellent sensitivity and negative predictive value at concentration limits of 20, 50 and 100 mg/liter. However, both specificity and positive predictive value were low at these respective levels, thus limiting the overall utility of serum CRP in the initial empiric management of the febrile, neutropenic child with cancer.

Adolescent↗

Bordetella bronchiseptica pneumonia and bacteremia following bone marrow transplantation.

Bordetella bronchiseptica is a frequent cause of respiratory infections in animals but rarely causes disease in humans. We describe a patient with B. bronchiseptica pneumonia and bacteremia that developed following bone marrow transplantation. B. bronchiseptica infection persisted despite antimicrobial therapy and may have progressed because of the combined effects of the patient's underlying immunosuppression and the antimicrobial antagonism between doxycycline and ciprofloxacin.

Adult↗

Detection of interleukin 1 beta but not tumor necrosis factor-alpha in cerebrospinal fluid of children with aseptic meningitis.

Tumor necrosis factor-alpha and interleukin 1 beta have been shown to be mediators of meningeal inflammation in animal models of bacterial meningitis. The presence of both cytokines in cerebrospinal fluid (CSF) of patients with bacterial meningitis has been documented recently. In this study, we measured concentrations of interleukin 1 beta and tumor necrosis factor-alpha in CSF samples from 36 patients with nonbacterial (aseptic) meningitis, 13 of whom had culture-proved enteroviral meningitis, and from 14 control patients. None of the samples from patients with aseptic meningitis and from the controls had detectable tumor necrosis factor activity in CSF. Thirty-two (89%) of 36 patients with aseptic meningitis had detectable interleukin 1 beta in CSF (mean +/- SEM, 48 +/- 11 pg/mL). These concentrations were significantly smaller than those previously reported in patients with bacterial meningitis (944 +/- 128 pg/mL). Only 2 of the 14 control patients had detectable CSF interleukin 1 beta concentrations of 21 and 42 pg/mL. A significant correlation was evident between interleukin-1 beta concentrations and white blood cell counts in the CSF of patients with aseptic meningitis. Our data suggest that the initial events of CSF inflammation in children with aseptic meningitis are different than those in patients with bacterial meningitis, and the participation of these two cytokines, especially tumor necrosis factor-alpha, is less critical to the process.

Adolescent↗

Tumor necrosis factor alpha and interleukin 1 beta in synovial fluid of infants and children with suppurative arthritis.

Tumor necrosis factor alpha and interleukin 1 beta concentrations were measured in synovial fluid of 24 infants and children with diagnoses of suppurative arthritis (n = 16) and other kinds of arthritis (n = 8). Large concentrations of tumor necrosis factor alpha (range, 100 to 85,000 pg/mL) were found in 12 (75%) of 16 patients with bacterial infection and in none of the patients with noninfectious origins. Large concentrations of interleukin 1 beta (greater than 200 pg/mL) were found in 15 (94%) of 16 patients with bacterial infection and in none of the other patients. In the latter group, small concentrations of interleukin 1 (range, 40 to 120 pg/mL) were present in 5 (63%) of 8 patients. Serum samples obtained simultaneously were negative for both cytokines. Tumor necrosis factor alpha and interleukin 1 beta concentrations correlated significantly and with leukocyte counts in synovial fluid. We conclude that large concentrations of tumor necrosis factor alpha and interleukin 1 beta are produced locally in patients with suppurative arthritis and they may be potentially useful in differentiating this condition from other kinds of arthritis.

Adolescent↗

Cerebrospinal fluid prostaglandins, interleukin 1 beta, and tumor necrosis factor in bacterial meningitis. Clinical and laboratory correlations in placebo-treated and dexamethasone-treated patients.

Prostaglandins (PGs), interleukin 1 beta (IL-1 beta), and tumor necrosis factor alpha (TNF alpha) are likely mediators of local inflammatory reactions. We measured PGE2, PGI2, IL-1 beta, and TNF concentrations in paired cerebrospinal fluid (CSF) samples (on admission, CSF1, and 18 to 30 hours later, CSF2) from 80 infants and children with bacterial meningitis. Forty patients received dexamethasone sodium (0.6 mg/kg per day in four intravenous doses) and 40 received an intravenous saline placebo. In CSF1, PGE2, PGI2, IL-1 beta, and TNF were detected in 90%, 56%, 98%, and 71% of specimens with mean (+/- SEM) concentrations of 462 +/- 65, 377 +/- 62, 1266 +/- 242, and 799 +/- 227 pg/mL, respectively. Concentrations of PGE2 correlated significantly with PGI2, IL-1 beta, TNF, and lactate and inversely correlated with glucose concentrations in the first CSF specimens. The PGE2, PGI2, IL-1 beta, and TNF were still detected in 40%, 18%, 97%, and 60%, respectively, of second CSF specimens obtained from placebo-treated patients. Compared with patients who had detectable PGI2 or TNF alpha concentrations in CSF2 specimens, those placebo-treated patients with no detectable PGI2 or TNF alpha activity in CSF2 had a lower incidence of neurological sequelae. Dexamethasone-treated patients had significantly lower PGE2, IL-1 beta, and lactate concentrations and higher glucose concentrations in CSF 18 to 30 hours later, shorter duration of fever, and a lower incidence of neurological sequelae than did placebo-treated patients.

Bacterial Infections↗

Pentoxifylline modulates meningeal inflammation in experimental bacterial meningitis.

Pentoxifylline has been shown to decrease endotoxin-induced tumor necrosis factor alpha production and reverse the inflammatory actions of interleukin-1 (IL-1) and tumor necrosis factor on leukocyte function. Because of the potential role of this cytokine-leukocyte interaction in the pathogenesis of bacterial meningitis, we investigated the ability of pentoxifylline to modulate meningeal inflammation in the rabbit meningitis model. Pentoxifylline treatment (initially an intravenous injection of 20 mg/kg followed by 6 mg/kg per h) started 20 min before intracisternal injection of 20 ng of Haemophilus influenzae type b lipooligosaccharide (endotoxin) reduced significantly concentrations in cerebrospinal fluid of leukocytes (P less than 0.0001), protein (P less than 0.001), and lactate (P less than 0.001) during the 9-h infusion compared with values in intravenous-saline-treated rabbits. When pentoxifylline was given 1 h after H. influenzae type b endotoxin, the mean peak lactate and leukocyte concentrations in cerebrospinal fluid were significantly lower than those in control animals. Pentoxifylline also significantly decreased lactate and protein concentrations (P less than 0.05) and tended to diminish leukocyte counts (P = 0.08) compared with results in control animals after antibiotic-induced release of endotoxin in animals with H. influenzae meningitis. In this regard, dexamethasone was superior to pentoxifylline and no synergism was observed when the drugs were combined. Additionally, pentoxifylline attenuated meningeal inflammatory changes induced by intracisternal inoculation of 10 ng of rabbit recombinant IL-1 beta compared with results in either dexamethasone- or saline-treated animals. We conclude that pentoxifylline is effective in this animal model in modulating the meningeal inflammatory response following intracisternal inoculation of H. influenzae type b endotoxin or organisms or rabbit recombinant IL-1beta.

Animals↗

Specific detection of Haemophilus influenzae type b lipooligosaccharide by immunoassay.

Three monoclonal antibody (MAb)-based immunoassays were developed for specific detection of Haemophilus influenzae type b (Hib) lipooligosaccharide (LOS). (i) Hib LOS was captured onto microtiter plates by polyclonal Hib-directed antibodies and detected with MAbs to the oligosaccharide component of Hib LOS in an enzyme-linked immunosorbent assay, (ii) The high affinity of polymyxin B for lipid A was used to bind Hib LOS to microtiter wells, and the oligosaccharide-specific MAbs were used as the detection system in the polymyxin B-MAb assay. (iii) Hib LOS solubilized in detergent was captured by MAbs, and the immobilized LOS was detected with a chromogenic Limulus amebocyte lysate method in the immunolimulus assay. Endotoxin concentrations were measured in in vitro samples and cerebrospinal fluid samples from rabbits with experimental Hib meningitis. The results were compared with those obtained with the standard chromogenic Limulus amebocyte lysate assay. There were significant correlations between the results of all four assays. These new immunoassays provide methods for specific detection of Hib LOS in laboratory fluids and in research involving quantification of Hib endotoxin in experimental animal models.

Animals↗