Preferential production of interferon-gamma by CD4+ T cells expressing the homing receptor integrin alpha4/beta7.

Recent studies indicate that T helper type 1 (Th1) and 2 (Th2) lymphocytes differ in their expression of molecules that control T-cell migration, including adhesion molecules and chemokine receptors. We investigated the relationship between cytokine production and expression of the homing receptor integrin alpha4/beta7 on T cells. We began by analysing cytokine production by human CD4+ CD45RA- memory/effector T cells following brief (4 hr) stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin. alpha4/ beta7high CD4+ T cells were more likely to produce the Th1 cytokine interferon-gamma (IFN-gamma) than were alpha4/beta7- CD4+ T cells in all six subjects studied. In contrast, production of the Th2 cytokine interleukin-4 (IL-4) was similar on alpha4/ beta7high and alpha4/beta7- CD4+ T cells. In addition, we found that human CD4+ CD45RA- T cells that adhered to the alpha4/beta7 ligand mucosal addressin cell adhesion molecule-1 (MAdCAM-1) had a greater capacity to produce IFN-gamma than did non-adherent cells, suggesting that the association between alpha4/beta7 expression and IFN-gamma production has functional significance. These results suggested that primary activation under Th1-promoting conditions might favour expression of alpha4/beta7. We directly examined this possibility, and found that naïve murine CD4+ T cells activated under Th1-promoting conditions expressed higher levels of alpha4/beta7 compared to cells activated under Th2-promoting conditions. The association between alpha4/beta7 expression and IFN-gamma production by CD4+ T cells may help to determine the cytokine balance when MAdCAM-1 is expressed at sites of inflammation in the intestine or elsewhere.

Successful non-surgical treatment of Candida tropicalis endocarditis with liposomal amphotericin-B (AmBisome).

Fungal endocarditis in children is most commonly a complication of palliative or curative surgery for congenital heart disease, rheumatic valvulitis and prolonged indwelling central venous and umbilical catheters. We describe here the case of a 3-y-old patient with chronic diarrhoea and prolonged total parenteral alimentation who developed severe C. tropicalis endocarditis and was treated successfully using a liposomal preparation of amphotericin-B (AmBisome) without surgical intervention.

Current status of pediatric liver transplantation.

Increased survival for young liver transplant recipients has greatly improved. Increasing success has led to broader indications, thereby increasing the number of potential recipients. Pediatric liver centers are developing new strategies to cope with the ever-increasing demands for suitable size appropriate grafts. UNOS is in the process of updating guidelines to regulate the sharing of organs which become available from new surgical techniques. In the future, alternative therapies, such as artificial liver assist devices and techniques of cellular transplantation and genetic modification of hepatocytes, may decrease the number of children who die while waiting for a suitable organ or even obviate the need for the liver transplantation.

Bacteriologic response to oral cephalosporins: are established susceptibility breakpoints appropriate in the case of acute otitis media?

Bacteriologic response to cefuroxime axetil and cefaclor administered for 10 days was evaluated in acute otitis media (AOM) in patients aged 6-36 months. Middle ear fluid culture was obtained by tympanocentesis before treatment, on day 4 or 5 after initiation of treatment, and if clinical relapse occurred before day 17. Bacteriologic failure was observed in 32% of patients receiving cefaclor versus 15% of patients receiving cefuroxime axetil (P = .009). Failure rates increased with increasing MIC: For Streptococcus pneumoniae, 0.5 microg/mL (established as cutoff value for cefuroxime by the National Committee for Clinical Laboratory Standards [NCCLS]) discriminated between success and failure. For Haemophilus influenzae, high failure rates were observed for cefaclor, even with low MICs (< or = 1.0 microg/mL), and with both drugs they tended to increase with increasing MIC, even for values below the cutoff suggested by the NCCLS (8.0 and 4.0 microg/mL for cefaclor and cefuroxime, respectively). Thus, for AOM caused by H. influenzae, lower susceptibility cutoff levels for MICs should be established.

Rapid detection of Brucella melitensis from blood cultures by a commercial system.

To assess the capability of the Peds Plus medium of the Bactec 9240 blood culture system to recover Brucella melitensis within the routine seven-day protocol used by most clinical microbiology laboratories, inoculated blood culture bottles were monitored by the Bactec 9240 instrument for four weeks, and blind subcultures were performed once a week. A total of 2579 blood cultures were drawn, 42 (1.6%) of which were positive for Brucella melitensis. Forty-one of the 42 (97.6%) positive cultures were detected by the Bactec 9240 instrument within two to six days; a single positive culture was missed by the instrument and detected by blind subculture performed on day 7.

Comparison of BACTEC 9240 Peds Plus medium and isolator 1.5 microbial tube for detection of Brucella melitensis from blood cultures.

The sensitivity and time to detection of Brucella melitensis by the BACTEC 9240 and the Isolator blood culture systems were compared in a prospective volume-controlled study. Blood sample aliquots, obtained from children with suspected brucellosis, were inoculated into a BACTEC 9240 Peds Plus bottle and into an Isolator 1.5 Microbial Tube. Overall, 122 pairs of blood samples for culture were obtained, and 28 (23%) were positive by at least one method. The BACTEC 9240 system detected all 28 positive cultures (sensitivity, 100%), and the Isolator system detected 22 positive cultures (sensitivity, 79%) (P = 0.023). Among those 22 cultures positive by both methods, 21 (95%) and 15 (68%) were found to be positive within 3 days by the BACTEC and the Isolator systems, respectively; 8 (36%) were found to be positive at least 1 day earlier by the BACTEC instrument, and the remaining 14 were found to be positive by the two systems on the same day (P = 0.045). The BACTEC 9240 blood culture system is more sensitive than the Isolator system for the detection of B. melitensis and is superior in terms of time to detection of the organism.

Reduction of nasopharyngeal carriage of pneumococci during the second year of life by a heptavalent conjugate pneumococcal vaccine.

Children 12-18 months old were randomized to receive one dose of a conjugate heptavalent pneumococcal vaccine, two doses of the same vaccine, or one dose of a 23-valent native polysaccharide vaccine. Before immunization, pneumococci included in the conjugate vaccine were isolated from 24% of the children, and an antibiotic-resistant pneumococcus was isolated from 22% of the children. The vaccines had no effect on carriage of non-vaccine-type pneumococci. In contrast, there was a significant reduction in carriage of vaccine-type pneumococci 3 months after one dose and 1 month after a second dose of conjugate vaccine (from 25% to 9% and 7%, respectively; P < .001). No effect was seen after vaccination with the nonconjugate vaccine. One year after immunization, carriage of antibiotic-resistant vaccine-type pneumococci in children receiving conjugate vaccine was lower than that in children receiving the nonconjugate vaccine (4% vs. 14%, P = .042). Conjugate pneumococcal vaccines may reduce spread of pneumococci in the community.

Impaired bacteriologic response to oral cephalosporins in acute otitis media caused by pneumococci with intermediate resistance to penicillin.

BACKGROUND: Penicillin resistance of Streptococcus pneumoniae, one of the most common causes of acute otitis media, has recently increased and is now highly prevalent in many regions. However, its contribution to clinical failure still must be proved. Because the role of antibiotics in acute otitis media is to eradicate the pathogens present in the middle ear fluid, we conducted a randomized controlled study to determine bacterial eradication of pathogens in acute otitis media by two commonly used oral cephalosporins, cefuroxime axetil (30 mg/kg/day) and cefaclor (40 mg/kg/day). METHODS: Patients 6 to 36 months old with pneumococcal otitis media seen in the Pediatrics Emergency Room were studied. An initial middle ear fluid culture was obtained at enrollment, and a second culture was obtained on Day 4 or 5 during treatment. Follow-up was done also on Days 10, 17 and 42 after initiation of treatment. In cases of clinical relapse a third culture was obtained. RESULTS: In total 78 patients were enrolled, 41 in the cefuroxime axetil group and 37 in the cefaclor group. Of the 78 S. pneumoniae isolates 31 (40%) were intermediately penicillin-resistant (MIC 0.125 to 1.0 microgram/ml). Of the 47 patients with penicillin-susceptible organisms 3 (6%) had bacteriologic failure vs. 4 of 19 (21%) and 7 of 11 (64%) of those with MIC of 0.125 to 0.25 microgram/ml and 0.38 to 1.0 microgram/ml, respectively (P < 0.001). For intermediately resistant pneumococci, in 7 of 12 (58%) of those receiving cefaclor the isolate was not eradicated vs. only 4 of 19 (21%) of those receiving cefuroxime axetil (P = 0.084). MIC to the administered cephalosporin of > 0.5 microgram/ml was associated with bacteriologic failure. Clinical failure was observed in 9 of 14 (64%) patients with bacteriologic failure vs. 10 of 52 (19%) patients with bacteriologic eradication (P = 0.003). CONCLUSION: Intermediately penicillin-resistant S. pneumoniae is associated with an impaired bacteriologic and clinical response of acute otitis media to cefaclor and cefuroxime axetil. This effect was more pronounced with cefaclor than with cefuroxime axetil.

Severe complications of measles requiring intensive care in infants and young children.

OBJECTIVE: To evaluate the characteristics of severe complications of measles in patients admitted to a pediatric intensive care unit. DESIGN: Clinical description of a case series. SETTING: The Pediatric Intensive Care Unit of Soroka Medical Center, Beer-Sheva, Israel, during a measles epidemic. PATIENTS: Fifteen pediatric patients with measles requiring intensive care. RESULTS: Fifteen of 237 hospitalized children with measles required intensive care in the Pediatric Intensive Care Unit. Eleven patients were malnourished; none had been vaccinated for measles. All 15 patients required mechanical ventilation for pneumonia that had caused severe respiratory distress. Twelve of 15 patients were severely hypoxemic before intubation. Seven had a clinical syndrome consistent with adult respiratory distress syndrome. Other complications on admission to the intensive care unit included spontaneous pneumothorax in three patients, empyema in two, encephalopathy in seven, shock in three, sepsis in five, hypocalcemia in 11, thrombocytopenia in eight, and coagulopathy in seven. Complications during treatment included pneumothorax in four patients, fibrosing alveolitis in one, brain infarct in one, thrombus formation in three, and nosocomial sepsis in one. Four patients had long-term sequelae (chronic lung disease, subacute sclerosing panencephalitis, hemiplegia, and partial amputation of a limb), and seven patients recovered uneventfully. Four patients died; all had adult respiratory distress syndrome, three had pneumothorax, and one had nosocomial sepsis. CONCLUSIONS: Patients with measles who require intensive care have a high risk for death or long-term complications, even when treated in a modern pediatric intensive care unit. Adult respiratory distress syndrome and air leaks were the most severe complications in these patients. To reduce the severity of these complications, mechanical ventilation should be based on using the lowest possible inspiratory pressure and fraction of inspired oxygen, while accepting an arterial oxygen pressure less than 60 mm Hg. Secondary bacteremia was an early and prominent complication, and antibiotic treatment should be instituted early in patients with measles requiring intensive care.

Commercial dialysate inhibits TNF alpha mRNA expression and NF-kappa B DNA-binding activity in LPS-stimulated macrophages.

Continuous ambulatory peritoneal dialysis is known to interfere with the normal inflammatory responses of macrophages in the peritoneal cavity. Commercial peritoneal dialysis solution (CDS) has been shown to inhibit tumor necrosis factor alpha (TNF alpha) release from LPS stimulated peritoneal macrophages. To further dissect the mechanism of this inhibition, we used human blood-derived macrophages or the murine macrophage cell line, P388D1, that were stimulated with LPS after pretreatment with CDS, and tested TNF alpha mRNA levels by Northern hybridization or reverse transcriptase polymerase chain reaction. Time course studies demonstrated that CDS lowered TNF alpha mRNA levels within 15 minutes of pretreatment of cells. In addition, the CDS inhibited DNA binding activity of NF-kappa B that is probably involved in regulation of LPS-mediated transcriptional activation of the TNF alpha gene. Inhibition was dependent on both the low pH and the lactate in the CDS, but was independent of the osmolarity or glucose concentration. The rate of catabolism of TNF alpha mRNA was not affected by CDS as demonstrated by actinomycin D chase experiments. Thus, impairment of LPS-stimulated macrophage function by CDS is associated with low TNF alpha mRNA which may be the result of the low activity of NF-kappa B. Since NF-kappa B is involved in transcription regulation of a large number of "early activation" genes, CDS may interfere with the production of additional immunomodulatory proteins that are encoded by genes possessing NF-kappa B site(s) in their promoter region.

Fetal pseudohypoaldosteronism: another cause of hydramnios.

Pseudohypoaldosteronism (PHA) is a rare hereditary salt-wasting syndrome which is caused by decreased renal tubular responsiveness to aldosterone. The syndrome consists of hyponatremia, hyperkalemia, dehydration, failure to thrive and increased urinary salt loss. A case of PHA was previously described where fetal polyuria was the probable cause of hydramnios. We present four new cases of PHA, from two families, who were born after pregnancies complicated by severe hydramnios and premature labor. We suggest that PHA should be included in the differential diagnosis of hydramnios, since appropriate investigations might lead to the early diagnosis and treatment of a life-threatening disease.

Nephrocalcinosis in pseudohypoaldosteronism and the effect of indomethacin therapy.

We report four patients with pseudohypoaldosteronism, aged 5 months to 5 years. All patients had hypercalciuria and three had nephrocalcinosis. Two patients with nephrocalcinosis were treated with indomethacin. Polydipsia decreased and appetite and weight gain improved within 14 days of therapy. Hypercalciuria, polyuria, and creatinine clearance decreased 30% to 50% and urinary prostaglandin E2 levels decreased fourfold to eightfold.

Pseudohypoaldosteronism in a preterm infant: intrauterine presentation as hydramnios.

After a pregnancy complicated by severe hydramnios, a preterm infant had clinical and biochemical evidence of pseudohypoaldosteronism. Fetal polyuria probably caused the hydramnios.

Detection and treatment of brucellosis by screening a population at risk.

Brucellosis presents a difficult diagnostic challenge in view of its protean manifestations, multiple organ involvement and variable clinical course. The purpose of the present study was to determine whether active screening of a population at risk, identified through index cases, would enhance the detection rate of brucellosis and improve treatment. During a 1-month period all 98 individuals sharing risk factors with 4 diagnosed symptomatic cases of brucellosis in one Bedouin town in southern Israel were approached and 86 agreed to undergo screening. Symptomatic brucellosis was found in 8 (9%) of the screened population and an additional 5 (6%) asymptomatic individuals were found to be seropositive. These 13 were followed for 12 months. All symptomatic cases were treated and cured. Of the 5 asymptomatic seropositive individuals 2 showed a further elevation of Brucella antibody titers. One became symptomatic, was treated and was cured. This screening program provided 53% of all reported cases from the Bedouin town during the entire year of the study. Screening a population at risk increased the detection rate of brucellosis and improved the treatment.