Elpis Mantadakis

Prevalence of priapism in children and adolescents with sickle cell anemia

A questionnaire survey was conducted of patients with homozygous sickle cell anemia (Hb SS) and sickle cell beta(0)-thalassemia (Hb S-beta(0)) between 5 and 20 years of age to determine the prevalence and characteristics (number of episodes, timing, duration, cause, or precipitating event) of priapism. Ninety-eight male patients or their parents were surveyed by the same male investigator using a structured verbal interview, which was modified according to the age of the patient. Ninety-four patients had Hb SS and four Hb S-beta(0) thalassemia. Eleven (11%) patients were known to have experienced priapism previously. In response to the questionnaire, 16 of the remaining 87 (18%) patients reported having had priapism on one or more occasions. The actuarial probability of experiencing priapism by 20 years of age was 89% (+/- 9%). The mean age at the initial episode was 12 years, the mean number of episodes per patient was 15.7 (median, 1; range, 1-100), and the mean duration of an episode was 125 minutes. Episodes typically occurred around 4:00 am, and 75% of the patients surveyed had at least one episode starting during sleep or upon awakening from sleep. The prevalence of priapism in children and adolescents with SCA is much higher than previously described. Since early intervention and treatment may prevent irreversible penile fibrosis and impotence, patients and parents should be educated about this complication in advance of its occurrence.

Pharmacological Considerations for the Proper Clinical Use of Aminoglycosides

Aminoglycosides constitute one of the oldest classes of antimicrobials. Despite their toxicity, mainly nephrotoxicity and ototoxicity, aminoglycosides are valuable in current clinical practice, since they retain good activity against multidrug-resistant Gram-negative pathogens, such as Pseudomonas aeruginosa and Acinetobacter spp. Time-kill studies have shown a concentration-dependent and partially concentration-dependent bacterial killing against Gram-negative and Gram-positive bacteria, respectively. Pharmacodynamic data gathered over recent decades show that the administration of aminoglycosides by an extended-interval dosing scheme takes advantage of the maximum potential of these agents, with the goal of achieving an area under the concentration-time curve (AUC) of 100 mg • h/L over 24 hours and a peak plasma drug concentration (Cmax) to minimum inhibitory concentration (MIC) ratio of 8–10. Several clinical conditions that are common in seriously ill patients result in expansion of the extracellular space and can lead to a lower than desirable Cmax with the usual loading dose. Extended-interval dosing schemes allow adequate time to decrease bacterial adaptive resistance, a phenomenon characterized by slow concentration-independent killing. Adaptive resistance is minimized by the complete clearance of the drug before the subsequent dose, thus favouring the extended-interval dosing schemes. The efficacy of these schemes is also safeguarded by the observed post-antibiotic sub-MIC effect and post-antibiotic leukocyte enhancement, which inhibit bacterial regrowth when the serum aminoglycoside levels fall below the MIC of the pathogen.In everyday clinical practice, aminoglycosides are usually used empirically to treat severe sepsis and septic shock while awaiting the results of antimicrobial susceptibility testing. The European Committee on Antimicrobial Susceptibility Testing acknowledges the regimen-dependent nature of clinical breakpoints for aminoglycosides, i.e. of MIC values that classify bacterial isolates into sensitive or resistant, and bases its recommendations on extended-interval dosing. To a large extent, the lack of correlation between in vitro antimicrobial susceptibility testing and clinical outcome is derived from the fact that the available clinical breakpoints for aminoglycosides are set based on mean pharmacokinetic parameters obtained in healthy volunteers and not sick patients. The nephrotoxicity associated with once-versus multiple-daily administration of aminoglycosides has been assessed in numerous prospective randomized trials and by several meta-analyses. The once-daily dosing schedule provides a longer time of administration until the threshold for nephrotoxicity is met. Regarding ototoxicity, no dosing regimen appears to be less ototoxic than another. Inactivation of aminoglycosides inside the bacterial pathogens occurs by diverse modifying enzymes and by operation of multidrug efflux systems, making both of these potential targets for inhibition.In summary, despite their use for several decades, the ideal method of administration and the preferred dosing schemes of aminoglycosides for most of their therapeutic indications need further refinement. Individualized pharmacodynamic monitoring has the potential of minimizing the toxicityand the clinical failures of these agents in critically ill patients.

Serum Procalcitonin for Prediction of Renal Parenchymal Involvement in Children with Urinary Tract Infections: A Meta-analysis of Prospective Clinical Studies

OBJECTIVE To determine by meta-analysis whether serum procalcitonin (PCT) is a useful marker of acute renal parenchymal involvement (RPI) in children with culture-proven urinary tract infection (UTI), as diagnosed by acute-phase DMSA (Tc-99m dimercaptosuccinic acid) renal scintigraphy. STUDY DESIGN We searched PubMed and the Cochrane Central Register of Controlled Trials for prospective studies involving children with culture-proven UTIs. Additional eligibility criteria were measurement of serum PCT at presentation and performance of DMSA scintigraphy within 14 days. RESULTS Overall, 10 studies eligible for inclusion, involving a total of 627 children, were identified. Half of these studies evaluated children with a first episode of UTI; 8 involved children with febrile UTIs. Using a cutoff value of 0.5 to 0.6 ng/mL, the pooled diagnostic odds ratio of serum PCT for UTI with RPI was 14.25 (95% confidence interval, 4.70 to 43.23). High statistical between-study heterogeneity that could mainly be attributed to 2 studies was observed. The remaining 8 studies uniformly favored PCT use. CONCLUSIONS In children with culture-proven UTI, a serum PCT value >0.5 ng/mL predicts reasonably well the presence of RPI, as evidenced by DMSA scintigraphy. PCT may aid in the identification of children with UTI, necessitating more intense evaluation and management.

Thrombocytopenic purpura after measles-mumps-rubella vaccination: a systematic review of the literature and guidance for management.

OBJECTIVE To determine the incidence of immune thrombocytopenic purpura (ITP) after measles-mumps-rubella (MMR) immunization compared with natural measles and rubella, its clinical course and outcome, and the risk of recurrence after repeat MMR vaccination. STUDY DESIGN We performed a systematic review of the Ovid MEDLINE (1950 to present) bibliographic database. We selected studies that reported cases of thrombocytopenia in a known number of children who were immunized with MMR vaccine before development of ITP. We also extracted data from the same and other studies regarding bleeding manifestations and the resolution of MMR-associated thrombocytopenia or thrombocytopenic purpura within 6 months. Finally, we studied the risk of ITP recurrence after MMR immunization or reimmunization. RESULTS On the basis of 12 studies, the incidence of MMR-associated ITP ranged from 0.087 to 4 (median 2.6) cases per 100,000 vaccine doses. Severe bleeding manifestations were rare, and MMR-associated thrombocytopenia resolved within 6 months from diagnosis in 93% of the children. MMR vaccination of unimmunized patients with ITP and revaccination of patients with prior ITP did not lead to recurrence of thrombocytopenia. CONCLUSIONS MMR-associated ITP is rare, self-limited, and non-life threatening, and susceptible children with ITP should be immunized with MMR at the recommended ages.

Clinical presentation of zygomycosis

Zygomycetes are filamentous fungi with a worldwide distribution. This class of fungi encompasses two orders, i.e. the Mucorales and the Entomophthorales. Members of the latter are associated with chronic cutaneous and subcutaneous infections that are limited to the tropics and rarely disseminate to internal organs. The order Mucorales includes several species involved in rhinocerebral, pulmonary, cutaneous, gastrointestinal and other less frequent infections in immunocompetent and immunocompromised individuals, and is characterized by a tendency to disseminate. Portals of entry of zygomycetes are usually the lungs, skin, and gastrointestinal tract. A characteristic property of zygomycetes is their tendency to invade blood vessels and to cause thrombosis-processes that result in subsequent necrosis of involved tissues. Risk factors associated with zygomycosis include prolonged neutropenia and use of corticosteroids, solid organ or haematopoietic stem cell transplantation, AIDS, poorly controlled diabetes mellitus, iron chelation with deferoxamine, burns, wounds, malnutrition, extremes of age, and intravenous drug abuse. Recently, the widespread use of voriconazole for prophylaxis or treatment of aspergillosis in patients with haematological malignancies has been linked with a rise in the numbers of cases of invasive zygomycosis. As the symptoms, clinical signs and imaging findings of these infections are non-specific, a high index of suspicion is required for timely diagnosis. Early diagnosis, correction of the underlying predisposing factors, aggressive surgical debridement of all infected tissues and lengthy administration of antifungals are the only potentially curative options for this rare but emerging invasive fungal infection.

Elective splenectomy in children with idiopathic thrombocytopenic purpura

PURPOSE The aim of this study was to review the safety and efficacy of elective splenectomy in children with idiopathic (immune) thrombocytopenic purpura (ITP). METHODS The authors reviewed the medical records of children with ITP treated with elective splenectomy at Childrens Medical Center of Dallas since 1961. Indication for splenectomy was symptomatic thrombocytopenia unresponsive to medical management. RESULTS Thirty-eight evaluable patients who had elective splenectomy for ITP were identified. Twenty-one (55%) were girls and 17 (45%) were boys. Twenty-two had splenectomy since January 1990. Age at diagnosis ranged from 6 months to 15.9 years (median 9 years), and age at splenectomy ranged from 3.6 to 16.4 years (median 11.8). Laparoscopic splenectomy was performed in 11 patients. No patient died and only one (2.6%) had postoperative hemorrhage. There were no other complications related to surgery. No cases of postsplenectomy sepsis were observed. At follow-up ranging from 1 month to 19.9 years (median 2.1 years), 29 patients (76.3%) had a normal platelet count (>150 x 109/L) and 4 (10.5%) had a platelet count between 50 and 150 x 109/L. Only two of the five (13.2%) remaining patients who continued to have a platelet count less than 50 x 109/L had hemorrhagic manifestations necessitating intermittent therapy with corticosteroids. CONCLUSION Laparoscopic or open splenectomy is a safe and effective procedure for children with chronic or refractory ITP and should be considered when medical management fails or causes excessive toxicity.

A 7-year survey of dermatophytoses in Crete, Greece

Dermatophytoses are of worldwide distribution. Epidemiological studies concerning dermatophyte infections have been performed in many countries and differences in the incidence and the aetiological agents have been reported in different geographical locations. This study was undertaken to investigate the prevailing species of dermatophytes in the island of Crete, Greece, and their pattern of infection during a 7‐year period (1997–2003). A total of 5544 samples obtained from 3751 patients with clinically suspected dermatomycoses were examined mycologically in the laboratory of Clinical Microbiology at the University Hospital of Crete, Greece. Skin, hair and nail specimens were subjected to direct microscopy and culture. Dermatophytes were isolated from 520 patients (13.9%). Trichophyton rubrum was the most frequently isolated dermatophyte accounting for 48% of the infections, followed by Microsporum canis (17.9%), Trichophyton mentagrophytes var. interdigitale (14.2%) and Epidermophyton floccosum (6%). Tinea unguium, tinea pedis, tinea corporis, tinea capitis, tinea cruris, tinea manuum and tinea facei were the clinical types of dermatophytoses in decreasing order of frequency. Trichophyton rubrum is the predominant dermatophyte in our area. As the epidemiology of dermatophytoses is changing over time it is important to review periodically the incidence of dermatophytes and their distribution.

Comparative Efficacies of Procalcitonin and Conventional Inflammatory Markers for Prediction of Renal Parenchymal Inflammation in Pediatric First Urinary Tract Infection

OBJECTIVES To compare the reliability of procalcitonin (PCT) with conventional laboratory parameters in predicting for renal parenchymal inflammation (RPI). METHODS The study cohort consisted of 57 children who were admitted for a first-episode urinary tract infection. All patients underwent measurement of the leukocyte count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum PCT. RPI was evaluated by technetium-99m dimercaptosuccinic acid (DMSA) scintigraphy within 7 days of admission. If the first DMSA findings were abnormal, another analysis was performed 6 months later. The cutoff points for ESR, CRP, and PCT were established by comparing the areas under their receiver operating characteristic curves. Statistical analysis was performed using 1-way analysis of variance. RESULTS Of the 57 children, 27 were diagnosed with RPI on the basis of positive DMSA results. The ESR, CRP, and PCT levels were significantly greater (P < .001) in the patients with RPI than in those without RPI. In contrast, the leukocyte count was the same in both groups (P > .05). PCT was a more sensitive and specific marker for differentiating upper and lower urinary tract infection than ESR and CRP. Persistent lesions at the site of previous RPI were found in 12 patients in the follow-up DMSA analysis, with total regression evident in the remaining 15. The PCT levels were significantly greater in those with persistent renal lesions than in those with total regression (P = .005). CONCLUSIONS Serum PCT is a more reliable biologic marker than the ESR, CRP, or leukocyte count for the early prediction of RPI in children with a first episode of urinary tract infection. In addition, the greater the elevation of PCT at admission, the more positive the correlation for subsequent permanent renal damage.

Acute Tc-99m DMSA Scan for Identifying Dilating Vesicoureteral Reflux in Children: A Meta-analysis

Controversy exists regarding the type and/or sequence of imaging studies needed during the first febrile urinary tract infection (UTI) in young children. Several investigators have claimed that because acute-phase Tc-99m dimercaptosuccinic acid (DMSA) renal-scan results are abnormal in the presence of dilating vesicoureteral reflux, a normal DMSA-scan result makes voiding cystourethrography (VCUG) unnecessary in the primary examination of infants with UTI. To evaluate the accuracy of acute-phase DMSA scanning in identifying dilating (grades III through V) vesicoureteral reflux documented by VCUG in children with a first febrile UTI, we performed a meta-analysis of the accuracy of diagnostic tests as reported from relevant studies identified through the PubMed and Scopus databases. Patient-based and renal unit–based analyses were performed. Overall, 13 cohort studies were identified. Nine studies involved patients younger than 2 years, 3 involved children aged 16 years or younger, and 1 involved exclusively neonates. Girls constituted 22% to 85% of the involved children. Pooled (95% confidence intervals) sensitivity and specificity rates of DMSA scanning were 79% and 53%, respectively, for the patient-based analysis (8 studies) and 60% and 65% for the renal unit–based analysis (5 studies). The respective areas under the hierarchical summary receiver operating curves were 0.71 and 0.67. Marked statistical heterogeneity was observed in both analyses, as indicated by I2 test values of 91% and 87%, respectively. Acute-phase DMSA renal scanning cannot be recommended as replacement for VCUG in the evaluation of young children with a first febrile UTI.

A Comprehensive Review of Acute Promyelocytic Leukemia in Children

The outcome of patients with acute promyelocytic leukemia (APL) has substantially improved since the successful introduction of tretinoin, and nowadays combining tretinoin with chemotherapy is potentially curative for at least 70–75% of patients with newly diagnosed APL. In most pediatric series, APL represents ≤10% of childhood acute myelogenous leukemia. APL in children is more common in girls and in obese children. It is characterized by a higher incidence of hyperleukocytosis, an increased incidence of microgranular morphology and by more frequent occurrence of the PML/RARα isoforms bcr 2 and bcr 3 compared to adults. Tretinoin-based therapy is curative for the majority of children with APL. Recent data indicate that ≧2 negative RT-PCR assays for PML/RARα on bone marrow performed at least 1 month apart after completing therapy are strongly associated with long-term remissions, while conversion to PCR positivity for PML/RARα during remission is highly predictive of impending relapse. Data from recent studies in adults and limited data from children show that arsenic trioxide is the single most effective agent in APL and deserves immediate study in newly diagnosed children in an effort to further improve prognosis and to limit exposure to conventional cytotoxic chemotherapy.