Pre-micro RNA polymorphism detection in small versus large vessel disease in stroke Egyptian patients.

Stroke is the main cause of adult disability and is responsible for around 11% of deaths all over the world. Ischemic stroke encompasses about 80-85% of total stroke cases. Several studies have shown the relation between microRNAs polymorphism and ischemic stroke. The aim of the study was to evaluate the influence of three common single nucleotide polymorphisms in pre-miRNAs (hsa-miR-146a/rs2910164, hsa-miR-196a2/rs11614913 and hsa-miR-499/rs3746444) on individual susceptibility to the risk of ischemic stroke subtypes in Egyptian population with 117 ischemic stroke patients. Results showed that hsa-miR-146a/rs2910164 was significantly associated with the risk of small vessel disease stroke in Egyptian population with no significant association between hsa-miR-196a2/rs11614913 and hsa-miR-499/rs3746444 with the risk of ischemic stroke. Therefore, it can be concluded that miR-146a/rs2910164 polymorphism is involved in the vulnerability to small vessel disease ischemic stroke risk in Egyptian population.

Amphora algae with low-level ionizing radiation exposure ameliorate D-galactosamine-induced inflammatory impairment in rat kidney.

d-Galactosamine (d-GalN) is a well-known toxin that causes many metabolic and morphological abnormalities resulting in advanced renal failure and liver damage. Occupational exposure to low-level ionizing radiation (<1 Gy) was shown to enhance cell protection via attenuating an established inflammatory process. The present study was therefore aimed to investigate the protective impact of Amphora coffaeiformis extract and low dose gamma radiation against d-GalN induced renal damage in rats. Forty-eight adult male Swiss albino rats were distributed equally into eight groups. The measurements included antioxidants activities (superoxide dismutase, catalase and glutathione peroxidase) as well as lipid peroxidation level in kidney tissue. Also, kidney function tests and inflammatory markers (tumor necrosis factor alpha and nuclear factor kappa-light-chain-enhancer of activated B cells) were measured. Additionally, relative quantification of kidney nuclear factor erythroid 2-related factor 2 (Nrf-2) gene was estimated. Histopathological examination was also performed in kidney tissue. The results revealed decreases in antioxidant activities and downregulation of Nrf-2 expression accompanied by increases in lipid peroxidation level, kidney function tests and inflammatory markers in d-GaIN group. The treatment with Amphora algal extract and low dose gamma radiation ameliorated the previous measurements which were harmony with histopathological findings. In conclusion, A coffaeiformis extract and low dose gamma radiation provided marked functional and histological effects in the treating acute renal damage induced by d-GalN in rats.

Emotional intelligence and perceived stress among female dental students at King Khalid University, Saudi Arabia.

OBJECTIVE: To assess the emotional intelligence and identify the perceived sources of stress among female dental students and interns at King Khalid University College of Dentistry (KKUCOD), to investigate whether specific stressors were related to the year of study and gender, and to evaluate the relationship between emotional intelligence (EI) and perceived stress (PS). MATERIALS AND METHODS: Total of 150 female undergraduates from 5th and 6th years and dental interns were invited to complete a questionnaire using face-to-face interview. Data on EI was collected using a scale developed by Schutte et al. while a modified version of the Dental Environment Stress (DES) was applied to assess the stress perceived by dental students. RESULTS: 120 students agreed to join the study with a response rate of 84%. Mean EI score for the sample was 120 (SD = 11.56), and the mean PS score was 70.37 (SD = 16.19). One-way ANOVA revealed a significant difference between different age groups and the educational, environmental score (P < 0.05). Correlational analysis showed that the PS scale and its factors correlated positively with each other (P < 0.01) and directly with the total EI score (P > 0.01); except for the living accommodation factor, negative correlations with overall EI score were significant. CONCLUSION: The present study showed that female interns and undergraduate students in clinical years of study at College of Dentistry reported higher EI and PS. The educational environmental score was found to be significantly different among different age groups. In contrary to most published literature, a direct association between EI and PS scores was found, except for the living accommodation factor. This might be attributed to the fact that the study was conducted 1 month prior to final exams. Living accommodation, personal factors, educational environment, academic work and clinical factors were identified as significant predictors of PS.

Molecular docking targeting autophagy pathway mediate abrogation of NASH by specific functional foods: update review.

Autophagy is a very well-conserved self-digestive mechanism that transports unwanted or disposable cytoplasmic debris to lysosomes for destruction, including misfolded proteins and damaged organelles. Advanced liver illnesses can develop from the prevalent clinical condition known as non-alcoholic steatohepatitis (NASH). There is no effective treatment, is still unclear. Therefore, in order to create novel therapeutics, it is necessary to comprehend the pathogenic pathways causing disease onset and progression. Natural components from medicinal plants are currently the subject of a larger number of studies since they provide fresh promise for NASH. This review provided an overview of the aetiology of NASH, in addition the role of natural products as alternative or complementary therapeutic agent for management of NASH via autophagy induction. It was concluded that, alternative and complementary supplement of natural functional food as Arabica coffee that rich with chlorogenic acid targeting autophagy mechanism mediate amelioration effect of NASH.

Pomegranate Peel Extract Sensitizes Hepatocellular Carcinoma Cells to Ionizing Radiation, Induces Apoptosis and Inhibits MAPK, JAK/STAT3, ß-Catenin/NOTCH, and SOCS3 Signaling.

Tumor resistance is typically blamed for the failure of radiotherapy and chemotherapy to treat cancer in clinic patients. To improve the cytotoxicity of tumor cells using radiation in conjunction with specific tumor-selective cytotoxic drugs is crucial. Pomegranate has received overwhelmingly positive feedback as a highly nutritious food for enhancing health and treating a variety of ailments. In the present study, we aimed to examine the effects as well as mechanism of action of pomegranate peel extract (PPE) and/or γ-radiation (6-Gy) on hepatocellular carcinoma (HCC) cell lines HepG2. The findings of this study showed that PPE treatment of HepG2 cells considerably slowed the proliferation of cancer cells, and its combination with γ-irradiation potentiated this action. As a key player in tumor proliferation, and inflammatory cascade induction, the down-regulation of STAT3 following treatment of irradiated and non-irradiated HepG2 cells with PPE as recorded in the present work resulted in reduction of tumor growth, via modulating inflammatory response manifested by (down-regulation of TLR4 expression and NFKB level), suppressing survival markers expressed by reduction of JAK, NOTCH1, ß-catenin, SOCS3, and enhancing apoptosis (induction of tumor PPAR-γ and caspase-3) followed by changes in redox tone (expressed by increase in Nrf-2, SOD and catalase activities, and decrease in MDA concentration). In conclusion, PPE might possess a considerable therapeutic potential against HCC in addition to its capability to enhance response of HepG2 cells to gamma radiation.

Endostatin and Cystatin C as Potential Biomarkers for Early Prediction of Preeclampsia.

Preeclampsia (PE) is characterized by new onset hypertension and proteinuria. Undoubtedly, some individuals do not fit precisely into this description, and it could be challenging to spot newly developed PE in females who already have hypertension or renal illness. Monitoring the disease's progression enables the optimization of delivery time while minimizing premature births. The current study explores the diagnostic benefits of serum endostatin and cystatin C in addition to serum and urinary magnesium (Mg) and fractional excretion magnesium (FEMg) for early prediction of PE. The population sample included 82 pregnant women divided into 3 groups: normal pregnancy group served as a control (n = 26), nonpreeclampsia (NPE, n = 34) group included pregnant women with one or more risk factors but did not progress to PE, and pregnant women who developed preeclampsia (PE, n = 22) group. Blood samples were withdrawn at two sampling times: at 12th to 16th and 24th to 26th weeks of gestation. Compared to normal pregnancy, results (X̅ ± SD) indicated a significant increase in serum endostatin in NPE at the first sample (10.78 ± 3.63 ng/mL) and the second sample (28.03 ± 3.79 ng/mL), while cystatin C was at the first sample (0.68 ± 0.06 mg/dL) and the second sample (0.71 ± 0.07 mg/dL). In the PE group, the serum endostatin was 18.86 ± 4.37 ng/mL at the first sampling time and 53.56 ± 9.76 ng/mL for the second sample. Serum cystatin C was also elevated in PE with X̅ ± SD equivalent to 0.73 ± 0.08 and 0.89 ± 0.08 mg/dL at the first and second samples, respectively. On the other hand, serum and urinary Mg in addition to FEMg levels did not significantly differ across the groups under study. Receiver operating characteristic (ROC) curve analysis proved that both endostatin and cystatin C could be good indicators for PE. The findings imply that measuring endostatin and cystatin C at early pregnancy and before progression to PE may be effective in detecting the likelihood of PE. Endostatin could be more precise and sensitive in assessing the probability of PE than cystatin C; however, coupling of the two parameters may be promising.

Evaluation of miRNA-7, miRNA-10 and miRNA-21 as diagnostic non-invasive biomarkers of hepatocellular carcinoma.

Aim of the study: Liver cancer (hepatocellular carcinoma - HCC) remains a serious health challenge; it is the fourth leading cause of death worldwide. Egypt ranks fifteenth worldwide and the third in Africa in terms of HCC burden. The present study aimed to assess some microRNAs (miRNAs) including miRNA-7, miRNA-10, and miRNA-21, serum markers such as cluster of differentiation-14 (CD-14) and transforming growth factor b1 (TGF-b1), and other biochemical parameters as non-invasive tools for HCC diagnosis. Material and methods: The study included 100 participants divided into five groups: group I (20 normal subjects as a healthy group), group II (20 participants with chronic HCV infection but non-cirrhotic), group III (20 volunteers with chronic HCV infection and compensated cirrhosis), group IV (20 patients with chronic HCV infection and decompensated cirrhosis), and group V (20 participants with HCC). Levels of miR-7, miR-10, and miR-21 were evaluated using qRT-PCR. Serum ALT, AST, total bilirubin, total protein, albumin, PT, INR, and platelet count were determined. FIB-4 and APRI test levels were also calculated. CD-14 and TGF-ß1 serum levels were estimated using enzyme-linked immunosorbent assay (ELISA) kits. Results: The expression levels of miR-21 followed by miR-10 showed high sensitivity and specificity in predicting HCC. Serum CD-14 and TGF-b1 levels were significantly increased in all patient groups. Conclusions: From the study, it is concluded that the expression level of miR-21 has the highest sensitivity and specificity, followed by miR-10, which has high sensitivity and low specificity as non-invasive markers for HCC detection, while miR-7 exhibits high sensitivity and reasonable specificity in fibrosis detection.

Nattokinase attenuates bisphenol A or gamma irradiation-mediated hepatic and neural toxicity by activation of Nrf2 and suppression of inflammatory mediators in rats.

Nattokinase (NK), a protease enzyme produced by Bacillus subtilis, has various biological effects such as lipid-lowering activity, antihypertensive, antiplatelet/anticoagulant, and neuroprotective effects. Exposure to environmental toxicants such as bisphenol A (BPA) or γ-radiation (IR) causes multi-organ toxicity through several mechanisms such as impairment of oxidative status, signaling pathways, and hepatic and neuronal functions as well as disruption of the inflammatory responses. Therefore, this study is designed to evaluate the ameliorative effect of NK against BPA- or IR-induced liver and brain damage in rats. Serum ammonia level and liver function tests were measured in addition to brain oxidative stress markers, amyloid-beta, tau protein, and neuroinflammatory mediators. Moreover, relative quantification of brain nuclear factor-erythroid 2-related factor-2 (Nrf2)/heme oxygenase-1 (HO-1) genes, as well as apoptotic markers in brain tissue, was carried out in addition to histopathological examination. The results showed that NK improved liver functions, impaired oxidative status, the cholinergic deficits, and minified the misfolded proteins aggregates. Furthermore, NK alleviated the neuroinflammation via modulating NF-κB/Nrf2/HO-1 pathway and glial cell activation in addition to their antiapoptotic effect. Collectively, the current results revealed the protective effect of NK against hepatic and neurotoxicity derived from BPA or IR.

Correction to 'On the computation of hybrid modes in planar layered waveguides with multiple anisotropic conductive sheets'.

[This corrects the article DOI: 10.1098/rspa.2018.0288.].

Tumor necrosis factor in mediating experimental Haemophilus influenzae type B meningitis.

Tumor necrosis factor (TNF) could possibly be instrumental in mediating injury to the CNS during bacterial meningitis. In CSF of rabbits with meningitis induced with Haemophilus influenzae type b (Hib) lipooligosaccharide (LOS), TNF activity was first detected 45 min after intracisternal (IC) injection of 20 ng Hib LOS and white blood cells (WBC) first appeared 75 min later. The peak TNF activity (45 ng/ml) was observed at 120 min after IC and persisted for 5 h. When 1-2 X 10(7) CFU of Hib was used to induce meningitis, peak CSF TNF activity was comparable with that after 20 ng Hib LOS, but the activity persisted for 14 h. Dexamethasone (DXM) (1 mg/kg per i.v.) given 1 h before or simultaneously with IC Hib LOS reduced significantly TNF activity and meningeal inflammation. Goat anti-human TNF alpha antibodies given IC with 20 ng Hib LOS or 2 X 10(6) CFU of Hib resulted in a significant reduction in CSF TNF concentrations, which was also associated with reduced meningeal inflammation in Hib LOS-inoculated animals. We conclude that TNF participates in mediating meningeal inflammation associated with Hib experimental meningitis, and that DXM, when given before or with Hib LOS, inhibits CSF TNF production and modulates the meningeal inflammatory response.

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.

Evaluation of the safety and efficacy of repeated sedations for the radiotherapy of young children with cancer: a prospective study of 1033 consecutive sedations.

PURPOSE: A prospective observational study to examine our current practice of either conscious sedation (C.S.) or general anesthetic (G.A.) for children undergoing radiation therapy (we use the term sedation to include both C.S. and G.A.). Specifically, the study examines the reasons for selection of patients, choice of drugs, safety and effectiveness of the procedure, side effects of repeated daily sedation, and compliance of the family with the regimen. METHODS AND MATERIALS: Recorded data included patient demographics, sedation technique, time for various stages of the procedure, breathing support required, sedation outcome, and complications. RESULTS: One hundred ninety-eight consecutive children underwent 4232 procedures involving either simulation or radiation treatment, an average of 21 procedures each. Seventy-four (37%) required sedation for a total of 1033 procedures, an average of 14 sedations each. For those patients who received sedation, the age ranged from 9 months to 14 years (median, 3.8) and 96% had a mold, (85% of the head and neck). The doctor's assessment of the need for sedation was correct 89% of the time. Thirty-seven percent required sedation at the start of treatment, but, even after 30 fractions, 15% still required sedation. Presedation status correlated with successful sedation and treatment (p = 0.0001). Ninety-six percent had some form of i.v. access, usually a portacath (76%); 883 sedations were performed with G.A. and 148 with C.S.; 93% of sedations were completed satisfactorily, 5% with some difficulty, and the patient was unable to be treated in 2%. With G.A., satisfactory sedation was achieved 97% of the time, whereas, with C.S., satisfactory sedation was achieved only 68% of the time. There were no complications for 97% of observations. Not one serious complication occurred. An endotracheal tube was used only twice during G.A. For C.S., the results for chloral hydrate, meperidine, and midazolam were, respectively, at least one complication, 23%, 0%, 5%; satisfactory sedation for treatment, 60%, 60%, 82%; and unable to treat 20%, 13%, 5%. For G.A., only 1 patient was unable to be treated. The median time from start of medication to the end of radiation treatment was a median of 10 min (75% complete within 15 min) for G.A., vs. 30 min (75% complete in 50 min) for C.S. On multivariate analysis, the only significant factor predicting a successful outcome was a G.A. using propofol (odds ratio, 20.6), vs. C.S. using either chloral hydrate, meperidine, or midazolam. (p = 0.0001). CONCLUSION: In this study, there were no serious complications of sedation in 1033 procedures. As a result of the study, we developed improved methods for better preparation of the patient and family to try to reduce the need for sedation, and reduce the indications for C.S., while confirming the safety and efficacy of a G.A. with propofol for children needing sedation for daily radiation therapy.

Radiation therapy for retinoblastoma: a retrospective review of 120 patients.

PURPOSE: To characterize the patient population and treatment outcomes in patients with Retinoblastoma (RB) referred for External Beam Orbital Radiotherapy (EBORT) to King Faisal Specialist Hospital & Research Centre (KFSH&RC), Riyadh, Saudi Arabia from 1976 to 1993. METHODS AND MATERIALS: A retrospective study of 120 patients with RB affecting a total of 192 eyes. Patients were divided into three groups. Group A are 60 patients (64 eyes) treated with EBORT to the intact eye to preserve vision. Reese-Ellsworth (RE) Staging was: 1: 12%; 2: 10%; 3: 12%; 4: 23%; and 5: 43%. Twenty-eight patients (47%) also received Vincristine, Adriamycin, and Cyclophosphamide chemotherapy (C/T). Mean follow-up, per patient, was 48.5 months. Standard treatment until 1992 was 45 Gy in 12 fractions of 3.75 Gy, three times weekly over 18 days. Assuming the alpha/beta ratio for early effects and tumor control at 10, Tk = 21 days, Tpot = 5 days, then the Biological Equivalent Dose (BED) was 62 Gy10 for early effects, and 101 Gy3 for late effects. Group B are 28 patients (28 eyes) treated for curative intent with EBORT to the orbit for locally advanced disease, usually after enucleation (24 eyes). Nineteen patients (83%) also had C/T. Mean follow-up was 22.6 months. Group C are 37 patients with advanced disease treated with radiotherapy for palliation. Seventeen (46%) also received C/T. Mean follow-up was 11.7 months. RESULTS: Group A-following EBORT useful vision was retained in RE Stage 1 to 5: 7 of 7, 6 of 6, 4 of 8, 10 of 15, and 7 of 28 eyes, respectively. There was no significant difference between patients who received adjuvant chemotherapy and those who did not. Complications included cataract (27%), retinopathy (25%), vitreous hemorrhage (19%), and orbital deformities (11%). In Group B the local control rate was 71%. In Group C, 10 (27%) of the 37 patients were alive at last contact, and 27 (73%) were either terminal or dead of disease. None of Group A or B patients had positive CSF cytology, bone scan, or bone marrow examination. In Group C 19% had positive CSF cytology, and bone marrow, and 14% had a positive bone scan. CONCLUSIONS: 1) EBORT preserved useful vision in a significant proportion of patients even in eyes with advanced RE Stage RB, but longer follow-up is likely to reveal an even higher complication rate with this regime. 2) High dose per fraction probably contributed to the increased complications. 3) Chemotherapy did not demonstrate any effect on retaining vision in this study. 4) For disease that is confined to within the eye clinically and radiologically, invasive procedures for CSF cytology, bone marrow examination, and bone scan do not seem warranted. 5) The optimum technique, fractionation, and dosage for RB is still not well defined.

Cerebrospinal fluid interleukin 1-beta and tumor necrosis factor concentrations and outcome from neonatal gram-negative enteric bacillary meningitis.

Concentrations of interleukin 1-beta and tumor necrosis factor in cerebrospinal fluid (CSF) of 42 neonates with Gram-negative enteric bacillary meningitis were determined and correlated with outcome and other CSF indices. At the time of diagnosis interleukin 1-beta was detected in CSF of 40 infants and peak concentrations correlated significantly with outcome from disease. Days of interleukin 1-beta concentrations of greater than 200 pg/ml or greater than or equal to 20 pg/ml were significantly correlated with days that CSF cultures were positive and that K1 antigen and endotoxin were detected in CSF. Tumor necrosis factor activity was detected in CSF of 25 of 27 infants; there was no correlation between outcome and CSF tumor necrosis factor concentrations. The results provide a possible rationale for therapeutic intervention to improve outcome.

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.

Comparative study of cefepime versus ceftazidime in the empiric treatment of pediatric cancer patients with fever and neutropenia.

BACKGROUND: In view of the recent trend toward monotherapy in the treatment of bacterial infection, we evaluate the clinical efficacy and safety of cefepime vs. ceftazidime for the empiric treatment of febrile episodes in neutropenic pediatric cancer patients. METHODS: In a single site, open label study, 104 neutropenic pediatric cancer patients [96% with absolute neutrophil count (ANC) of <500 neutrophils/mm3] with a median age of 6 years were randomized (1:1) to receive either intravenous cefepime or ceftazidime (50 mg/kg/dose every 8 h; < or = 6 g/day) for empiric treatment of fever (temperature >38.0 degrees C occurring at least twice in 24 h, or single >38.5 degrees C). Febrile episodes were classified as either microbiologically or clinically documented infection or fever of unknown origin. Therapy continued until the ANC was > or = 1,000 neutrophils/mm3 or there was an increasing ANC in low risk patients (maximum duration of treatment, 8 weeks). The primary efficacy endpoints assessed were clinical and microbiologic response to assigned drug therapy. Secondary outcome measures were rate of early discontinuation of study drug and use of concomitant antibiotic therapy to modify initial study drug regimen. RESULTS: Of 68 patients who could be evaluated for efficacy, 74% (26 of 35) of cefepime-treated patients and 70% (23 of 33) of ceftazidime-treated patients responded to treatment. The small number of study patients precluded statistical analysis of results. In a modified intent-to-treat analysis, 59% of the patients treated with cefepime and 47% of ceftazidime-treated patients responded to therapy. Cefepime patients developed fewer new infections than ceftazidime patients (9% vs. 21%, respectively) and early discontinuation of study drug therapy occurred slightly more often in the ceftazidime group. Further, the use of concomitant systemic antimicrobial therapy (mostly vancomycin) occurred less often in the cefepime-treated patients, as compared with the ceftazidime group [35% [17 of 49] vs. 44% (24 of 55), respectively]. No deaths or serious adverse events were considered to be related to study therapy. The most frequent adverse event was rash that was moderate in severity, and it occurred equally in both groups. CONCLUSION: Cefepime appears to be safe and effective compared with ceftazidime for initial empiric therapy of febrile episodes in neutropenic pediatric cancer patients.

The changing epidemiology of bacteremia in neutropenic children with cancer.

Gram-positive bacteria have been the predominant organisms causing bacteremia in febrile neutropenic cancer patients during the past decade. Recently we have noted an increase in Gram-negative bacteremia in children and adolescents with cancer. Therefore we retrospectively reviewed 153 episodes of bacteremia during a 6-year period to investigate changes in the etiology of bacteremia in pediatric oncology patients. In the early 3-year period (January, 1988, to December, 1990) Gram-positive organisms comprised 73 (74%) of the 99 isolates, and Staphylococcus epidermidis was the most common isolate. In the later 3-year period (January, 1991, to December, 1993) Gram-negative organisms were seen with greater frequency and represented 50% of isolates (P = 0.004). Pseudomonas aeruginosa was the most commonly isolated organism during this period (22% of all isolates). We speculate that the recent utilization of more intensive chemotherapy regimens has caused an alteration in the epidemiology of bacteremia in children and adolescents with cancer which could influence the initial empiric antibiotic regimens and the outcome of such infections.

Bone marrow transplantation from matched siblings in patients with fanconi anemia utilizing low-dose cyclophosphamide, thoracoabdominal radiation and antithymocyte globulin.

Nineteen patients with Fanconi anemia (FA) and bone marrow failure underwent bone marrow transplantation (BMT) from matched siblings. Median age at BMT was 8.7 years. Conditioning consisted of low-dose cyclophosphamide (CY 5 mg/kg x 4 days) and thoracoabdominal irradiation (TAI 400 cGy). Graft-versus-host disease (GVHD) prophylaxis was cyclosporin A (CsA) in 13 patients and CsA plus methotrexate in 6 patients. Antithymocyte globulin (ATG) was added in the pretransplant as well as the post-transplant period. All patients received high-dose acyclovir from day 2 pre-BMT to day 28 post BMT, and intravenous immunoglobulins (IVIG), 500 mg/kg weekly from day 7 pre-BMT to day 90 post BMT. No fungal prophylaxis was given. All patients engrafted, (median, 14 days for an absolute neutrophil count > or =0.5 x 10(9)/l; median, 37 days for platelet count > or =20 x 10(9)/l). Fourteen (74%) patients are alive with sustained engraftment and are transfusion independent. Three (16.6%) patients developed acute GVHD; none developed chronic GVHD. Five (26%) patients developed invasive fungal infections, and two (10%) developed fatal CMV disease. We believe the addition of ATG may have contributed to the increased incidence of severe life-threatening fungal and viral infections in our series.

Transfusion-dependent congenital dyserythropoietic anemia type I successfully treated with allogeneic stem cell transplantation.

Until recently, therapy for patients with severe congenital dyserythropoietic anemia (CDA) has been limited to blood transfusions and chelation therapy. Three children with transfusion-dependent CDA type I underwent allogeneic stem cell transplantation (SCT) from matched sibling donors. Conditioning was with cyclophosphamide 50 mg/kg/day for 4 days, busulphan 4 mg/kg/day for 4 days, and antithymocyte globulin (ATG) 30 mg/kg for four doses pre-SCT. All patients engrafted and are alive, and transfusion independent. To our knowledge, this is the first report of successful SCT in the management of CDA type I.

Antimicrobial agents in pediatrics.

For proper use of antimicrobial agents in infants and children, special precautions should be taken. These include knowledge of the pharmacokinetic properties of these agents, especially in neonates, and of host factors related to gestational and chronological ages of the patient. Failure to recognize such factors can result in either lack of therapeutic response of drug-related adverse effects. In this article, special aspects of the pharmacokinetics of antibiotics and the clinical pharmacology and indications for use of the beta-lactam antibiotics in infants and children are presented.