Haematological Changes Associated with Hepatitis B Virus Infection in Individuals with and without Sickle Cell Disease.

BACKGROUND: Hepatitis B virus infection, a major public health problem that primarily affects the liver, may cause reduction in the levels of haemoglobin, haematocrit and in the extreme, could cause aplastic anaemia. The haematological characteristics could be detected with a complete blood count which could provide invaluable information for diagnosis and management of the disease. AIM: To determine the effect of HBV infection on the blood count of individuals with sickle cell disease (SCD) and apparently normal healthy (Non-SCD). SETTING: Non-SCD participants were recruited from the community while SCD patients in steady state were recruited from SCD routine clinics. METHODS: The study was a cross - sectional study carried out on 1017 non-SCD and 1017 SCD individuals. Haematology Autoanalyzer was used to determine the complete blood count. Granulocyte-to-lymphocyte ratio (GLR), platelet to white blood cell count ratio (PWR) and platelet-to-lymphocyte ratio (PLR) were calculated. ELISA for HBsAg and HBV core antigen IgM antibodies were used to identify participants with HBV. RESULTS: The non- SCD individuals infected with HBV had significantly higher WBC (7.51 ± 5.8 X109/L)) compared to a WBC (6.1 ± 3.4 X109/L) in uninfected individuals (p =0.001). PWR for HBV negative (49.9±28.6) was higher than that for HBV positive participants (41.4±17.6) (p=0.034). Mean platelet volume (MPV) of 9.93 ± 1.1fl in SCD individuals with HBV was significantly higher than 8.30 ± 0.95fl in SCD individuals without HBV (p=.001). CONCLUSIONS: PWR and MPV may be useful as surrogate marker for detection of HBV disease progression in apparently normal healthy non - SCD and SCD populations to institute prompt appropriate ancillary investigation and treatment.

CONTEXTE: L'infection par le virus de l'hépatite B, un problème majeur de santé publique qui affecte principalement le foie, peut entraîner une réduction des taux d'hémoglobine et d'hématocrite et, dans l'extrême, peut provoquer une anémie aplastique. Les caractéristiques hématologiques peuvent être détectées par un hémogramme complet qui pourrait fournirdes informations précieuses pour le diagnostic et la et la gestion de la maladie. OBJECTIF: Déterminer l'effet de l'infection par le VHB sur sanguine complète d'individus atteints de drépanocytose (SCD) et d'individus apparemment normaux en bonne santé (non-SCD). SITE: Les participants de non-SCD ont été recrutés dans la communauté tandis que les patients drépanocytaires en état stable ont été recrutés dans les cliniques de routine de la drépanocytose. MÉTHODES: L'étude était une étude transversale menée sur 1017 personnes non-SCD et 1017 personnes SCD. sur 1017 personnes nonSCD et 1017 personnes SCD. Un autoanalyseur hématologie a été utilisé pour déterminer la formule sanguine complète. Le rapport granulocytes/ lymphocytes (GLR), le rapport plaquettes/blancs (PWR) et le rapport plaquettes/lymphocyte (PLR). ont été calculés. Les tests ELISA pour les anticorps IgM de l'Ag HBs et de l'antigène central du VHB ont été utilisés pour identifier les participants atteints du VHB. RÉSULTATS: Les individus non atteints de DSC et infectés par le VHB présentaient les caractéristiques suivantes un nombre significativement plus élevé de GB (7,51 ± 5,8 X109/L) par rapport à une WBC (6,1 ± 3,4 X109/L) chez les individus non infectés (p =0,001). Le TPM pour lesparticipants négatifs pour le VHB (49,9±28,6) était plus élevé que celuipour les participants positifs au VHB (41,4±17,6) (p=0,034). Le volume moyen des plaquettes Le volume plaquettaire moyen (VPM) de 9,93 ± 1,1fl chez les personnes atteintes de MCS avec VHB était significativement plus élevé que celui des personnes atteintes de MCS sans VHB (8,30 ± 0,95fl) (p=0,001). sans VHB (p=0,001). CONCLUSIONS: Le PWR et le MPV peuvent être utiles comme marqueurs de substitution pour la détection de la progression de la maladie VHB chez population de SCD et Non-SCD apparemment normale, en bonne santé afin d'instituer rapidement les examens complémentaires et le traitement appropriés.

Annual stroke incidence in Nigerian children with sickle cell disease and elevated TCD velocities treated with hydroxyurea.

BACKGROUND: Elevated transcranial Doppler (TCD) velocities accurately predict stroke risk in children with sickle cell disease (SCD). Chronic blood transfusion, the gold standard for primary stroke prevention, is faced with numerous challenges in Africa. Hydroxyurea (HU) has been shown to reduce elevated TCD velocities in children with SCD. AIM: To determine the effectiveness of HU in reducing the risk of primary stroke in a cohort of Nigerian children with SCD and elevated velocities treated with HU. METHODS: Children with SCD and TCD velocities ≥170 cm/sec treated with HU were prospectively followed with 3-monthly TCD and neurological evaluations for ≥12 months to determine the incidence of primary stroke. RESULTS: One hundred and four children, 53 males, and 51 females were enrolled into the study. Their ages ranged from 2 to 16 years with a mean of 6 years. At first TCD examination, velocities ranged from 173 to 260 cm/sec with conditional and abnormal risk velocities in 60 (57.7%) and 44 (42.3%) children, respectively. Follow up ranged from 1 to 8 years with a mean of 3.6 years. Mean TCD velocities showed a significant decline from 198.2 (standard deviation [SD] = 15.6) cm/sec to 169.3 (SD = 21.4) cm/sec (P < 0.001). One stroke event occurred in the cohort, giving a stroke incidence of 0.27/100 person years. CONCLUSION: HU significantly reduces TCD velocities in Nigerian children with SCD and elevated TCD velocities, with a corresponding reduction in the incidence of primary stroke. HU may represent a potential alternative for primary stroke prevention in low and middle income countries where the burden of SCD resides.

PERCEPTION AND EXPERIENCE AND OF NIGERIAN PAEDIATRICIANS TO DENTAL REFERRAL FOR CHILDREN WITH CHRONIC ILLNESSES.

BACKGROUND: Interdisciplinary collaboration in the management of patients offers several advantages especially for children with chronic illnesses who are often at risk for other health conditions. Diseases in other parts of the body can be detected by a physician and lead to subsequent referral to the appropriate managing team. This study assessed the perception and experience of dental referral among Nigerian paediatricians as well as factors that may influence their decision to refer to a dentist. METHODS: Self administered questionnaires were used to obtain socio-demographic data, history of exposure to dental teachings as well as experience with dental referral. Two hundred and sixty nine paediatricians and paediatric practitioners were involved in the study. Descriptive statistics and measures of central tendencies generated. Associations were tested with Chi Squares and Statistical significance was set at P <0.05. RESULTS: A total of 269 respondents participated in the study out of whom 142(52.8%) trained at institutions where there was a sister dental school, but 243(90.3%) of them had no official dentistry postings. Majority of the respondents 259(96.3%) were in favour of routine professional oral check-up for children but only 83(30.9%) endorsed the recommended bi annual oral checks. A referral rate of 0.76-1.9% was obtained. CONCLUSION: Although paediatricians are a known source of dental referral for children globally, a lot needs to be done to equip the physicians with the necessary knowledge and skill that will enable them participate more actively in the promotion of oral health for Nigerian children.

Pattern of childhood leukaemia in University College Hospital, Ibadan.

BACKGROUND: Leukaemias are haematological malignancies characterized by unregulated clonal proliferation of haematopoietic cells. OBJECTIVE: To determine the pattern of childhood leukaemia in Ibadan. METHODOLOGY: This was a retrospective study of leukaemia cases diagnosed at the University College Hospital (UCH), Ibadan between January 1991 and December 2010 in children less than 15 years of age. Data obtained was subjected to statistical analysis using the Statistical Package for Social Sciences version 20. RESULTS: There were 64 cases of childhood leukaemia, accounting for 10.2% of childhood cancers seen during this study period. The male to female ratio was 2:1 and modal age group was between 10 and 14 years. Thirty (46.9%) cases were acute lymphoblastic leukaemia (ALL), 22 (34.4%) were acute myelogenous leukaemia (AML) and 12 (18.8%) were unspecified acute leukaemias. There was no case of chronic myeloid or lymphocytic leukaemia. CONCLUSION: There has been a relative increase in the frequency of leukaemia cases at UCH, Ibadan, which may be largely explained by increased awareness and referrals. There is a need for further collaborative multicentre studies of childhood leukaemias in Nigeria and other developing countries and focused research on childhood leukaemias in order to unravel the aetiology.

Chronic blood transfusion for primary and secondary stroke prevention in Nigerian children with sickle cell disease: a 5-year appraisal.

BACKGROUND: Chronic blood transfusion (CBT) diminishes the risk of primary and secondary stroke in sickle cell disease (SCD). We appraised CBT and assessed its feasibility as an option for stroke prevention in a setting of limited resources. METHODS: All new cases of SCD seen in the Paediatric Hematology/Neurology units of the University College Hospital, Ibadan, Nigeria over a 5-year period were screened and followed up to identify those who had an indication for CBT for stroke prevention. Caregivers were counseled and offered CBT when indicated. Children of caregivers who accepted chronic transfusion were carefully followed up and outcomes documented. RESULTS: Five (10%) of the caregivers of the 50 children who had an indication for CBT for stroke prevention consented to the treatment. They all had homozygous sickle cell anemia and had suffered a stroke. None of the children with abnormal TCD velocities consented to CBT. Two children experienced transfusion reactions, fatal in one. The mean annual cost of chronic transfusion (without chelation) was $3,276 (SD = 1,168). Major reasons given for declining CBT were high costs of blood transfusion, unavailability of blood, the need to regularly seek for blood donors, and the indefinite duration of blood transfusions. CONCLUSION: High economic costs, unavailability of blood, need to regularly seek for blood donors, cultural beliefs, and high frequency of transfusion reactions are major challenges to a successful CBT program in Nigeria. There is a need for government subsidy on blood transfusions and improved efforts towards provision of safe and affordable blood.

Health status of children in institutionalised homes in South West Nigeria.

AIMS AND OBJECTIVES: To determine the nutritional and immunisation status as well as morbidity pattern of children in institutionalised care in south-western Nigeria. SUBJECTS AND METHODS: The study was cross sectional and involved children under the age of fifteen years in seven institutions in Oyo and Ogun states, south western Nigeria. Children admitted into these homes were either orphans or those separated from their parents through child abandonment, illness and juvenile delinquency. A history of current and recent illnesses in the preceding one month as well as immunisation was obtained for each child. Physical examination including growth assessment was then performed after which blood specimens were collected for haematocrit estimation, haemoglobin electrophoresis and examination for malaria parasites. RESULTS: A total of 161 children were studied comprising 74 (46.0%) males and 87 (54.0%) females. Their ages ranged from 1.12 to 168 months with a mean (standard deviation) of 94.5 (47.0) months. Only 24.5 % of the children were reported to have completed the immunisation schedule. Fifty five (34.2%) of the 161 children were reported to have been ill in the preceding period of one month, the leading symptoms being fever (14.9%), cough (10.3%) and diarrhoea (3.9%). Forty six (28.6%) of the children were stunted, 34 (21.1%) underweight and 106 (65.8%) anaemic. CONCLUSION: The health status of children in institutionalised care is poor and needs better supervision and support to facilitate growth and wellbeing.

Stroke recurrence in Nigerian children with sickle cell disease treated with hydroxyurea.

AIMS AND OBJECTIVES: To compare the outcome after a first clinical stroke, following treatment with and without hydroxyurea (HU). SUBJECTS AND METHODS: A retrospective review of a cohort of Nigerian children with SCD, who had suffered a first stroke, was carried out. Outcomes in the group of children who received and did not receive HU were compared. RESULTS: Thirty two children presented with stroke and one died of haemorrhagic stroke at presentation. All the children had haemoglobin SS phenotype, and ischaemic stroke was the predominant form seen. Mean age at first clinical stroke was 7 years, 7 months (SD=2 years, 4 months). Thirteen children received HU while 18 declined HU therapy. Maximum dose of HU ranged from 20-25 mg/kg/ day. The secondary stroke incidence of 7/100 person years in the HU group was significantly lower than the 28/100 person years in the non-HU group (P=0.001, OR 3.808, 95% CI 1.556, 9.317). Children who did not receive HU were more likely to drop out of school and to have moderate-severe motor disabilities requiring caregiver assistance for daily living. CONCLUSION: In settings where facilities for chronic blood transfusion are not accessible or feasible, HU therapy should be considered for secondary stroke prevention in children with SCD.

Correlates of steady-state haematocrit and hepatosplenomegaly in children with sickle cell disease in Western Nigeria.

BACKGROUND: Sickle cell disease is a common genetic disorder in Nigeria. OBJECTIVES: To determine the steady state haematocrit, liver size and spleen size in children with sickle cell disease and the factors that influence them. METHODS: This was a retrospective study of children with sickle cell disorders who attended the anaemia clinic of the Children's Outpatient Department, University College Hospital, Ibadan between the years 2000-2009. Relevant data extracted from their case notes included socio-demographic variables, haemoglobin phenotype, steady state haematocrit and liver and splenic sizes. Means were compared with t-test and correlation tested with Pearson correlation. Statistical significance was set at p < 0.05. RESULTS: A total of 415 (Male: female ratio 1.1:1) children were studied and 385 (92.8%) and 30 (7.2%) of the children were of haemoglobin (Hb) SS and Hb SC phenotypes respectively. Their ages ranged from 0.5-17 years with a mean (SD) of 7.3 (4.4) years. Mean (SD) steady state haematocrit for children with HbSC was 28.3 (4.5) % and significantly higher than 24.1 (3.7) % in HbSS. Mean steady state haematocrit was also higher in children from higher than lower socio-economic classes. There was a negative correlation of haematocrit with age, with hepatomegaly and splenomegaly. Steady state hepatomegaly occurred more frequently in HbSS than in HbSC. CONCLUSION: Haemoglobin phenotype, age and socio-economic status have some modifying influences on the steady-state features of sickle cell disease in Nigerian children. In addition, increasing liver and spleen sizes seem to be related to a decreasing haematocrit.

Age at diagnosis of sickle cell disease in a developing country.

In order to determine the age at diagnosis of sickle cell disease and some of the factors that influence the same at the University College Hospital Ibadan, a retrospective study of children with sickle cell disease who attended the children's outpatient department of the hospital between June 2000 and June 2009 was conducted by reviewing their case notes. A total of 457 children were studied (Male: Female ratio 1.1:1). Haemoglobin phenotype was SS in 421 children (92.1%) and SC in 36 children (7.9 %). Median age at diagnosis was 2.0 years (2.5 months - 14.0 years). Age at diagnosis was lower in children with Hb SS than HbSC (p = 0.01), in children from higher socioeconomic classes (p = 0.003) and in children with a history of dactylitis (N = 354, p = 0.000). Late diagnosis of haemogobinopathies in Ibadan calls for institution of neonatal screening to improve chances of survival.

Service uptake and performance of the prevention of mother-to-child transmission (PMTCT) programme in Ibadan, Nigeria.

The Prevention of Mother to Child Transmission (PMTCT) programme in the University College Hospital (UCH), Ibadan has been in existence for more than five years and has scaled up to other sites. The study evaluated the service uptake and performance of the programme using national key indicators. Antenatal and delivery records of women enrolled between July 2002 and June 2007 were reviewed. A total of 51952 women attended first antenatal visits and received HIV pre-test counselling. Of these, 51614 (99.5%) accepted HIV test and 49134 (95.2%) returned for their results. Out of the tested patients, 2152 (4.2%) were identified to be HIV positive. Partners of positive patients accepting HIV testing were 361 (16.7%) with 87 (18.6%) testing positive. There were a total of 942 deliveries out of which 39.2% of the mothers and 95.2% of the babies respectively received ARV prophylaxis. In all, 85.8% (788/918) of the mothers opted for formula as the method of infant feeding. Out of the 303 babies eligible for ELISA testing, 68.3% reported for the test and 17 (8.7%) tested positive. There has been progress in the programme, reflected in the increase in the number of new clients accessing the PMTCT service. However, partner testing and follow up of mother-infant pairs remain formidable challenges that deserve special attention.

Protocol for the Process Evaluation of the Online Remote Behavioural Intervention for Tics (ORBIT) randomized controlled trial for children and young people.

BACKGROUND: Process evaluations are an important component in the interpretation and understanding of outcomes in trials. The Online Remote Behavioural Intervention for Tics (ORBIT) study is a randomized controlled trial evaluating the effectiveness of an Internet-delivered behavioural intervention (called BIP TIC) compared to an Internet-delivered education programme aimed at children and young people with tics. A process evaluation will be undertaken alongside the main trial to determine precisely how the behavioural intervention works and ascertain whether, and if so, how, the intervention could be successfully implemented in standard clinical practice. This protocol paper describes the rationale, aims, and methodology of the ORBIT trial process evaluation. METHODS: The process evaluation will have a mixed-methods design following the UK Medical Research Council 2015 guidelines, comprising both quantitative and qualitative data collection. This will include analysing data usage of participants in the intervention arm; purposively sampled, semi-structured interviews of parents and children, therapists and supervisors, and referring clinicians of the ORBIT trial, as well as analysis of qualitative comments put into the online therapy platform by participants at the end of treatment. Qualitative data will be analysed thematically. Quantitative and qualitative data will be integrated in a triangulation approach, to provide an understanding of how the intervention works, and what resources are needed for effective implementation, uptake and use in routine clinical care. DISCUSSION: This process evaluation will explore the experiences of participants, therapists and supervisors and referring clinicians of a complex online intervention. By contextualising trial efficacy results, this will help understand how and if the intervention worked and what may be required to sustain the implementation of the treatment long term. The findings will also aid in our understanding of factors that can affect the success of complex interventions. This will enable future researchers developing online behavioural interventions for children and young people with mental health and neurological disorders to gain invaluable information from this process evaluation. TRIAL REGISTRATION: International Standard Randomised Controlled Trials Number, ISRCTN70758207. Registered on 20 March 2018. ClinicalTrials.gov, NCT03483493. Registered on 30 March 2018.

Isopod and insect root borers may benefit Florida mangroves.

Far from threatening the persistence and geographic extent of red mangrove (Rhizophora mangle) in Florida, wood-boring marine isopods may aid the plant to survive wave action by initiating branching of aerial prop roots. Evidence for a recent, sudden increase in density or range of one such isopod, Sphaeroma terebrans, is anecdotal and weak. Insect damage to mangrove aerial roots even before they descend to the water is at least as great as that wrought by isopods and also causes root branching. Aerial and submarine damage combine to stimulate root initiation so that, for every root produced aerially by the tree, at least 1.4 roots reach the substrate. Similar responses to herbivory, which have been reported for other plants, suggest that herbivores may both benefit and harm plants, and that their impact may be more difficult to assess in specific instances than has been realized.

Situation analysis of the existing infant feeding pattern at the commencement of the prevention of mother to child transmission (PMTCT) of HIV programme in Ibadan.

OBJECTIVES: To evaluate breastfeeding and weaning practices associated socio-demographic factors and knowledge about mother-to-child transmission of HIV among mothers in Ibadan. METHODS: A cross sectional survey was conducted among 513 mothers of children aged 6- 24 months, attending infant welfare clinics. Data collection was by a structured questionnaire, which was supplemented by focus group discussions to further explore some of the issues covered in the survey. RESULTS: Breast-feeding rate was 99.4%, the duration of which ranged from 1-22 months with a median of 14 months among those who had stopped breastfeeding. Only 145 (28.3%) mothers breastfed their babies exclusively for six months and 259(50.8%) initiated breastfeeding within one hour of birth; both were associated with at least secondary level of education. The main obstacle to exclusive breastfeeding was the belief that water is required to quench thirst in babies. Expression of breast milk was not favoured by majority of the mothers (68%) most of whom felt that the milk would get contaminated. Wet nursing was rarely practiced (0.4%). Most of the mothers, 436 (85%) were aware that HIV could be transmitted through breast milk but the attitude towards a mother who did not breast feed was negative in 96.8% ofrespondents. CONCLUSIONS: Adherence to recommended infant feeding options for HIV-exposed infants are likely to be faced with challenges in a culture where breastfeeding is the norm and exclusive breastfeeding rate is low. There is need for counseling and health education on prevention of mother-to-child transmission of HIV.

Early deaths and other challenges to childhood cancer survival in Ibadan, Nigeria.

OBJECTIVES: To determine the frequency of early deaths and the associated risk factors in children suffering from cancer at the University College Hospital, Ibadan. DESIGN: A retrospective study involving review of case notes of children suffering from cancer. SETTING: Department of Paediatrics, University College Hospital, Ibadan, Nigeria. SUBJECTS: All cases of childhood cancer managed in the Department between January 1998 and December 2004. Inclusion criteria were histological or cytological confirmation of diagnosis, suggestive clinical features and availability of details about the course of the illness. MAIN OUTCOME MEASURES: Interval between diagnosis and death, rate of early death (death within 30 days of diagnosis) and risk factors for early death. RESULTS: Eighty eight cases of childhood cancer were seen out of whom 52 died during the period. Four cases with incomplete data were excluded from subsequent statistical analysis. There were 29 (34.5%) early deaths defined as death within 30 days of diagnosis. The odds of early death were increased in the presence of bilateral kidney involvement, masses in the liver, splenic masses, pulmonary metastasis and stage D of Burkitt lymphoma. Logistic regression analysis revealed that pulmonary metastasis was a significant independent predictor ofearly death. CONCLUSIONS: Early childhood cancer mortality rate is high. Early diagnosis and referral for appropriate care may reduce childhood cancer mortality in Nigeria.

Causes of death in childhood cancer at the Department of Paediatrics, University College Hospital, Ibadan.

There is a dearth of information on the mortality of children with cancer in Nigeria but the few available reports suggest a poor outcome. The objectives of this study were to determine the underlying and immediate causes of death from childhood cancer. The mortality summary cards of all cases of childhood cancer seen at the Department of Paediatrics, University College Hospital, Ibadan between January 1998 and December 2004 were reviewed. Eighty-eight cases of childhood cancer were seen, out of whom 52 (59.1%) died, but only the 48 deaths with complete data were analyzed. These deaths comprised of 37 males and 11 females giving a male:female ratio of 3.4:1. Their ages ranged from 1 to 13 years with a mean of 7.3 +/- 3.4 years. The majority (71.4%) of all patients presented with diffuse or metastatic disease at diagnosis and this was associated with increased risk of dying. Of the 48 cases reviewed, 39 (81.3%) died without any remission of the primary tumour including 5 (10.4%) with disease progression despite treatment and 15 (31.3%) who died before treatment; only 4 cases (8.3%) died from tumour relapse. The immediate causes of death were infections (39.6%), bone marrow suppression (29.2%), treatment-related mortality (27.1%), organ failure (22.9%), bleeding (16.7%) and other metabolic causes (8.3%). Potentially reversible factors such as infections, bone marrow suppression and treatment-related events are the commonest causes of death from childhood cancer in Ibadan. Therefore, early presentation, prompt identification and effective management of these problems may reduce childhood cancer mortality in Nigeria.

A case of human bite by an 11-year old HIV positive girl in a paediatrics ward.

Biting is a possible mode of transmission of HIV infection, though the risk of such transmission is believed to be low. Children infected with HIV are at risk of psychological complications as a result of direct or indirect effects associated with the disease. We report the case of an 11 year old HIV positive girl with clinical stage IV disease, who was involved in multiple disputes while on admission on the ward. During one of the disputes she inflicted a deep bite injury on a 10-year old boy, HIV post-exposure prophylaxis (PEP) was commenced 6 hours after the bite and he has remained HIV negative 12 months later. What is peculiar about this case is that the incident occurred in a hospital setting and biting is not usually expected among children of this age. In the era of HIV/AIDS, it is recommended that persons involved in childcare be aware of this potential risk during interactions among children. It is also essential for health care personnel to have sufficient knowledge about PEP in order to reduce the risk of HIV transmission in similar settings. In addition, a multidisciplinary approach to the management of children living with HIV is important in order to identify and address psychosocial factors that may influence symptoms and medical treatment outcome. The risk of transmission of HIV through human bites and the psychosocial impact of the disease on children are also discussed.

Utility of retrograde ureterocelogram in management of complex ureterocele.

INTRODUCTION: Symptomatic pediatric ureterocele has diverse manifestations, making evidence-based management impractical. Thus, detailed visualization of ureterocele anatomy prior to first surgical incision is invaluable. Retrograde ureterocelogram (RUC) is a simple, underutilized radiologic technique that can be performed during cystoscopy. This study sought to determine whether RUC changes surgical management by more accurately depicting the complex ureteral and ureterocele anatomy, compared with renal ultrasound (US) and voiding cystourethrography (VCUG). METHODS: Patients who underwent surgical management of ureterocele from 2003 to 2015 were identified; those who received concomitant fluoroscopic RUC were selected for the case series. Data collected included: demographics, pre-operative evaluation, surgical interventions, and outcomes. The RUC images were individually examined, and the anatomic impression compared with previous renal US and VCUG. Novel RUC findings not previously appreciated by the pre-operative evaluation were noted. The RUC was performed by cystoscopically inserting a needle into the ureterocele and injecting contrast retrograde. If indicated, simultaneous PIC (Positioning the Instillation of Contrast) cystography was performed. RESULTS: Of the 43 patients that underwent surgery for suspected ureterocele, 28 underwent cystoscopy + RUC (10 M: 18 F) at a median age of 4.6 months and median follow-up of 37.0 months. All patients had prior US, 25 had prior VCUG, and 20 had prior radionuclide studies. Ureteroceles were either duplex system (n = 21) or single system (n = 7); 17 were ectopic into the bladder neck or urethra; seven were intravesical; and four were pseudoureteroceles. Fourteen patients underwent concomitant transurethral incision of the ureterocele (TUIU); two were deferred for surgery; and 11 received concomitant definitive surgery (e.g., nephrectomy). The RUC illuminated novel aspects of the anatomy in 20 of the 28 patients. No adverse events occurred. Notably, in nine of the 28 children, significant observations from RUC prompted change to the pre-operative surgical plan. DISCUSSION: Retrograde ureterocelogram clearly revealed ureterocele ectopy, pseudoureterocele, ureterocele disproportion, and unsuspected duplex systems, making it a useful adjunct to standard US and VCUG studies. Retrograde ureterocelogram can also be used to fluoroscopically verify decompression of the ureterocele post incision, document severity of ureteral dilation, and teach residents about the great damage generated by ureterocele variations. Limitations of RUC included increasing radiation dose and overall cost. The study design was limited by its small size, retrospective approach, selection bias, and availability of RUC images. CONCLUSIONS: While not indicated in routine ureterocele management, intraoperative RUC further defined ureterocele anatomy in nearly all cases and yielded changes to the original surgical plan frequently enough to merit greater use in complex patients.

Sensitivity of bone marrow hematopoietic colony-forming cells from mice, dogs, and humans to carminomycin, marcellomycin, aclacinomycin A, and N,N-dibenzyldaunorubicin and its relationship to clinical toxicity.

The sensitivity of bone marrow granulocyte-macrophage colony-forming cells to 4 anthracyclines, carminomycin, marcellomycin, aclacinomycin A, and N,N-dibenzyldaunorubicin, was studied using the agar diffusion chamber technique which allows exposure of target cells to drug metabolized by the chamber-bearing host after i.v. injection. Colony-forming cells from mice, dogs, and humans were all found to have exponential dose-response curves for the agents studied, with variation of the slopes between species and agents. Species sensitivities as determined by the assay related well to the available toxicological and clinical data for specific drugs. The rank order of sensitivity of human marrow colony-forming cells to five anthracyclines tested in this and a previous study related very closely to doses producing moderate leukopenia in Phase I and II clinical studies. A dose of 200 mg/sq m of N,N-dibenzyldaunorubicin would be expected to produce moderate leukopenia in future clinical trials. This assay may be useful in predicting human bone marrow toxicity of new agents before actual clinical trial because of the ability to study the survival of human colony-forming cells directly.

Evaluation of some anthracycline antibiotics in an in vivo model for studying drug-induced human leukemia cell differentiation.

Human acute promyelocytic leukemia cells (HL-60) were induced to undergo terminal differentiation by treatment in vivo with marcellomycin. This was accomplished by cloning HL-60 cells in 0.3% agar in diffusion chambers, which were subsequently implanted in the peritoneal cavities of mice. These animals were given injections i.v. with anthracycline antibiotics, and the chambers were transferred to a second recipient 24 hr later. After an additional 8 days, the chambers were removed, the cloning efficiency was determined, and colonies were scored for the presence of differentiated cells based on their ability to reduce nitro blue tetrazolium (NBT). Marcellomycin produced dose-dependent decreases in cloning efficiency and increases in the number of differentiated cells present in chambers. At all dose levels of marcellomycin tested, three types of colonies were observed; these were colonies consisting entirely of undifferentiated cells and approximately equal numbers of colonies consisting of solely differentiated cells and those with mixtures of both differentiated and undifferentiated cells. An 8-fold increase in colonies containing differentiated cells (both pure and mixed) was observed after a single injection of marcellomycin (10 mg/kg), a dose which reduced cloning efficiency by 40%. At that dosage level, aclacinomycin A also induced differentiation, while doxorubicin was ineffective, a finding consistent with the effects of these anthracyclines on HL-60 cells in suspension culture. In addition to the functional changes accompanying differentiation, commitment was characterized by a limitation in proliferative potential. Thus, the average size of uniform NBT-positive colonies was approximately 16 cells, and few clones of NBT-positive cells greater than 32 cells in number were observed; this contrasted with NBT-negative clones which contained up to 100 cells. This finding suggests that HL-60 cells undergo an average of four and a maximum of five divisions upon commitment to granulocytic differentiation. The in vivo system described may be useful in further evaluation of differentiation-inducing agents for therapeutic potential after an initial in vitro screen to identify active compounds.

Primary structure of human plasma membrane Ca(2+)-ATPase isoform 3.

The complete coding sequence of the human plasma membrane calcium ATPase (PMCA) isoform 3 was determined from overlapping genomic and cDNA clones. The cDNAs for the two major alternative splice variants 3a (3CII) and 3b (3CI) code for proteins of 1173 and 1220 amino-acid residues, respectively, which show 98% identity with the corresponding rat isoforms. On a multiple human tissue Northern blot, a major PMCA3 transcript of about 7 kb was detected exclusively in the brain, demonstrating the highly restricted pattern of expression of this isoform to human neuronal tissues. With the elucidation of the human PMCA3 primary structure, complete sequence information is now available for the entire family of human PMCA isoforms.