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Biomedical subjects

P B Hesseling

Publications and source records attributed to P B Hesseling.

At least 19 recordsLinked to original sources
PubMed2006

Improved outcome in South African children of mixed ethnicity treated for all.

A historical cohort study with an analytical component was conducted to determine whether risk-appropriate chemotherapy can improve survival in children of mixed ethnicity with ALL. Eighty-one coloured children treated for ALL in South Africa were divided into 2 groups: group A (n = 39), treated prior to 1992, and group B (n = 42), treated after 1992. A comparison was made of survival, treatment complications, and supportive measures. The two groups were comparable. The mean nadirs of the white cell count (p < .01), platelet count (p = .01), and hemoglobin value (p < .01) were significantly lower in group B. The survival rate of 37% in group A improved to 66% in group B (p = .025). The results show that a risk-adapted regimen increased survival in children of mixed ethnicity in the Western Cape, despite increased hematological toxicity and episodes of febrile neutropenia.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Isoniazid pharmacokinetics in children treated for respiratory tuberculosis.

AIMS: To define the pharmacokinetics of isoniazid (INH) in children with tuberculosis in relation to the N-acetyltransferase 2 (NAT2) genotype. METHODS: The first order elimination rate constant (k) and area under the concentration curve (AUC) were calculated in 64 children <13 years of age (median 3.8) with respiratory tuberculosis from INH concentrations determined 2-5 hours after a 10 mg/kg INH dose. The NAT2 genotype was determined; 25 children were classified as homozygous slow (SS), 24 as heterozygous fast (FS), and 15 as homozygous fast (FF) acetylators. RESULTS: The mean (SD) k values of the genotypes differed significantly from one another: SS 0.254 (0.046), FS 0.513 (0.074), FF 0.653 (0.117). Within each genotype a median regression of k on age showed a significant decrease in k with age. The mean (SD) INH concentrations (mg/l) two hours after INH administration were SS 8.599 (1.974), FS 5.131 (1.864), and FF 3.938 (1.754). A within genotype regression of 2-hour INH concentrations on age showed a significant increase with age. A within genotype regression of 3-hour, 4-hour, and 5-hour concentrations on age also showed a significant increase with age in each instance. In ethnically similar adults, mean (SD) 2-hour INH concentrations (mg/l) for each genotype were significantly higher than the children's: SS 10.942 (1.740), FS 8.702 (1.841), and FF 6.031 (1.431). CONCLUSIONS: Younger children eliminate INH faster than older children and, as a group, faster than adults, and require a higher mg/kg body weight INH dose to achieve serum concentrations comparable to adults.

Adolescent↗
PubMed2004

Incidence of acute lymphoblastic leukaemia in white and coloured children in the Western Cape.

UNLABELLED: Objectives. To record the age-specific incidence rate (ASIR) for diagnosed acute lymphoblastic leukaemia (ALL) in coloured and white children aged 0 - 12 years in the Western Cape (WC). DESIGN: A retrospective population-based study using the 1991 population census to calculate the mean annual childhood population and the ASIR for ALL in the 0 - 4, 5 - 9 and 10 - 12-year age groups in rural and Cape Town metropolitan areas for the period 1983 - 1999. Odds ratios were calculated using EpiInfo 2000. SETTING: Registry records of the paediatric cancer units at Tygerberg and Red Cross War Memorial Children's hospitals where all children with ALL in the WC were initially treated. SUBJECTS: All white and coloured children aged 0 - 12 years diagnosed as having ALL from 1983 - 1999. OUTCOME MEASURES: The ASIR by age and ethnic group in rural and metropolitan patients in the WC. RESULTS: The estimated annual childhood population in 1991 was 709 151 with 80.4% coloured and 19.6% white children, of whom 60% were resident in the Cape Town metropolitan area and 40% in the rural area of the WC. Of 246 children with ALL diagnosed in the period 1983 - 1999, 144 were male and 102 female. The ASIR in coloured children aged 0 - 4 years was 17.1/10(6) in the rural and 30.5/10(6) in the metropolitan area, compared with 55.7/10(6) and 56.2/10(6) respectively in white children. In the 5 - 9-year age group the ASIR in coloured children was 10.0/10(6) in the rural and 16.6/10(6) in the metropolitan area compared with 27.6/10(6) and 26.7/10(6) respectively in white children. The 10 - 12-year age group had comparable incidence rates in both populations and geographical areas. Only one case occurred within a 20 km radius of the Koeberg nuclear reactor. CONCLUSIONS: White children have an ASIR for ALL comparable to rates of diagnosis in the USA, while only half as many coloured children aged 0 - 9 years were diagnosed in both the rural and metropolitan areas. This contrast may indicate significant underdiagnosis of ALL in coloured children over the period in question. The change in health policy since 1994, which has improved access to primary health care, may improve the rate of diagnosis among coloured and black children.

Adolescent↗
PubMed2003

Long term survival of children with Burkitt lymphoma in Malawi after cyclophosphamide monotherapy.

BACKGROUND: Between 1991 and 1997, limited funding at times restricted available treatment for children with Burkitt lymphoma (BL) to cyclophosphamide (CPM) monotherapy at Lilongwe Central Hospital, Malawi. Our objective was to assess long-term survival in Malawian children with Burkitt lymphoma (BL) who had received one or more treatments with intravenous CPM at 40 mg/kg/dose at 14-day intervals. PROCEDURE AND RESULTS: The study population consisted of 92 children in whom BL had been confirmed on fine needle aspirates (FNA), a home address had been documented on discharge from hospital, and the treatment records could be verified. Only the clinical site(s) of disease had been recorded. The M:F ratio was 1.4 and median age 8 years. A clinical officer on motorcycle attempted to locate the given addresses and interview parents or other sources. In 19 patients, the address was incorrect. Of 73 evaluable patients, 40 children are alive at a mean follow-up time of 59 (range: 29-104) months. The survival rate was 63.5% in 52 children with BL of the head only, and 33.3% in 21 children with primary disease involving the abdomen or other sites. Survivors had received a median number of 6 (range: 1-12), non-survivors 4 (range: 1-12), and untracable children 3 (range: 1-11) courses of CPM. CONCLUSIONS: We confirmed that CPM could cure children with facial and abdominal BL. The unavoidable bias in the selection of patients and the variable amount of CPM given, precludes accurate survival estimates. A prospective study with proper staging, assessment of FNA, marrow and cerebrospinal fluid with modern techniques, a standard treatment protocol, and adequate follow-up will better define the current therapeutic value of CPM monotherapy. CPM can be purchased at about 3 US dollars per 500 mg.

Adolescent↗
PubMed2003

Haemophilia patients aged 0-18 years in the Western Cape.

OBJECTIVES: To record the number of haemophilicas aged 0-18 years in the Western Cape (WC), what event led to the diagnosis, the level of clotting factor, treatment, functional status of their joints and impact of the disease on the family. DESIGN: A prospective study of patients registered with the South African National Haemophilia Registry and new patients, utilising the patients' paediatricians, hospital records, patient and guardian interviews, physical examination and provincial nurse haemophilia co-ordinators. SETTING: Haemophilia care centres at the three WC academic hospitals, regional hospitals and homes of patients. Two elective medical students, MHH and JJH, collected the information. SUBJECTS: All boys with confirmed haemophilia A or B in the WC. OUTCOME MEASURES: Events that led to diagnosis, degree of haemophilia, use of clotting factor, functional status, and effect on family. RESULTS: Of 78 patients (59 haemophilia A, 19 haemophilia B) identified, 49 could be studied. Forty-three per cent had severe, 29% moderate and 22% mild disease (6% unknown). Family history was present in 49%, but led to diagnosis in only 12%. The most common first symptoms were subcutaneous and mucosal bleeding. Delay in diagnosis varied from 0 to 9 months. Twenty-nine per cent of guardians were suspected of child abuse. RSA produced clotting factor was used 'on demand' in 73% of patients, for periodic prophylaxis in 20% and as continuous prophylaxis in 7%. Joints were functionally restricted in 43% of patients. The majority of guardians (59%) said the disease had a major impact on the family. CONCLUSIONS: The diagnosis of haemophilia in children with a positive family history was often delayed. Haemophilia causes significant morbidity in our patients and their families.

Adolescent↗
PubMed2001

Infants exposed to alcohol prenatally: outcome at 3 and 7 months of age.

To investigate early recognition of the consequences of alcohol exposure in utero, we studied 79 infants at the ages of 3 and 7 months. Twenty-nine of them were exposed to varying levels of maternal alcohol intake and 50 had no exposure and formed a control group. Special attention was paid to fetal alcohol syndrome-related facial features, neurological development and behavioural performance of the infants. To monitor facial features, pictures were taken at 3 and 7 months of age. Significant differences in facial features were found between the alcohol-exposed and non-exposed children at 3 months only. An age-adequate neurological examination showed no significant difference at 3 months but a significant difference at 7 months of age between the alcohol-exposed infants and the controls. Mothers reported more misbehaviour in the exposed than in the non-exposed group. These results indicate that it is possible to recognise alcohol-related defects within the 1st year of life thus allowing early intervention.

Alcohol Drinking↗
PubMed2000

Viral isolates during febrile neutropaenia in children with cancer.

We prospectively studied South African children with cancer for viral isolates during episodes of febrile neutropaenia. Viruses were found in seven (31.8 per cent) and bacteria in five (22.7 per cent) of 22 episodes. The most common isolate was the herpes simplex virus and the most common source was from nasopharyngeal aspirates. There was no dual detection of viral and bacterial isolates. This study emphasizes the important contribution of viruses to febrile neutropaenia.

Adolescent↗
PubMed2000

High-dose intense chemotherapy in South African children with B-cell lymphoma: morbidity, supportive measures, and outcome.

BACKGROUND: Twenty-five percent of South African children aged 6-71 months are undernourished and have stunted growth. The tolerance and efficacy of short, high-dose intense chemotherapy for B-cell lymphomas in such a population were unknown. PROCEDURE: Nineteen consecutive children diagnosed with B-cell lymphoma after 1993 at Tygerberg Hospital (TBH) in the Republic of South Africa (RSA) were treated according to the LMB-89 protocol. RESULTS: Among the 19 children treated according to the LMB-89 protocol, there were 3 children in group A (completely resected St. Jude stage I and abdominal stage II), 14 in group B (nonresected stage I, nonabdominal stage II, all stage III, stage IV with bone marrow involvement but <70% Burkitt cells and without CNS involvement) and 2 in group C (patients with >70% Burkitt cells in bone marrow and/or CNS involvement). Overall survival for these children was 79% (median follow-up 53.5 months,range 20-70 months) compared to 25% (median follow-up 131 months, range 71-173months) for 24 children who had been treated with COM+/-P prior to 1993 (P = 0.002). Toxicity was noteworthy in the children treated with LMB-89. They had a mean of 2.6 episodes of febrile neutropenia and 1.9 episodes of stomatitis per patient and required intensive support, but there were no toxic deaths. CONCLUSIONS: A major step forward was achieved for South African children with B-cell lymphoma. Despite a high prevalence of malnutrition and endemic infections in the RSA, the implementation of the LMB-89 protocol significantly improved survival with manageable morbidity. Our findings suggest that treatment centres that cannot measure methotrexate (MTX) serum levels should not exceed 3.0 g/m(2) of MTX. If supportive care facilities are limited, consideration should be given to reducing the doses of cyclophosphamide and of doxorubicin in the treatment schedules.

Antineoplastic Agents↗
PubMed1999

Neuroblastoma in southern Africa: epidemiological features, prognostic factors and outcome.

We retrospectively analysed the epidemiological features and the importance of biochemical, histological and genetic parameters in predicting survival in 14 Namibian and 34 South African children treated for neuroblastoma (NB) from 1983 to 1997. Curative treatment consisted mainly of total (13%) or partial (44%) resection after chemotherapy (cyclophosphamide and doxorubicin x6 courses or carboplatin, etoposide, epirubicin and cyclophosphamide x6 courses). Localized radiotherapy with curative intent was given to 33% of patients. The male:female ratio was 0.9. The median age was 18 months (range 1-116) and was comparable in white, black and mixed ethnic patients. Primary disease was located in the abdomen (75%), thorax (15%), pelvis (5%) or elsewhere (5%). Evans stage distribution was: stage I, 2%; stage II, 19%; stage III, 21%; stage IV, 50%; and stage IVS, 8%. Stage III/IV disease was more common in black than in white children (p = 0.0001). Urinary vanillyl mandelic acid was elevated in 63% of those tested. Survival after 5-163 months' follow-up was 90% for stages I and II combined (median 2983, range 798-4661 days), 51% for stage III (median 367, range 61-5001 days), 6% for stage IV (median 227, range 20-4379 days) and 50% for stage IVS (median 532, range 54-1543 days). All seven children with para-spinal tumours survived. Individual factors associated with significantly poorer survival were elevated serum lactate dehydrogenase (p < 0.001), Joshi histological risk categorization adapted for age (p = 0.039), n-myc amplification (p = 0.006) and diploidy or tetraploidy (p = 0.006). All seven children with serum ferritin exceeding 149 ng/ml at the time of diagnosis died and survival was 33% in children with 1p deletion and 67% in those without, but the numbers were too small to achieve significance. These findings confirm the benefit of simple biochemical tests and histology in identifying those who are likely to respond favourably to conventional chemotherapy and surgery. Supportive genetic tests on formalin-fixed paraffin-embedded tumour tissue contributed to predicting outcome in 21 patients.

Abdominal Neoplasms↗
PubMed1999

Experience with high dose dexamethasone in the treatment of chronic symptomatic immune thrombocytopaenia.

OBJECTIVE: To evaluate the efficacy of high dose dexamethasone (HDD) as treatment for symptomatic chronic immune thrombocytopaenia (ITP). DESIGN: A non-randomised intervention study with final evaluation one year after treatment, comparing findings before and after intervention. SETTING: Tygerberg University Hospital, South Africa. PARTICIPANTS: A consecutive sample of six children with chronic (duration more than six months) ITP. The diagnosis of ITP was based on a platelet count of < 100 x 10(9)/1 together with appropriate clinical, laboratory and bone marrow findings. INTERVENTIONS: All children treated with dexamethasone 0.5 mg/kg/day intravenously for four days every 28 days for a total of six cycles. MAIN OUTCOME MEASURES: A rise in platelet count maintained for a least one year associated with the disappearance of symptoms due to thrombocytopaenia. RESULTS: Treatment was easy to administer and well tolerated with transient side effects in only two children. Three patients had a rise in platelet count of > 50 x 10(9)/1 during treatment and three had platelet counts of > 30 x 10(9)/1 after completion of therapy but only one at one month and one at six months after completion of the six courses respectively. None of the patients showed a sustained rise in platelet count during and after HDD treatment. CONCLUSION: HDD did not cause a significant sustained rise in the platelet count in children with chronic symptomatic ITP. If high dose prednisone and IVIG fail, a splenectomy should be considered in children over five years of age.

Anti-Inflammatory Agents↗
PubMed1998

Skeletal tuberculosis: dactylitis and involvement of the skull.

A re-emergence of tuberculosis (TB) is occurring world wide in both developed and developing countries. The clinical picture caused by infection with M. tuberculosis may simulate many other disease entities and may result in unnecessary investigations with a delay in diagnosis and treatment. Skeletal TB tends to be isolated to one anatomical site. We report a 6-year-old boy with disseminated skeletal TB with dactylitis resembling sickle cell anaemia and lytic lesions similar to those which are often seen in neuroblastoma, Langerhans' cell histiocytosis and leukaemia. The clinician should be aware that TB can mimic almost any disease and recognise the radiographic appearances of skeletal tuberculous lesions.

Arthritis, Infectious↗
PubMed1998

Bone mineral density in long-term survivors of childhood cancer.

Bone mineral density (BMD) of the lumbar spine was measured in 97 long-term survivors of childhood cancer 5-23 years after diagnosis using dual-energy X-ray absorptiometry (DXA). They had been treated for acute leukemia (n = 22), brain tumors (n = 16), lymphomas (n = 16), Wilms' tumor (n = 10), neuroblastoma (n = 7) and other cancers (n = 26). The correlations between BMD and the Z-scores for weight for height, height for age and weight for age at diagnosis and follow-up were evaluated with stepwise multiple regression. Correlations with cumulative corticosteroid and radiation dose were examined with Spearman's correlation coefficient. The number of nature of fractures were noted. A BMD Z-score of below -2 was present in 13 and a BMD Z-score of -1 to -2 in 31 children. In total, a low BMD was observed in 45% of children. Height for age at follow-up correlated significantly with BMD Z-score. Increasing doses of cranial irradiation (18-54 Gy) were associated with lower BMD (p = 0.001, Spearman). This was true also for 22 children with acute lymphoblastic leukemia (ALL) who had received 18-24 Gy cranial irradiation (p = 0.04, Spearman). Fractures occurred in 14 children following trauma. The difference in BMD Z-scores of children with and without fractures did not achieve statistical significance although the majority of the children with fractures had low BMD Z-scores. The significant inverse correlation between height for age at follow-up and BMD must be interpreted with the realization that DXA is not a volumetric measurement of BMD and that short stature is associated with a smaller skeletal mass.

Absorptiometry, Photon↗
PubMed1997

Hepatocellular carcinoma in children.

Hepatocellular carcinoma (HCC) occurs more frequently in subsaharan Africa and the Orient than in other geographical regions, but remains an uncommon tumour of childhood. We review six children with HCC (mean age 13 years) treated by the paediatric oncology unit at Tygerberg Hospital in Cape Town over an 8-year period (1983 - 1990). Patients presented with epigastric and right upper quadrant discomfort and hepatomegaly. The hepatitis B serum antigen (HbsAg) was positive in three patients; serum alpha-fetoprotein (AFP) levels were markedly elevated in three (range 100 - 453,000 microg/l). Age and sex did not differ significantly and all patients initially had irresectable advanced-stage tumours. Morphologically, three were highly malignant adult-type pleomorphic HCCs, two were differentiated tumours, and one a fibrolamellar subtype. The mean 2-year survival was 33% and the 5-year survival 16.6%. The biological behaviour and response to treatment of the tumours varied. Whereas three patients had a poor response to therapy, two with poorly-differentiated tumours, negative HbsAg, and normal serum AFP levels responded to doxorubicin/cisplatinum chemotherapy. This facilitated radical surgical excision. One patient of this group has survived for more than 75 months following surgical resection and remains well. HCC remains an uncommon tumour of childhood with a high mortality. Aggressive chemotherapeutic regimes in combination with surgical resection may lead to improved survival in some cases. Prevention of hepatitis B remains a priority.

Adolescent↗
PubMed1997

Hodgkin's disease in children in southern Africa: epidemiological characteristics, morbidity and long-term outcome.

We reviewed 39 children < 15 years of age treated for Hodgkin's disease (HD) from 1973 to 1996. There were seven black, 12 white and 20 coloured children (of mixed ethnic origin). The M:F ratio was 2.9:1 and the median ages 147, 124 and 119 months in white, coloured and black children, respectively. Coloured and black children came mainly from a poor socio-economic background. Cervical lymphadenopathy was present in 74% and systemic symptoms in 51% of cases. Five per cent had clinical stage I, 41% stage II, 28% stage III and 26% stage IV disease. Two children underwent a staging splenectomy. The majority of white children presented with stages I and II and the majority of black and coloured children with stages III and IV HD. Nodular sclerosing (59%), mixed cellularity (40%) and lymphocyte-depleted (43%) were the most common histological subtypes in white, coloured and black children, respectively. Epidemiologically, white children fitted the criteria for HD type I and coloured and black children the criteria for HD type III. Nineteen children were treated with ChlVPP (chlorambucil, vinblastine, prednisone, procarbazine) and 20 with MOPP (mustine, Oncovin, procarbazine, prednisone) and/or ABVD (Adriamycin, bleomycin, vinblastine, DTIC) with involved field radiotherapy to bulky mediastinal disease. The projected 10-year survival after ChlVPP or MOPP/ABVD therapy was similar at 52%. In stages I and II, HD projected survival at 5 and 10 years was 85%, and in stages III and IV it was 82% at 5 and 48% at 10 years. The relapse rate was 47% in stage II, 45% in stage III and 44% in stage IV. Tuberculosis was suspected and treated in five children at the time of, and in seven children (three confirmed) subsequent to, the diagnosis of HD. Varicella developed in six and herpes zoster in five children. Five treatment-related deaths were due to septicaemia following splenectomy (two), marrow failure, corpulmonale and secondary leukaemia.

Adolescent↗
PubMed1997

An analysis of prognostic variables in acute lymphocytic leukaemia in a heterogenous South African population.

The records of all 96 children below the age of 15 years diagnosed with acute lymphoblastic leukaemia at Tygerberg Hospital in the Republic of South Africa between 1983 and 1995 were reviewed to determine risk factors which may predict poor outcome. Age < 2 and > 8 years, and white cell count > 20 x 10(9)/l at diagnosis were significant predictors of poor outcome. Sex, FAB classification, immunophenotype, hepatomegaly, splenomegaly, BFM risk score, and the presence of mediastinal glands did not predict outcome. The presence of the established risk factors could not adequately explain the difference in 5-year event-free survival in the three ethnic groups which was 67 per cent in white, 17 per cent in black, and 38 per cent in children of mixed ethnic origin. In an attempt to improve survival in black children, our stratification of risk groups will in future be based on factors that include ethnicity, age and WCC > or = 20 x 10(9)/l at diagnosis. Pediatric oncology services in developing countries should adapt therapy to the risk factors of their local populations.

Adolescent↗