Research Articles (Paediatric Surgery)

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African multi-site 2-year neuropsychological study of school-age children perinatally infected, exposed, and unexposed to human immunodeficiency virus
(Oxford University Press, 2020-10) Boivin, Michael J.; Chernoff, Miriam; Fairlie, Lee; Laughton, Barbara; Zimmer, Bonnie; Joyce, Celeste; Barlow-Mosha, Linda; Bwakura-Dangarembizi, Mutsawashe; Vhembo, Tichaona; Ratswana, Mmule; Kamthunzi, Portia; McCarthy, Katie; Familiar-Lopez, Itziar; Jean-Philippe, Patrick; Coetzee, Joan; Abrahams, Nasreen; Gous, Hermien; Violari, Avy; Cotton, Mark F.; Palumbo, Paul E.
Background Children living with human immunodeficiency virus (HIV) are at neuropsychological risk for cognitive and motor dysfunction. However, few prospective, multi-site studies have evaluated neuropsychological outcomes longitudinally among perinatally infected African children who received early antiretroviral treatment (ART). Methods We enrolled 611 children aged 5 to 11 years at 6 sites (South Africa [3], Zimbabwe, Malawi, Uganda). Of these, there were 246 children living with HIV (HIV+) who were initiated on ART before 3 years of age in a prior clinical trial comparing nevirapine to lopinavir/ritonavir (International Maternal Pediatric Adolescent Acquired Immunodeficiency Syndrome Clinical Trials [IMPAACT] P1060); 183 age-matched, exposed but uninfected (HEU) children; and 182 unexposed and uninfected (HUU) children. They were compared across 3 assessment time points (Weeks 0, 48, and 96) on cognitive ability (Kaufman Assessment Battery for Children, second edition [KABC-II]), attention/impulsivity (Tests of Variables of Attention [TOVA]), motor proficiency (Bruininks-Oseretsky Test, second edition [BOT-2]), and on the Behavior Rating Inventory of Executive Function (BRIEF). The cohorts were compared using linear mixed models, adjusting for site, child’s age and sex, and selected personal/family control variables. Results The HIV+ cohort performed significantly worse than the HEU and HUU cohorts for all KABC-II, TOVA, and BOT-2 performance outcomes across all 3 time points (P values < .001). The HUU and HEU cohorts were comparable. For the KABC-II planning/reasoning subtests, the HIV+ children showed less improvement over time than the HUU and HEU groups. The groups did not differ significantly on the BRIEF. Conclusions Despite initiation of ART in early childhood and good viral suppression at the time of enrollment, the HIV+ group had poorer neuropsychological performance over time, with the gap progressively worsening in planning/reasoning. This can be debilitating for self-management in adolescence.
Application of irradiation as an immunosuppressive agent
(Health & Medical Publishing Group, 1987-04) Du Toit, D. F.; Heydenrych, J. J.
ENGLISH ABSTRACT: The concept of using total lymphoid irradiation (TLI) for immunosuppression is based on the prolonged and profound immunosuppressive effects observed after TLI in the treatment of patients with Hodgkin's disease. Pre-operative TLI of allograft recipients has been shown to be immunosuppressive when used alone or together with chemical immunosuppression. Fractionated TLI and allogeneic bone marrow injections produce stable chimaerism without graft-versus-host disease in inbred mice, rats and mongrel dogs and transplantation tolerance of skin and cardiac grafts in rats. In the primate, TLI and bone marrow injection result in significant tolerance of liver and kidney allografts. In 1959 sublethal whole-body irradiation was used as an immunosuppressive agent for the first successful related-human renal allografts between non-identical twins. Despite the dangers of myelosuppression, recent clinical experience has shown TLI to be a useful immunosuppressant for organ transplantation, allowing decreased dosage of concomitant immunosuppressive drugs.
Chasing the ubiquitous RET proto-oncogene in South African MEN2 families - Implications for the surgeon
(2010) Moore, S. W.; Zaahl, M. G.
The RET proto-oncogene (REarranged during Transfection; RET) plays an important role in the causation of many thyroid tumours. Germline RET proto-oncogene missense mutations have been clearly linked to medullary thyroid carcinoma (MTC) and the inherited cancer syndrome multiple endocrine neoplasia type 2 (MEN2A, MEN2B). Methods. We investigated a cohort of MEN2-related patients referred to Tygerberg Hospital, W Cape (2003 2009). The study cohort was divided into three groups based on pathology (viz. MEN/MTC, phaeochromocytoma, and a miscellaneous group of MEN pathologies). Families with identified high-risk factors were recalled. Serum calcitonin levels were monitored where indicated. DNA was extracted from whole blood by standard techniques and polymerase chain reaction (PCR) products screened for RET gene variations by heteroduplex singlestrand duplication techniques (heteroduplex single-strand conformation polymorphism analysis) being validated with automated sequencing techniques showing conformational variants in acrylamide gel. Results. We screened 40 persons, male/female ratio 1:1.5. Three ethnic groups were represented (white (12), black (11) and mixed race (17)). Nine were index MTC cases, 5 phaeochromocytoma, 3 Hirschsprung's diseaseMEN associations and 2 miscellaneous (1 neuroblastoma, 1 intestinal neuronal dysplasia), while 1 fell into the MEN2B category. The remaining 19 were unaffected relatives screened for carrier status, among whom a familial recurrence was observed in 7. On genetic testing, an RET point mutation at the highrisk 634 cysteine allele was identified in 11 cases. A further cysteine radical mutation at the 620 position was related to MEN2 in 3 families plus 1 other family referred from elsewhere. Other less-recognised gene variations were detected throughout the RET gene in 70% of cases and included the 691 position on codon 11 (11 cases); the 432 position (4 cases, 1 homozygous) intronic mutations on exon 4 (1 case); and an IVS19-37G/C and a D1017N variation in exon 19 in 2 MEN families. Fifteen MTC patients have had thyroidectomies, of which 2 were prophylactic (C-cell hyperplasia; early occult MTC). A further 3 are awaiting prophylactic surgery. Conclusion. RET gene mutation carries a risk of MEN2 and MTC in all ethnic groups in South Africa. Prophylactic surgery may prevent MTC, so genetic screening is important to identify and treat high-risk patients.
Haemoperitoneum and associated torsion of the testicle in the newborn
(Health & Medical Publishing Group, 1974) Heydenrych, J. J.
A case of haemoperitoneum and concomitant torsion of the testes is reported - the first case in the English literature. The management of the case and the aetiological factors responsible for haemoperitoneum and torsion of the testes in the newborn are discussed. The role of vitamin K in the prevention of a possible subcapsular haematoma is discussed. At laparotomy approximately 80 ml of blood were aspirated from the peritoneal cavity. On the anterolateral aspect of the right lobe of the liver a 4 cm long tear (capsule and parenchyma) was discovered. Many abnormalities predispose towards torsion of the testis, the commonest of which is a horizontal position of the testes, but other factors which may contribute to the condition include a long mesorchium, broad flat chord and an unduly large tunica vaginalis. There are doubts whether torsion can occur in an anatomically normal testis. Although trauma is usually blamed for torsion of the testis, torsion can occur during sleep. Although haemoperitoneum in the newborn is always due to birth trauma, abnormalities in the blood clotting factors are important. There is a correlation between haemoperitoneum and breech extraction of the baby. In the case under discussion, trauma was probably produced by hyperextension, severe flexion or compression of the soft tissue structures against a hard bony prominence of the pelvic bones.
How to manage obsessive-compulsive disorder (OCD) under COVID-19 : a clinician's guide from the International College of Obsessive Compulsive Spectrum Disorders (ICOCS) and the Obsessive-Compulsive and Related Disorders Research Network (OCRN) of the European College of Neuropsychopharmacology
(Elsevier Inc., 2020-07) Fineberg, N. A.; Van Ameringen, M.; Drummond, L.; Hollander, E.; Stein, D. J.; Geller, D.; Walitza, S.; Pallanti, S.; Pellegrini, L.; Zohar, J.; Rodriguez, C. I.; Menchon, J. M.; Morgado, P.; Mpavaenda, D.; Fontenelle, L. F.; Feusner, J. D.; Grassi, G.; Lochner, C.; Veltman, D. J.; Sireau, N.; Carmi, L.; Adam, D.; Nicolini, H.; Dell'Osso, B.
The rapid advance of the coronavirus COVID-19 pandemic has significantly increased mortality but also has demonstrated considerable potential to negatively impact mental health, including in the young [1,2]. From a public mental health perspective, guidelines for responding to mass trauma and disaster emphasize the importance of focusing on resilience. In the immediate and ongoing response, consensus guidelines emphasize the importance of interventions that maintain calm, build community, and sustain hope [3,4].
Lessons from the hepatoblastoma- familial polyposis connection
(Health and Medical Publishing Group (HMPG), 2012-11) Moore, S. W.; Tshifularo, N.; Grobbelaar, J. J.
Background. Approximately one-third of hepatoblastoma (HB) patients have associated congenital abnormalities, but familial recurrence is rare, except in association with familial adenomatous polyposis (FAP). This correlation may be missed if not actively sought, with implications for long-term outcome and management. Methods. We retrospectively investigated 3 families with an HB-familial polyposis connection, from a cohort of 113 FAP families (1989 - 2010). Data were analysed to assess clinical problem, treatment, complications and management. Long-term morbidity and functional outcome were analysed to identify management difficulties. Results. Three FAP families (2.65%) had an HB association. In one case, undiagnosed FAP at the time of HB diagnosis was only detected 5 years later, when the mother presented with advanced colorectal carcinoma. A chromosome 5 APC gene mutation (exon 15 codon 793 C→T) was then identified. In a second case, a nonrelated boy presented with a stage 4 multifocal HB with lung metastases. Genetic studies identified an APC gene mutation (exon 6 codon 232 C→T). Further family investigation showed >20 related FAP patients. A third HB-FAP association was identified in a known FAP family early in the study, prior to the availability of genetic testing. Conclusion. Although a rare association, a family history of FAP in HB patients is an important ‘hidden connection’. Germline variation may be outside the usual FAP gene site. Identifying families with unknown HB/FAP is important due to long-term management implications and follow-up.
Missed opportunities for retention in pre-ART care in Cape Town, South Africa
(Public Library of Science -- PLoS, 2014-05) Du Toit, Elizabeth; Van Schalkwyk, Cari; Dunbar, Rory; Jennings, Karen; Yang, Blia; Coetzee, David; Beyers, Nulda; Fox, Matthew
Background: Few studies have evaluated access to and retention in pre-ART care. Objectives: To evaluate the proportion of People Living With HIV (PLWH) in pre-ART and ART care and factors associated with retention in pre-ART and ART care from a community cohort. Methods: A cross sectional survey was conducted from February – April 2011. Self reported HIV positive, negative or participants of unknown status completed a questionnaire on their HIV testing history, access to pre-ART and retention in pre-ART and ART care. Results: 872 randomly selected adults who reported being HIV positive in the ZAMSTAR 2010 prevalence survey were included and revisited. 579 (66%) reconfirmed their positive status and were included in this analysis. 380 (66%) had initiated ART with 357 of these (94%) retained in ART care. 199 (34%) had never initiated ART of whom 186 (93%) accessed pre-ART care, and 86 (43%) were retained in pre-ART care. In a univariable analysis none of the factors analysed were significantly associated with retention in care in the pre-ART group. Due to the high retention in ART care, factors associated with retention in ART care, were not analysed further. Conclusion: Retention in ART care was high; however it was low in pre-ART care. The opportunity exists, if care is better integrated, to engage with clients in primary health care facilities to bring them back to, and retain them in, pre-ART care.
Paediatric blunt abdominal trauma : are we doing too many computed tomography scans?
(Medpharm Publications, 2013-02) Arnold, M.; Moore, S. W.
Blunt abdominal trauma in childhood contributes significantly to both morbidity and mortality. Selective non-operative management of blunt abdominal trauma in children depends on both diagnostic and clinical factors. Computed tomography (CT) scanning is widely used to facilitate better management. Increased availability of CT may, however, result in its overuse in the management of blunt abdominal trauma in children, which carries significant radiation exposure risks. Aim. To evaluate the use and value of CT scanning in the overall management and outcome of blunt abdominal trauma in children in the Tygerberg Academic Hospital trauma unit, Parow, Cape Town, South Africa, before and after improved access to CT as a result of installation of a new rapid CT scanner in the trauma management area (previously the scanner had been 4 floors away). Methods. Patients aged 0 - 13 years who were referred with blunt abdominal trauma due to vehicle-related accidents before the introduction of the new CT scanner (group 1, n=66, November 2003 - March 2009) were compared with those seen in the 1-year period after the scanner was installed (group 2, n=37, April 2009 - April 2010). Details of clinical presentation, imaging results and their influence on management were retrospectively reviewed. A follow-up group was evaluated after stricter criteria for abdominal CT scanning (viz. prior evaluation by paediatric surgical personnel) were introduced (group 3, n=14, November 2011 - May 2012) to evaluate the impact of this clinical screening on the rate of negative scans. Results. There were 66 patients in group 1 and 37 in group 2. An apparent increase in CT use with increased availability was accompanied by a marked increase in negative CT scans (38.9% compared with 6.2%; p<0.006). Despite a slightly higher prevalence of associated injuries in group 2, as well as a slightly longer length of hospital stay, there was a similar prevalence of intra-abdominal injuries detected in positive scans in the two groups. In addition, rates of small-bowel perforation in the two groups were similar. The rate of negative scans in group 3 was 46.2% (6/13), but all except one of these patients had a severe brain injury preventing adequate clinical evaluation of intra-abdominal injury. Conclusion. CT scanning for blunt abdominal trauma in children is essential in the presence of appropriate clinical indications. Ease of access probably increases availability, but the rate of negative scans may increase. Management guidelines should be in place to direct CT scanning to cases in which clinical examination and/or other modalities indicate a likelihood of intra-abdominal injury. The principle of ‘as low (radiation) dose as reasonably achievable’ (ALARA) should be adhered to because of the increased radiation exposure risks in children.
Problems related to cytomegalovirus infection and biliary atresia
(Health and Medical Publishing Group (HMPG), 2012-11) Zabiegaj-Zwick, C.; Nel, E. D.; Moore, S. W.
Background. Human cytomegalovirus (CMV) infection is related to biliary disease, being cholestatic in its own right. It has also been associated with intrahepatic bile duct destruction and duct paucity, indicating a possible role in the pathogenesis and progression of extrahepatic biliary atresia (BA). BA patients who are CMV-IgM-positive appear to have greater liver damage than uninfected patients, consequently affecting outcome. Methods. We reviewed the medical records of 74 patients diagnosed with hepatobiliary disease between 2000 and 2011, assessing clinical outcome and potential risk factors. Patients, categorised into those with and those without BA, were compared in terms of CMV infection. Results. The 74 patients included 39 (52%) BA and 35 non-BA patients; following the exclusion of patients due to insufficient data, 27 (69%) BA and 31 non-BA patients were reviewed. Twenty-one (78%) BA patients were CMV-positive (IgM/IgG), including 20 IgM-positive patients versus 8 in the non-BA group (p<0.01). Two (7.5%) CMV-IgM-positive BA infants were HIV-exposed versus 7 (35%) in the non-BA group (p<0.01). Long-term outcomes included 3 deaths in the non-HIV CMV-positive group and a higher rate of severe early liver damage, suggesting a poorer outcome in CMV affected patients. Conclusions. Our results suggest a correlation between CMV exposure/infection and BA which affects clinical outcome. HIV positivity does not preclude BA and should be investigated further.

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