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1.
AIDS Care ; 32(8): 965-969, 2020 08.
Article in English | MEDLINE | ID: mdl-32434383

ABSTRACT

Access to antiretroviral treatment (ART) in South Africa is suboptimal and erratic. For those on treatment, compliance remains a significant challenge. Interruptions to ART have negative implications for the individual and the epidemic. ART is therefore not a sustainable solution and there is an urgent need for a cure. As HIV cure research expands globally, the need to engage community members about cure is becoming a priority. It is vital that potential trial participants understand basic HIV cure research concepts. An online interactive educational tool was co-created with HIV stakeholders to engage and inform HIV research trial participants. The study was conducted with patients at the FAMCRU HIV clinic at Tygerberg Hospital in Cape Town, South Africa. The educational tool comprises two modules that provide information on HIV prevention, treatment and cure research. Participants completed a questionnaire before and after interacting with the programme. There was a significant increase in knowledge scores of participants demonstrated after using the tool. The interactive tool was successful in increasing participants' knowledge of HIV prevention, treatment and cure research.


Subject(s)
Audiovisual Aids , Biomedical Research/ethics , Clinical Trials as Topic/ethics , HIV Infections/psychology , Patient Education as Topic/methods , Patient Participation , HIV Infections/prevention & control , HIV Infections/therapy , Humans , Patient Selection/ethics , Research Subjects/psychology , South Africa
2.
Childs Nerv Syst ; 33(10): 1775-1784, 2017 Oct.
Article in English | MEDLINE | ID: mdl-29149382

ABSTRACT

Traumatic brain injury (TBI) is a major public health problem associated with high morbidity and mortality rates in children in both high- and low- and middle-income countries. Predicting outcome after pediatric TBI is challenging given the wide range of injury and non-injury-related factors which may have an impact. Some of these factors are relevant globally (like heterogeneity in patient and injury-related factors and research methodology) and others are more specific to local contexts (like sociodemographic and cultural factors). The assessment of rehabilitation outcomes post-TBI are similarly challenging given the various methodological limitations, disparities in access to rehabilitation, and limited awareness of deficits, which are encountered globally, as well as the lack of services in the local settings. In this article, we discuss these global and local challenges to outcome and rehabilitation assessment following pediatric TBI.


Subject(s)
Brain Injuries, Traumatic/rehabilitation , Brain Injuries, Traumatic/therapy , Pediatrics , Treatment Outcome , Animals , Humans
3.
Int J Obes (Lond) ; 38(2): 292-8, 2014 Feb.
Article in English | MEDLINE | ID: mdl-23736363

ABSTRACT

OBJECTIVE: To investigate if phentermine treatment induces phentermine abuse, psychological dependence (addiction) or phentermine drug craving in overweight, obese and weight loss maintenance patients. To investigate whether amphetamine-like withdrawal occurs after abrupt cessation of long-term phentermine treatment. DESIGN: Clinical intervention trial with interruption of phentermine treatment in long-term patients. SUBJECTS: 269 obese, overweight or formerly obese subjects (age: 20-88 years, BMI: 21-74 kg m(-2)) treated with phentermine long-term (LTP, N=117), 1.1-21.1 years, or short-term (ATP, N=152), 4-22 days, with phentermine doses of 18.75-112.5 (LTP) and 15-93.75 (ATP) mg per day. MEASUREMENTS: Module K of the Mini International Neuropsychiatric Interview modified for phentermine (MINI-SUD), Severity of Dependence Scale (SDS), 45-item Cocaine Craving Questionnaire-NOW (CCQ-NOW) modified for phentermine (PCQ-NOW), and Amphetamine Withdrawal Questionnaire (AWQ) modified for phentermine (PWQ). RESULTS: MINI-SUD interviews were negative for phentermine abuse or psychological dependence in all LTP patients. SDS examination scores were low for all LTP and ATP patients, indicating they were not psychologically dependent upon phentermine. PCQ-NOW scores were low for all LTP and ATP patients, indicating neither short-term nor long-term phentermine treatment had induced phentermine craving. Other than an increase in hunger or eating, amphetamine-like withdrawal symptoms did not occur upon abrupt phentermine cessation as measured by sequential PWQ scores. CONCLUSIONS: Phentermine abuse or psychological dependence (addiction) does not occur in patients treated with phentermine for obesity. Phentermine treatment does not induce phentermine drug craving, a hallmark sign of addiction. Amphetamine-like withdrawal does not occur upon abrupt treatment cessation even at doses much higher than commonly recommended and after treatment durations of up to 21 years.


Subject(s)
Appetite Depressants/administration & dosage , Obesity/drug therapy , Phentermine/administration & dosage , Weight Loss/drug effects , Adult , Aged , Aged, 80 and over , Appetite Depressants/adverse effects , Behavior, Addictive/chemically induced , Drug Administration Schedule , Female , Guideline Adherence , Humans , Male , Middle Aged , Phentermine/adverse effects , Substance-Related Disorders/etiology , Surveys and Questionnaires , Time Factors , United States , United States Food and Drug Administration
4.
Hum Reprod ; 29(2): 276-8, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24327539

ABSTRACT

In vitro maturation (IVM) of immature oocytes retrieved from surgically resected ovaries has been proposed as a method of fertility preservation in ovarian cancer patients undergoing definitive surgery. While there had been several reports of successful derivation of mature oocytes and or embryos, there have been no reports as yet of successful pregnancies. In this case report, we present a pregnancy and live birth from a young patient, with stage IIIC ovarian cancer, who had undergone fertility sparing surgery. The immature oocytes recovered after oophorectomy were fertilized after IVM. The embryos obtained were cryopreserved and later transferred to achieve a singleton healthy pregnancy leading to a live birth.


Subject(s)
Cryopreservation , Embryo Transfer , In Vitro Oocyte Maturation Techniques , Oocytes/cytology , Ovarian Neoplasms/complications , Ovarian Neoplasms/therapy , Ovariectomy , Female , Fertility Preservation , Humans , Infertility, Female/etiology , Infertility, Female/therapy , Ovary/surgery , Pregnancy , Pregnancy Complications , Pregnancy Outcome , Young Adult
5.
S Afr Med J ; 112(3): 209-213, 2022 03 02.
Article in English | MEDLINE | ID: mdl-35380522

ABSTRACT

This article highlights ethical issues that may arise in the relationship between curatorship applications and neuropsychology. In South Africa (SA), curatorship applications for the elderly diagnosed with dementia require substantiation from two medical professionals, one of whom should be a practising psychiatrist deemed competent to provide this. Concurrently, there is often a request for a psychologist to conduct a neuropsychological assessment and to produce a relevant report. The process may result in ethical issues at various stages of the assessment. The balance between protecting the patient's rights v. freedom of autonomy becomes a central issue. Psychiatrists and psychologists are cautioned to adhere to best practices throughout the assessment, maintaining a critical and reflective stance. The limitations of cognitive assessment as a predictor of functionality should be considered. Furthermore, neuropsychological training in SA differs across institutions, resulting in variable practitioner competency. 'Competency' itself is an ambiguous legal term that may be interpreted variably. This article outlines the definitions and requirements of the curatorship process, as well as the role and limitations of neuropsychology, with emphasis on the ethical dilemmas that may arise.


Subject(s)
Neuropsychology , Aged , Humans , Neuropsychological Tests , Neuropsychology/education , Neuropsychology/methods , South Africa
6.
Clin Oncol (R Coll Radiol) ; 34(4): e149-e159, 2022 04.
Article in English | MEDLINE | ID: mdl-34750056

ABSTRACT

AIMS: Image-defined risk factors (IDRFs) in neuroblastoma predict surgical complications and management outcomes. As there is a lack of data regarding the association of IDRFs with clinical and pathological factors, this study evaluated the prognostic value of IDRFs to predict neuroblastoma survival outcomes. MATERIALS AND METHODS: This was a retrospective study including 345 patients and reviewed diagnostic imaging for 20 IDRFs, pleural effusions and ascites. The IDRFs were grouped into five 'primary IDRFs' cohorts with vascular encasement, involvement of multiple body compartments, organ infiltration, airway obstruction and intraspinal extension. The association between clinical, histopathological and biological characteristics of neuroblastoma and management was evaluated. RESULTS: More patients without IDRFs had operations compared with patients with IDRFs, with a trend towards significance (64.4% versus 35.6%, P = 0.082). Patients with multiple compartment tumour involvement (P = 0.003) and organ infiltration (P < 0.001) had a higher risk of surgical complications. The 5-year overall survival of the group with more than one IDRF was 0.0% and those with pleural effusions or ascites 6.7%, associated with the worst outcome (P = 0.005). The total number of IDRFs was not predictive of the metastatic remission rate (P = 0.585) or overall survival (P = 0.142), with no conclusive association found between IDRF groups and clinical or biological markers. CONCLUSIONS: Patients with more than one IDRF had the shortest survival time, whereas those with pleural effusions and ascites at diagnosis had a poor outcome. Standardised reporting of IDRFs is crucial for predicting prognosis.


Subject(s)
Neuroblastoma , Pleural Effusion , Ascites/etiology , Ascites/pathology , Biomarkers, Tumor , Humans , Neoplasm Staging , Neuroblastoma/diagnostic imaging , Neuroblastoma/surgery , Pleural Effusion/pathology , Prognosis , Retrospective Studies , Risk Factors , South Africa/epidemiology , Tomography, X-Ray Computed
7.
Clin Oncol (R Coll Radiol) ; 33(8): 517-526, 2021 08.
Article in English | MEDLINE | ID: mdl-33781675

ABSTRACT

AIMS: Diagnostic and post-induction 123I-meta-iodobenzylguanidine (123I-mIBG) scans have prognostic significance in the treatment of neuroblastoma, but data from low- and middle-income countries are limited due to resource constraints. The aim of this study was to determine the association between neuroblastoma-associated tumour markers (lactate dehydrogenase [LDH], ferritin and MYCN amplification) and 123I-mIBG scans (modified Curie scores and metastatic disease patterns) in predicting complete metastatic response rates (mCR) and overall survival. MATERIALS AND METHODS: Two hundred and ninety patients diagnosed with high-risk neuroblastoma in South Africa between January 2000 and May 2018 and a subanalysis of 78 patients with diagnostic 123I-mIBG scans were included. Data collection included LDH, ferritin and MYCN amplification at diagnosis. Two nuclear physicians independently determined the modified Curie scores and pattern of distribution for each diagnostic and post-induction 123I-mIBG scans with high inter-rater agreement (r = 0.952) and reliability (K = 0.805). The cut-off values for the diagnostic and post-induction modified Curie scores of ≥7.0 (P = 0.026) and 3 (P = 0.009), respectively, were generated. The association between the tumour markers and the modified Curie score of the 123I-mIBG scans was determined using post-induction mCR and 2-year overall survival. RESULTS: Diagnostic LDH (P < 0.001), ferritin (P < 0.001) and the diagnostic modified Curie scores (P = 0.019) significantly predicted mCR. Only ferritin correlated with diagnostic modified Curie scores (P = 0.003) but had a low correlation coefficient of 0.353. On multivariable analysis, the only significant covariate for 2-year overall survival at diagnosis was LDH <750 U/l (P = 0.024). A post-induction chemotherapy modified Curie score ≤3.0 had a 2-year overall survival of 46.2% compared with 30.8% for a score >3.0 (P = 0.484). CONCLUSION: LDH, ferritin and the diagnostic 123I-mIBG scans significantly predicted mCR, but only LDH predicted 2-year overall survival. Ferritin and the modified Curie scores correlated with each other. MYCN amplification neither correlated with any aspect of the 123I-mIBG scans nor significantly predicted mCR or 2-year overall survival. LDH and ferritin are therefore appropriate neuroblastoma tumour markers to be used in low- and middle-income countries with limited or no access to mIBG scans and/or MYCN amplification studies.


Subject(s)
3-Iodobenzylguanidine , Neuroblastoma , Biomarkers, Tumor/genetics , Child , Humans , Neuroblastoma/diagnostic imaging , Neuroblastoma/genetics , Radionuclide Imaging , Reproducibility of Results
8.
J Exp Biol ; 213(2): 339-46, 2010 Jan 15.
Article in English | MEDLINE | ID: mdl-20038669

ABSTRACT

Sticky viscous prey capture threads form the spiral elements of spider orb-webs and are responsible for retaining insects that strike a web. These threads are formed of regularly spaced aqueous droplets that surround a pair of supporting axial fibers. When a thread is flattened on a microscope slide a small, opaque granule can usually be seen within each droplet. These granules have been thought to be the glycoprotein glue that imparts thread adhesion. Both independent contrast and standard regressions showed that granule size is directly related to droplet volume and indicated that granule volume is about 15% of droplet volume. We attempted to find support for the hypothesized adhesive role of granules by establishing an association between the contact surface area and volume of these granules and the stickiness of the viscous threads of 16 species in the context of a six-variable model that describes thread stickiness. However, we found that granule size made either an insignificant or a small negative contribution to thread stickiness. Consequently, we hypothesize that granules serve to anchor larger, surrounding layers of transparent glycoprotein glue to the axial fibers of the thread, thereby equipping droplets to resist slippage on the axial fibers as these droplets generate adhesion, elongate under a load, and transfer force to the axial fibers.


Subject(s)
Silk/physiology , Spiders/physiology , Adhesiveness , Animals , Microscopy, Electron, Scanning , Phylogeny , Predatory Behavior , Spiders/genetics
9.
Science ; 222(4630): 1341-3, 1983 Dec 23.
Article in English | MEDLINE | ID: mdl-6318311

ABSTRACT

Steroid hormones, when complexed to their receptors, recognize and bind specific DNA sequences and subsequently induce increased levels of transcription. The mechanisms of steroid hormone action were analyzed by constructing chimeric DNA molecules from portions of mouse mammary tumor virus envelope and long terminal repeat (LTR) regions ligated to the thymidine kinase (tk) gene of herpes simplex virus. This construction allowed the tk gene to be expressed in a hormone-responsive fashion upon transfection into Ltk- cells. Comparison of transcription data with in vitro binding data showed that hormone-responsive transcription can be directly correlated to the presence of steroid hormone receptor binding sites on the DNA. There are at least two such receptor binding sites in the LTR region, one between -202 and -137 and another between -137 and -50 base pairs from the RNA cap site, as well as a site near the 5' end of the envelope region. These results strengthen the hypothesis that steroid-receptor complexes regulate genes primarily by binding to DNA sites near the promoter region and thereby modulate transcription.


Subject(s)
DNA, Viral/metabolism , Glucocorticoids/pharmacology , Mammary Tumor Virus, Mouse/analysis , Receptors, Glucocorticoid/metabolism , Receptors, Steroid/metabolism , Transcription, Genetic/drug effects , Animals , Binding Sites , Cell Line , Chimera , Glucocorticoids/metabolism , Mice , Repetitive Sequences, Nucleic Acid , Transfection , Triamcinolone Acetonide/metabolism
11.
Neuron ; 23(1): 45-54, 1999 May.
Article in English | MEDLINE | ID: mdl-10402192

ABSTRACT

The Drosophila latheo (lat) gene was identified in a behavioral screen for olfactory memory mutants. The original hypomorphic latP1 mutant (Boynton and Tully, 1992) shows a structural defect in adult brain. Homozygous lethal lat mutants lack imaginal discs, show little cell proliferation in the CNS of third instar larvae, and die as early pupae. latP1 was cloned, and all of the above mentioned defects of hypomorphic or homozygous lethal lat mutants were rescued with a lat+ transgene. lat encodes a novel protein with homology to a subunit of the origin recognition complex (ORC). Human and Drosophila LAT both associate with ORC2 and are related to yeast ORC3, suggesting that LAT functions in DNA replication during cell proliferation.


Subject(s)
DNA-Binding Proteins/genetics , Drosophila Proteins , Drosophila/genetics , Memory/physiology , Mutation/genetics , Neurons/pathology , Olfactory Pathways/physiopathology , Amino Acid Sequence/genetics , Animals , Animals, Genetically Modified , Brain/abnormalities , Brain/pathology , Brain/physiopathology , Cell Division/physiology , Central Nervous System/pathology , Congenital Abnormalities/genetics , Drosophila/growth & development , Memory Disorders/genetics , Molecular Sequence Data , Mutation/physiology , Origin Recognition Complex , Pupa/physiology , Sequence Homology, Amino Acid , Transcription, Genetic/genetics , Transgenes/physiology
12.
S Afr Med J ; 108(6): 484-489, 2018 May 25.
Article in English | MEDLINE | ID: mdl-30004328

ABSTRACT

BACKGROUND: Euthanasia/physician-assisted suicide have been a controversial and sometimes taboo topic for a long time, not only in South Africa (SA) but also internationally. A recent (SA) judicial case has seen the topic debated again. Consensus on accepting or abolishing these practices in SA has yet to be reached. All relevant role players need to be adequately engaged before policy can be informed. OBJECTIVES: To determine the views of future doctors (medical students) regarding euthanasia and physician-assisted suicide (PAS) and to ascertain their stance on its legalisation in South Africa (SA). METHODS: A paper-based, semi-quantitative descriptive study design consisting of 16 questions, using convenience sampling of third- to fifth-year medical students at Stellenbosch University, was used. RESULTS: The overall response rate was 69.3% (N=277). In total, 52.7% of participants (n=146) felt that the practices of euthanasia/PAS should be legalised in SA. Responses varied depending on patient morbidities. If a patient had terminal disease with intractable suffering, 41.9% of participants would terminate the patient's life upon request. A further 36.1% of participants stated that they would have no part in ending a patient's life, while 35.0% said that they would be comfortable with providing the patient with the correct means to end their life (PAS). The majority (80.1%) of participants indicated that they would prefer a dedicated ethics committee to decide who receives euthanasia/PAS. Many factors influenced participants' responses, but differences in opinion between and within the various religious groups were particularly evident in the responses received. CONCLUSIONS: More than half the respondents in this study were open to legalising euthanasia/PAS, substantially more than in previous studies. However, only 41.9% of respondents would consider actually performing euthanasia/PAS, for certain patients. Views of other healthcare workers as well as the public are required before policy can be informed.

13.
Rev Sci Instrum ; 89(5): 052402, 2018 May.
Article in English | MEDLINE | ID: mdl-29864884

ABSTRACT

An Electron Beam Ion Source Charge Breeder (EBIS-CB) has been developed at Argonne National Laboratory as part of the californium rare ion breeder upgrade. For the past year, the EBIS-CB has been undergoing commissioning as part of the ATLAS accelerator complex. It has delivered both stable and radioactive beams with A/Q < 6, breeding times <30 ms, low background contamination, and charge breeding efficiencies >18% into a single charge state. The operation of this device, challenges during the commissioning phase, and future improvements will be discussed.

14.
Mol Cell Biol ; 4(9): 1823-33, 1984 Sep.
Article in English | MEDLINE | ID: mdl-6208481

ABSTRACT

We have found that cytoskeletal extracts of cultured chicken embryo fibroblasts contain at least seven distinct polypeptides (two major and five minor) which cross-react with antiserum to chicken smooth muscle tropomyosin. These polypeptides range in apparent molecular weight from 31,000 to 47,000, and each is encoded by mRNAs which specifically hybridize to cloned muscle tropomyosin cDNAs. These nonmuscle tropomyosin species and their respective mRNAs are electrophoretically distinct from those of chicken skeletal muscle and appear by genomic DNA blotting to comprise a part of a multigene tropomyosin family. In Rous sarcoma virus-transformed chicken embryo fibroblasts, synthesis of the tropomyosins is differentially repressed such that the synthesis of the major species (cp35 and cp33, cytoskeletal proteins of molecular weight 35,000 and 33,000, respectively) and three minor species is drastically reduced, whereas the synthesis of two of the minor species (cp32 and cp31) remains essentially unchanged. Analysis of cellular mRNA and runoff nuclear transcription experiments indicate that the repression of tropomyosin synthesis by Rous sarcoma virus transformation occurs at the level of transcription. This repression of tropomyosin synthesis is partially mimicked in normal chicken embryo fibroblasts during incubation in high-NaCl medium, a condition in which chicken embryo fibroblasts acquire many characteristics of transformed cells.


Subject(s)
Avian Sarcoma Viruses/genetics , Cell Transformation, Neoplastic , Transcription, Genetic , Tropomyosin/genetics , Animals , Cells, Cultured , Chick Embryo , Cloning, Molecular , Electrophoresis, Polyacrylamide Gel , Fibroblasts/metabolism , Muscles/metabolism , Nucleic Acid Hybridization , Protein Biosynthesis , RNA/genetics , Tropomyosin/biosynthesis , Tropomyosin/isolation & purification
15.
Mol Cell Biol ; 18(5): 2758-67, 1998 May.
Article in English | MEDLINE | ID: mdl-9566895

ABSTRACT

In a two-hybrid screen for proteins that interact with human PCNA, we identified and cloned a human protein (hCdc18) homologous to yeast CDC6/Cdc18 and human Orc1. Unlike yeast, in which the rapid and total destruction of CDC6/Cdc18 protein in S phase is a central feature of DNA replication, the total level of the human protein is unchanged throughout the cell cycle. Epitope-tagged protein is nuclear in G1 and cytoplasmic in S-phase cells, suggesting that DNA replication may be regulated by either the translocation of this protein between the nucleus and the cytoplasm or the selective degradation of the protein in the nucleus. Mutation of the only nuclear localization signal of this protein does not alter its nuclear localization, implying that the protein is translocated to the nucleus through its association with other nuclear proteins. Rapid elimination of the nuclear pool of this protein after the onset of DNA replication and its association with human Orc1 protein and cyclin-cdks supports its identification as human CDC6/Cdc18 protein.


Subject(s)
Cell Cycle Proteins/metabolism , Cell Nucleus/metabolism , Cyclin-Dependent Kinases/metabolism , DNA-Binding Proteins/metabolism , Nuclear Proteins/metabolism , S Phase/physiology , Amino Acid Sequence , Cell Compartmentation , Cell Cycle Proteins/genetics , Cloning, Molecular , Cytoplasm/metabolism , DNA Replication , Humans , Molecular Sequence Data , Nuclear Localization Signals , Nuclear Proteins/genetics , Origin Recognition Complex , Protein Binding , Sequence Analysis, DNA , Sequence Homology, Amino Acid
16.
Rev Sci Instrum ; 78(11): 113105, 2007 Nov.
Article in English | MEDLINE | ID: mdl-18052463

ABSTRACT

The Interaction of Materials with Particles and Components Testing (IMPACT) experimental facility is furnished with multiple ion sources and in situ diagnostics to study the modification of surfaces undergoing physical, chemical, and electronic changes during exposure to energetic particle beams. Ion beams with energies in the range between 20 and 5000 eV can bombard samples at flux levels in the range of 10(10)-10(15) cm(-2) s(-1); parameters such as ion angle of incidence and exposed area are also controllable during the experiment. IMPACT has diagnostics that allow full characterization of the beam, including a Faraday cup, a beam imaging system, and a retarding field energy analyzer. IMPACT is equipped with multiple diagnostics, such as electron (Auger, photoelectron) and ion scattering spectroscopies that allow different probing depths of the sample to monitor compositional changes in multicomponent and/or layered targets. A unique real-time erosion diagnostic based on a dual quartz crystal microbalance measures deposition from an eroding surface with rates smaller than 0.01 nm/s, which can be converted to a sputter yield measurement. The monitoring crystal can be rotated and placed in the target position so that the deposited material on the quartz crystal oscillator surface can be characterized without transfer outside of the vacuum chamber.

17.
S Afr Med J ; 107(3): 232-238, 2017 Feb 27.
Article in English | MEDLINE | ID: mdl-28281429

ABSTRACT

BACKGROUND: Allogeneic haemopoietic stem cell transplant (Allo-HSCT) is a specialised and costly intervention, associated with significant morbidity and mortality. It is used to treat a broad range of paediatric conditions. South Africa (SA) is an upper middle-income country with limitations on healthcare spending. The role of paediatric Allo-HSCT in this setting is reviewed. OBJECTIVES: To review paediatric patients who underwent Allo-HSCT at the Groote Schuur Hospital/University of Cape Town Private Academic Hospital transplant unit in Cape Town, South Africa, and received post-transplant care at Red Cross War Memorial Children's Hospital, over the period January 2006 - December 2014 in respect of indications for the transplant, donor sources, conditioning regimens, treatment-related morbidity and overall survival (OS). METHODS: A retrospective analysis of patient records was performed and a database was created in Microsoft Access. Descriptive analyses of relevant demographic, clinical and laboratory data were performed. Summary statistics of demographic and clinical parameters were derived with Excel. OS was calculated from the date of transplant to the date of an event (death) or last follow-up using the Kaplan-Meier method in Statistica. RESULTS: A total of 48 children received Allo-HSCT: 24 for haematological malignancies, 20 for non-oncological haematological conditions, 3 for immune disorders and 1 for adrenoleukodystrophy. There were 28 boys (median age 7.5 years) and 20 girls (8.5 years). There were 31 sibling matched peripheral-blood stem cell (PBSC) transplants and 1 maternal haploidentical PBSC transplant. Stem cells were mobilised from bone marrow into peripheral blood by administering granulocyte-colony stimulating factor to donors. PBSCs were harvested by apheresis. Eight patients received 10/10 HLA-matched grafts from unrelated donors. Six were PBSC grafts and 2 were bone marrow grafts. Three of the unrelated PBSC grafts were from SA donors. Eight transplants used umbilical cord blood from international registries. OS for patients with non-oncological disorders was 91.3% (median follow-up 3.9 years), while that for oncology patients was 56.8% (1.9 years). Two of the survivors developed chronic graft-versus-host disease. CONCLUSIONS: OS for non-oncological conditions was excellent, while outcomes for oncological disorders were on par with those in high-income settings. Transplantation offers many patients the opportunity for long-term survival and has been shown to be both feasible and rewarding in a less well-resourced environment servicing an economically diverse population.

18.
J Mol Biol ; 172(4): 405-16, 1984 Feb 05.
Article in English | MEDLINE | ID: mdl-6363717

ABSTRACT

To increase our understanding of protein-DNA interaction in general, and in particular that of lac repressor with lac operator, we have investigated the interaction of tight binding (Itb) repressors with wild type (WT) operator and Oc operators. Nine Oc and a WT operator were cloned and sequenced. Three different Oc and an O+ were then chosen for the footprint analysis of six Itb repressors and WT repressor. Distinct protection patterns for the various repressor-operator pairs were observed at low repressor concentrations whereas, at high repressor concentrations, a stretch of 24 bases of the lower strand of the four different operators was protected in most cases. This protection pattern at high repressor concentration was almost completely redundant for all repressor-operator pairs, in spite of the fact that the affinities of the various pairs differed by more than three orders of magnitude. Two exceptions to this general observation were the two tight binding repressors R67 and R78a. These had been mapped in a region that codes for amino acid residues involved in subunit interaction. The two repressors showed reduced protection of O+ and of some Oc operators at the 3' (right) end of the lower strand. Dimethylsulfoxide, which is known to increase the affinity of O+ for repressor, did not increase the number of bases protected by WT repressor on the lower strand of O+. The footprinting results presented here clearly demonstrate that lac repressor can maximally protect about 24 bases of the lower strand of the operator and that the number and kind of interactions occurring in this region determine the strength of the repressor-operator interaction.


Subject(s)
DNA, Bacterial/genetics , Escherichia coli/genetics , Lac Operon , Repressor Proteins/genetics , Transcription Factors/genetics , Base Sequence , Lac Operon/drug effects , Mutation , Repressor Proteins/pharmacology
19.
Infant Behav Dev ; 38: 135-46, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25645599

ABSTRACT

The aim of this study was to assess the effect of massage therapy on the growth and development of infants of HIV-infected mothers in a low socio-economic community in Cape Town. It was a prospective, randomised, controlled intervention trial that included massage therapy and control groups of HIV-infected mothers and their normal birth weight infants who were enrolled in the prevention of mother-to-child transmission (PMTCT) programme. Participants were recruited at the 6-week clinic visit and followed up every 2 weeks until their infants were 9 months of age. Mother-infant pairs in the massage therapy and control groups included 73 and 88 at 6 weeks and 55 and 58 at 9 months, respectively. Mothers in the intervention group were trained to massage their infants for 15 min daily. The socioeconomic status, immunity, relationship with the partner and mental pain of mothers; the infants' dietary intake, anthropometry and development (Griffiths Mental Development Scales); and haematological and iron status of mothers and infants were assessed at baseline and follow-up. Nine infants (5.3%) were HIV-infected on the HIV DNA PCR test at 6 weeks. Despite significantly higher levels of maternal mental pain, infants in the massage therapy compared to control group scored higher in all five of the Griffiths Scales of Mental Development and significantly higher in the mean quotient (p=0.002) and mean percentile (p=0.004) for the hearing and speech scale at 9 months. Based on the mean difference in scores, the massage therapy group showed greater improvement for all five scales compared to the control group. The mean difference in scores was significantly greater for the hearing and speech quotient (21.9 vs. 11.2) (p<0.03) and the general quotient percentile (19.3 vs. 7.7) (p=0.03) in the massage therapy compared to the control group. These scales remained significant when adjusting for the relationship with the partner and maternal mental pain. Both groups had lower scores in the performance scale at 9 months although this was significantly worse in the control compared to the massage therapy group when adjusting for maternal CD4 count, anaemia, relationship with the partner and mental pain. There were no significant differences in the anthropometric measurements between the two groups. In conclusion, based on the Griffiths Scales, massage therapy improved the overall development and had a significant effect on the hearing and speech and general quotient of HIV-exposed infants in this study.


Subject(s)
Developing Countries , Developmental Disabilities/psychology , Developmental Disabilities/therapy , HIV Seropositivity/psychology , Massage/psychology , Poverty Areas , Urban Population , Adult , Cognition Disorders/diagnosis , Cognition Disorders/psychology , Cognition Disorders/therapy , Developmental Disabilities/diagnosis , Developmental Disabilities/ethnology , Female , Humans , Infant , Language Development Disorders/diagnosis , Language Development Disorders/psychology , Language Development Disorders/therapy , Male , Prospective Studies , South Africa , Young Adult
20.
AIDS ; 11(1): 59-66, 1997 Jan.
Article in English | MEDLINE | ID: mdl-9110076

ABSTRACT

OBJECTIVE: To evaluate the effects of treatment with alternating and simultaneous regimens of zidovudine and didanosine on neuropsychological function in patients with symptomatic HIV-1 disease, focusing on patients with possible HIV-1-associated central nervous system (CNS) compromise at entry. DESIGN: Randomized non-blinded clinical trial. SETTING: Government medical research center. PATIENTS: Thirty-eight patients with symptomatic HIV-1 disease, of whom 21 had evidence of CNS compromise at entry. RESULTS: After 12 weeks of therapy, overall significant improvements in memory (P < 0.01) and focused attention (P < 0.001) were seen on both regimens. These gains, however, were largely limited to those patients with HIV-1-associated CNS compromise at entry (P < 0.05). Improvements were also noted in receptive vocabulary, reading, perceptual discrimination and reasoning, divided attention, motor strength, and in mood and affect. Improvements in those latter functions were generally of limited magnitude and were of comparable size for both compromised and non-compromised patients. There was no overall difference between the two drug regimens in the effects on CNS parameters. CONCLUSIONS: Therapy-related improvements were noted particularly for patients with HIV-1-associated CNS compromise. Neuropsychological functions that have been implicated in AIDS dementia--memory and attention--showed the greatest gains. In contrast to the previously described superiority of the simultaneous regimen with regard to immunologic and virologic parameters, there was no difference between the regimens with regard to CNS measures. This supports the contention that the CNS constitutes a relative independent compartment in terms of HIV disease and treatment.


Subject(s)
AIDS Dementia Complex/drug therapy , Anti-HIV Agents/administration & dosage , Didanosine/administration & dosage , Zidovudine/administration & dosage , AIDS Dementia Complex/psychology , Adult , Drug Therapy, Combination , Female , Humans , Male , Neuropsychological Tests
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