Lymphomas diagnosed in Uganda during the HIV/AIDS pandemic

Background: There are numerous reports from different countries documenting a change in frequency and profile of lymphomas after the onset of the HIV/AIDS pandemic. In Uganda little is known concerning the distribution of lymphoma subtypes diagnosed at the Department of Pathology, Makerere University College of Health Sciences during this period.Objective: To examine the frequency and diagnostic profile of lymphomas diagnosed in Uganda in the HIV/AIDS era.Design: Retrospective study.Setting: Department of Pathology, Makerere University College of Health Sciences, Kampala, Uganda.Subjects: One thousand and thirteen patients diagnosed with lymphomas in the period 1980-1989.Results: The most common type of non-Hodgkin lymphoma was Burkitt lymphoma (36%). The frequencies of lymphocytic and histiocytic types were 34.5% and 8.2% respectively.Conclusion: There was a decrease in histopathologically diagnosed lymphomas in Uganda in the period 1980-1989. Burkitt lymphoma continues to be the most common subtype diagnosed, some major lymphoma subtypes like T-cell and follicular lymphomas were not reported in the country in the HIV/AIDS era

Regularity of laboratory supplies and delivery of histopathology services in the department of Pathology, Makerere University College of Health Sciences, Uganda, between January 2002 and April 2003

A retrospective study was undertaken in the department of Pathology, Makerere University College of Health Sciences and Mulago Hospital, Uganda, between January 2002 and April 2003 to determine the regularity of laboratory supplies and delivery of histopathology services. The requisition forms and dates of final reporting were obtained from department of Pathology records. The information on delivery of supplies was retrieved from Mulago hospital stores. Formalin (450 L) and isopropyl (2,505 L) were requisitioned, but only 145 L (32.2%) and 70 L (2.8%) respectively were received. Xylene 5L (11.1%) were issued out of 45 L requisitioned. Paraffin wax (900 Kg) was ordered and 200 Kg (22.2%) were supplied. Hematoxylin (850 gms) and silver nitrate (3,700 g) were ordered and none of each was issued. Eosin (100 gms) was supplied out of 200 g requisitioned. Microscope slides (721 packets) and cover slips (520 packets) were requisitioned, only 127 packets (17.6 %) and 90 packets (17.3 %) respectively were supplied. Surgical blades (2,836) were requisitioned and 760 (26.8 %) were given. No detergents and disinfectants were supplied. On average, it took 5 days to get supplies. Turnaround time of making diagnosis was 9 days. Approximately 52 specimens were either lost or misplaced out of 6,700 samples processed during this period. The amount of supplies received was far much lower than the amount requested. Give the high turnaround time in the histopathology service, a computerized laboratory logistics and inventory management systems (LMIS) should be established at the health settings in the country in order to ensure continuous availability of laboratory supplies and improve the turnaround time in laboratory services.KEY WORDS: Laboratory; Supplies; Histopathology; Service

Determination of LDL-cholesterol: direct measurement by homogeneous assay versus Friedewald calculation among Makerere University undergraduate fasting students

The treatment of patients for coronary heart disease risk requires knowledge of the plasma lipid levels. Low density lipoprotein cholesterol (LDL) levels make a strong basis for therapeutic decisions. Although there are incongruities among values of LDL from different methods of determining LDL, the clinician is not routinely informed of the method used. The purpose of this study was to compare LDL levels determined by the Friedewald equation with those assayed by the Kyowa Madox method. The lipid results previously measured by Kyowa Madox method among Makerere University fasting students and reported earlier wereretrieved. The measured values of total cholesterol (TC), High Density Lipoprotein cholesterol (HDL) and triacylglycerols (TG) were used to calculate LDL using Friedewald equation in which LDL= TC-HDL-TG/2.2mmol/L. The values obtained were compared non parametrically with the assayed values previously reported. Our results showed a high value of correlation between measured and calculated LDL so that in general, the two methods can be used interchangeably in this population. However, in cases of dyslipidaemia, the calculated values tend to be lower than the assayed values. It is therefore recommended that clinical laboratories should report the LDL values along with the determination method used, the alert values, the reference ranges, the desirable ranges and the therapeutic targets. © 2010 International Formulae Group. All rights reserved.Keywords: Homogeneous assay, LDL cholesterol, direct measurement, Friedewald equation, comparison

Colorectal cancer in patients from Uganda: A histopathological study

No Abstract. Keywords: Colorectal cancer, HNPCC, Endoscopy, Uganda, Histopathology, Lynch syndrome

Internalizing Mental Disorders and Accelerated Cellular Aging Among Perinatally HIV-Infected Youth in Uganda.

Introduction: Internalizing mental disorders (IMDs) in HIV+ children and adolescents are associated with impaired quality of life and non-adherence to anti-retroviral treatment. Telomere length is a biomarker of cellular aging, and shorter telomere length has been associated with IMDs. However, the nature of this association has yet to be elucidated. Objective: We determined the longitudinal association between IMDs and relative telomere length (rTL) and the influence of chronic stress among Ugandan perinatally HIV-infected youth (PHIY). Methods: IMDs (depressive disorders, anxiety disorders, and post-traumatic stress disorder) and IMDs were assessed using the locally adapted Child and Adolescent Symptom Inventory-5. In 368 PHIY with any IMD and 368 age- and sex-matched PHIY controls without any psychiatric disorder, rTL was assessed using quantitative polymerase chain reaction. Hierarchical cluster analysis was used to generate the three chronic stress classes (mild, moderate, and severe). t-tests were used to assess the difference between baseline and 12 month rTL and the mean difference in rTL between cases and controls both at baseline and at 12 months. Linear regression analysis was used to model the effects of chronic stress on the association between IMDs and rTL, controlling for age and sex. Results: We observed longer rTL among cases of IMDs compared with controls (p < 0.001). We also observed a statistically significant reduction in rTL between baseline and 12 months in the combined sample of cases and controls (p < 0.001). The same statistical difference was observed when cases and controls were individually analyzed (p < 0.001). We found no significant difference in rTL between cases and controls at 12 months (p = 0.117). We found no significant influence of chronic stress on the association between IMDs and rTL at both baseline and 12 months. Conclusion: rTL is longer among cases of IMDs compared with age- and sex-matched controls. We observed a significant attrition in rTL over 12 months, which seems to be driven by the presence of any IMDs. There is a need for future longitudinal and experimental studies to understand the mechanisms driving our findings

Pressure-dependent EPANET extension

In water distribution systems (WDSs), the available flow at a demand node is dependent on the pressure at that node. When a network is lacking in pressure, not all consumer demands will be met in full. In this context, the assumption that all demands are fully satisfied regardless of the pressure in the system becomes unreasonable and represents the main limitation of the conventional demand driven analysis (DDA) approach to WDS modelling. A realistic depiction of the network performance can only be attained by considering demands to be pressure dependent. This paper presents an extension of the renowned DDA based hydraulic simulator EPANET 2 to incorporate pressure-dependent demands. This extension is termed “EPANET-PDX” (pressure-dependent extension) herein. The utilization of a continuous nodal pressure-flow function coupled with a line search and backtracking procedure greatly enhance the algorithm’s convergence rate and robustness. Simulations of real life networks consisting of multiple sources, pipes, valves and pumps were successfully executed and results are presented herein. Excellent modelling performance was achieved for analysing both normal and pressure deficient conditions of the WDSs. Detailed computational efficiency results of EPANET-PDX with reference to EPANET 2 are included as well

The 5-HTTLPR-rs25531 S-A-S-A Haplotype and Chronic Stress Moderate the Association Between Acute Stress and Internalizing Mental Disorders Among HIV+ Children and Adolescents in Uganda.

Background: Internalizing mental disorders (IMDs) among HIV-positive (HIV+) children and adolescents are associated with poor disease outcomes, such as faster HIV disease progression. Although it has been suggested that the development of IMDs is moderated by interaction of stressful life events and vulnerability factors, the underlying etiology is largely unknown. Serotonin transporter gene [solute carrier family 6 member A4 (SLC6A4)] and human tryptophan hydroxylase 2 gene (TPH2) polymorphisms have been implicated in the development of IMDs. This study investigated the association between acute stress and IMDs, and moderation by chronic stress and genetic variants in SLC6A4 and TPH2. Hypothesis: Acute stress acts through genetic and environmental vulnerability factors to increase the risk of developing IMDs. Methods: Polymorphisms in SLC6A4 (5-HTTLPR, rs25531, 5-HTTLPR-rs25531, and STin2 VNTR) and TPH2 (rs1843809, rs1386494, rs4570625, and rs34517220) were genotyped in 368 HIV+ children and adolescents (aged 5-17 years) with any internalizing mental disorder (depression, anxiety disorders, or posttraumatic stress disorder), and 368 age- and sex-matched controls, who were also HIV+. Chronic and acute stress categories were derived by hierarchical cluster analysis. Logistic regression analysis was used to assess the independent moderating effect of chronic stress and each selected polymorphism on the association between acute stress and IMDs. Results: We observed a statistically significant association between severe acute stress and IMDs (p = 0.001). Children and adolescents who experienced severe acute stress were twice as likely to develop IMDs, compared to children and adolescents who experienced mild acute stress (p = 0.001). Chronic stress interacted with severe acute stress to increase the risk of IMDs (p = 0.033). Acute stress was found to interact with 5-HTTLPR-rs25531 S-A-S-A haplotype to increase the risk for IMDs among Ugandan HIV+ children and adolescents (p = 0.049). We found no evidence for a combined interaction of acute stress, chronic stress, and 5-HTTLPR-rs25531 on IMDs. Conclusion: The odds of having an internalizing mental disorder (IMD) were higher among HIV+ children and adolescents who experienced severe acute stress compared to HIV+ children and adolescents who experienced mild acute stress. Chronic stress and 5-HTTLPR-rs25531 independently moderated the association between acute stress and IMDs

TERT rs2736100 and TERC rs16847897 genotypes moderate the association between internalizing mental disorders and accelerated telomere length attrition among HIV+ children and adolescents in Uganda.

BACKGROUND: Internalizing mental disorders (IMDs) (depression, anxiety and post-traumatic stress disorder) have been associated with accelerated telomere length (TL) attrition; however, this association has not been investigated in the context of genetic variation that has been found to influence TL. We have previously reported an association between IMDs and accelerated TL attrition among Ugandan HIV+ children and adolescents. This study investigated the moderating effects of selected single nucleotide polymorphisms in the telomerase reverse transcriptase gene (TERT) (rs2736100, rs7726159, rs10069690 and rs2853669) and the telomerase RNA component gene (TERC) (rs12696304, rs16847897 and rs10936599) on the association between IMDs and TL, among Ugandan HIV+ children (aged 5-11 years) and adolescents (aged 12-17 years). RESULTS: We found no significant interaction between IMDs as a group and any of the selected SNPs on TL at baseline. We observed significant interactions of IMDs with TERT rs2736100 (p = 0.007) and TERC rs16847897 (p = 0.012), respectively, on TL at 12 months. CONCLUSIONS: TERT rs2736100 and TERC rs16847897 moderate the association between IMDs and TL among Ugandan HIV+ children and adolescents at 12 months. Understanding the nature of this association may shed light on the pathophysiological mechanisms underlying advanced cellular aging in IMDs

Uganda Genome Resource : A rich research database for genomic studies of communicable and non-communicable diseases in Africa

Summary The Uganda Genome Resource (UGR) is a well-characterized genomic database with a range of phenotypic communicable and non-communicable diseases and risk factors generated from the Uganda General Population Cohort (GPC), a population-based open cohort established in 1989. The UGR comprises genotype data on ∼5,000 and whole-genome sequence data on ∼2,000 Ugandan GPC individuals from 10 ethno-linguistic groups. Leveraging other platforms at MRC/UVRI and LSHTM Uganda Research Unit, there is opportunity for additional sample collection to expand the UGR to advance scientific discoveries. Here, we describe UGR and highlight how it is providing opportunities for discovery of novel disease susceptibility genetic loci, refining association signals at new and existing loci, developing and testing polygenic scores to determine disease risk, assessing causal relations in diseases, and developing capacity for genomics research in Africa. The UGR has the potential to develop to a comparable level of European and Asian large-scale genomic initiatives