Research Articles (Anatomical Pathology)
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- ItemA biobank to support HIV malignancy research for sub-Saharan Africa(Health & Medical Publishing Group, 2016) Schneider, Johann Wilhelm; Sanderson, Micheline; Geiger, Dieter; Nokta, Mostafa; Silver, SylviaSub-Saharan Africa has one of the highest incidences of infection with HIV globally, but more people in this region are living longer owing to increased access to antiretroviral therapy. However, along with increased care and treatment, this population is expected to have an increase in HIV-associated cancers, as is being seen in the USA and other developed countries. To support translational research in HIV-associated cancers, Stellenbosch University in Cape Town, South Africa, was funded to house the state-of-the-art AIDS and Cancer Specimen Resource Sub-Saharan Africa Regional Biorepository (SSA RBR) to proactively obtain, manage and process biospecimens and associated clinical data representing both AIDS-defining and non-AIDS-defining cancers for research. The SSA RBR furthermore functions as the biorepository for AIDS Malignancy Consortium sub-Saharan clinical trial activities in this region. Although the site had much experience with cryopreservation and storage of specimens, capacity building revolving around operations under International Society for Environmental and Biological Resources/National Cancer Institute best practices took place in such areas as custodianship v. ownership, data sharing and facilities management. The process from selection until launch took 14 months.
- ItemColonic perineurioma (benign fibroblastic polyp) : case report and review of the literature(BioMed Central, 2018) Van Wyk, Abraham Christoffel; Van Zyl, Hennie; Rigby, JonathanBackground: Colorectal perineuriomas are uncommon benign mucosal-based proliferations of mesenchymal cells that express perineurial markers, often associated with colonic crypts displaying a serrated/hyperplastic architecture. The vast majority of cases arise distal to the splenic flexure and have been described as sessile polyps. Using molecular analysis, BRAF mutations have been demonstrated in the serrated crypt epithelium. We report a new case of perineurioma presenting as a pedunculated polyp in the transverse colon, with prominent hemosiderin deposits in the uninvolved lamina propria that separated the perineurial proliferation from the surface epithelium, a previously unreported histological finding. By using immunohistochemistry, we demonstrated the presence of BRAF V600E mutated protein in the serrated crypt epithelium. In addition, a review of the literature on colorectal perineurioma is provided. Case presentation: A 5 mm pedunculated polyp was removed from the transverse colon of a 42 year old man who presented with epigastric pain, weight loss and rectal bleeding. A proliferation of uniform plump spindled cells expanded the lamina propria and separated serrated colonic crypts. The epithelial component closely resembled microvesicular hyperplastic polyp. Immunohistochemical stains for epithelial membrane antigen (EMA), glucose transporter 1 (GLUT1) and collagen IV were positive in the stromal proliferation. A mutation-specific monoclonal antibody directed against BRAF V600E showed positive cytoplasmic staining in the serrated crypt epithelium but not in the perineurial proliferation. Conspicuous hemosiderin deposition was seen in the inflamed lamina propria between the perineurial proliferation and the surface epithelium. Conclusion: Although the majority of colorectal perineuriomas occur in the sigmoid colon and rectum and are described as sessile polyps, colorectal perineurioma can present as a pedunculated polyp proximal to the splenic flexure as described in this case. Conspicuous hemosiderin deposition can be seen in the superficial lamina propria. BRAF mutations are limited to the serrated crypt epithelium.
- ItemComplex patterns of genomic admixture within Southern Africa(PLOS, 2013-03) Petersen, Desiree C.; Libiger, Ondrej; Tindall, Elizabeth A.; Hardie, Rae-Anne; Hannick, Linda I.; Glashoff, Richard H.; Mukerji, Mitali; Indian Genome Variation Consortium; Fernandez, Pedro; Haacke, Wilfrid; Schork, Nicholas J.; Hayes, Vanessa M.Within-population genetic diversity is greatest within Africa, while between-population genetic diversity is directly proportional to geographic distance. The most divergent contemporary human populations include the click-speaking forager peoples of southern Africa, broadly defined as Khoesan. Both intra- (Bantu expansion) and inter-continental migration (European-driven colonization) have resulted in complex patterns of admixture between ancient geographically isolated Khoesan and more recently diverged populations. Using gender-specific analysis and almost 1 million autosomal markers, we determine the significance of estimated ancestral contributions that have shaped five contemporary southern African populations in a cohort of 103 individuals. Limited by lack of available data for homogenous Khoesan representation, we identify the Ju/’hoan (n = 19) as a distinct early diverging human lineage with little to no significant non- Khoesan contribution. In contrast to the Ju/’hoan, we identify ancient signatures of Khoesan and Bantu unions resulting in significant Khoesan- and Bantu-derived contributions to the Southern Bantu amaXhosa (n = 15) and Khoesan !Xun (n = 14), respectively. Our data further suggests that contemporary !Xun represent distinct Khoesan prehistories. Khoesan assimilation with European settlement at the most southern tip of Africa resulted in significant ancestral Khoesan contributions to the Coloured (n = 25) and Baster (n = 30) populations. The latter populations were further impacted by 170 years of East Indian slave trade and intra-continental migrations resulting in a complex pattern of genetic variation (admixture). The populations of southern Africa provide a unique opportunity to investigate the genomic variability from some of the oldest human lineages to the implications of complex admixture patterns including ancient and recently diverged human lineages.
- ItemCongenital tuberculosis : a report of a probable case(Health & Medical Publishing Group, 1978) Le Roux, F. B.; Schwersenski , J.; Greeff, M. J.Extensive miliary pulmonary tuberculosis in a 17-day-old infant born to a mother with pulmonary tuberculosis is described. It was assumed that the patient probably had congenital tuberculosis. We report our findings to draw attention to a rare disease where a high index of suspicion, timely diagnosis and adequate management are essential if treatment is to be successful.
- ItemCYP2D6 genotyping and use of antidepressants in breast cancer patients : test development for clinical application(Springer Verlag, 2012-05) Van der Merwe, Nicole; Bouwens, Christianne S. H.; Pienaar, Rika; Van der Merwe, Lize; Yako, Yandiswa Y.; Geiger, Dieter H.; Kotze, Maritha J.Approximately 25 % of clinically important drugs and numerous environmental carcinogens are metabolised by CYP2D6. Variation in the CYP2D6 gene and concomitant use of tamoxifen (TAM) with certain antidepressants may increase recurrence risk in breast cancer patients due to reduced enzyme activity. In this study we determined the appropriateness of adding CYP2D6 genotyping to the breast cancer genetic testing options already available in South Africa, which include BRCA mutation screening and transcriptional profiling to assess estrogen receptor (ER) status. A total of 114 South African breast cancer patients, including 52 Caucasian and 62 Coloured (Mixed ancestry), and 63 Caucasian control individuals were genotyped for the most common inactivating allele (CYP2D6*4, rs3892097) previously identified in the CYP2D6 gene. In the initial validation data set consisting of 25 Caucasian and 62 Coloured patients, the CYP2D6*4 allele frequency was significantly higher in Caucasian compared to Coloured patients (24 % vs. 3 %, p≤0.001), similar to previous findings in the general South African population. Extended CYP2D6 genotyping was subsequently performed in an implementation data set of 27 Caucasian breast cancer patients, to determine the prevalence of depression and use of antidepressants in a clinical setting. A medical history of depression and/or use of antidepressants was reported in 37 % (10/27) of these breast cancer patients genotyped for CYP2D6*4. This translational research study has led to increased awareness among clinicians of the potential benefits of CYP2D6 genotyping to facilitate prevention of cumulative risk in a high-risk genetic subgroup of breast cancer patients considered for concomitant treatment of TAM and antidepressants that may reduce enzyme function. © Springer Science+Business Media, LLC 2012.
- ItemDiagnostic yield of fine needle aspiration biopsy in HIV-infected adults with suspected mycobacterial lymphadenitis(Health & Medical Publishing Group, 2014-01) Razack, R.; Louw, M.; Wright, C. A.Background: Fine needle aspiration biopsy (FNAB) has been shown to be the diagnostic procedure of choice for superficial lymphadenitis in tuberculosis endemic regions. Methods: We conducted a retrospective laboratory-based study to determine the bacteriological yield of clinically suspected mycobacterial tuberculous lymphadenitis following FNAB in adults, and specifically HIV-positive patients, to determine the need for the introduction of automated nucleic acid amplification tests (NAATs) such as the Xpert MTB/RIF assay as the initial diagnostic modality. Results: A diagnostic yield of 80% was achieved, significantly higher in HIV-positive v. HIV-negative patients (84% v. 52%, respectively; p<0.001). Conclusion: The results justify using automated NAATs such as the Xpert MTB/RIF assay as the initial diagnostic modality to expedite management in HIV-infected patients.
- ItemExome sequencing combined with semantic discovery identifies strong disease-associated candidates in a single case of relapsing remitting multiple sclerosis(BioMed Central, 2012-10) Jalali Sefid Dashti; Kotze, Maritha; Janse Van Rensburg, Susan; Christoffels, Alan; Gamieldien, JunaidAs known disease-associated variants identified through large cohort-based studies often explain only a small percentage of genetic risk in multifactorial disorders such as multiple sclerosis (MS), alternative methods for identification and prioritization of variants that directly and/or indirectly play a role in disease development have become increasingly important. We were tasked with identifying possible genetic causes in a case of atypical relapsing remitting MS (RRMS) that also presented with porphyrialike symptoms and where demyelination was halted in the patient upon iron supplementation. As the patient had no parents or siblings that could be used as references for filtering exome variants, we aimed to develop a new prioritization strategy based on the combination of a predicted deleterious effect on the protein and existing knowledge of the biological roles of the genes and their contribution to relevant phenotypes.
- ItemExome sequencing in a family with luminal-type breast cancer underpinned by variation in the methylation pathway(MDPI, 2017-02-22) Van der Merwe, Nicole; Peeters, Armand V.; Pienaar, Fredrieka M.; Bezuidenhout, Juanita; Van Rensburg, Susan J.; Kotze, Maritha J.ENGLISH ABSTRACT: Panel-based next generation sequencing (NGS) is currently preferred over whole exome sequencing (WES) for diagnosis of familial breast cancer, due to interpretation challenges caused by variants of uncertain clinical significance (VUS). There is also no consensus on the selection criteria for WES. In this study, a pathology-supported genetic testing (PSGT) approach was used to select two BRCA1/2 mutation-negative breast cancer patients from the same family for WES. Homozygosity for the MTHFR 677 C>T mutation detected during this PSGT pre-screen step was considered insufficient to cause bilateral breast cancer in the index case and her daughter diagnosed with early-onset breast cancer (<30 years). Extended genetic testing using WES identified the RAD50 R385C missense mutation in both cases. This rare variant with a minor allele frequency (MAF) of <0.001 was classified as a VUS after exclusion in an affected cousin and extended genotyping in 164 unrelated breast cancer patients and 160 controls. Detection of functional polymorphisms (MAF > 5%) in the folate pathway in all three affected family members is consistent with inheritance of the luminal-type breast cancer in the family. PSGT assisted with the decision to pursue extended genetic testing and facilitated clinical interpretation of WES aimed at reduction of recurrence risk.
- ItemFamilial dilated (congestive) cardiomyopathy. Occurrence in two brothers and an overview of the literature(Health and Medical Publishing Group (HMPG), 1984) Przybojewski, J. Z.; Van Der Walt J. J.; Van Eeden P. J.; Tiedt F. A. C.Two young White brothers had dilated (congestive) cardiomyopathy. The elder came to autopsy after a chronic course of congestive cardiac failure; the younger underwent repeated cardiac catheterization and transvenous right ventricular endomyocardial biopsy specimens demonstrated histopathological features in keeping with a diagnosis of idiopathic dilated cardiomyopathy. These brothers may have the familial form of the disease, although post-viral myocarditis cardiomyopathy cannot be entirely excluded. The literature relating to familial dilated (congestive) cardiomyopathy is reviewed.
- ItemFatal tumour pulmonary embolism(Wiley Open Access, 2017) Masoud, Salim Rashid; Koegelenberg, Coenraad Frederik Nicolaas; Van Wyk, Abraham Christoffel; Allwood, Brian W.A 30-year-old female with no significant past medical history was referred to our facility with sudden onset of shortness of breath. She had a low clinical probability for pulmonary thromboembolism and a computed tomography angiogram showed enlarged pulmonary arteries but no in situ thrombi. She developed recurrent episodes of hypotension and hypoxia, and was transferred to the intensive care unit where she died despite active resuscitation. An autopsy revealed extensive lymphatic and pulmonary vascular tumour emboli as the immediate cause of death. Pulmonary tumour embolism is a very rare cause of death, but can occur in patients who have an occult neoplasm.
- ItemHistological and immunohistochemical evaluation of sentinel lymph nodes in breast cancer at a tertiary hospital in the Western Cape, South Africa(Health & Medical Publishing Group, 2016-04-19) Van Zyl, Adri; Schneider, Johann W.Background. Breast carcinoma remains the most prevalent cancer among women, with over 300 000 deaths annually worldwide. Axillary lymph node status is essential for the clinical staging of breast carcinoma and remains the single most important predictor of disease-free survival in breast carcinoma. Objective. To determine effective histological examination of sentinel lymph node (SLN) sections for the detection of metastatic breast carcinoma. Methods. A prospective hospital-based study was done, including 20 patients with confirmed infiltrating breast carcinoma who underwent tumour excision or simple mastectomy as well as SLN biopsies. All the lymph nodes harvested were sectioned and embedded. Three sets of 15 consecutive serial sections were prepared from each case at one sitting, each measuring 3 - 5 μm in thickness and mounted on separate slides. Each set of 15 consecutive sections was grouped into three levels, each comprising 5 serial sections. The first 4 sections were stained with haematoxylin and eosin (H&E). The fifth section was stained for pancytokeratins, using MNF116. Results. Twenty patients who met the inclusion criteria of this study underwent SLN biopsies and simple mastectomies or tumour excisions. Twelve SLNs of 11 patients contained metastatic carcinoma, all detected at level I, with one case requiring MNF116 immunohistochemistry staining, revealing metastatic carcinoma, measuring 0.08 × 0.08 mm (micrometastases). The size of metastatic carcinoma ranged between 0.08 × 0.08 mm (micrometastases) and 25 × 15 mm. Nine cases showed macrometastases, varying in size between 2 × 3.5 mm and 25 × 15 mm. Tumour sections of three patients with infiltrating carcinoma, of no specific type (NST), revealed lymphovascular invasion. The breast tumour sizes of these cases measured 40 × 25 mm (1/1 node involved), 30 × 20 mm (1/3 nodes involved) and 15 × 12 mm (1/1 node involved), respectively. Nine patients (19 nodes in total, mean 2.1, range 1 - 5) did not have demonstrable metastatic disease in the 45 sections of levels I - IX, including MNF116 on every fifth section. Patients with negative SLNs varied in age between 29 and 68 years and had breast tumour sizes ranging between 10 × 10 mm and 30 × 30 mm, respectively. Conclusion. This study supports a conservative and cost-effective approach that comprises embedding of the entire SLN and the histopathological examination of four H&E-stained sections, which will usually demonstrate metastatic carcinoma. In the event of absence of metastatic carcinoma, immunohistochemical staining for pancytokeratin will detect tumour cells in a small percentage of cases. Examination of additional H&E- or pancytokeratin-stained sections is not cost effective. This finding can guide decisions pertaining to protocols for the histopathological assessment of SLN in breast carcinoma especially in resource-limited settings.
- ItemHyperplastic polyp or sessile serrated lesion? the contribution of serial sections to reclassification(BMC (part of Springer Nature), 2020) Jaravaza, Diana R.; Rigby, Jonathan M.Background: The histological discrimination of hyperplastic polyps from sessile serrated lesions can be difficult. Sessile serrated lesions and hyperplastic polyps are types of serrated polyps which confer different malignancy risks, and surveillance intervals, and are sometimes difficult to discriminate. Our aim was to reclassify previously diagnosed hyperplastic polyps as sessile serrated lesions or confirmed hyperplastic polyps, using additional serial sections. Methods: Clinicopathological data for all colorectal hyperplastic polyps diagnosed in 2016 and 2017 was collected. The slides were reviewed and classified as hyperplastic polyps, sessile serrated lesion, or other, using current World Health Organization criteria. Eight additional serial sections were performed for the confirmed hyperplastic polyp group and reviewed. Results: Of an initial 147 hyperplastic polyps from 93 patients, 9 (6.1%) were classified as sessile serrated lesions, 103 as hyperplastic polyps, and 35 as other. Of the 103 confirmed hyperplastic polyps, 7 (6.8%) were proximal, and 8 (7.8%) had a largest fragment size of ≥5mm and < 10 mm. After 8 additional serial sections, 11 (10.7%) were reclassified as sessile serrated lesions. They were all less than 5mm and represented 14.3% of proximal polyps and 10.4% of distal polyps. An average of 3.6 serial sections were required for a change in diagnosis. Conclusion: Histopathological distinction between hyperplastic polyps and sessile serrated lesions remains a challenge. This study has uncovered a potential role for the use of additional serial sections in the morphological reappraisal of small hyperplastic polyps, especially when proximally located.
- ItemIncidence of Hodgkin lymphoma in HIV-positive and HIV-negative patients at a tertiary hospital in South Africa (2005 - 2016) and comparison with other African countries(Health & Medical Publishing Group, 2018-06-26) Naidoo, N.; Abayomi, A.; Locketz, C.; Musaigwa, F.; Grewal, R.Background. Hodgkin lymphoma (HL) is the most common non-AIDS-defining cancer in HIV-positive patients. Studies on South African (SA) populations have described the prevalence as 7 - 17% of all lymphomas, 8 - 27% of head and neck lymphomas, 9% of lymph node biopsies and 4% of HIV-related malignancies. Objectives. To describe the incidence of HL at our centre between 2005 and 2016 by year, gender, HIV status, histological subclassification and bone marrow involvement, and compare these findings with similar SA and African studies. Methods. This was a retrospective study of all incident HL cases diagnosed in the Department of Pathology, National Health Laboratory Service, Tygerberg Academic Hospital, Cape Town. Follow-up, relapsed and referral cases were excluded. A positive diagnosis of HL was confirmed by either lymph node or bone marrow biopsy and was based on morphological and immunohistochemical findings in accordance with the World Health Organization classification. Results. There were 303 incident cases of HL diagnosed. The incidence increased from 2005 to 2011, with a spike in cases in 2008 and a subsequent decline overall after 2011. The highest proportion of cases was in the 25 - 49-year-old age category (51.1%). There were 77 HIV-positive patients (25.4%), of whom 53 (68.8%) had CD4+ counts <500 cells/µL. In keeping with other African studies, the main subtypes were nodular sclerosis HL (49.8%) and mixed-cellularity HL (23.1%). Bone marrow biopsy following lymph node diagnosis of HL confirmed involvement in 23.7% of patients. Conclusions. Absolute numbers of cases of HL at our centre have increased since the roll-out of antiretroviral therapy (ART) to the public sector. The recent change in policy to make ART available to all HIV-positive patients independent of CD4+ count suggests that patients will survive longer and are therefore at increased risk of developing HL. We anticipate that numbers of HL cases will increase or remain high in the coming years, and we need to prepare for this.
- ItemThe initial impact of the COVID-19 pandemic on the diagnosis of new cancers at a large pathology laboratory in the public health sector, Western Cape Province, South Africa(Health & Medical Publishing Group, 2021) Van Wyk, A. C.; De Jager, L. J.; Razack, R.; Van Wyk, S. S.; Kleinhans, W.; Simonds, H. M.; Schubert, P. T.Background. The COVID-19 pandemic has disrupted cancer diagnostic services. A decline in the number of new cancers being diagnosed over a relatively short term implies a delay in diagnosis and subsequent treatment. This delay is expected to have a negative effect on cancerrelated morbidity and mortality. The impact of the pandemic on the number of new cancer diagnoses in our setting is unknown. Objectives. To assess the impact of COVID-19 on the number of new cancers diagnosed at our institution in the first 3 months following the implementation of lockdown restrictions, by focusing on common non-cutaneous cancers. Methods. A retrospective laboratory-based audit was performed at a large anatomical pathology laboratory in Western Cape Province, South Africa. The numbers of new diagnoses for six common cancers (breast, prostate, cervix, large bowel, oesophagus and stomach) from 1 April 2020 to 30 June 2020 were compared with the corresponding period in 2019. Results. Histopathological diagnoses for the six cancers combined decreased by 193 (–36.3%), from 532 new cases in the 2019 study period to 339 in the corresponding period in 2020. Substantial declines were seen for prostate (–58.2%), oesophageal (–44.1%), breast (–32.9%), gastric (–32.6%) and colorectal cancer (–29.2%). The smallest decline was seen in cervical cancer (–7%). New breast cancers diagnosed by cytopathology declined by 61.1%. Conclusions. The first wave of the COVID-19 pandemic and the associated response resulted in a substantial decline in the number of new cancer diagnoses, implying a delay in diagnosis. Cancer-related morbidity and mortality is expected to rise as a result, with the greatest increase in mortality expected from breast and colorectal cancer.
- ItemKaposi's sarcoma in a renal allograft recipient with cytomegalovirus infection : a case report(Health & Medical Publishing Group, 1982) Le Roux, F. B.; Burman, N. D.; Becker, W. B.There are increasing reports of Kaposi's sarcoma arising in immunosuppressed patients, including renal allograft recipients. Furthermore, evidence is accumulating that cytomegalovirus infection may be an aetiological factor in kaposi's sarcoma. We report an additional case in a renal allograft recipient treated with corticosteroids, azathioprine and niridazole, who also had active cytomegalovirus infection.
- ItemMetastatic hepatocellular carcinoma of the heart. A case report(HMPG, 1978) Villet W.T.; Burger E.G.; Bezuidenhout D.J.J.A metastatic tumour growing in the heart more than 2 years after total removal of the primary hepatic growth is a rare event. Jaundice as a result of bile production by the metastasis is most unusual. The primary tumour did not recur in the regenerated liver. Features which may prove useful in making a clinical diagnosis are briefly considered. Death resulted from a thrombo-embolus from the right atrium lodging in the opening of the tricuspid valve.
- ItemMorular metaplasia of the endometrium misdiagnosed as adeno-acanthoma in a patient with tubal pregnancy : a case report(Health & Medical Publishing Group, 1986) Von der Heyden, U.; Deale, C. J. C.; Nel, J. T.A 41-year-old woman underwent a fractional dilatation and curettage for menorrhagia and a diagnosis of adeno-acanthoma was made from the curettings. However, the subsequently hysterectomy and bilateral salpingo-oophorectomy specimen revealed the presence of a clinically undiagnosed tubal pregnancy and extensive immature squamous metaplasia (morules) of the endometrium. No malignancy was present. A review of the original curettings lead to the recognition of the benign lesion already present at that stage. Difficulties in the differential diagnosis are discussed. The presence of endometrial polyps is considered as a possible factor responsible for the morular metaplasia rather than the tubal pregnancy, which seems to be a previously undescribed and interesting coincidence.
- ItemMucocutaneous lymph node syndrome (Kawasaki disease). A report of 2 cases(HMPG, 1980-12) Van Der Merwe P.L.; Gie R.P.; Hunter J.; Mouton, S. C. E.; Schwar, G. T.; Gleeson, C. M.Two cases of Kawasaki disease, both with cardiac involvement. are reported in South African children and the diagnostic problems are discussed. In patient 1 an ECG showed the development of an .inferior myocardial infarction, and in patient 2 an aneurysm of the left coronary artery was found at postmortem examination.
- ItemMycobacterial transport medium for routine culture of fine needle aspiration biopsies(BMJ Publishing Group, 2010-01) Wright, C. A.; Bamford, C.; Prince, Y.; Vermaak, A.; Hoek, K. G. P.; Marais, B. J.; Warren, RobFine needle aspiration biopsy (FNAB) offers a simple outpatient technique for specimen collection in child tuberculosis suspects with peripheral lymphadenopathy. To perform FNAB with mycobacterial culture on an outpatient basis requires use of a sterile transport medium to facilitate bedside inoculation, maintain organism viability and reduce contamination risk en route to the laboratory. The mycobacterial yield and time to positive culture following bedside inoculation into standard mycobacterial growth indicator tubes were compared with initial inoculation into an inexpensive "in-house" liquid growth medium. Of 150 FNAB performed, 57 (38%) cultured Mycobacterium tuberculosis complex. There was one case each with non-tuberculous mycobacteria and Mycobacterium bovis BCG; the remaining 55 being M tuberculosis. Results were concordant in 142 (94.7%) bedside and laboratory inoculation pairs. There was no significant difference in time to positive culture between bedside and laboratory inoculation (16.2 days (SD 0.87) vs 17.1 days (SD 0.85)). Provision of inexpensive specimen transport bottles and practical tuition in FNAB should improve cost-effective diagnosis of tuberculosis at the primary healthcare level.
- ItemNon-allopathic adjuvant management of osteoarthritis by alkalinisation of the diet(AOSIS Publishing, 2015) Van Velden, David P.; Reuter, Helmuth; Kidd, Martin; Muller, F. OttoBackground: Osteoarthritis (OA) is a chronic condition. Nonsteroidal anti-inflammatory drugs recommended for treatment have serious adverse effects. A compelling body of anecdotal evidence alerted the authors to the therapeutic potential of dietary supplementation with Multiforce® (MF) Alkaline Powder for relief of OA symptoms. Aim: The aim of the study was to test the hypothesis that dietary supplementation with MF relieves clinical signs and symptoms of OA of the hands. Setting: The study was done at the MEDSAC hospital in Somerset West, Western Cape, South Africa. Methods: The research was conducted in two stages. An open interventional study (n = 40) confirmed the notion that MF 7.5 g twice daily is likely to be an effective alternative or adjunct for relief of symptoms of OA of the hands. The main study was conducted with 100 eligible, consenting volunteers (aged 47–89 years) according to a randomised, placebo-controlled, crossover design. Study duration was 56 days, 28 days per regimen; crossover to alternate regimens took place on day 28. Results: Compared to placebo, MF intake over 28 days was associated with significant reductions ( p < 0.005) in pain, tenderness and stiffness of interphalangeal and metacarpophalangeal joints of the hand. Confirmation of systemic alkalinisation by MF, which is rich in organic anions in the form of citrate salts, was reflected by a significant and sustained increase in urine pH. Conclusion: A dietary supplement, Multiforce® Alkaline Powder, containing citrate salts which are converted into bicarbonate in vivo, was efficacious and safe as sole therapeutic intervention, significantly attenuating OA-associated signs and symptoms of the hands.