Elizabeth Dimba

Global Oral Health Inequalities in Incidence and Outcomes for Oral Cancer Causes and Solutions

The mouth and oropharynx are among the ten most common sites affected by cancer worldwide, but global incidence varies widely. Five-year survival rates exceed 50% in only the best treatment centers. Causes are predominantly lifestyle-related: Tobacco, areca nut, alcohol, poor diet, viral infections, and pollution are all important etiological factors. Oral cancer is a disease of the poor and dispossessed, and reducing social inequalities requires national policies co-ordinated with wider health and social initiatives – the common risk factor approach: control of the environment; safe water; adequate food; public and professional education about early signs and symptoms; early diagnosis and intervention; evidence-based treatments appropriate to available resources; and thoughtful rehabilitation and palliative care. Reductions in inequalities, both within and between countries, are more likely to accrue from the application of existing knowledge in a whole-of-society approach. Basic research aimed at determining individual predisposition and acquired genetic determinants of carcinogenesis and tumor progression, thus allowing for targeted therapies, should be pursued opportunistically.

Catha edulis (Khat) Induces Cell Death by Apoptosis in Leukemia Cell Lines

Abstract: Khat is the Celastraceus edulis plant, a flowering evergreen tree or large shrub, which grows in the Horn of Africa and southwestern Arabia. Khat use has been associated with development of oral cancer, but its molecular effects remain controversial. This study describes a novel cytotoxic effect of whole khat extract on three leukemia cell lines. Cells were exposed to khat extract and harvested for analysis by fluorescent and electron microscopy, trypan blue exclusion, as well as immunoblotting to characterize the mode of cell death. In a separate series, cells were pretreated with a panel of caspase inhibitors for possible inhibitory effects. Khat induced a rapid cell death effect in HL‐60, Jurkat, and NB4 cells that occurred within 2 h of exposure. The treated cells retained their ability to exclude trypan blue dye, a key feature in the apoptotic process. Exposed cells consistently developed morphological features of manifest apoptosis. Z‐VAD, a pan‐caspase inhibitor, completely inhibited toxic activity for up to 8 h, with partial inhibition by other caspase‐specific agents. Western blot analysis showed specific cleavage of caspase‐3 in khat‐exposed cells. This study shows that khat induces cell death by apoptosis in a process sensitive to inhibition by caspase inhibitors, suggesting that subcellular interactions could be of particular relevance for the biological effects of khat in the cell death process and possibly carcinogenesis.

Camptothecin and khat (Catha edulis Forsk.) induced distinct cell death phenotypes involving modulation of c-FLIPL, Mcl-1, procaspase-8 and mitochondrial function in acute myeloid leukemia cell lines

BackgroundAn organic extract of the recreational herb khat (Catha edulis Forsk.) triggers cell death in various leukemia cell lines in vitro. The chemotherapeutics camptothecin, a plant alkaloid topoisomerase I inhibitor, was tested side-by-side with khat in a panel of acute myeloid leukemia cell lines to elucidate mechanisms of toxicity.ResultsKhat had a profound effect on MOLM-13 cells inducing mitochondrial damage, chromatin margination and morphological features of autophagy. The effects of khat on mitochondrial ultrastructure in MOLM-13 correlated with strongly impaired routine respiration, an effect neither found in the khat-resistant MV-4-11 cells nor in camptothecin treated cells. Enforced expression of anti-apoptotic Bcl-2 protein provided protection against camptothecin-induced cell death and partly against khat toxicity. Khat-induced cell death in MOLM-13 cells included reduced levels of anti-apoptotic Mcl-1 protein, while both khat and camptothecin induced c-FLIPL cleavage and procaspase-8 activation.ConclusionKhat activated a distinct cell death pathway in sensitive leukemic cells as compared to camptothecin, involving mitochondrial damage and morphological features of autophagy. This suggests that khat should be further explored in the search for novel experimental therapeutics.

Challenging the global retinoblastoma survival disparity through a collaborative research effort

Imagine two children with unilateral retinoblastoma. One lives in North America, while the other lives in sub-Saharan Africa. In North America, a mother notices a funny white-eye reflex in photographs of her child. It is consistently present in various photos taken over the last month. Curious, she surfs the internet and discovers that a white-eye reflex could be a sign of cancer. Mother and child visit their family doctor, who confirms the mothers worst fear: it is retinoblastoma. Two days later, the affected eye is removed at the local childrens hospital. The next week, histopathology results confirm no risk of tumour spread, while a few weeks later, genetic testing of the tumour and blood indicates the RB1 mutation was sporadic. The child is fitted with a prosthetic eye and goes on to lead a normal, productive life. In Africa, a mother notices a white reflection in her childs eye, most prominent at dusk. Since it does not cause her child pain or discomfort, she ignores it at first, distracted as she continues to care and provide for all of her children. Months later, the white reflection is still prominent. She takes the child to the local dispensary, where the healthcare worker reassures her that there is nothing wrong. When the eye appears to worsen, she consults a traditional healer. He prescribes a herbal medication for the child, and instructs her to administer it twice daily. The eye shows no improvement, and it eventually begins to protrude from the socket. The mother takes the baby to the city hospital, struggling to gather the funds needed for transportation to the city. The hospital doctors tell her the eye must come out; it is cancer of the eye. When the eye is removed, mother …

Khat induces G1‐phase arrest and increased expression of stress‐sensitive p53 and p16 proteins in normal human oral keratinocytes and fibroblasts

Khat is a psychostimulant plant used by over 10 million people daily, mainly in eastern Africa and the Middle East. Previous studies have suggested an association between khat use and oral lesions such as hyperkeratosis and oral cancer. This study investigated the effects of an extract of khat on primary normal human oral keratinocytes (NOK) and normal human oral fibroblasts (NOF). Low (sublethal) concentrations of khat inhibited the proliferation of both cell types in a dose-dependent and time-dependent manner. Both NOK and NOF treated with khat accumulated in the G1-phase of the cell cycle and showed increased expression of the stress-sensitive p53 protein after 24 h. Normal human oral keratinocytes showed a profound increase in p16(INK4A) (p16) after 24 h and showed morphological changes suggesting cell differentiation. Normal human oral fibroblasts showed growth inhibition and increased expression of p21(WAF1/CIP1) (p21) within 24 h. The concentrations of khat tested in this study were within the range of those found in the oral cavity of khat chewers. The results show that stress induced by khat modulates the cell cycle in oral keratinocytes and fibroblasts. It is further speculated whether khat could have similar effects in vivo, especially in keratinocytes.

The pattern and occurrence of ameloblastoma in adolescents treated at a university teaching hospital, in Kenya: A 13-year study

UNLABELLED Ameloblastoma presenting in the adolescent age group is rare with few studies documenting their occurrence. AIM The aim of this study was to carry out an analysis of the pattern and occurrence of ameloblastoma in those less than 20 years of age. MATERIALS AND METHOD Patients from the University of Nairobi Dental teaching Hospital treated for ameloblastoma were included in the study over a 13-year period. The study highlights the demographic, clinic-radiographic and histologic features of benign locally aggressive lesions. RESULTS A total of 127 patients were recorded of which, 27 (21.3%) were below the age of 20 years; no case was reported below the age of 10 years. 18.5% were below the age of 14 years and 81.5% were 15-19 years old. The gender predilection was ∼1:1. All of the tumours occurred in the mandible, with radiographic features of a multilocular radiolucencies (85.2%); and a fewer unilocular lesions (14.8%). The management is in a staged-wise approach: resection and/or disarticulation with temporary reconstruction using mandibular stainless steel or titanium plates and delayed bone grafting. CONCLUSION The occurrence of ameloblastoma can mimic an odontogenic cyst, clinicians therefore need to be vigilant when examining adolescents so that conservative treatment is started early in order to reduce the subsequent morbidity.

Clinicopathologic features of ameloblastoma in Kenya: a 10-year audit.

This study describes the clinical and pathologic features of ameloblastomas seen in the 2 main craniofacial treatment centers in Kenya in the 10-year period between January 1995 and December 2005. A total of 184 patient records were analyzed for this study. Eighty-two (44.6%) of the patients were male, and 102 (55.4%) were female with an overall age range of 10 to 80 years (mean, 30.2 years; SD, 14.1 years). There was no significant difference in gender presentation of ameloblastomas, although females presented at a slightly older age. The mean age for males was 29.9 years, and for females, it was 30.5 years. Patients generally tended to seek medical advice late, with the mean duration at first presentation of 46.3 months for males and 44.4 months for females. Most of the ameloblastomas (n = 172; 93.5%) were located in the mandible, 11 (6.0%) were in the maxilla, and 1 (0.5%) was in the soft tissues. Presenting symptoms included swelling (n = 182; 98.9%), pain (n = 64; 36.0%), mobile teeth/history of extraction (n = 104; 57.5%), purulent discharge (n = 39; 21.7%) and paresthesia (n = 10; 5.6%). The posterior mandible was the most commonly affected site, whereas maxillary ameloblastomas tended to occur in anterior sites. One hundred fifty-three ameloblastomas (83.2%) were of the solid/multicystic subtype; 8 (5.3%) were unicystic; 1 (0.5%) was of extraosseous origin; 1 (0.5%) was desmoplastic; 9 (6.0%) were malignant, and 12 of the records had no histopathologic pattern specified.

keratocystic odontogenic tumours of the jaws and associated pathologies - a 10 year clinicopathologic audit in a referral teaching hospital in kenya

AIM To establish the pattern of occurrence and the clinicopathological features of keratocystic odontogenic tumour (KCOT) over a 10-year period. MATERIALS AND METHOD Patients from the University of Nairobi Dental Hospital treated for KCOT were included in the study over a 10-year period. The study highlights the demographic, clinico-radiological and histological features of these tumours. RESULTS A total of 22 confirmed cases of KCOTs were recorded with equal gender prevalence; (M:F = 1.44:1). The age range of the patients was from 10 to 69 years with a peak in the second decade of life (mean = 27.5 yrs). Of the 22 cases, 15 (68.2%) occurred in the mandible of which eight (53.3%) involved the body, five (33.4%) the angle and ramus. Six (27.3%) occurred in the maxilla, and one (4.5%) was in both jaws and was associated with Gorlin-Goltz Syndrome. The most common presenting complaint in most patients was swelling 54.6%, and in 18.2% was incidental finding. Eight (36.4%) cases showed satellite cysts upon pathologic evaluation. Thirteen (59.1%) cases were managed by surgical excision, while nine (40.9%) were managed by enucleation. CONCLUSION Based on the outcome of this study, KCOT present mostly in body, angle and ramus of the mandible and its peak is in the second decade of life.

Oral health training programs for community and professional health care workers in Nairobi East District increases identification of HIV-infected patients.

Background Better knowledge and skills for diagnosis and management of human immunodeficiency virus (HIV) related oral lesions by primary healthcare workers (PHWs) may increase recognition of HIV-related oral lesions (HROLs) and may improve implementation of HIV testing in Kenya. For this purpose training programs at health facility and community level were evaluated. Design and Methods A pre-post control-test group design in two administrative divisions of Nairobi East District was used. Clinical competencies of PHWs (n = 32 intervention, and n = 27 control) at health facility level were assessed 9 months after training, and after 6 months for community health workers, (CHWs) (n = 411 intervention and n = 404 control) using written questionnaires, clinical data and patient interviews. Effects on referral for HIV testing and actual HIV testing were assessed by comparing laboratory registries pre- and post training. Results PHWs in intervention (n = 27; 84%) and control (n = 15; 60%) divisions, and CHWs in intervention (n = 330; 80%) and control (189; 47%) divisions, completed all questionnaires. Trained PHWs significantly increased their knowledge of HROLs (p<0.02), frequency of oral examinations, diagnosis of HROLs and referral of patients with HROLs for HIV testing. Trained CHWs significantly gained knowledge about HROLs (p<0.02) and referred more patients with HROLs to health facilities. Overall percentage of HIV-positive test results was three-fold for HROLs compared to non-HROLs. Specifically, 70% of patients with oro pharyngeal candidiasis (OPC), the most commonly diagnosed HROL, were confirmed as being HIV-positive. Increase in overall HIV testing rates (1.6% pre-, 1.2% post training) and overall percentage of HIV-positive results (13% pre-, 16% post-intervention) was not significant. Conclusion Training programs significantly increased PHW and CHW knowledge, recognition and management of HROLs but increased neither overall HIV testing rates nor overall percentage of positive tests. Speculation is that the health system and patient-related barriers seriously limit HIV testing. Trial Registration Netherlands Trial Register NTR2627 (date registered 22nd November 2010), and NTR2697 (date registered 13th January 2011).

Clinical features and types of paediatric orofacial malignant neoplasms at two hospitals in Nairobi, Kenya.

AIM To evaluate the clinical features and histopathological types of orofacial malignant neoplasms in children. PATIENTS AND METHODS The study involved patients aged 15 years and below diagnosed with malignancy at two main referral hospitals in Kenya during the period from July, 2008 to December, 2008. A questionnaire and clinical examination chart were used to document data. Data analysis was done using SPSS 12.0 programme. RESULTS 65 children (44 males, 21 females) with ages ranging from 0.25 to 14 years were evaluated. The main complaints were swelling 61 (94%) and visual disturbance 29 (45%). The mean duration of symptoms was 0.17-36 months. The commonest signs were leucocoria (white reflection from the retina) 23 (35%), proptosis 19 (29%) and loss of vision 15 (23%). The commonest sites were orbit 30 (46%) and maxilla 11 (17%). Most neoplasms were retinoblastoma 26 (40%), followed by 14 (21%) cases of Burkitts lymphoma (BL) and occurred in patients under 5 years of age (40 cases) followed by 19 cases in children aged 5-10 years. CONCLUSIONS Overall, malignancies were more common in males than females with most having been diagnosed in children aged less than 10 years. Retinoblastoma and BL were the most common neoplasms.