Human papillomavirus genotypes in a subset of head and neck squamous cell carcinoma.

BACKGROUND: Squamous cell carcinoma originating from the oral cavity, lip, larynx and pharynx are grouped under head and neck squamous cell carcinomas (HNSCC). OBJECTIVE: To report on human papillomavirus (HPV) genotypes involved in HNSCC. STUDY DESIGN: A retrospective review of archival HNSCC specimens and patient demographic and clinical data accessioned between January, 2007 and December, 2009 in the Department of Pathology, Korle-Bu Teaching Hospital, Accra, Ghana. RESULTS: Cases from 58 males and 20 females included 29 from the oral cavity, 33 from the larynx, 11 from the pharynx and 5 from the parotid gland. HPV DNA was found in 15 (19.23%) of the tumors with 12 being HPV-16, 2 HPV-18 and 1 dual infection with HPV-16 and HPV-18, giving HPV-16 prevalence of 86.7%. Higher prevalence of HPV DNA was found in males than females. There was a trend towards subjects younger than 58 years being more likely to have HPV-positive tumors.The 15 HPV-positive cases were distributed in location as 8 of 33 (24.2%) from the larynx, 4 of 29 (13.8%) from the oral cavity, and 2 of 11 (18.2%) from the pharynx and 1 of 5 (20%) from the parotid gland. CONCLUSION: Oncogenic HPV infection was found in 19.23% of HNSCCs, with genotype 16 predominating. HPV-related HNSCC tended to occur at younger age compared to non-HPV-related HNSCC. The commonest site for HPV-associated HNSSC in Ghana is the larynx, rather than the oropharynx as reported in other studies. Host factors may be responsible for the site difference and more work is required to further elucidate this.

Laboratory diagnosis of homozygous alpha thalassaemia.

BACKGROUND: Alpha-thalassaemia is one of the most prevalent haemoglobinopathies in the world. The molecular basis of the condition is mainly due to deletion of one or more alpha genes and occasional point mutations. The diagnosis and treatment of microcytic hypochromic anaemia is at times a problematic medical issue in Ghana due to co-existence of a-thalassaemia traits and iron deficiency anaemia (IDA) since there is no routine laboratory procedure for the diagnosis of the former. OBJECTIVE: To identify the alpha thalassaemias and determine a simple laboratory method of differentiating them from other causes of microcytic hypochromic, anaemia. METHODS: Venous blood samples of random 216 adult OPD patients at the Central Laboratory of Korle-Bu Hospital were taken for full blood count, iron studies, PCR and restriction enzyme analysis to tag -a3.7-thalassaemia variants. RESULTS AND CONCLUSION: Of the 200 accepted subjects, 114 (57.0%) were -a/aa, 11 (5.5%) were -a/-a and 75(37.5%) áá/áá. Differences among the entire red cell indices and serum iron measurements between -a/-a and aa/aa, and-a/-a and -a/-aa were found to be statistically significant (P<0.05 in each case) and consistent with previous studies, but there were no significant (P>0.05) differences between -a/aa and aa/aa RBC parameters. However, selective analysis based on Hb<13.0 g/dl for males and <12.0 g/dl for females indicated that combination of RBC indices with iron studies can be used to differentiate -a/-a from IDA. Calculation of RBC/PCV ratios of anaemic aa/aa, and -a/-a was yet another tool as the latter was found to have higher ratio.

Knowledge of Pharmacogenetics among Healthcare Professionals and Faculty Members of Health Training Institutions in Ghana.

BACKGROUND: Pharmacogenetics has a potential for optimizing drug response and identifying risk of toxicity for patients. Pharmacogenetics knowledge of healthcare professionals and the unmet need for pharmacogenetics education in health training institutions are some of the challenges of integrating pharmacogenetics into routine medical practice. AIM: To assess pharmacogenetics knowledge among healthcare professionals and faculty members of health training institutions in Ghana. METHOD: Semi-structured questionnaires were used to interview healthcare professionals from selected public and private hospitals. Faculty members from health training institutions were also interviewed. RESULTS: The respondents were Medical doctors 42 (46.7%), Pharmacists 29 (32.2%) and Nurses 19 (21.1%). Healthcare professionals rated their knowledge of Pharmacogenetics as Excellent 5 (5.6%), Very Good 10 (11.2%), Good 53 (60%) and Poor 19 (21.4%). Thirty-two faculty members from health training institutions were also interviewed. Faculty members rated their knowledge of pharmacogenetics as Excellent 2 (6.3%), Very Good 3 (9.4%), Good 9 (28.1%), Fair 12 (37.5%) and Poor 6 (18.8%). Thirty seven percent (12) of these faculty members said pharmacogenetics was not part of their institutions' curriculum, 7 (22%) did not know if pharmacogenetics was part of their curriculum and only 13 (40.6%) said it was part of their curriculum. CONCLUSION: Few healthcare professionals and faculty members of training institutions are aware of the discipline of pharmacogenetics. There is the need for continuous professional education on pharmacogenetics and development of competency standards for all healthcare professionals in Ghana.

Sickle Cell Disease: Reappraisal of the Role of Foetal Haemoglobin Levels in the Frequency of Vaso-Occlusive Crisis.

BACKGROUND: Foetal haemoglobin has been implicated in the modulation of sickle cell crisis. Its level is generally inversely proportional to the severity of sickle cell disease (SCD) for a given sickle cell phenotypes. The main aim of therapy for vaso-occlusive crisis (VOC), which is the hallmark of SCD, is to reduce the chances of sickling through the prevention of polymerization of HbS. One way of preventing this polymerization is by increasing foetal haemoglobin levels. OBJECTIVES: To determine the relationship between HbF levels and the frequency of crisis in SCD patients in Ghana. METHOD: A longitudinal retrospective survey covering a period of 30 months was carried out on adult SCD patients at the Sickle Cell Clinic of the Korle-Bu Teaching Hospital. RESULTS: Eighty-three adults aged 15 to 65 years made up of 40 males and 43 femalea were studied. Analysis of variance (ANOVA) gave significant results in Hb and HbF levels. Higher HbF levels were positively related to less frequent crisis and were significantly high in SCD patients than in controls. HbF effects on the clinical manifestations on SCD were variable. CONCLUSION: Threshold values of HbF play a role in reducing the frequency of vaso-occlusive crisis in SCD patients and this finding contributes to the body of available literature on SCD severity. However our work does not give the apparent threshold level of helpful HBF Level in SCD.

Relationship between oxidative stress and haematological indices in patients with diabetes in the Ghanaian population.

BACKGROUND: Persistent hyperglycaemia is a hallmark of Diabetes Mellitus (DM). It causes increased production of free radicals, especially reactive oxygen species (ROS), - resulting in oxidative stress. Reactive Oxygen Species have been implicated in the development of haematological complications in patients with diabetes. Superoxide Dismutase (SOD) is one of the most effective antioxidant enzyme defense systems against free radicals. METHODS: From February through May 2014, we assessed the relationship between oxidative stress and haematological profiles among individuals with and without diabetes. A cross sectional study of 66 case patients and 44 age-matched controls were recruited from the National Diabetes Management and Research Centre (NDMRC), Korle-Bu Teaching Hospital, Accra, Ghana. Blood samples were obtained from study participants with consent. We determined the haematological profiles of study participants and measured their oxidative stress levels using a standardized kit for SOD activity. RESULTS: Higher white blood cell (WBC) counts were seen in the diabetes cohort (p-value = 0.023). The SOD activity tended to be lower in diabetes patients (p-value = 0.144 however) while higher neutrophil levels seemed to correlate with SOD activity (R = 0.249; R2 = 6.2 %; p-value = 0.049). There did not appear to be a correlation between fasting blood glucose (FBG) and SOD activity (R = -0.044; p-value = 0.727). CONCLUSION: The study reports similar oxidative stress levels, as measured by SOD activity, in diabetic and non-diabetic adults. The SOD activity did not appear to correlate with FBG and several other haematological parameters. Further study would be required to investigate the relationship between these haematological indices and diabetic micro- and macro-vascular complications in our population.

Truncated forms of a novel yeast protein suppress the lethality of a G protein alpha subunit deficiency by interacting with the beta subunit.

In Saccharomyces cerevisiae, the mating pheromone-initiated signal is transduced by a heterotrimeric G protein and normally results in transient cell cycle arrest and differentiation. A null allele of the G alpha (GPA1/SCG1) subunit results in cell death due to unchecked signaling from the G beta gamma (STE4, STE18, respectively) heterodimer. We have identified three high copy suppressors of gpa1 lethality. Two of these genes encode known transcription factors. Mat alpha 2p and Mcm1p. The third is a truncated form of a novel gene, SYG1. Overexpressed wild type SYG1 is a weak suppressor of gpa1. In contrast, the isolated mutant allele SYG1-1 is a strong suppressor that completely blocks the cell cycle arrest and differentiation phenotypes of gpa1 cells of both mating types. One deletion mutant (SYG1 delta 340) can suppress the cell cycle arrest associated with gpa1, but the cells retain a differentiated morphology. SYG1-1 can suppress the effects of overexpressed wild type G beta but is not able to suppress the lethality of an activated G beta mutant (STE4Hpl). Consistent with these genetic observations, the suppressing form of Syg1p can interact with the STE4 gene product, as determined by a two-hybrid assay. SYG1-1 is also capable of promoting pheromone recovery in wild type cells, as judged by halo assay. The sequence of SYG1 predicts eight membrane-spanning domains. Deletion mutants of SYG1 indicate that complete gpa1 suppression requires removal of all of these hydrophobic regions. Interestingly, this truncated protein localizes to the same plasma membrane-enriched subcellular fraction as does full-length Syg1p. Three hypothetical yeast proteins, identified by their similarity to the SYG1 primary sequence within the gpa1 suppression domain, also appear to have related structures. The properties of Syg1p are consistent with those of a transmembrane signaling component that can respond to, or transduce signals through, G beta or G beta gamma.