Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Cases of ectopic pregnancies as seen in Lagos State University Teaching Hospital, Ikeja, Nigeria

Objective: To determine the prevalence rate, the major forms of ectopic pregnancy and to correct some of the inadequacies in filling of the laboratory forms. Materials and Methods: Relevant data on 91 ectopic pregnancy specimens received at the Lagos State University Teaching Hospital (LASUTH), Ikeja between May 1 2001 and 30 November 2004 were collected from the laboratory forms and analyzed. Results>/b>: A total of 91 ectopic pregnancy cases were received during the 3 year period. The total gynaecological and pregnancy-related specimens were 613 and 472 respectively. Ectopic pregnancy accounted for 14.4% of all the gynaecological and 19.28% of pregnancy-related specimens received in the laboratory. The ages of the patients presenting with ectopic pregnancies ranged from 17 to 36 years with the age group 25 – 29 years representing the highest percentage of 51.6%. The ages of the patient studied were not recorded in 62.2% of cases. 96.70% of the pregnancy specimens were tubal while ovarian occurred in 3.3% of cases. Each of the fallopian tubes had 50% chance of being involved. The sites of the tubal ectopic pregnancy were not specified in 73.2% of cases. A case of bilateral ectopic pregnancy was received. The tubes were recorded as having ruptured in 37.8% of cases. Results showed that lymphocytes are the commonest inflammatory cells seen in the fibro-muscular wall of the fallopian tubes. Conclusion: The rate of ectopic pregnancy is on the increase in Lagos(1). The high rate of tubal rupture associated with ectopic pregnancy can be reduced through the creation of better awareness of this condition in the society, as this will ensure early presentation and referral of cases to hospital. Doctors should be encouraged to fill the relevant portions of the laboratory forms correctly before sending specimens to the laboratories. Keywords: Ectopic pregnancy, Incidence rate, Histopathological laboratory forms Nigerian Journal of Health and Biomedical Sciences Vol. 5 (2) 2006: 79-8

Vascular Tumors in Nigeria Middle Belt: A Histopathological Survey

Introduction: Prosthetic Dentistry pertains to provision of artificial substitutes for missing oral structures. It was reported as an unpopular dental specialty in Nigeria, which necessitated the current follow up research. Objective: To assess the level of acceptability and interest in Prosthetic Dentistry, highlight major factors influencing dental graduates in their choice of specialties, deduce possible explanations for their observed impact on Prosthetics and offer useful suggestions necessary to achieve a positive change . Methodology: A cross sectional study was conducted using a structured questionnaire distributed among all resident dentists in five teaching hospitals. Results: Seventy-eight dentists with a mean age of 31.2 years 4.8 comprising 9 Senior Registrars, 29 House Officers and 40 Registrars responded. Thirty-two respondents decided on their specialty of choice during clinical training while only 3(3.8%) took the decision pre-university Two of the respondents [2.6%] considered prosthetics a first choice specialty, in contrast to Oral and Maxillofacial Surgery 16(20.5%), Orthodontics 15(19.2%) and Conservative 14(17.9%), Table 3. A similar pattern in the distribution of specialties of choice was also recorded for consultants/lecturers. The most stated reason that influenced the participants in deciding their specialty of choice is challenges associated, followed by influence of their lecturers. Most respondents showed positive attitudes towards basic procedures in prosthetics. Seventy-five dentists (96.2%) claimed acrylic denture was always provided as against metal denture, fixed denture and maxillofacial prostheses that were never or occasionally provided. The most frequently mentioned suggestion to improving prosthetics dentistry specialty popularity were adequate supply of materials and equipment (48.7%) followed by provision of more teaching aids 9(11.5%). Conclusion: The most stated reason that influenced the participants in deciding their specialty of choice is challenges associated, followed by influence of their lecturers. The study established apparent low interest of dental graduates in prosthetics which this may be attributed to the narrow prosthodontic services being provided currently in the country, which has hitherto made the practice unstimulating. Urgent steps should be taken to address the anomaly. Keywords: Prosthetic Dentistry; Nigerian Dental Resident Doctors,Choice of Specialties.NQJHM Vol. 16 (4) 2006: pp. 114-11

Sub-chronic toxicity studies of the Aqueous Leaf Extract of Rauvolfia Vomitoria (Afzel)

The cumulative effects of the aqueous leaf extracts of Rauvolfia vomitoria on body tissues was studied. Six groups of male rats consisting of 5 rats per group were given doses of the leaf extract ranging from 0.03g kg-1-1.2g kg-1 to drink at will from their drinking bottles for 42 days. During the period of the study, weights of the animals were monitored weekly with their gross appearances. At the end of the 42nd day, the rats were killed by cervical dislocation. Post-mortem of each of the animals was performed. The liver, kidney, stomach, heart and lungs were excised. The organs from the groups given plant extract were compared with those of the controls. Body weight of both the treated and the control animals rose progressively as the period increased. The pathological features like oedema and hypertrophy noticed in the tissues are considered to be of no serious consequence as they disappeared after cessation of therapy. There abnormalities may possibly not develop with R. vomitoria used for a short period. It is therefore, considered to be non-hazardous.. Keywords: Rauvolfia vomitoria,toxicity, organs, histopathological studies Nigerian Journal of Health and Biomedical Science Vol. 6 (1) 2007: pp. 18-2

The choice of Morbid Anatomy as a career by medical undergraduates in a developing country

Background: The distribution of medical manpower among the various specialties should be of interest to Government, health administrators and medical educators of any nation. Objective: To examine the factors that influence specialty choice of medical students in Ilorin Medical School and the influence of undergraduate medical education on this with special focus on Morbid Anatomy. Method: A survey of 157 medical students who have completed their posting in Morbid Anatomy was undertaken using an objective semi-structured questionnaire. The questionnaire included a first part detailing the demographic characteristics of the students and the second part asking such questions relating to their specialty preferences, factors influencing their choices, their impression of Morbid-Anatomy as a specially and the improvement they would like to see in its teaching. Results: The four most popular specialties were Paediatrics (26.1%). Surgery (21.7%) Internal Medicine (14.7%) and Obstetrics & Gynaecology (14.0%). These are determined by factors like: natural interest (44.6%) possibilities of job satisfaction (17.2%) humanitarian drive (12.7%) personal convenience (5.1%) and gender issue (7.6%). Others include quality of teaching and financial reward (3.2% each), personal aptitude (2.6%) and family influence (0.6%). 1.3% of the respondents adduced no reason for their choice of specialty. While 64.3% of the respondents consider Morbid Anatomy as interesting and important, only (21.3%) would pick it as first for future career. Majority of the students would want improvement in quality of teaching, allocating more time to morbid anatomy with more practical sessions especially exposure to autopsy practice. Conclusion: Health administrators, planners and medical educators must develop strategies to attract medical students to unpopular specialties like morbid anatomy. This may include improving quality of teaching, giving priority to employment of specialists in such field and the use of role models to encourage medical students. Keywords: Morbid Anatomy, undergraduate education careerNQJHM Vol. 15 (2) 2005: pp. 64-6

Analysis of Fallopian Tubes seen in the Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria:- An Histopathological Survey

OBJECTIVE: The aim of this study is to appraise the major diseases of the fallopian tubes and causes of damage in this environment MATERIALS AND METHODS: A retrospective study of a 4-year review of consecutive fallopian tube specimens received at the Department of Morbid Anatomy of the Lagos State University Teaching Hospital (LASUTH), Ikeja, Lagos, conducted between 1st of May, 2001 and 31st July, 2005. . RESULTS: Over the study period, a total of 237 fallopian tubes were studied. The ages of the patients range from 18 to 54 years with the peak incidence in the 21 to 30 years with the median age of 26. 85(46.4%) of the specimens received from 183 patients had ages indicated. Ectopic pregnancy is the commonest indication for sending fallopian tubes to the laboratory for investigation in 63.9% of cases. No case of cancer of the fallopian tubes or tuberculous salpingitis was seen in this study. CONCLUSION: Tubal pregnancy is the commonest indication for sending fallopian tubes to the laboratories for analysis in 63.9% of cases. Malignant tumours of the fallopian tubes and tuberculous salpingitis are rare in this environment. Keywords: Fallopian tubes, Tubal pregnancy, Histopathological Survey Nigerian Journal of Health and Biomedical Science Vol. 6 (1) 2007: pp. 49-5

EFFECT OF CHRONIC EXPOSURE TO LOW LEVELS OF LEAD ON RENAL FUNCTION AND RENAL ULTRASTRUCTURE IN SD RATS

Chronic exposure to lead is associated with adverse effects on renal function in laboratory animals and man. There is controversy concerning the direction of change of renal function parameters following chronic lead intoxication. The renal effects of low-dose lead exposure, as opposed to acute and pharmacological doses, require further scrutiny. In order to determine the effect of prolonged low-dose lead exposure, male Sprague Dawley rats (initial weight, 150.5±17.4g; final weight, 300.5 ± 17.4g; n=10) administered lead acetate (100 p.p.m.) in drinking water over a period of 3 months, were investigated for renal function parameters. Treated rats had elevated blood pressures (114.4±4.2 vs. 95.7±3.5 mmHg; P<0.01). There was no significant difference in renal blood flow (3.99±0.28 vs. 4.19±0.63 ml/min; P=NS). GFR was comparable in the two groups (0.77±0.05 vs. 0.88±0.06 ml/min; P=NS). No significant difference in serum creatinine was observed (57.8±7.5 vs. 49.0±2.7 mmol/l; P=NS). Renal histology showed minimal interstitial changes in the experimental group. Interestingly, significant sodium (P<0.01); potassium (P<0.05) and chloride (P<0.05) retention were observed in the lead treated rats. Elevation of blood pressure occurred at a stage when low-level lead exposure did not alter renal function parameters appreciably. These results suggest that hypertension may be a forerunner of significant renal damage following chronic exposure to low-levels of lead and further underscore fluid and electrolyte retention as a significant mechanism responsible for elevated blood pressure in the chronic stages of lead exposure

Brief Communication - Clinico-pathological patterns of testicular malignancies in Ilorin, Nigeria-a report of 8 cases

Background : The incidence of testicular cancers has been increasing in many populations over the past decades and concerns have been expressed about the possible decrease in semen quality in the period. It may account for one of the factors responsible for increasing male infertility in Ilorin, Nigeria. Objective: To find out the incidence, age distribution clinical presentation, duration before presentation and the occurrence of various Histopathological subtypes of testicular tumours in Ilorin. Design: A retrospective study. Setting: A teaching hospital (University of Ilorin) Patients: Testicular biopsies were done on patients presenting at the hospital with suspected cases of malignancies. Materials and Mehtods: All consecutives cases of testicular malignancies diagnosed in the department of pathology, university of Ilorin Teaching Hospital, during the period of thirteen years (1990-2003) were included in this study. Relevant clinical details such as age, clinical presentation and side of involvement of the testis were also recorded. The slide preparations of this sample were retrieved and reviewed. Result: During the span of thirteen years (1990-2003), testicular cancers accounted for 0.05% of all sample received and 0.14% of the male biopsies. Most of the diagnosed cases were in the first decades of life and are mainly germ cells tumours of which yolk sac tumours are commonest subtypes. Conclusion: Incidence of testicular cancers is still low in this environment and may not account for major contributory factors in male infertility in Ilorin

Effect of chronic co-administration of metformin and vitamin C on plasma glucose and lipid concentrations in normal rats.

In clinical setting, uncomplicated diabetes mellitus type 2 is managed with anti-oxidants (eg ascorbic acid, alpha-tocopherol, etc.) with standard oral hypoglycaemic agents, which is aimed at limiting its glucose auto-oxidation and lipid peroxidation complications. The current study is an experimental animal study aimed at investigating the effect of co-administration of metformin and ascorbic acid (Vitamin C) on plasma glucose and lipid levels in non-diabetic rats which could serve as a template for future studies in this area. The hypoglycaemic and hypolipidaemic activities of metformin, ascorbic acid, and metformin-ascorbic acid combination were studied in 4 groups consisting of 6 rats per group and weighing 120-155 g, by administering oral doses of 5, 10 and 15 (for co-administration) mg/kg/day of the drugs, respectively, for 30 days. The acute oral toxicity of the combination was also conducted using limit dose test of Up and Down Procedure of Acute Oral Toxicity test. Results of the study showed that metformin and metformin-ascorbic acid combination induced significant and comparable hypoglycaemia. The drug combination also lowered plasma total cholesterol, low density lipoprotein-cholesterol (LDL-c), very low density lipoprotein-cholesterol (VLDL-c) significantly but had no effect on plasma high density lipoprotein-cholesterol (HDL-c). The LD50 estimate of the drug combination was greater than 5000 mg/kg body weight/oral route. The results of this study suggest the drug combination could have hypoglycaemic and lipid-lowering effects

Histopathological Pattern of Carcinoma of Cervix in Olabisi Onabanjo University Teaching Hospital, Sagamu, Nigeria

AIM: To document the prevalence and histological types of cervical carcinoma in Sagamu, Ogun State, Nigeria and to suggest ways of reducing the incidence. SETTING: The department of Morbid anatomy and Histopathology laboratory of the Olabisi Onabanjo Teaching Hospital, Sagamu, Ogun State. MATERIALS AND METHODS: The materials for this study comprised slides and tissue blocks of all cases of cervical cancers diagnosed in department of Morbid Anatomy and Histopathology, OOUTH, Sagamu from January 2003 to December 2004.These were retrieved and reviewed. Relevant clinical information extracted from the case notes, request and report forms included the ages of patients, histological types and stages of the disease. RESULTS: Cervical cancers represent 50% of cervical tissue biopsies and 60% of all gynaecological cancers in Sagamu, South West, Nigeria. It occurs commonly between the ages of 31 to 70years with the peak in the 41 to 50years age brackets.93.6% of malignant cervical neoplasms were found to be squamous cell carcinoma variety. Adenosquamous carcinoma and Adenocarcinoma constituted 3.2% each respectively. Five cases (13.9%)were carcinoma-in-situ (CIN III). Well differentiated squamous cell carcinoma represents 39%, poorly differentiated carcinoma and moderately differentiated carcinoma represent 33.3% and 17.7% respectively.45.2% of the patients present with stages 3 and 4 of the disease. CONCLUSION: The incidence of cervical carcinoma is high in Sagamu and may be related to sexual activities in this environment. Efforts should be geared towards mass education about the cause of the disease. Routine cytological screening of the population for cervical cancers is highly necessary as early detection and treatment of the cancers will go a long way reducing the mortality and morbidity of the disease. The sentinel node (SN) procedure has emerged as an alternative to systematic lymphadenectomy and it is our candid opinion that our surgeons be trained to master the this procedure NQJHM Vol. 16 (3) 2006: pp. 80-8