Non-compartmental toxicokinetic studies of the Nigerian Naja nigricollis venom.

Snakebite envenoming (SBE) is a neglected public health problem, especially in Asia, Latin America and Africa. There is inadequate knowledge of venom toxicokinetics especially from African snakes. To mimic a likely scenario of a snakebite envenoming, we used an enzyme-linked immunosorbent assay (ELISA) approach to study the toxicokinetic parameters in rabbits, following a single intramuscular (IM) administration of Northern Nigeria Naja nigricollis venom. We used a developed and validated non-compartmental approach in the R package PK to determine the toxicokinetic parameters of the venom and subsequently used pharmacometrics modelling to predict the movement of the toxin within biological systems. We found that N. nigricollis venom contained sixteen venom protein families following a mass spectrometric analysis of the whole venom. Most of these proteins belong to the three-finger toxins family (3FTx) and venom phospholipase A2 (PLA2) with molecular weight ranging from 3 to 16 kDa. Other venom protein families were in small proportions with higher molecular weights. The N. nigricollis venom was rapidly absorbed at 0.5 h, increased after 1 h and continued to decrease until the 16th hour (Tmax), where maximum concentration (Cmax) was observed. This was followed by a decrease in concentration at the 32nd hour. The venom of N. nigricollis was found to have high volume of distribution (1250 ± 245 mL) and low clearance (29.0 ± 2.5 mL/h) with an elimination half-life of 29 h. The area under the curve (AUC) showed that the venom remaining in the plasma over 32 h was 0.0392 ± 0.0025 mg h.L-1, and the mean residence time was 43.17 ± 8.04 h. The pharmacometrics simulation suggests that the venom toxins were instantly and rapidly absorbed into the extravascular compartment and slowly moved into the central compartment. Our study demonstrates that Nigerian N. nigricollis venom contains low molecular weight toxins that are well absorbed into the blood and deep tissues. The venom could be detected in rabbit blood 48 h after intramuscular envenoming.

HPV Involvement in Head and Neck Cancers: Comprehensive Assessment of Biomarkers in 3680 Patients.

BACKGROUND: We conducted a large international study to estimate fractions of head and neck cancers (HNCs) attributable to human papillomavirus (HPV-AFs) using six HPV-related biomarkers of viral detection, transcription, and cellular transformation. METHODS: Formalin-fixed, paraffin-embedded cancer tissues of the oral cavity (OC), pharynx, and larynx were collected from pathology archives in 29 countries. All samples were subject to histopathological evaluation, DNA quality control, and HPV-DNA detection. Samples containing HPV-DNA were further subject to HPV E6*I mRNA detection and to p16(INK4a), pRb, p53, and Cyclin D1 immunohistochemistry. Final estimates of HPV-AFs were based on HPV-DNA, HPV E6*I mRNA, and/or p16(INK4a) results. RESULTS: A total of 3680 samples yielded valid results: 1374 pharyngeal, 1264 OC, and 1042 laryngeal cancers. HPV-AF estimates based on positivity for HPV-DNA, and for either HPV E6*I mRNA or p16(INK4a), were 22.4%, 4.4%, and 3.5% for cancers of the oropharynx, OC, and larynx, respectively, and 18.5%, 3.0%, and 1.5% when requiring simultaneous positivity for all three markers. HPV16 was largely the most common type. Estimates of HPV-AF in the oropharynx were highest in South America, Central and Eastern Europe, and Northern Europe, and lowest in Southern Europe. Women showed higher HPV-AFs than men for cancers of the oropharynx in Europe and for the larynx in Central-South America. CONCLUSIONS: HPV contribution to HNCs is substantial but highly heterogeneous by cancer site, region, and sex. This study, the largest exploring HPV attribution in HNCs, confirms the important role of HPVs in oropharyngeal cancer and drastically downplays the previously reported involvement of HPVs in the other HNCs.

Lymphoepithelial cyst of the pancreas in female children--report of two cases.

Lymphoepithelial cyst (LEC) of the pancreas is almost always reported as a case report or in small series mostly in male adult patients with vague clinical manifestations and difficult pre-operative diagnosis. Between the years 2007 and 2012, two female children with LEC of the pancreas were operated on at the Children's Surgical Unit of Murtala Mohammad Specialist Hospital, Kano in northern Nigeria. Satisfactory outcomes were achieved after distal pancreatectomy and splenectomy in one and a Whipple procedure in the other. This benign lesion of the pancreas should be considered in the differential diagnosis of cystic lesions of the pancreas in children.

Clinicopathological pattern and management of retinoblastoma in Kano, Nigeria.

BACKGROUND: The aim of the study is to evaluate the pattern of presentation and the mode of management of retinoblastoma seen in Aminu Kano Teaching Hospital, Kano from 2001 to 2005. MATERIALS AND METHODS: The clinic register was used to obtain the case folders of all children treated for retinoblastoma and this was used to obtain information on patient's age, sex, and clinical sign(s) at presentation such as orbital mass, leucocoria, proptosis, hyphaema without history of trauma, unexplained hypopyon, or uveitis. Also documented were X ray/B mode ultrasound scan findings, type of surgery performed, histological diagnosis, and adjuvant chemotherapy where applicable. RESULTS: Forty-two patients were reviewed, 15 males and 27 females (M: F = 1.0: 1.8). The age ranged between 2 and 6 years and the peak age of presentation was 3 years in 22 patients (52%). The tumor was unilateral in 40 patients (95%) and bilateral in 2 patients (5%). Most of the patients (46%) presented late with fungating orbital mass. Other signs include leucocoria 22%, proptosis 19%, hyphema 7%, Hypopyon 2%, squint 2%, and buphthalmos 2%. Thirty-one patients (74%) had exenteration and enucleation was performed in 11 patients (26%). The tumor was histologically confirmed in 41 patients (98%) and was poorly differentiated in 23 patients (55%), 1 patient (2%) had toxocara granuloma. Thirty-nine patients required adjuvant chemotherapy and only 2 received 6 (full) courses. CONCLUSION: Retinoblastoma, a treatable tumor is characterized by late presentation as illustrated in our study. There is need to create public awareness and educate mothers on this tumor so that there is early diagnosis, appropriate referral, and prompt treatment. The goal is to increase number of children successfully cured of this disease in our environment.

A review of the utilization of fine needle aspiration in clinical practice and research in Nigeria.

BACKGROUND: Research and publications are critical to advancements in the quality of healthcare delivery. This article attempts to highlight the prospects and challenges of fine needle aspiration (FNA) cytology as a tool for research in Nigeria. MATERIALS AND METHODS: Data available in local and international bibliographic databases for the period 1986-2005 (20 years) were collated and analyzed. RESULTS: The theme of Nigerian FNA-focused studies correlated with the recognized disease patterns in the country which are tuberculous lymphadenitis, breast tumors and Burkitt's lymphoma. The accuracy of FNA in these situations was high and comparable to the experience in developed countries. It was found that the total number of articles published during two contiguous periods (1986-1995 and 1996-2005) had increased from 5 to 18. Also, in majority of cases, the articles were not published in specialized pathology journals. CONCLUSIONS: The utilization of FNA is apparently lagging in Nigeria. Given its potential in resource-constrained settings, we are of the opinion that it should be used more often in clinical and translational research.

A histopathologic study of salivary gland tumors in Kano, northern Nigeria.

Significant differences in the global distribution of salivary gland tumors have been reported, but no formal study has been carried out here in Kano, the largest city in northern Nigeria. We therefore undertook this eight-year retrospective study of all histologically diagnosed salivary neoplasms at the histopathology laboratory of our referral teaching hospital in Kano. Seventy-eight salivary gland tumors were diagnosed during the eight-year study period accounting for 0.4% of all neoplasms. Benign tumors were more prevalent, comprising 56.4%, while malignancies were 43.6%. Pleomorphic adenoma and mucoepidermoid carcinoma were the commonest histological types constituting 48.7% and 23.1% respectively, while the most frequent sites were parotid, submandibular and minor salivary glands accounting for 49%, 26% and 24% respectively. As in most studies of black populations there were no adenolymphomas. Age distribution was bimodal with a benign peak in the third decade and a malignant peak in the sixth. Our findings were broadly similar to most other African reports but somewhat at variance with Western literature. Improved hospital attendance with more comprehensive reporting would yield more representative data.

Population differences in breast cancer: survey in indigenous African women reveals over-representation of triple-negative breast cancer.

PURPOSE: Compared with white women, black women experience a disproportionate burden of aggressive breast cancer for reasons that remain unknown and understudied. In the first study of its kind, we determined the distribution of molecular subtypes of invasive breast tumors in indigenous black women in West Africa. PATIENTS AND METHODS: The study comprised 507 patients diagnosed with breast cancer between 1996 and 2007 at six geographic regions in Nigeria and Senegal. Formalin-fixed and paraffin-embedded sections were constructed into tissue microarrays and immunostained with 15 antibodies. Five molecular subtypes were determined, and hierarchical cluster analysis was conducted to explore subgroups for unclassified cases. RESULTS: The mean (+/- standard deviation) age of 378 patients in the first cohort was 44.8 +/- 11.8 years, with the majority of women presenting with large (4.4 +/- 2.0 cm) high-grade tumors (83%) in advanced stages (72% node positive). The proportions of estrogen receptor (ER) -positive, progesterone receptor-positive, and human epidermal growth factor receptor 2 (HER2) -positive tumors were 24%, 20%, and 17%, respectively. Triple negativity for these markers was predominant, including basal-like (27%) and unclassified subtype (28%). Other subtypes were luminal A (27%), luminal B (2%), and HER2 positive/ER negative (15%). The findings were replicated in the second cohort of 129 patients. The unclassified cases could be grouped into a bad prognosis branch, with expression of vascular endothelial growth factor, B-cell lymphoma extra-large protein, and Cyclin E, and a good prognosis branch, with expression of B-cell lymphoma protein 2 and Cyclin D1. CONCLUSION: These findings underscore the urgent need for research into the etiology and treatment of the aggressive molecular subtypes that disproportionately affect young women in the African diaspora.

Fine needle aspiration cytology in Nigeria.

OBJECTIVE: Fine needle aspiration cytology (FNAC) is a simple, safe and cheap method for the screening and diagnosis of a variety of inflammatory and neoplastic conditions. Being a relatively new diagnostic technique in Nigeria, scant information had been published on it. We conducted a nationwide study to describe the availability, organization and utilization of FNA in the country. STUDY DESIGN: A descriptive cross-sectional survey was done to describe the current state of the develop ment of FNAC in Nigeria. The respondents were pathologists and heads of pathology departments in leading medical institutions. RESULTS: It was found that the practice of cytology is widely disseminated throughout the country, with a growing number of pathologists who have taken an interest in cytology. But FNA in Nigeria faces many important challenges, not the least of which is the lack of opportunities for local training and continuing education in cytology. CONCLUSION: In our opinion, there is an immediate need for a comprehensive approach to cytopathology education in Nigeria.

Uses and limitations of fine needles aspiration cytology in the diagnostic work-up of patients with superficial lymphadenopathy.

Lymph node fine needle aspirations in 93 patients were studied to ascertain the usefulness of FNA cytology in determining the therapeutic approach. Cytologic results were compared with histologic diagnoses in 35 cases that underwent both aspiration and excisional biopsy. The cases with histological diagnoses included 17 (28.3%) of the 60 cytologically benign cases, 6 (75.0%) of the 8 cytologically suspicious cases, 10 (55.5%) of the 18 cytologically malignant cases and 2 (28.6%) of the 7 cytologically unsatisfactory cases. FNA in the present series showed a sensitivity of 90.0 per cent and specificity of 82.3 percent. It is concluded from this data that FNA can be an accurate, inexpensive and quick method of initial diagnosis in superficial lymphadenopathy.