Population-based prevalence of abnormal cervical cytology findings and local risk factors in Ibadan, Nigeria: implications for cervical cancer control programs and human papilloma virus immunization.

OBJECTIVE: To investigate the prevalence of abnormal cervical cytological findings and local risk factors in Ibadan, Nigeria. STUDY DESIGN: All women aged ≥15 years in each household in Idikan, Ibadan, were invited to participate in a population-based study. Structured questionnaires were administered to all consenting women. Conventional cervical Papanicolaou smears obtained from sexually active women were classified using the 2001 Bethesda system. The diagnoses were correlated with sociodemographic data and risk factors. RESULTS: Of 2,870 women aged ≥15 years estimated to live in Idikan, 1,204 sexually active women consented to pelvic examination and cervical smears. Results were available for 1,104 women (mean age: 39.8 years). Mean ages at menarche, first sexual intercourse and first pregnancy were 16.1, 20.3 and 20.7 years, respectively. Cytological results were categorized into atypical squamous cells of undetermined significance and atypical glandular cells 22 (1.99%); low-grade 43 (3.89%) and high-grade squamous intraepithelial lesions (HSIL) 17 (1.54%); invasive cancer 2 (0.18%) and normal 593 (53.8%) and reactive changes 427 (38.7%). The prevalence of epithelial abnormalities is 7.6%. Significant host-related factors in those with HSIL and invasive cancer included older age (mean 56.2 years), high parity and gravidity, lack of formal education and being divorced (p < 0.05). CONCLUSIONS: This study provides prevalence data and local risk factors for abnormal cervical cytology in a Nigerian population, which will be useful for planning future cervical cancer control programs.

Update on desmoid tumors.

Desmoid tumors (DTs) are histologically benign proliferations of stromal cells but may grow locally aggressive. Overall, DTs are rare (0.03% of all neoplasms). A minority of DTs is associated with Gardner syndrome and mutations of the familial adenomatous polyposis (FAP) gene. Most spontaneous DTs are associated with mutations of the beta-catenin gene. This mutation results in the activation of Wnt/catenin signaling. Due to their variable clinical presentation and behavior, no standard approach for DTs can be recommended. In most cases of DTs of the extremities surgical extirpation is indicated, whereas in many other cases, a multimodal and multidisciplinary concept should be followed. In this review article, we discuss the diagnosis, pathogenesis, and treatment options for DTs, including targeted therapy with tyrosine kinase inhibitors.

The effect of electromagnetic radiation in the mobile phone range on the behaviour of the rat.

Electromagnetic radiation (EMR) is emitted from electromagnetic fields that surround power lines, household appliances and mobile phones. Research has shown that there are connections between EMR exposure and cancer and also that exposure to EMR may result in structural damage to neurons. In a study by Salford et al. (Environ Health Perspect 111:881-883, 2003) the authors demonstrated the presence of strongly stained areas in the brains of rats that were exposed to mobile phone EMR. These darker neurons were particularly prevalent in the hippocampal area of the brain. The aim of our study was to further investigate the effects of EMR. Since the hippocampus is involved in learning and memory and emotional states, we hypothesised that EMR will have a negative impact on the subject's mood and ability to learn. We subsequently performed behavioural, histological and biochemical tests on exposed and unexposed male and female rats to determine the effects of EMR on learning and memory, emotional states and corticosterone levels. We found no significant differences in the spatial memory test, and morphological assessment of the brain also yielded non-significant differences between the groups. However, in some exposed animals there were decreased locomotor activity, increased grooming and a tendency of increased basal corticosterone levels. These findings suggested that EMR exposure may lead to abnormal brain functioning.

Immunocytochemistry in the diagnosis of small blue cell tumours of childhood.

OBJECTIVE: This study attempts to define a limited, cost effective, reliable primary panel of antibodies for immunohistology, as an adjunct to morphological features, for the diagnosis of Small Blue Cell Tumors (SBCT) which would be convenient for use in low resource settings to improve their diagnostic accuracy. The choice of antibodies is based on the common childhood tumors in Ibadan and limited by financial constraints and availability of antibodies. MATERIALS & METHODS: Twenty-five representative cases of previously diagnosed small blue cell tumours of childhood were selected from the file of the Department of Pathology, University College Hospital, Ibadan. The retrieved blocks were cut and stained with antibodies to desmin, leucocyte common antigen, cytokeratin, chromogranin, neuron-specific-enolase, vimentin and neurofilament using the avidin-biotin technique as previously described. RESULTS: Of the 25 cases studied 24 (96%) gave interpretable immunostaining reaction and the immunophenotype of these were defined. The staining quality equaled that produced on the control well-fixed positive control sections. The final diagnosis of six of the 25 cases changed based on immunostaining. Four cases previously diagnosed as lymphoma were confirmed to be rhabdomyosarcoma (3 cases) and neuroblastoma, one case each of rhabdomyosarcoma and neuroblastoma were both reclassified as lymphoma. CONCLUSION: Based on our findings, the use of a small first-line panel of antibodies to leucocyte common antigen, desmin and neuron-specific-enolase are ideal for immunohistochemical discrimination of SBCT, as an adjunct to morphology, in low-resource settings.

Immunocytochemistry in the diagnosis of small blue cell tumours of childhood

Objective: This study attempts to define a limited; cost effective; reliable primary panel of antibodies for immunohistology; as an adjunct to morphological features; for the diagnosis of Small Blue Cell Tumors (SBCT) which would be convenient for use in low resource settings to improve their diagnostic accuracy. The choice of antibodies is based on the common childhood tumors in Ibadan and limited by financial constraints and availability of antibodies. Materials et methods: Twenty-five representative cases of previously diagnosed small blue cell tumours of childhood were selected from the file of the Department of Pathology; University College Hospital; Ibadan. The retrieved blocks were cut and stained with antibodies to desmin; leucocyte common antigen; cytokeratin; chromogranin; neuron-specific-enolase; vimentin and neurofilament using the avidin-biotin technique as previously described. Results: Of the 25 cases studied 24 (96) gave interpretable immunostaining reaction and the immunophenotype of these were defined. The staining quality equaled that produced on the control well-fixed positive control sections. The final diagnosis of six of the 25 cases changed based on immunostaining. Four cases previously diagnosed as lymphoma were confirmed to be rhabdomyosarcoma (3 cases) and neuroblastoma; one case each of rhabdomyosarcoma and neuroblastoma were both reclassified as lymphoma. Conclusion: Based on our findings; the use of a small first-line panel of antibodies to leucocyte common antigen; desmin and neuron-specific-enolase are ideal for immunohistochemical discrimination of SBCT; as an adjunct to morphology; in low-resource settings

Worldwide distribution of human papillomavirus types in cytologically normal women in the International Agency for Research on Cancer HPV prevalence surveys: a pooled analysis.

BACKGROUND: The proportion of women infected with human papillomavirus (HPV) varies greatly across populations, as might the distribution of HPV types. We aimed to compare HPV-type distribution in representative samples of women from different world regions. METHODS: Women were randomly selected from the general population of 13 areas from 11 countries (Nigeria, India, Vietnam, Thailand, Korea, Colombia, Argentina, Chile, the Netherlands, Italy, and Spain). A standardised protocol was used for cervical specimen collection. All HPV testing was by GP5+/6+ PCR-based EIA. The proportion of HPV-positive women infected with different HPV types was compared by study area and between pooled regions with age-adjusted odds ratios (ORs) with corresponding 95% floating CIs. FINDINGS: 15 613 women aged 15-74 years without cytological abnormalities were included in a pooled analysis. Age-standardised HPV prevalence varied nearly 20 times between populations, from 1.4% (95% CI 0.5-2.2) in Spain to 25.6% (22.4-28.8) in Nigeria. Although both overall HPV prevalence and HPV16 prevalence were highest in sub-Saharan Africa, HPV-positive women in Europe were significantly more likely to be infected with HPV16 than were those in sub-Saharan Africa (OR 2.64, p=0.0002), and were significantly less likely to be infected with high-risk HPV types other than HPV16 (OR 0.57, p=0.004) and/or low-risk HPV types (OR 0.44. p=0.0002). Women from South America had HPV-type distribution in between those from sub-Saharan Africa and Europe. Heterogeneity between areas of Asia was significant. INTERPRETATION: Heterogeneity in HPV type distribution among women from different populations should be taken into account when developing screening tests for the virus and predicting the effect of vaccines on the incidence of infection.

Mobilization for cervical cancer screening: lessons from a poor-urban Yoruba community in Nigeria.

Cervical cancer is a major public health problem worldwide and it remains one of the commonest malignancies in Nigeria. Screening remains the most effective tool for the detection of pre-invasive stages of cervical cancer, giving the opportunity for prompt and effective treatment before the emergence of invasive disease. In Nigeria, as in most developing countries, the concept of screening for cancer and its pre-emptive treatment is underdeveloped. The fact that the facilities and logistics for cervical cancer screening are generally located in the hospital setting, a place where one goes when ill, according to local beliefs, makes acceptance more difficult. That Nigeria urgently needs to set up or develop cervical screening programmes that will reach women outside the hospital setting in a culturally acceptable milieu is not in doubt. A community cervical screening survey for the prevalence of cervical intraepithelial neoplasia and HPV infection was initiated in Idikan, a poor-urban inner core area of Ibadan. The challenges and experiences encountered in the execution of the project which could serve as useful knowledge to those undertaking similar exercises, requiring mass mobilization for cancer screening of an uninformed group, are highlighted. Our experience in the course of this study is important as it brought out the probable influences of community dynamics and social organization in illness decisions and prescriptions for health operative in this particular population group. Cervical cancer screening programmes should therefore make provisions to accommodate the occasional outcomes as we had encountered. In addition, screening programmes in developing societies would require sensitive designs that should address the cultural attitudes, personal conflicts, expectations of treatment and overall context of preventive care.

Prevalence of papillomavirus infection in women in Ibadan, Nigeria: a population-based study.

To investigate the prevalence of and the risk factors for cervical infection with human papillomavirus (HPV) in an inner-city area of Ibadan, Nigeria, we interviewed and obtained a sample of cervical cells from 932 sexually active women aged 15 years or older. A total of 32 different HPV types were identified with an HPV prevalence of 26.3% overall and 24.8% among women without cervical lesions; or age-standardised to the world standard population of 28.3 and 27.3%, respectively. High-risk HPV types predominated, most notably HPV 16, 31, 35 and 58. In all, 33.5% of infections involved more than one HPV type. Unlike most populations studied so far, HPV prevalence was high not only among young women, but also in middle and old age. Single women (odds ratio, OR=2.1; 95% confidence interval, CI=1.1-3.9) and illiterate women (OR=1.7; 95%CI=1.1-2.5) showed increased HPV positivity. Associations were also found with anti-Herpes simplex-2 antibodies (OR=1.6; 95% CI: 1.1-2.1) and with the husband's extramarital relationships (OR=1.6: 95% CI: 1.0-2.6). High prevalence of HPV in all age groups may be a distinctive feature of populations where HPV transmission continues into middle age and cervical cancer incidence is very high.

Primary extranodal non-Hodgkin's lymphoma of the upper aerodigestive tract--a descriptive analysis of the pattern seen in the University College Hospital, Ibadan.

This retrospective review highlights primary extranodal non-Hodgkin's lymphoma (NHL), of the upper aerodigestive tract as seen in Ibadan over a ten-year period. There was a male preponderance (m:f ratio of 2:1), with a mean age of 42.5 years and a bimodal age presentation at the fourth and fifth decades. The Waldeyer's ring was the commonest affected site while the tonsil is the highest involved subsite. Sixty-eight percent of the patients had regional lymphadenopathy and thirty eight percent also 'B' symptom at presentation. The peculiar presentations of this NHL are the short duration (10 months) of symptoms, mainly intermediate/high grade diffuse large cell lymphoma especially in the Waldeyer's ring and sinonasal region with absence of low-grade small cell lymphoma. The majority of patients (64.3%) presented with Stage IV disease, which shows that the disease has an aggressive course with high mortality and generally poor outcome with 53.6% of the patients dead within one-year onset of symptoms. The overall mean survival period was 14 months. Comparison of the median survival of the patients that died when matched with the site, Ann Arbor staging, histological grade/subtype and treatment modality yielded no significant differences. These further confirm the aggressive nature of the disease in our environment.

Focal segmental glomerulosclerosis in malignant hypertension.

OBJECTIVE: Focal segmental glomerulosclerosis (FSG) may occur in primary malignant hypertension (MHT) either as a result of glomerular hyperfiltration or fibrinoid necrosis (FN), and may contribute to renal dysfunction. To determine the frequency of occurrence and distribution of FSG in primary MHT we studied renal biopsy specimens from 38 black Africans--30 postmortem and 8 needle-biopsy specimens. SUBJECTS: There were 31 male subjects and 7 female, with a mean age of 46 (+/- 7) years. RESULTS: Mean blood pressure (BP) was 206 +/- 15/137 +/- 9 mmHg, median 24-hour proteinuria (interquartile (IQ) range) was 5.1 g (3.3-6.5 g), median serum albumin 3.4 g (3.2-3.8 g) and median serum creatinine 540 mumol/l (425-752 mumol/l). Mucoid intimal proliferation was present in all the sections but FN was seen in 29 (76%). Glomerulosclerosis was present in all the sections, and was axially distributed in 7 (18%), segmentally in 22 (58%), and globally in 9 (24%). Median 24-hour proteinuria was 2.8 g (0.8-3.5 g IQ range), 5.6 g (1.7-8.1 g) and 3.4 g (2.6-4.0 g) respectively, and corresponding values of serum creatinine were 770 mumol/l (106-1,274 mumol/l IQ range), 522 mumol/l (248-991 mumol/l) and 1,230 mumol/l (920-1,558 mumol/l) respectively. CONCLUSION: The distribution of glomerulosclerosis did not appear to relate to proteinuria or serum creatinine, although cases with segmentally distributed glomerulosclerosis appeared to have the highest proteinuria, and those with global glomerulosclerosis appeared to have the highest serum creatinine levels. FSG therefore occurs prominently in primary MHT and may contribute to renal dysfunction.

Schwannoma of the left brachial plexus mimicking a cervicomediastinal goiter in a young Nigerian lady.

The schwannoma is thought to arise from the schwann cells of the nerve sheath. This tumor is usually solitary and may arise from any cranial or peripheral nerve. It is encapsulated and appears to arise focally on a nerve trunk so that the nerve itself is stretched over the tumor rather than running through it as in neurofibroma. This report is unusual as the tumor started as a cervical swelling which subsequently grew into the mediastinum simulating a retrosternal goiter. The patient, a 25 year-old female was referred to the University College Hospital, Ibadan, 24 hours after an attempted thyroidectomy at a private hospital. The history was of a painless anterior neck swelling of 4 years duration devoid of symptoms of hyperthyroidism with associated dysphagia and weakness of the left hand. Examination showed an asthenic young woman. Her voice was hoarse but there were no eye signs suggestive of thyrotoxicosis. On the anterior neck was a sutured skin-crease scar over a diffuse anterior neck swelling which one could not get below. The left hand showed wasting of the thenar and hypothenar eminences. Thyroid function test results were within normal limits, indirect laryngoscopy showed a left vocal cord paralysis, packed cell volume was 38%. Her chest x-ray showed a huge left retrosternal and apical soft tissue mass displacing the trachea to the right (figure 1). A fine needle aspiration cytology was reported as a chronic lymphocytic thyroiditis. A presumptive diagnosis of thyroid carcinoma with retrosternal extension was made. At surgery, manipulation of the mass was difficult as the tissue was soft, slimy and ruptured easily. Severe hemorrhage was encountered necessitating a median sternotomy to control the bleeding vessels. Her post-operative period was stormy, however she thereafter made gradual progress to warrant her discharge six weeks post surgery.

Superlattice formation in the lithiated vanadium oxide phases Li(0.67)V(6)O(13) and LiV(6)O(13).

Two new lithiated phases of V(6)O(13) were formed by carefully tuning the temperature of electrochemical lithiation in a "coffee-bag" type Li-ion battery at 2.78 V versus Li/Li(+). These were studied by single-crystal X-ray diffraction. A phase with the composition Li(2/3)V(6)O(13) was obtained at 308 K with a unit cell three times the volume of the original V(6)O(13) cell. A single crystal discharged at ambient temperature was shown to be LiV(6)O(13) and twice the unit-cell volume of the original V(6)O(13) cell. On lithiation, the structures retain their basic V(6)O(13) structure of alternating single and double layers of VO(6) octahedra. The lithium ions occupy chemically equivalent sites, where they coordinate fivefold to O atoms, and associate with the single layers of VO(6) octahedra. The insertion of lithium causes a significant elongation of one of the V-O bonds in each structure, which expands from 1.65 to 1.89 A; this is due to the charge reduction of a specific V atom.

HMG1 and 2: architectural DNA-binding proteins.

HMG1 and 2 (high mobility group proteins 1 and 2; renamed HMGB1 and 2) contain two DNA-binding HMG-box domains (A and B) and a long acidic C-terminal domain. They bind DNA without sequence specificity, but have a high affinity for bent or distorted DNA, and bend linear DNA. The individual A and B boxes (which, although broadly similar, show both structural and functional differences) exhibit many of the structure-specific properties of the whole protein. The acidic tail modulates the affinity of the tandem HMG boxes in HMG1 and 2 for a variety of DNA targets, including four-way junctions, but not distorted DNA minicircles, to which the proteins bind with very high affinity. HMG1 and 2 appear to play important architectural roles in the assembly of nucleoprotein complexes in a variety of biological processes, for example V(D)J recombination, the initiation of transcription, and DNA repair.

Structural requirements for cooperative binding of HMG1 to DNA minicircles.

DNA minicircles, where the length of DNA is below the persistence length, are highly effective, preferred, ligands for HMG-box proteins. The proteins bind to them "structure-specifically" with affinities in the nanomolar range, presumably to an exposed widened minor groove. To understand better the basis of this preference, we have studied the binding of HMG1 (which has two tandem HMG boxes linked by a basic extension to a long acidic tail) and Drosophila HMG-D (one HMG box linked by a basic region to a short and less acidic tail), and their HMG-box domains, to 88 bp and 75 bp DNA minicircles. In some cases we see cooperative binding of two molecules to the circles. The requirements for strong cooperativity are two HMG boxes and the basic extension; the latter also appears to stabilize and constrain the complex, preventing binding of further protein molecules. HMG-D, with a single HMG box, does not bind cooperatively. In the case of HMG1, the acidic tail is not required for cooperativity and does not affect binding significantly, in contrast to a much greater effect with linear DNA, or even four-way junctions (another distorted DNA substrate). Such effects could be relevant in the hierarchy of binding of HMG-box proteins to DNA distortions in vivo, where both single-box and two-box proteins might co-exist, with or without basic extensions and acidic tails.

Lu2SiO5 by single-crystal X-ray and neutron diffraction.

The structure of dilutetium silicon pentaoxide, Lu2SiO5, has isolated ionic SiO4 tetrahedral units and non-Si-bonded O atoms in distorted OLu4 tetrahedra. The OLu4 tetrahedra form edge-sharing infinite chains and double O2Lu6 tetrahedra along the c axis. The edge-sharing chains are connected to the O2Lu6 double tetrahedra by isolated SiO4 units. The structure has been determined by neutron diffraction.

(Li0.91Mn0.09)Mn2O4.

Lithium manganese oxide crystals with composition (Li(0.91)Mn(0.09))Mn(2)O(4) were synthesized by a flux method. The crystals have a structure closely related to that of the cubic spinel LiMn(2)O(4), but 9% of the lithium ions in the tetrahedral 4a site are substituted by Mn(2+) ions. This substitution lowers the average Mn oxidation state below 3.5+, resulting in a Jahn-Teller distortion of the MnO(6) octahedron.

Acquired immunodeficiency syndrome-associated cancers in Sub-Saharan Africa.

Sub-Saharan Africa is considered home to more than 60% of all human immunodeficiency virus (HIV) infected cases, with an estimated adult prevalence of 8.0%. It is stated that this region has contributed more than 90% of childhood deaths related to HIV infection and about 93% of childhood acquired immunodeficiency syndrome (AIDS)-related deaths. Although no country in Africa is spared of the infection, the bulk is seen in East and South Africa, with the highest recorded rates of 20% to 50% in Zimbabwe. On the other hand, West Africa is less affected, while countries in Central Africa have relatively stable infection rates. Although infections, especially tuberculosis, have emerged as the most important HIV/AIDS-associated killers in recent times, AIDS-associated malignancies are increasingly identified in the late stages. As a result of incomplete data from African countries, it is unclear whether the epidemiology and risks of these cancers are the same as observed in the developed countries. Since the advent of AIDS, epidemic Kaposi's sarcoma (KS) has become more common in both sexes in Africa, with a dramatic lowering of the male to female ratio from 19:1 to 1.7:1, especially in East Africa. Although there has been a rising trend of AIDS-associated non-Hodgkin's lymphoma (NHL) worldwide, there is an apparently lower risk in Africa compared with that in the developing world. At present, there is no strong evidence linking increased incidence of invasive cervical cancer to the HIV epidemic; however, some studies have demonstrated an association between HIV and the increased prevalence of human papilloma virus (HPV) and cervical intraepithelial neoplasia (CIN). On the other hand, HIV infection is now established as a risk factor for the development of squamous cell neoplasia of the conjunctiva based on studies from Rwanda, Malawi, and Uganda. Despite the problems and limitations of information from sub-Saharan Africa, interesting trends of HIV/AIDS-related cancers have emerged from comparison of available data. Semin Oncol 28:198-206.

Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain.

Heterochromatin protein 1 (HP1) is localized at heterochromatin sites where it mediates gene silencing. The chromo domain of HP1 is necessary for both targeting and transcriptional repression. In the fission yeast Schizosaccharomyces pombe, the correct localization of Swi6 (the HP1 equivalent) depends on Clr4, a homologue of the mammalian SUV39H1 histone methylase. Both Clr4 and SUV39H1 methylate specifically lysine 9 of histone H3 (ref. 6). Here we show that HP1 can bind with high affinity to histone H3 methylated at lysine 9 but not at lysine 4. The chromo domain of HP1 is identified as its methyl-lysine-binding domain. A point mutation in the chromo domain, which destroys the gene silencing activity of HP1 in Drosophila, abolishes methyl-lysine-binding activity. Genetic and biochemical analysis in S. pombe shows that the methylase activity of Clr4 is necessary for the correct localization of Swi6 at centromeric heterochromatin and for gene silencing. These results provide a stepwise model for the formation of a transcriptionally silent heterochromatin: SUV39H1 places a 'methyl marker' on histone H3, which is then recognized by HP1 through its chromo domain. This model may also explain the stable inheritance of the heterochromatic state.

HMG1 and 2, and related 'architectural' DNA-binding proteins.

The HMG-box proteins, one of the three classes of high mobility group (HMG) chromosomal proteins, bend DNA and bind preferentially to distorted DNA structures. The proteins appear to act primarily as architectural facilitators in the assembly of nucleoprotein complexes; for example, in effecting recombination and in the initiation of transcription. HMG-box proteins might be targeted to particular DNA sites in chromatin by either protein-protein interactions or recognition of specific DNA structures.

Two DNA-binding sites on the globular domain of histone H5 are required for binding to both bulk and 5 S reconstituted nucleosomes.

We have previously shown the existence of two DNA-binding sites on the globular domain of H5 (termed GH5), both of which are required for nucleosome organisation, as judged by the protection of a 166 bp chromatosome intermediate during micrococcal nuclease digestion of chromatin. This supports a model in which GH5 contacts two duplexes on the nucleosome. However, studies of a nucleosome assembled on the 5 S rRNA gene have argued against the requirement for two DNA-binding sites for chromatosome protection, which has implications for the role of linker histones. We have used this proposed difference in the requirement for a second site on the globular domain in the two models as a means of investigating whether bulk and reconstituted 5 S nucleosomes are indeed fundamentally different. GH5 protects a 166 bp chromatosome in both "bulk" and 5 S systems, and in both cases protection is abolished when all four basic residues in site II are replaced by alanine. Binding to four-way DNA junctions, which present a pair of juxtaposed duplexes, is also abolished. Single mutations of the basic residues did not abolish chromatosome protection in either system, or binding to four-way junctions, suggesting that the residues function as a cluster. Both bulk and 5 S nucleosomes thus require a functional second DNA-binding site on GH5 in order to bind properly to the nucleosome. This is likely to reflect a similar mode of binding in each case, in which two DNA duplexes are contacted in the nucleosome. There is no indication from these experiments that linker histones bind fundamentally differently to 5 S and bulk nucleosomes.