Unveiling research training gaps in oncology: Evaluating a research capacity-building effort among Nigerian physicians.

Background: Cancers are a disease of growing public health importance in Africa, but cancer research capacity in the region is underdeveloped. The quest to foster and promote locally conceptualized and conducted oncology research in Africa have informed the African Research Group for Oncology's (ARGO) research capacity-building efforts in Nigeria. Aim: To evaluate the effectiveness of oncology research capacity-building initiatives among Nigerian senior trainees and junior faculty physicians. Subjects and Methods: Panel study design was employed to study Nigerian senior trainees and junior faculty physicians who participated in two research capacity-building symposia. Data were collected pre-and immediate post-symposia, and 3-month post-first symposium. Changes in knowledge were assessed using the Chi-square test and confidence levels using the Wilcoxon signed rank test. A P value of <0.05 was considered statistically significant. Results: : In the first symposium, the participants' pass rate in the knowledge-based questions improved from 9.8% to 46.7% to 81.5% at the baseline, immediate post-symposium, and 3-month post-symposium, respectively (P < 0.001). Likewise, the participants' confidence level in carrying out certain research-related activities increased after the second symposium (P < 0.001). Conclusion: The study concludes that building capacity for oncology research in low- and middle-income countries is possible with focused symposia and educational programs.

Mitochondria-targeted antioxidant MitoQ ameliorates ischaemia-reperfusion injury in kidney transplantation models.

BACKGROUND: Ischaemia-reperfusion (IR) injury makes a major contribution to graft damage during kidney transplantation. Oxidative damage to mitochondria is an early event in IR injury. Therefore, the uptake, safety, and efficacy of the mitochondria-targeted antioxidant MitoQ were investigated in models of transplant IR injury. METHODS: MitoQ uptake by warm and cooled pairs of pig and declined human kidneys was measured when preserved in cold static storage or by hypothermic machine perfusion. Pairs of pigs' kidneys were exposed to defined periods of warm and cold ischaemia, flushed and stored at 4°C with or without MitoQ (50 nmol/l to 250 µmol/l), followed by reperfusion with oxygenated autologous blood in an ex vivo normothermic perfusion (EVNP). Pairs of declined human kidneys were flushed and stored with or without MitoQ (5-100 µmol/l) at 4°C for 6 h and underwent EVNP with ABO group-matched blood. RESULTS: Stable and concentration-dependent uptake of MitoQ was demonstrated for up to 24 h in pig and human kidneys. Total blood flow and urine output were significantly greater in pig kidneys treated with 50 µmol/l MitoQ compared with controls (P = 0.006 and P = 0.007 respectively). In proof-of-concept experiments, blood flow after 1 h of EVNP was significantly greater in human kidneys treated with 50 µmol/l MitoQ than in controls (P ≤ 0.001). Total urine output was numerically higher in the 50-µmol/l MitoQ group compared with the control, but the difference did not reach statistical significance (P = 0.054). CONCLUSION: Mitochondria-targeted antioxidant MitoQ can be administered to ischaemic kidneys simply and effectively during cold storage, and may improve outcomes after transplantation.

Patient-Reported Barriers to Accessing Surgical Care in Northern Vanuatu.

BACKGROUND: The Lancet Commission on Global Surgery proposed that population access to essential surgical care within 2 h is a core indicator of health system preparedness. Little evidence exists to characterise access to surgical care for island nations, including Vanuatu, a lower middle-income country in the Western Pacific. METHODS: A descriptive, facility-based, survey of surgical inpatients was undertaken over a 6-month period at Northern Provincial Hospital (NPH), Espiritu Santo, Vanuatu. This evaluated demographics, access to surgical care using the 'three delays' framework and clinical outcomes. RESULTS: A total of 121 participants were surveyed (60% of all surgical admissions), of which 31% required emergency surgery. Only 20% of emergency surgical cases accessed care within 2 h. There were no emergency cases from Torba or Malekula. The first delay (delay in seeking care) had the biggest impact on timely access. There was a geographic gradient to access, gender preponderance (males), and a delay in seeking surgical care due to a preference for traditional healers. CONCLUSION: There is urgent need to improve access to surgical care in Vanuatu, particularly for Torba and Malekula catchments. Demographic, geographic, sociocultural, and economic factors impact on timely access to surgical care within the northern regions of Vanuatu and support the notion that addressing access barriers is more complex than ensuring the availability of surgical resources. Future priorities should include efforts to reduce the first delay, address the role of traditional medicine, and review the geographic disparities in access.

Challenges and Opportunities in the Provision of Surgical Care in Vanuatu: A Mixed Methods Analysis.

BACKGROUND: The Pacific island nation of Vanuatu faces a number of challenges in delivering surgical care to its population. We aimed to understand and document the barriers, opportunities and required actions to improve surgical care in the country using a mixed methods analysis which incorporated the perspectives of local health stakeholders. METHODS: A baseline quantitative assessment of surgical capacity in Vanuatu was carried out using the WHO situational analysis tool. Twenty semi-structured interviews were then conducted on the two main islands (Efate and Espiritu Santo) with surgeons, allied health staff, health managers, policy-makers and other key stakeholders, using a grounded theory qualitative case study methodology. Initial informants were identified by purposive sampling followed by snowball sampling until theoretical saturation was reached. Interviews were open and axially coded with subsequent thematic analysis. RESULTS: Vanuatu faces deficits in surgical infrastructure, equipment and human resources, especially in the rural provinces. Geographic isolation, poverty and culture-including the use of traditional medicine and low health literacy-all act as barriers to patients accessing timely surgical care. Issues with governance, human resourcing and perioperative care were commonly identified by stakeholders as key challenges facing surgical services. Increasing outreach clinics, developing efficient referral systems, building provincial surgical capacity and undertaking locally led research were identified as key actions that can improve surgical care. CONCLUSION: Documenting locally identified challenges and opportunities for surgical care in Vanuatu is an important first step towards developing formal strategies for improving surgical services at the country level.

Establishment of lipiodol as a fertility treatment - prospective study of the complete innovative treatment data set.

BACKGROUND: Our randomised controlled trial (RCT) found that a hysterosalpingogram (HSG) with the oil-soluble contrast medium (OSCM) lipiodol improves pregnancy rates amongst couples with unexplained and endometriosis-related infertility. These results were supported by the findings of our observational study of the first 100 women to undergo the procedure after it was offered as an innovative treatment in New Zealand from September 2003. AIM: To further assess the safety and efficacy of lipiodol procedures and present together the complete data set of the procedures performed in our RCT and those performed as innovative procedures (n = 296) prior to it being offered as a standard fertility treatment. METHODS: Women with infertility underwent a therapeutic lipiodol procedure by HSG technique with fluoroscopy X-ray screening. Primary outcomes were clinical pregnancy within six months of the procedure and live birth. RESULTS: The overall pregnancy rate for the 296 women was 40.2%. The live birth/ongoing pregnancy rate was 31.4%. The pregnancy rates for women under the age of 40 with endometriosis and unexplained infertility were 51.1 and 31.4%, respectively. CONCLUSION: Lipiodol can now be considered a standard treatment for both unexplained and endometriosis-related infertility. The precise mechanism behind the fertility-enhancing effect of lipiodol has yet to be elucidated. This study supports a mechanism of effect on the endometrium with possible enhanced receptivity of the endometrium to embryo implantation.

Evaluation of surgically excised mitral valves: revised recommendations based on changing operative procedures in the 1990s.

In 1990, 95 mitral valves from 54 women and 41 men (mean age, 61 years; age range, 8 to 85 years) were replaced (76%) or repaired (24%) at the Mayo Clinic. Functionally, 58% of the valves were purely regurgitant (MR), 25% were stenotic and regurgitant (MS-MR), and 17% were purely stenotic (MS). Postinflammatory (presumably rheumatic) disease accounted for 100% of MS cases, 92% of MS-MR cases, and 16% of MR cases. Other causes of pure MR included floppy valves (49%), ischemic heart disease (13%), infective endocarditis (9%), miscellaneous (9%), and indeterminate (4%). Thus, postinflammatory disease represented the major cause of both mitral stenosis (MS and MS-MR) and overall mitral valve disease in our surgical population. In contrast, floppy valves were the most commonly observed cause of pure MR. Among postinflammatory valves, 55% were completely excised and 45% had only the anterior leaflet removed; all were replaced. In contrast, floppy valves were incompletely excised in 96%; 67% were repaired and only 33% were replaced. Because mitral valves frequently are incompletely excised, rendering an accurate etiologic diagnosis requires not only a morphologic assessment of resected tissues but also a knowledge of the clinical history, operative details, and functional state of the valve.

New observations on the etiology of aortic valve disease: a surgical pathologic study of 236 cases from 1990.

Among 236 aortic valves surgically excised at the Mayo Clinic in 1990 (mean patient age, 66 years; age range, 10 to 92 years), 154 (65%) were stenotic, 58 (25%) were insufficient, and 24 (10%) were both stenotic and insufficient. Pure stenosis was related to calcification, and causes included degenerative (51%), bicuspid (36%), post-inflammatory (9%), and other (4%) reasons. Fourteen (9%) valves with pure stenosis also underwent ventricular septal myectomy, 12 for hypertrophy and two for co-existent hypertrophic cardiomyopathy. Pure insufficiency was not related to calcification, and causes included aortic root dilatation (50%), bicuspid valve (14%), post-inflammatory (14%), post-therapeutic (14%), and other (8%) reasons. Combined stenosis and insufficiency was secondary to degenerative calcification (46%), bicuspid and post-inflammatory etiologies (17% each), post-therapeutic (13%), and indeterminate (8%) causes. New observations include the following findings: (1) degenerative (senile) disease is the most common cause of aortic stenosis and combined stenosis and insufficiency at the Mayo Clinic, (2) aortic root dilatation is the most common cause of pure aortic insufficiency, (3) post-therapeutic aortic valve disease now leads to valve replacement in a substantial percentage of patients, particularly among those with insufficiency, (4) post-inflammatory (presumably rheumatic) disease is relatively uncommon in all three functional categories, (5) septal myectomy may be performed for hypertrophic states other than hypertrophic cardiomyopathy, and (6) adults with operated congenital heart disease are undergoing valve replacement for annular dilatation with insufficiency. Because of the increasing age of the general population, the prominence of age-related degenerative aortic valve calcification and aortic root dilatation may have important implications concerning future health care costs.

In vivo endogenous spore formation by Coxiella burnetii in Q fever endocarditis.

AIMS: To determine whether Coxiella burnetii, the aetiological agent of Q fever, undergoes endogenous spore-like formation, the crucial stage of the developmental cycle, in the infected cardiac valves of patients with chronic Q fever endocarditis. METHODS: Surgically removed valves from three cases of Q fever endocarditis were processed for electron microscopy. Sections were stained with potassium permanganate and uranyl acetate before being extensively examined by transmission electron microscopy. RESULTS: In all three cases endogenous spore-like formation was seen in the infected cardiac valves. CONCLUSIONS: As the factors that govern sporogenesis in C burnetii are still largely unknown, it is uncertain how important are the implications of the discovery of endogenous spore-like formation in Q fever endocarditis. However, this finding may add new dimensions to current thinking about the treatment of chronic Q fever.

Scrotal calcinosis: origin from dystrophic calcification of eccrine duct milia.

Scrotal calcinosis is a rare benign disorder considered idiopathic by most recent authors, although an origin from dystrophic calcification of epidermoid cysts has been proposed. In 3 of 4 cases which were otherwise typical of scrotal calcinosis, there was calcification of the contents of small cysts lined by stratified squamous epithelium. These structures were identified as eccrine duct milia because some of them communicated with eccrine ducts and there were ultrastructural features of eccrine duct differentiation in one case. The eccrine nature of the milia was confirmed using the immunoperoxidase technique for the demonstration of carcinoembryonic antigen (CEA) which serves as a marker of eccrine sweat glands. Since a transition could be seen between degenerating calcified milia and typical nodules, it appeared that the calcific deposits of scrotal calcinosis result from the breakdown of such lesions. Staining of deposits unassociated with cyst walls with the technique for the demonstration of CEA supported this conclusion. An advanced stage of evolution of the disease could account for the absence of visible cysts in many cases. We propose the term "hidrocalcinosis of the scrotum" for this distinctive form of cutaneous calcification.

Pulmonary veno-occlusive disease: diagnosis during life in four patients.

Pulmonary veno-occlusive disease is a rare form of primary pulmonary hypertension of unknown aetiology. Four cases were diagnosed in young patients. The diagnosis was suspected on the basis of clinical, radiological, echocardiographic, and catheter evidence and confirmed by taking a lung biopsy sample. In all patients the histology showed obstruction of the pulmonary veins by intimal fibrosis. The clinical course of all patients has been one of progressive deterioration. Although there is no specific treatment for this disease, to establish the diagnosis during life is of great importance in overall clinical management, including counselling the patient and family.

Changes in plasminogen activator inhibitor-1 levels in non-small cell lung cancer.

Increased urokinase plasminogen activator (uPA) levels are increased in a number of malignancies and have been correlated with decreased disease-free interval and decreased overall survival. We have, therefore, examined components of this plasminogen activating system in patients with Non-Small Cell Lung Cancer (NSCLC). Levels of uPA, urokinase-plasminogen activator receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1) were measured semiquantitatively in paraffin sections of tumours from 147 patients with NSCLC. Immunohistochemically stained sections of tumour were allocated a score for stain intensity and results correlated to: survival; tumour stage(T); nodal stage(N); stage grouping (I to IIIb), survival status and sex. Increased levels of PAI-1 were associated with a decreased survival in squamous cell carcinoma (SCC) X2 = 5.72, p = 0.017 (n = 74). There was a significant positive relationship between PAI-1 levels and N-stage (p = < 0.05), presence of nodal metastases (p = < 0.05), stage grouping (p = < 0.01) and extent of disease (p = < 0.05) in the total group and the SCC subgroup, but not adenocarcinoma. There was a significant positive relationship between PAI-1 levels and T-stage (p = < 0.05) in the total group, and survival status (p = < 0.05) in the SCC subgroup alone. uPA and uPAR levels were not significantly associated with tumour staging or survival. We conclude that increased PAI-1 antigen levels may be associated with a decreased survival in patients with SCC.