Stable thrombus formation on irradiated microvascular endothelial cells under pulsatile flow: Pre-testing annexin V-thrombin conjugate for treatment of brain arteriovenous malformations.

BACKGROUND: Our goal is to develop a vascular targeting treatment for brain arteriovenous malformations (AVMs). Externalized phosphatidylserine has been established as a potential biomarker on the endothelium of irradiated AVM blood vessels. We hypothesize that phosphatidylserine could be selectively targeted after AVM radiosurgery with a ligand-directed vascular targeting agent to achieve localized thrombosis and rapid occlusion of pathological AVM vessels. OBJECTIVE: The study aim was to establish an in vitro parallel-plate flow chamber to test the efficacy of a pro-thrombotic conjugate targeting phosphatidylserine. METHODS: Conjugate was prepared by Lys-Lys cross-linking of thrombin with the phosphatidylserine-targeting ligand, annexin V. Cerebral microvascular endothelial cells were irradiated (5, 15, and 25 Gy) and after 1 or 3 days assembled in a parallel-plate flow chamber containing whole human blood and conjugate (1.25 or 2.5 µg/mL). Confocal microscopy was used to assess thrombus formation after flow via binding and aggregation of fluorescently-labelled platelets and fibrinogen. RESULTS AND CONCLUSIONS: The annexin V-thrombin conjugate induced rapid thrombosis (fibrin deposition) on irradiated endothelial cells under shear stress in the parallel-plate flow device. Unconjugated, non-targeting thrombin did not induce fibrin deposition. A synergistic interaction between radiation and conjugate dose was observed. Thrombosis was greatest at the highest combined doses of radiation (25 Gy) and conjugate (2.5 µg/mL). The parallel-plate flow system provides a rapid method to pre-test pro-thrombotic vascular targeting agents. These findings validate the translation of the annexin V-thrombin conjugate to pre-clinical studies.

Frequency of cryptococcal meningitis in HIV-1 infected patients in north central Nigeria.

BACKGROUND: Cryptococcal meningitis (CM) is the most common severe life threatening fungal infection in AIDS patients. It is an important cause of morbidity and mortality There is paucity of data on the prevalence of CM in Nigeria. We aimed to determine the frequency of CM, the clinical presentation and immunological profile. METHODS: A cross sectional study was carried out at the Jos University Teaching Hospital (JUTH). A total of 100 HIV-1 infected patients suspected of having meningitis or meningoencephalitis were subjected to cerebrospinal fluid (CSF) analysis (including Indian ink preparation and fungal culture by conventional methods) and CD4 count was determined using flow cytometry (count bit Y-R 1004 Partec Muster Germany). RESULTS: The freguency of CM was 36% in our cohort. The commonest clinical presentation included headache (100.0%), neck stiffness (77.8%), fever (72.0%), vomiting 55.6%), personality changes (55.6%), photophobia (27.8%) and convulsions (27.8%). The mean duration of symptoms was 24 +/- 22 days with a median of 17 days. The mean CD4 count was 89 +/- 60 cells/mm3 with a median of 82 cells/mm3. CONCLUSION: The high prevalence of CM and the associated severe immunosuppression underscores the importance of early diagnosis of HIV infection which may reduce the incidence of CM. There is the urgent need for access to Amphotericin B and fluconazole in resource constrained settings in addition to a wide access to HAART.

Chronic kidney disease screening and renoprotection in type 2 diabetes.

BACKGROUND: Type 2 diabetes (T2D) is a major cause of chronic kidney disease. Control of hypertension and the use of angiotensin converting enzyme inhibitors (ACEI) and/or angiotensin II receptor blockers especially in those with proteinuria have been shown to protect against chronic kidney disease and delay its progression to kidney failure. METHODS: We reviewed the medical records of 169 patients at 12 months with a view of auditing the screening for chronic kidney disease and the use of renoprotective measures. RESULTS: Urinalysis was done in 49.1% and serum creatinine in 50.3%. No patient had glomerular filtration rate estimated. Seventy nine (67.6%) of the hypertensive patients were on anti-hypertensives. ACEI was used in 49 (45.8%) of these patients BP control was optimal in 29.1%. CONCLUSION: There is poor adherence to guidelines on chronic kidney disease screening and renoprotection in T2D.

Chronic Kidney Disease Screening and Renoprotection in Type 2 Diabetes

Background: Type 2 diabetes (T2D) is a major cause of chronic kidney disease. Control of hypertension and the use of angiotensin converting enzyme inhibitors (ACEI) and/or angiotensin II receptor blockers especially in those with proteinuria have been shown to protect against chronic kidney disease and delay its progression to kidney failure. Methods: We reviewed the medical records of 169 patients at 12 months with a view of auditing the screening for chronic kidney disease and the use of renoprotective measures. Results: Urinalysis was done in 49.1and serum creatinine in 50.3. No patient had glomerular filtration rate estimated. Seventy nine (67.6) of the hypertensive patients were on anti-hypertensives. ACEI was used in 49 (45.8) of these patients BP control was optimal in 29.1. Conclusion: There is poor adherence to guidelines on chronic kidney disease screening and renoprotection in T2D

Hepatocellular carcinoma in Jos, Nigeria.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common abdominal malignancy, representing 80-90% of primary liver malignancies around the world. There is a disturbing trend of increased incidence of HCC around the world. We therefore, determined the trend of HCC in Jos. METHODS: A ten-year retrospective review was done of all cases of HCC which diagnoses were histologically confirmed as recorded in the Cancer Registry of Jos University Teaching Hospital. The patients' clinical case notes (including surgical and radiological findings) were also reviewed. RESULTS: A total of 71 cases of HCC (31.3% of 227 liver biopsies in the same period) were diagnosed within the 10-year period. There were 46 males and 25 females with a male/female ratio of 1.8:1. The age range of the patients was 23 years to 75 years, with a mean age of 45.4 +/- 13.1 years. Seventy two percent (72%) of them were between ages 21 years and 50 years. Only 28% were between 51 years and 80 years. The highest rate of 12 (17.1%) was seen in the year 2004. CONCLUSION: The study showed that there was a high prevalence of HCC in Jos, and that HCC was more prevalent in the younger age group compared to what obtains in developed nations.

Primary hyperparathyroidism presenting with severe hypertension in a middle aged Nigerian--a case report.

OBJECTIVE: To draw attention to primary hyperparathyroidism as a cause of severe hypertension. RESULTS: A 47 year old Nigerian male presented with headache, occasional blurring of vision and dyspnoea on mild exertion of 2/12 duration. He had been troubled by painful osteoarthritis of the knees for 2 years for which he was taking NSAIDs. He was found to be severely hypertensive, BP 210/130mmHg and had bilateral knee crepitus. BP was resistant to control on Nifedipine R and Moduretic. Serum urea, creatinine, uric acid were normal but there was hyperacalcaemia and hyperchloraemia. Haematological indices, urinalysis, microscopy and culture of urine were normal. Parathyroid hormone level was raised. A parathyroid MIBI scan study showed an extensive area of significance towards the inferior pole of the right lobe of thyroid medially with a second area of very low significance medial to the left pole. These findings indicated the presence of a right inferior parathyroid adenoma. He had parathyroid surgery and a large adenoma in the right inferior gland and a smaller left inferior gland were removed and confirmed histologically. Corrected calcium and parathyroid hormone levels dropped to normal, and the BP was easily controlled with Lisinopril 5mg daily subsequently. He is not currently on antihypertensive medication two years post surgery. CONCLUSION: This case highlights the need for thorough investigation of cases of hypertension to exclude specifically secondary causes, which in some cases may be endocrine in origin and may easily be corrected.

Willingness of Nigerian healthcare workers to donate kidneys.

BACKGROUND: The attitude of healthcare workers (HCW) towards organ donation is cardinal to the successful implementation and sustainability of transplant programs. We present the outcome of a survey among HCW in a single tertiary institution in Nigeria regarding their willingness to be living-related kidney donors. METHODS: Self-administered questionnaires were randomly distributed to HCW evaluating their attitude towards living-related kidney donation. RESULTS: Of the 650 questionnaires distributed only 502 responded (clinical medical students 51%, physicians 31.7% and nurses 17.3%); 75.6% of respondents were willing to be living donors while 5.8% were against it, and 18.5% were undecided. Multivariate analysis identified willingness to receive, perceived risk associated with kidney donation, and attitude towards cadaveric donation as independent predictors of willingness of HCW to be living donors. CONCLUSION: Nigerian HCW have a positive attitude toward kidney donation.

Meigs' syndrome presenting as haemorrhagic pleural effusion.

BACKGROUND: The association of a benign ovarian tumor with ascites and hydrothorax that resolve after tumor resection, known as Meigs syndrome is a rare clinical entity. Rarer still is the haemorrhagic form of the syndrome OBJECTIVE: To describe a case of benign ovarian tumour associated with ascites and bloody pleural effusion. METHODS: A thirty-seven year old woman was referred for the further management of a pleural effusion. A detailed clinical evaluation was carried out, including pleural fluid cytology, chest CT scan and laparatomy. Treatment included antituberculous therapy and finally ovariectomy. RESULTS: The physical examination and a pelvic ultrasonographic scan revealed ascites in addition to a right sided ovarian mass. A chest CT-scan did not show any intrathoracic mass. Repeated pleural fluid cytology showed mesothelial cells but was negative for malignancy. An ovariectomy was performed and histological examination revealed a thecoma fibroma. The pleural effusion and ascites resolved spontaneously thus confirming the diagnosis of Meigs' syndrome. CONCLUSION: Meigs' syndrome should be considered in the differential diagnosis in female patients with hemorrhagic pleural effusion.