HIV/AIDS among pastoralists and refugees in north-east Africa: a neglected problem

The eight member states (Djibouti, Eritrea, Ethiopia, Kenya, Somalia, South Sudan, Sudan and Uganda) of the Intergovernmental Authority for Development (IGAD) have the largest proportions of cross-border mobile pastoralists and refugees in Africa. Although all IGAD countries have had national HIV/AIDS prevention, care and treatment programmes since the late 1980s, the IGAD Regional HIV & AIDS Partnership Program was (IRAPP) established in 2007 to mitigate the challenges of HIV among neglected pastoral and refugee communities. This article assesses vulnerability of pastoralists and refugee communities to HIV and interventions targeting these groups in the IGAD countries. Outcomes from this study may serve as a baseline for further research and to improve interventions. Published articles were accessed through web searches using PubMed and Google Scholar engines and unpublished documents were collected manually. The search terms were HIV risk behaviour, vulnerability, HIV prevalence and interventions, under the headings pastoralists, refugees, IGAD and north-east Africa for the period 2001–2014. Of the 214 documents reviewed, 78 met the inclusion criteria and were included. Most HIV/AIDS related studies focusing of pastoral communities in IGAD countries were found to be limited in scope and coverage but reveal precarious situations. Sero-prevalence among various pastoral populations ranged from 1% to 21% in Ethiopia, Kenya, Somalia and Uganda and from 1% to 5% among refugees in Sudan, Kenya and Uganda. Socioeconomic, cultural, logistic, infrastructure and programmatic factors were found to contribute to continuing vulnerability to HIV. Interventions need to be further contextualised to the needs of those impoverished populations and integrated into national HIV/AIDS programmes. HIV/AIDS remains a major public health concern among the pastoral and refugee communities of IGAD countries. This calls for IGAD to collaborate with national and international partners in designing and implementing more effective prevention and control programmes. Furthermore, interventions must extend beyond the health sector and improve the livelihood of these populations.     

Dietary honey and ginseng protect against carbon tetrachloride-induced hepatonephrotoxicity in rats

Liver diseases are amongst the most serious health problems in the world today and hepatocellular carcinoma is one of the world's deadliest cancers. The aim of the current study was to evaluate the protective effect of sider honey and/or Korean ginseng extract (KGE) against carbon tetrachloride (CCl₄)-induced hepato-nephrotoxicity in rat. Eighty male Sprague-Dawley (SD) rats were allocated into different groups and over a 4-week period, they orally received honey and/or KGE or were treated either with CCl₄ alone (100 mg/kg b.w) or with CCl₄ after a pretreatment period with honey, KGE or a combination of both. Clinical, clinico-pathological and histopathological evaluations were done and CCl₄-treated groups were compared with rats receiving no treatment and with rats given honey, KGE or a combination of these substances. The results indicated that oral administration of CCl₄ induced severe hepatic and kidney injury associated with oxidative stress. The combined treatment with CCl₄ plus honey and/or KGE resulted in a significant improvement in all evaluated parameters. This improvement was prominent in the group receiving CCl₄ after combined pretreatment with honey and KGE. Animals receiving honey and/or KGE (without CCl₄-treatment) were comparable to the control untreated group. It could be concluded that honey and KGE protect SD rats against the severe CCl₄-induced hepatic and renal toxic effects. Our results suggest that the protective activity of honey and KGE may have been related to their antioxidant properties.     

Prospective study of thymic carcinoids in patients with multiple endocrine neoplasia type 1

Little is known of the natural history of thymic carcinoids in multiple endocrine neoplasia type 1 (MEN1). This is important because in 1993 they were identified as a frequent cause of death, yet only small retrospective studies and case reports exist. We report results of a prospective study of 85 patients with MEN1 evaluated for pancreatic endocrine tumors and followed over a mean of 8 yr with serial chest computed tomography, magnetic resonance imaging (MRI), chest x-ray, and, since 1994, octreoscans [somatostatin receptor scintigraphy (SRS)]. Seven patients (8%) developed thymic carcinoids. Patients with and without carcinoids did not differ in clinical, laboratory, or MEN1 tumor features, except for male gender and the presence of a gastric carcinoid. All thymic tumors were hormonally inactive. Four thymic carcinoids lacked 11q loss of heterozygosity, although it was found in three pancreatic endocrine tumors. Computed tomography and/or MRI were more sensitive than SRS or chest x-ray in detecting tumors initially or with recurrence. All patients underwent resection of the thymic carcinoid, and in all patients followed more than 1 yr, the tumor recurred. Bone metastases developed in two patients and were detected early only on MRI, not SRS. This study provides information on early thymic carcinoids and allows modifications of existing guidelines to be recommended for their diagnosis, surveillance, and treatment.     

Fractionated gemtuzumab ozogamicin and standard dose cytarabine produced prolonged second remissions in patients over the age of 55 years with acute myeloid leukemia in late first relapse

Gemtuzumab ozogamicin (fGO), a humanized anti‐CD33 monoclonal antibody linked to calicheamicin in combination with intensive chemotherapy gives high response rates in adult acute myeloid leukemia (AML) patients in relapse. However, reduced intensity chemotherapy in combination with fractionated GO has not been tested in aged relapsing patients. Patients from our institution with CD33+ AML aged 55 years or more in first late relapse (≥6 months) were proposed participation in a GO compassionate use program. Induction therapy consisted in fractionated GO (fGO; 3 mg/m², days 1, 4, 7) with standard‐dose cytarabine (200 mg/m²/day, 7 days). Patients were consolidated with two courses of GO and intermediate dose cytarabine. Twenty‐four patients (median age 68 years) received fGO with cytarabine. Median follow‐up was 42 months. The response rate was 75%, including complete remission (CR) in 16 patients and CR with incomplete platelet recovery (CRp) in two patients. Two‐year overall survival (OS) was 51% (95% CI: 28–69) and 2 years relapse‐free survival (RFS) was 51% (95%CI: 25–72). Duration of second CR (CR2) was longer than first CR (CR1) in 9 out of 18 patients. Minimal residual disease (MRD) was negative in evaluable patients in CR2, particularly in NPM1 mutated cases. Toxicity was in line with that of the same fractionated single agent GO schedule. Fractionated GO with low intensity chemotherapy produced high response rates and prolonged CR2 in aged AML patients in first late relapse. Am. J. Hematol. 89:399–403, 2014. © 2013 Wiley Periodicals, Inc.     

Fatal outcome of posterior reversible encephalopathy syndrome (PRES) in a lupus nephropathy patient: A case report

Posterior reversible encephalopathy syndrome is a rare underestimated condition, that generally complicates a rise in blood pressure in an acute setting. This entity has been increasingly identified in patients with systemic lupus erythematosus disease. PRES is challenging to diagnose seeing as it presents with nonspecific neurological symptoms, such as head-aches, confusion, seizures, visual changes or a coma, and can mimic neuropsychiatric lupus. Imaging plays a necessary role in confirming this diagnosis, as it is characterized by vasogenic edema of the posterior white matter, in which the distribution is bilateral and symmetrical. Although this syndrome is rare, early diagnosis allows a prompt treatment and therefore a favorable outcome. We present a case report of PRES in a 14-year-old female previously diagnosed with lupus nephropathy, who presented to the emergency department with seizures and uncontrolled hypertension, that was unfortunately not reversible is this patient.     

Doppler echocardiography and arhythmogenic right ventricular dysplasia

The aim of this study is to evaluate new echocardiographic modes in diagnosis of arrhythmogenic right ventricular dysplasia (ARVD). Our study is prospective, including ten patients with ARVD and a control group of ten healthy subjects. Transthoracic echocardiography included evaluation of classical criteria's, cross sectional measurements of the right ventricular. M mode and pulsed tissue Doppler techniques were used for quantitative measurement of tricuspid annular motion at the lateral and septal positions. Assessed by M mode, the total amplitude of the tricuspid annular motion was decreased in the lateral and septal positions in the patients compared with the controls. The tissue Doppler velocity pattern showed decreased early diastolic peak annular (Ea) velocity and an accompanying decrease in early (Ea) to late diastolic(Aa) velocity ratio in all positions; the systolic annular velocity was decreased only in the lateral position. Tricuspid annular measurement are valuable, easy to obtain and allow quantitative assessment of right ventricular function. ARVC patients showed an abnormal velocity pattern that may be an early but non specific sign of disease.     

Her-2/neu expression and gene amplification in gastrinomas: correlations with tumor biology,growth, and aggressiveness

A proportion of gastrointestinal neuroendocrine tumors are aggressive; however, little is known of molecular determinants of their growth, and molecular studies have identified no useful prognostic factors. Overexpression of HER-2/neu is common in some nonendocrine tumors, frequently correlates with increased tumor aggressiveness, and can be used as a basis of treatment with trastuzumab. Little is known of its expression in malignant pancreatic endocrine tumors. In the present study HER-2/neu gene amplification and expression was determined in 43 gastrinomas from different patients. Results were correlated with clinical, laboratory, and tumor characteristics including tumor growth. HER-2/neu gene amplification was assessed by differential PCR, mRNA levels assessed by quantitative PCR, and protein by immunohistochemistry. Fourteen percent of patients had HER-2/neu gene amplification in tumors compared with levels in their WBCs. HER-2/neu mRNA varied over a 700-fold range. However, only 3% exceeded levels seen in normal pancreas, and immunohistochemistry did not show protein overexpression in any tumor (n = 10). HER-2/neu mRNA levels were significantly higher (P = 0.032) in tumors associated with liver metastases but not with tumor location or size. These results show that HER-2/neu amplification/overexpression does not seem to play a role in the molecular pathogenesis of most gastrinomas, as suggested in a previous study involving small numbers of cases. However, mild gene amplification occurs in a subset, and overexpression is associated with aggressiveness. Therefore, HER-2/neu levels could have prognostic significance as well as identify a patient subset with gastrinomas who might benefit from trastuzumab treatment.     

Gastric carcinoid tumors in multiple endocrine neoplasia-1 patients with Zollinger-Ellison syndrome can be symptomatic, demonstrate aggressive growth, and require surgical treatment

BACKGROUND: Gastric carcinoid tumors occur in 15% to 50% of patients with multiple endocrine neoplasia-1/Zollinger-Ellison syndrome (MEN-1/ZES) but are thought to be benign. We report 5 patients with MEN-1/ZES with symptomatic, aggressive gastric carcinoid tumors that required surgical procedures. METHODS: This was a retrospective chart review. RESULTS: Each patient had MEN-1/ZES. Each patient had innumerable gastric carcinoid tumors with symptoms. The fasting gastrin level was 47,000 pg/mL (normal, <200 pg/mL); the basal acid output was 79 mEq/hr (n = 3), and the age at surgical exploration was 47 +/- 6 years, with a duration of MEN-1 of 21 +/- 3 years and of ZES of 15 +/- 2 years. All patients had elevated 5-HIAA or serotonin levels. Somatostatin receptor scintigraphy showed increased stomach uptake in 4 patients (80%). Four patients had a total gastrectomy; 4 patients had lymph node metastases removed, and 3 patients had liver metastases resected. One patient who did not have a total gastrectomy had liver carcinoid metastases. CONCLUSIONS: These results demonstrate that gastric carcinoid tumors in patients with longstanding MEN-1/ZES may be symptomatic, aggressive, and metastasize to the liver. With increased long-term medical treatment and life expectancy, these tumors will become an important determinant of survival.     

Electron microscopic localisation of P2X4 receptor subunit immunoreactivity to pre- and post-synaptic neuronal elements and glial processes in the dorsal vagal complex of the rat

P2X receptors are ligand gated ion channels activated by extracellular ATP. There are seven P2X subunits, P2X(1-7), and all are expressed in the CNS. The P2X(4) receptor subunit (P2X(4)R) is likely to be important in the CNS as it has been reported to be expressed throughout the brain and spinal cord. However, P2X(4)Rs have been identified as restricted to neurones, only in glia or expressed in both neurones and glia with no discernible relationship to CNS region or epitope target of antibodies used for staining. In addition, although there are particularly high levels of mRNA encoding P2X(4)R in the brainstem, previous immunohistochemical studies have revealed only indistinct staining. We therefore examined the distribution of P2X(4)R in the dorsal vagal complex (DVC) of the brainstem using immunohistochemistry in sections obtained from adult Wistar rats transcardially perfused with aldehyde fixatives. When this revealed staining identifiable only as small puncta at the light microscope level, we examined the area with electron microscopy. This ultrastructural study revealed that P2X(4)R immunoreactivity (IR) was present in neurones at both pre- and post-synaptic sites as well as in glial cell processes and somata. This P2X(4)R-IR was localised adjacent to plasma membranes, as well as internally in membrane bound structures resembling endosomes. Immunoreactivity in endosomes was more prominent following antigen retrieval protocols. Localisation of P2X(4)R-IR in astrocytes, identified by the presence of glial fibrillary acidic protein (GFAP), was confirmed using immunofluorescence. The presence of P2X(4)Rs in the dorsal vagal complex is consistent with expression studies, but some reasons for a lack of correlation with pharmacological studies are discussed. The P2X(4)R is therefore expressed by neurones and glia in the dorsal vagal complex and may play a role in mediating extracellular signalling by ATP in this region.