Management of Opioid Use Disorder in Sickle Cell Anaemia amidst Growing Menace in the General Population

Nigeria has a very high number of sickle cell disease (SCD) population with addition of 150,000 babies born annually with the disease. Early infant diagnosis and good care make many of these babies survive to adulthood. Severe pain requiring moderately strong or very strong analgesics is a common presentation of patients with Sickle Cell Anaemia. Paediatricians find ready usefulness of Opioids which are very useful for the painful episodes among these patients. Therefore, the chances of abuse and addiction to these medications become very high and constitute additional burden on the deficient manpower in the health sector. Opioid Use Disorder among Sickle Cell Disease patients has subtle presentation, so a high index of suspicion is required to make both the diagnosis and referral to treatment centres. In this review, the epidemiology, pain pathophysiology, behavioural and pharmacologic therapy have been re-examined.

Isolation and characterisation of mesenchymal stem cells derived from human placenta tissue

AIM: To explore the feasibility of placenta tissue as a reliable and efficient source for generating mesenchymal stem cells (MSC). METHODS: MSC were generated from human placenta tissue by enzymatic digestion and mechanical dissociation. The placenta MSC (PLC-MSC) were characterized for expression of cell surface markers, embryonic stem cell (ECS) gene expression and their differentiation ability into adipocytes and osteocytes. The immunosuppressive properties of PLC-MSC on resting and phytohemagglutinin (PHA) stimulated allogenic T cells were assessed by means of cell proliferation via incorporation of tritium thymidine (3H-TdR). RESULTS: The generated PLC-MSC appeared as spindle-shaped cells, expressed common MSC surface markers and ESC transcriptional factors. They also differen-tiated into adipogenic and osteogenic lineages when induced. However, continuous cultivation up to passage 15 caused changes in morphological appearance and cellular senescence, although the stem cell nature of their protein expression was unchanged. In terms of their immunosuppressive properties, PLC-MSC were unable to stimulate resting T cell proliferation; they inhibited the PHA stimulated T cells in a dose dependent manner through cell to cell contact. In our study, MSC generated from human placenta exhibited similar mesenchymal cell surface markers; MSC-like gene expression pattern and MSC-like differentiation potential were comparable to other sources of MSC. CONCLUSION: We suggest that placenta tissues can serve as an alternative source of MSC for future experimental and clinical studies.

Simultaneous occurrence of colonic adenocarcinoma and MALT lymphoma:A series of three cases

Simultaneous development of adenocarcinoma and primary B cell lymphoma of mucosa-associated lymphoid tissue(MALT) lymphoma of the colon is rare;only one case has so far been reported out of 13 cases with the coexistence of colonic adenocarcinoma with involvement of the colon by lymphoma.We hereby present three more cases,two females(aged 75 and 71 years) and a male(aged 72 years).All three underwent colectomy based on a preoperative biopsy revealing colonic carcinoma.Histological examination of the resection specimens disclosed a colonic adenocarcinoma in two cases,whereas a tubulovillous adenoma with superficial foci of intraepithelial adenocarcinoma was seen in the thirdcase.Moreover,in all three cases,a coexisting MALT lymphoma was diagnosed in the colon(1 case),in both colon and adjacent lymph nodes(1 case) or in colonic lymph nodes and omentum(1 case).In the last case,a post-operative bone marrow biopsy revealed extensive infiltration of the bone marrow,due to which the patient received postoperative chemotherapy.Diagnostic and treatment issues are briefly discussed.

Biermer Disease: Initial Presentation and Follow-Up of 66 Patients in Internal Medicine Department in Senegal

Pernicious anemia in black people, is little known. Through this study we assess its diagnostic and evolutive aspects, and compare vitamin therapy B12 intramuscular and oral. Sixty six Biermer disease patients followed (January 2000-June 2014) at Internal Medicine Department of Aristide Le Dantec University Teaching Hospital (Senegal) are included. They were 26 men and 46 women (gender ratio: 0.65), who had a mean age of 47.84 years ± 15.25 years. Patients consulted for anemia (65 cases), acquired melanodermia (36 cases), gastrointestinal symptoms (30 cases), peripheral neuropathy (27 cases), venous thrombosis (2 cases), acute depression (1 case). Macrocytosis was observed in 52 cases. The mean hemoglobin in the vitamin B12 intramuscular group (52 patients) or oral group (14 patients) was the inclusion: 6.55 g/dl ± 3.12 g/dl vs 6.52 g/dl ± 2.18 g/dl (p = 0.04);and at day 8 treatment: 8.69 g/dl ± 2.49 g/dl vs 8.85 g/dl ± 1.9 g/dl (p = 0.43). Neurological and vascular presentations are unusual in contrast to macrocytic anemia. Oral administration of vitamin B12, simple and effective should be recommended in country with limited resources.

Why some tumours trigger neovascularisation and others don't:the story thus far

Background:Angiogenesis is not essential for tumours to develop and expand,as cancer can also grow in a nonangiogenic fashion,but why this type of growth occurs is unknown.Surprisingly,our data from mRNA transcription profiling did not show any differences in the classical angiogenic pathways,but differences were observed in mitochondrial metabolic pathways,suggesting a key role for metabolic reprogramming.We then validated these results with mRNA profiling by investigating differential protein expression via immunohistochemistry in angiogenic and non-angiogenic non-small cell lung cancers(NSCLCs).Methods:Immunohistochemical staining for 35 angiogenesis- and hypoxia-related biomarkers were performed on a collection of 194 angiogenic and 73 non-angiogenic NSCLCs arranged on tissue microarrays.Sequencing of P53 was performed with frozen tissue samples of NSCLC.Results:The non-angiogenic tumours were distinguished from the angiogenic ones by having higher levels of proteins associated with ephrin pathways,mitochondria,cell biogenesis,and hypoxia-inducible factor 1(HIF1) regulation by oxygen and transcription of HIF-controlled genes but lower levels of proteins involved in the stroma,cell-cell signaling and adhesion,integrins,and Delta-Notch and epidermal growth factor(EGF)-related signaling.However,proteins classically associated with angiogenesis were present in both types of tumours at very comparable levels.Cytoplasmic expression of P53 was strongly associated with non-angiogenic tumours.A pilot investigation showed that P53 mutations were observed in 32.0%of angiogenic cases but in 71.4%of non-angiogenic tumours.Conclusions:Our observations thus far indicate that both angiogenic and non-angiogenic tumours experience hypoxia/HIF and vascular endothelial growth factor(VEGF) pathway protein expression in a comparable fashion.However,angiogenesis does not ensue in the non-angiogenic tumours.Surprisingly,metabolic reprogramming seems to distinguish these two types of neoplastic growth.On the basis of these results,we raise the hypothesis that in some,but not in all cases,initial tissue remodeling and/or inflammation could be one of the secondary steps necessary to trigger angiogenesis.In the non-angiogenic tumours,in which neovascularisation fails to occur,HIF pathway activation could be the driving force toward metabolic reprogramming.

The Impact of Human Immunodeficiency Virus Infection (HIV) on Lymphoma in South Africa

Human immunodeficiency virus (HIV) infection is endemic in South Africa. Non-Hodgkin lymphoma (NHL) occurs with increased frequency in HIV seropositive individuals. The increase in NHL has been more marked in the last decade, with HIV being the major contributor to this increase. More than 70% of the adult NHL patients at Chris Hani Baragwanath Academic Hospital (CHBAH), Soweto, Johannesburg, are HIV seropositive. In addition, HIV has impacted on the clinical presentation—being more aggressive and atypical. Histologically, HIV-NHL typically manifests as B-cell, high grade lymphomas, including diffuse large B-cell lymphoma (DLBCL);Burkitt lymphoma (BL);B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL and plasmablastic lymphoma. The latter two entities, which were previously rare or unknown, have gained prominence in the last decade, occurring primarily in HIV seropositive individuals. HIV-NHL, being associated with all these adverse prognostic factors results in a poorer overall survival.

A Rare Entity of Angioimmunoblastic T-Cell Lymphoma

Introduction: Angioimmunoblastic T Cell Lymphoma (AITL) is a well-recognized subtype of peripheral T cell lymphoma. It occurs predominantly in the lymph nodes with presence of systemic symptoms and carries a dismal prognosis. AITL accounts for about 1% - 2% of all cases of non-Hodgkin lymphoma. Case presentation: A 59-year-old gentleman of Chinese ethnicity with no prior medical illness presented to Tengku Ampuan Afzan Hospital with a two-month history of fever, anorexia, unintentional weight loss and generalized lymphadenopathies. Physical examination revealed diffuse lymphadenopathies involving the cervical, axillary and inguinal regions bilaterally. He had hepatosplenomegaly. An excisional biopsy of the cervical and inguinal lymph nodes was compatible with AITL. The bone marrow biopsy demonstrated disease infiltration. He was treated with 6 cycles of Etoposide-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) induction chemotherapy followed by consolidation high dose therapy-autologous stem cell transplant (HDT-ASCT). He achieved complete remission on 18-Fluoro- deoxyglucose Positron Emission Tomography (18-FDG-PET) imaging. His bone marrow biopsy showed disease clearance. Conclusion: The diagnosis of AITL remains challenging and often poses a dilemma to clinicians and lymphoma pathologists. The natural history of AITL remains very variable with many of them relapsing subsequently despite achieving prior complete remission.

MGUS:Proposal for outpatient management

The term monoclonal gammopathy of undetermined significance(MGUS) indicates the presence of a monoclonal protein(M-protein) without features of multiple myeloma, Waldenstrom's macroglobulinemia, primary amyloidosis or malignant lymphoproliferative disorders(LPD). While several guidelines on the treatment of LPD exist, many doubts and perplexities still exist on who should treat a MGUS, when and how. Even where MGUS does not require any therapy, the risk of progression to a LPD is 1% per year. This risk does not diminish over time and persists even in patients(pts) whose condition has remained stable for decades, and a prolonged follow up is, therefore, recommended. We met primary care doctors to share and agree on criteria for the management of outpatients with MGUS. Our aim is to draw up guidelines or, at least, suggestions that may help to determine which MGUS pts could be cared for by the primary care doctor and which should be followed by the hematologist. We suggest that once a MGUS is diagnosed, the primary care physician will attend patients with M-protein < 15 g/L if Ig G and pts with M-protein< 10 g/L if Ig A or Ig M, without end-organ damage and without signs and symptoms of LPD. However, a hematological evaluation is recommended for patients with M-protein Ig G > 15 g/L, or M-protein Ig A > 10 g/L, or Ig M > 10 g/L, or any M-protein with end-organ damage(not attributable to any others causes) or with signs and symptoms of LPD, or rapidly increasing M-protein(> 5 g/L per year).

Long-term effect of autologous progenitor cell therapy to induce neo angiogenesis in patients with critical limb ischemia transplantated via intramuscular vs combined intramuscular and distal retrograde intra venous

Critical limb ischemia is a medical condition that decreases blood flow and limb oxygen supply;this disease in its late stages of progression leads to only two possible options: either surgical bypass revascularization or limb amputation. We investigated a novel method using autologous transplantation of progenitor cells derived from mobilized peripheral blood bone marrow mononuclear cells to evaluate its long-term effect as a cell therapy to induce neo-angiogenesis and restore blood flow in the affected ischemic limbs. A total of 20 ischemic limbs from critical limb ischemia diagnosed patients, non candidates to surgical revascularization were transplanted with autologous progenitor cells by either intramuscular combined with intravenous (group A) or intramuscular (group B) procedure. Patients were monitored during 31 months. Treatment efficacy was evaluated according to the following parameters: ankle brachial index which increased at a range of 0.29-1.0 in group A and 0.40-0.90 in group B;pain-free walking distance which increased at a range of 50-600 m in group A and 50-300 m in group B;and blood perfusion (measured by Laser Doppler) which increased at a range of 48-299 in group A and 135-225 in group B. We achieved 90% treated ischemic limbs free of amputation in both transplanted groups. Results here described provide a safe, efficient and minimally invasive therapy with progenitor cells to induce angiogenesis and preserve limbs from amputation in CLI diagnosed patients.