Insights in the pathophysiology of haemorrhagic strokes in a sub-Sahara African country, an epidemiological and MRI study.

OBJECTIVE: Intra-cerebral Haemorrhage (ICH) seems more prevalent in sub-Saharan Africa (SSA) than in High-Income Countries (HIC) with poorer clinical outcome. Higher impact of hypertension and/or amyloid angiopathy could account for this disproportion. Here, we sought to (i) retrospectively compare ICH clinical and imaging patterns in Belgium and Guinea and in a subsequent cohort (ii) prospectively compare brain MRI characteristics to seek evidence for a different proportion of amyloid angiopathy patterns. METHODS: Ninety one consecutive patients admitted for spontaneous ICH at Brussels Erasme-ULB Hospital and at Conakry Ignace Deen-UGANC were retrospectively compared in terms of ICH volume estimated with the ABC/2 method, clinical characteristics and modified ranking (mRS) score at 30 days. mRS was dichotomised as good outcomes (≤3) and poor outcomes (>3). A prospective cohort of 30 consecutive patients with ICH admitted at CHU Conakry Ignace Deen-UGANC was prospectively included to undergo brain MRI. Results of the Guinean MRI were compared to 30 patients randomly selected from Brussels' initial cohort. Paired Student's t-test and Mann-Whitney u-test were used for group comparisons. RESULTS: Age of ICH onset was higher in Belgium (68 ± 17 years vs. 56 ± 14 years, P < 0.01) while ICH volume and 30-day mortality rate were higher in Guinea (20 ml vs. 11 ml, P < 0.01 and mortality 33% vs. 10 %, P < 0.01). ICH burden in survivors in Conakry and Brussels showed respectively good outcomes in 56.7% and 60.4% (P = 0.09) and poor outcomes in 10.3% vs. 29.6% (P < 0.001). MRI analysis of the prospective cohort failed to disclose significant differences regarding brain MRI characteristics. CONCLUSIONS: Intra-cerebral Haemorrhage affected patients 15 years younger in Guinea with larger haematoma volumes and higher mortality than in Belgium. MRI findings did not show more prevalent amyloid angiopathy pathology suggesting that better primary prevention of hypertension could positively impact ICH epidemiology in Guinea.

OBJECTIF: L'hémorragie intracérébrale (HIC) semble plus répandue en Afrique subsaharienne (ASS) que dans les pays à revenu élevé (PRE), avec des résultats cliniques moins bons. Un impact plus élevé de l'hypertension et/ou de l'angiopathie amyloïde pourrait expliquer cette disproportion. Ici, nous avons cherché à (i) comparer rétrospectivement les schémas cliniques et d'imagerie de l'HIC en Belgique et en Guinée et dans une cohorte subséquente (ii) comparer de manière prospective les caractéristiques de l'IRM cérébrale pour rechercher des preuves d'une proportion différente des profils d'angiopathie amyloïde. MÉTHODES: 91 patients consécutifs admis pour HIC spontanée à l'hôpital Erasme-ULB de Bruxelles et à Ignace Deen-UGANC de Conakry ont été rétrospectivement comparés en termes de volume d'HIC estimé avec la méthode ABC/2, les caractéristiques cliniques et le score de classement modifié (mRS) à 30 jours. Le mRS a été dichotomisé en bons résultats (≤3) et mauvais résultats (>3). Une cohorte prospective de 30 patients consécutifs atteints d'HIC admis au CHU Ignace Deen-UGANC de Conakry a été incluse de manière prospective pour subir une IRM cérébrale. Les résultats de l'IRM guinéenne ont été comparés à ceux de 30 patients sélectionnés aléatoirement dans la cohorte initiale de Bruxelles. Le test t de Student apparié et le test u de Mann-Whitney ont été utilisés pour les comparaisons de groupe. RÉSULTATS: L'âge d'apparition de l'HIC était plus élevé en Belgique (68 ± 17 ans vs 56 ± 14 ans, P < 0,01) tandis que le volume de l'HIC et le taux de mortalité à 30 jours étaient plus élevés en Guinée (20 ml vs 11 ml, P < 0,01 et mortalité 33% vs 10%, P <0,01). La charge de l'HIC chez les survivants à Conakry et à Bruxelles a montré respectivement de bons résultats dans 56,7% et 60,4% (P = 0,09) et de mauvais résultats dans 10,3% vs 29,6% (P < 0,001). L'analyse IRM de la cohorte prospective n'a pas permis de révéler de différences significatives concernant les caractéristiques de l'IRM cérébrale. CONCLUSIONS: L'HIC a touché des patients 15 ans plus jeunes en Guinée avec des volumes d'hématomes plus importants et une mortalité plus élevée qu'en Belgique. Les résultats de l'IRM n'ont pas montré de pathologie angiopathique amyloïde plus répandue, ce qui suggère qu'une meilleure prévention primaire de l'hypertension pourrait avoir un impact positif sur l'épidémiologie de l'HIC en Guinée.

Carbohydrate knowledge, lifestyle and insulin: an observational study of their association with glycaemic control in adults with type 1 diabetes.

BACKGROUND: The ability to achieve optimal glycaemic control varies widely among individuals with type 1 diabetes. The present study aimed to explore the factors that are associated with optimal glycaemic control compared to suboptimal control. METHODS: An observational study design was used to explore the association of various factors with glycaemic control. Surveys were completed by individuals who attended the type 1 diabetes clinic at a tertiary hospital in New South Wales (NSW), Australia. Clinical and demographic information and attendance at dietary review were also collected. RESULTS: One hundred and three individuals completed the survey. Those with optimal control [glycated haemoglobin ≤7.0% (53 mmol mol-1 )] had a significantly shorter mean (SD) duration of diabetes [10.1 (12.6) years versus 18.8 (12.8) years, P = 0.005), were less likely to omit basal and bolus insulin (18.2% versus 47.5%, P = 0.016; 36.4% versus 61.8%, P = 0.034, respectively), and were less likely to report low confidence in managing their diabetes (9.1% versus 35.4%, P = 0.017). Participants who were able to identify carbohydrate sources were significantly more likely to have attended dietary review in the past 12 months (60.5% versus 20.0%, P = 0.001). However, they were not more likely to have better glycaemic control. CONCLUSIONS: The present study identified that consistency in taking insulin and confidence in self-management was associated with better glycaemic control. An association was also found between recent dietary review and better carbohydrate knowledge, although this did not translate into better glycaemic control. Future investigation into the application of carbohydrate knowledge is required.

Effect of polyglycerol esters additive on palm oil crystallization using focused beam reflectance measurement and differential scanning calorimetry.

The effect of 0.1-0.7% (w/w) of polyglycerol esters (PGEmix-8) on palm oil crystallization was studied using focused beam reflectance measurement (FBRM) to analyze the in-line changes of crystal size distribution during the crystallization. FBRM results show that 0.1-0.5% (w/w) of PGEmix-8 did not significantly affect nucleation but slightly retarded crystal growth. The use of 0.7% (w/w) additive showed greater heterogeneous nucleation compared to those with lower dosages of additive. Crystal growth was also greatly reduced when using 0.7% (w/w) dosage. The morphological study indicated that the palm oil crystals were smaller and more even in size than when more additive was added. Isothermal crystallization studies using differential scanning calorimetry (DSC) showed increased inhibitory effects on palm oil crystal growth with increasing concentration of PGEmix-8. These results imply that PGEmix-8 is a nucleation enhancing and crystal growth retarding additive in palm oil crystallization at 0.7% (w/w) dosage.

Significant improvements in pain after a six-week physiotherapist-led exercise and education intervention, in patients with osteoarthritis awaiting arthroplasty, in South Africa: a randomised controlled trial.

BACKGROUND: A major challenge facing those with late stage osteoarthritis is delayed surgery due to waiting lists. In South Africa patients wait years for a hip/knee arthroplasty. Affected patients require effective management to address their pain, especially while awaiting surgery. Existing literature is mostly available from high income countries exploring effects of interventions during short waiting periods. Research is warranted in low income countries where long waiting periods are common. This study explored the effects of a six-week physiotherapist-led exercise and education intervention on pain in this population. METHODS: A randomised controlled trial was performed at two public hospitals in South Africa. Ethical approval and informed consent was obtained. 74 participants from arthroplasty waiting lists were randomly allocated to an intervention (n = 35) or control group (n = 39). The intervention included six physiotherapist-led group-based sessions (two hours/week of education, exercise and relaxation). The control group received usual care. Data collection was conducted by blinded physiotherapists at baseline, week six, 12 and month six. The primary outcome was pain, measured by the Brief Pain Inventory. Additionally, participants completed an open-ended questionnaire at month six, to gain insight regarding the intervention. Analysis was by intention to treat using two-way analysis of variance and post-hoc Tukey comparisons. Answers to subjective questions were analysed according to common themes that emerged. RESULTS: The intervention group had significant improvements compared with the control group with moderate to large effect sizes (ES) on pain severity [week 6: p < 0.01, ES = 0.94, 95 % CI (0.45,1.41), month 6: p = 0.02. ES = 0.74, 95 % CI (0.26,1.2)] and moderate to large effects on pain interference [week 6: p < 0.01, ES = 1.2, 95 % CI (0.70,1.69), week 12: p = 0.04, ES = 0.68, 95 % CI (0.20,1.14), month 6: p < 0.01, ES = 0.98, 95 % CI (0.49,1.45)]. 53 % of participants reported that the intervention improved their pain. CONCLUSIONS: The intervention resulted in sustained significant improvements in pain severity and interference in patients with hip/knee osteoarthritis, awaiting arthroplasty compared with a control group. Additionally, participants' individual feedback supported observed significant improvements in pain. Such an intervention appears to be effective in managing pain in this population and should be incorporated into practice for appropriate patients. Further research is being conducted to explore long term and postoperative outcomes. CLINICAL TRIAL REGISTRATION: Pan African Clinical Trial Registry, PACTR201409000885765 , PACTR201507001186115 .

Unique and Overlapping Functions of Formins Frl and DAAM During Ommatidial Rotation and Neuronal Development in Drosophila.

The noncanonical Frizzled/planar cell polarity (PCP) pathway regulates establishment of polarity within the plane of an epithelium to generate diversity of cell fates, asymmetric, but highly aligned structures, or to orchestrate the directional migration of cells during convergent extension during vertebrate gastrulation. In Drosophila, PCP signaling is essential to orient actin wing hairs and to align ommatidia in the eye, in part by coordinating the movement of groups of photoreceptor cells during ommatidial rotation. Importantly, the coordination of PCP signaling with changes in the cytoskeleton is essential for proper epithelial polarity. Formins polymerize linear actin filaments and are key regulators of the actin cytoskeleton. Here, we show that the diaphanous-related formin, Frl, the single fly member of the FMNL (formin related in leukocytes/formin-like) formin subfamily affects ommatidial rotation in the Drosophila eye and is controlled by the Rho family GTPase Cdc42. Interestingly, we also found that frl mutants exhibit an axon growth phenotype in the mushroom body, a center for olfactory learning in the Drosophila brain, which is also affected in a subset of PCP genes. Significantly, Frl cooperates with Cdc42 and another formin, DAAM, during mushroom body formation. This study thus suggests that different formins can cooperate or act independently in distinct tissues, likely integrating various signaling inputs with the regulation of the cytoskeleton. It furthermore highlights the importance and complexity of formin-dependent cytoskeletal regulation in multiple organs and developmental contexts.

Superior masenteric vein thrombosis.

A 43 year-old woman presented with severe non-specific abdominal pain of 1-week duration. She was on oral contraceptive pills for the past 6 years. Clinically patient appeared ill with no specific abnormal physical sign. Moderate amount of free fluid in the peritoneal cavity on ultrasound prompted an urgent abdominal computed tomography (CT) scan, which revealed thrombosis of the superior mesenteric vein. Further investigations revealed a hypercoagulable state with protein C deficiency. Patient responded well to anticoagulation and supportive therapy. One month later patient readmitted with vomiting and signs of intestinal obstruction. Barium study revealed a moderately long tight stricture at mid jejunum with proximal dilation. A by-pass surgery was carried out. She was well at 3 months follow-up.

188rhenium-TDD-lipiodol in treatment of inoperable primary hepatocellular carcinoma--a case report.

INTRODUCTION: The aim of this study was to investigate the potential of using 188Re Lipiodol for selective internal radiation therapy of inoperable hepatocellular carcinoma (HCC). CLINICAL PICTURE: A 33-year-old female with poorly-differentiated multicentric HCC, elevated alpha-fetoprotein (AFP) and increased serum alkaline phosphatase. TREATMENT: Over a 2-month interval, the patient was treated twice with 4GBq of 188Re-TDD-Lipiodol. OUTCOMES: There was good localisation of 188Re Lipiodol in the tumours, but also in thyroid (first treatment) and gastrointestinal tract (both treatments). So far (5 months post-treatment), the patient remains well with stable disease. CONCLUSIONS: 188Re Lipiodol can be an effective radiopharmaceutical for the treatment of HCC; however, more work must be done to minimise the uptake in bowel.

Unrelated donors selected prospectively by block-matching have superior bone marrow transplant outcome.

Previous retrospective studies have demonstrated improved outcome in patients whose donors were matched for non-HLA markers in the MHC as well as for HLA genes. Forty patients receiving transplants from unrelated donors were typed prospectively for HLA and non-HLA markers. Non-HLA markers near HLA-B (beta-block markers) and in the DRB1 introns (delta-block markers) were used to assess MHC match between donors and recipient. Patients whose donors were matched at the beta- and delta-blocks had improved event free survival (63%) compared to patients whose donors were mismatched at one or both blocks (25%) (p < 0.05). Patients whose donors were matched at the beta-block had significantly less severe acute graft versus host disease (p < 0.05). In order to investigate the basis for improved outcome block matching was correlated with HLA matching as determined by DNA sequencing. Beta-block matching was highly correlated with matching for exons 2 and 3 of HLA-B but less so for HLA-C. Delta-block matching was highly correlated with matching for exon 2 of HLA DRB1. It is concluded that matching for non-HLA markers in the MHC improves matching for HLA genes. Further studies are required to determine whether matching for non-HLA markers improves outcome to a greater extent than matching for the HLA genes alone.

Treating high risk childhood solid tumours with autologous peripheral blood stem cell transplantation--early experience in University Hospital, Kuala Lumpur.

Although survival rates for childhood cancers have improved steadily over the past two decades, the outcome for advanced stage solid tumours remains poor. Many of these tumours are chemosensitive but most chemotherapeutic regimens are limited by their haematological toxicities. Much attention is now focused on mega-dose chemotherapy followed by stem cell rescue in the treatment of disseminated neuroblastoma, rhabdomyosarcoma, germ cell tumour and brain tumours. There is a preferential shift towards peripheral blood stem cell transplantation instead of bone marrow transplantation because of its advantages of faster engraftment, decreased transfusion and antibiotic usage and shortened hospitalisation. This mode of therapy is dependent on technologies including peripheral blood stem cell harvesting, cell cryopreservation and thawing. These technologies were recently made available in Malaysia and we report our early experience.

Adult allogeneic bone marrow transplantation: initial experience in the University Hospital, Kuala Lumpur.

Prior to 1993, bone marrow transplantation for adult patients was not available in Malaysia. Adult allogeneic bone marrow transplantation commenced in Malaysia when the first transplant was conducted at the University Hospital, Kuala Lumpur on 2 November 1993. Up till July 1995, 10 adult bone marrow transplants had been conducted at the University Hospital. Five patients had acute myeloid leukaemia in first remission, 4 had chronic myeloid leukaemia and 1 had acute lymphoblastic leukaemia in first partial remission. The age range of patients at the time of transplant is 16-40 years (mean 25.5 years). All patients engrafted successfully and the survival for the first 100 days post-transplant is 90%. One patient demonstrated haematological relapse post-transplant but achieved remission with donor buffy-coat infusion. The mean drug cost incurred was RM28,269 for the first 100 days. Locally available adult allogeneic bone marrow transplantation is safe, affordable and has comparable results with reputable overseas transplant centres.

Yersinia enterocolitica septicaemia from transfusion of red cell concentrate stored for 16 days.

Two cases of transfusion transmitted Yersinia enterocolitica biotype 3, serotype 09 infection occurred in south east Scotland within four months of each other. In one case, a 79 year old man died the day after receiving a unit of red cell concentrate that had been stored for 29 days after donation. In the second case a 78 year old man died three days after transfusion of a unit of red cell concentrate that had been collected 16 days before transfusion. The donors of both units had no symptoms attributed to gastrointestinal infection. Early outdating of blood for transfusion after three weeks of storage is unlikely to eradicate Y enterocolitica associated fatalities from blood transfusion, and alternative methods should be considered.