Pathophysiology of bleeding diathesis in haemophilia-A: A sequential and critical appraisal of non-FVIII related haemostatic dysfunctions and their therapeutic implications

Haemophilia-A is characterized by deficiency of FVIII, but the bleeding diathesis is not a mere reflection low FVIII activity. The pathophysiology of haemophilic bleeding diathesis is a complex interplay between defective procoagulant function and up-regulated fibrinolysis. Moreover, haemophilic bleeding diathesis is frequently compounded by treatment-related and infective complications such as FVIII inhibitors, hepatitis, HIV infection, non-steroidal anti-inflammatory drugs (NSAID) induced gastritis, and infective mucosal injuries such as H pylori gastritis and intestinal and urinary helminthiasis. Hence, pathophysiology of haemophilic bleeding is multi-factorial, encompassing both FVIII and non-FVIII haemostatic defects. Currently available literature on pathophysiologic roles of non-FVIII haemostatic defects in haemophilia is fragmented. This articles is aimed at providing a composite and comprehensive review of the roles of non-FVIII haemostatic defects and their therapeutic implications in haemophilic bleeding diathesis, which will enable a holistic approach towards clinical management of the bleeding diathesis. This is necessary because FVIII therapy alone maybe insufficient in managing complicated haemophilic bleeding unless compounding non-FVIII-related haemostatic dysfunctions and comorbidities are identified, targeted and treated. This will necessitate appropriate use of non-FVIII therapeutic modalities, which may include anti-fibrinolytic agents, FVIII by-passing agents, immune modulation, and anti-microbial agents. Lots of work has been done in the areas of non-FVIII agents and FVIII by-pass therapy in the management of haemophilia, but more research is needed to validate many of these targeted therapeutic techniques. Meanwhile, healthcare personnel must consider the roles of both FVIII and non-FVIII haemostatic defects when evaluating haemophilic bleeding diathesis for the purpose of choosing appropriate and optimal treatment options.Keywords: Haemophilia, Bleeding diathesis, Pathophysiology, Targeted therapy, Non-FVIII therapy, FVIII by-pas

Review: Determinants and modifiers of bleeding phenotypes in haemophilia-A: General and tropical perspectives

Haemophilia-A is an X-linked recessive bleeding disorder characterized by deficiency of FVIII. Although severity of haemophilia is largely determined by the extent to which different mutations abolish FVIII production, the overall phenotypic variations among haemophiliacs is determined by a combination of several other factors, which range from general to tropical factors on the one hand, and from genetic to immunologic and infective factors on the other hand. Determinants and modifiers of haemophilic bleeding phenotypes are important predictors of prognosis. However,  tropical determinants of haemophilic bleeding phenotypes are virtually ignored because majority of haemophilia research originated from developed non-tropical countries. The aim of this paper is to present a balanced review of the haemophilic bleeding phenotypes from general and tropical perspectives. Hence, we present a concisely updated comprehensive review of the  pathophysiologic and clinical significance of general vis-à-vis tropical determinants and modifiers of haemophilic bleeding phenotypes from genetic, immunologic and infective perspectives. Understanding of general phenotypic determinants such as FVIII gene mutations, immunological (inhibitors) and infective (e.g. hepatitis and HIV)  complications, classical thrombophilias (e.g. FV-Leiden) and non-classical thrombophilias (e.g. non-O blood groups) will throw more light into the mechanisms by which some tropical prothrombotic gene mutations (such as sickle b-globin gene) and certain chronic tropical pro-haemorrhagic parasitic infections (such as urinary and gastrointestinal helminthiasis) may modify frequency, intensity and pattern of bleeding among haemophiliacs in the tropics. The clinical significance of iron deficiency within the context of helminthiasis and haemophilia is also reviewed. More research is needed to determine the precise effect of non-classical thrombophilias such as sickling disorders and ABO blood groups on haemophilic bleeding phenotypes. Meanwhile, tropical healthcare workers should incorporate regular screening and treatment for common prohaemorrhagic parasitic diseases and iron deficiency into standard of care for management of haemophilia.Keywords: Haemophilia Bleeding Phenotype Thrombophilia ABO blood  group Sickle cell Helminthiasis Iron deficienc

Age and growth analysis of the fish Mastacembelus armatus (Lacepede) from River Nayar, Garhwal Himalaya, Uttarakhand

The ability to age fish accurately is essential in understanding the dynamics of fish population. Age and growth determination in Mastacembelus armatus was assessed by the scale method which was verified by the length-frequency distribution method. The scales were small, elongated and the focus was shifted slightly uppish from the centre. The fish length and scale radius relationship was found linear (Scale radius = 6.974 + 0.452 Fish length; r = 0.9746) and authenticated the age analysis. Back calculation method was used to find out the size of fish at annulus formation, which confirmed four age rings in M. armatus  at the size of 14.07±0.92,  26.05±4.99,  37.96± 2.59  and  48.48±6.06 cm respectively. First two age rings were observed in the fish length group 30-40 cm, the third ring was observed in 40-50 cm and the fourth ring in 50-60 cm length group. The finding was dully validated by length-frequency distribution method. The growth annual increment (h) of M. armatus shows that the length increment was 14.07, 13.32, 11.91 and 10.52 cm during 1st, 2nd, 3rd and 4th year respectively. It shows that the fish grows continuously during its entire life period. The average growth (? h) was observed as 12.12 cm. annually. The assessment of age and growth rate of fish is a prerequisite to generate the information on recruitment, longevity and fluctuations in fishery caused by various year classes which is an important tool for rational exploitation of fish stock

MICROBICIDAL AND CYTOTOXIC ACTIONS OF METHANOLIC CRUDE EXTRACTS OF A. MULTIFLORA.-ROXB

Objective: The study presented here was carried out for the evaluation of microbicidal and cytotoxic potential of methanolic extract of leaves of Ammannia multiflora. The microbicidal activity was tested against 16 bacteria. The cytotoxic activity was tested against brine shrimp species Artemia salina. Methods: The microbicidal effect of the plant extracts was tested in vitro by the disc diffusion method with 16 standard bacterial strains. Artemia salina; a brine shrimp species; was used to assess cytotoxic activity. Results: Among the subjected 16 different bacteria; in case of S. boydii; the zone of inhibition was higher (22.0 mm) at 500 µg/ml concentration. Whereas in the case of E. foecalis, the zone of inhibition was higher (8.0 mm) at 250 µg/ml concentration. In S. pyogenes; zone of inhibition was higher at 500 µg/ml concentration (13.0 mm). The growth of S. saprophyticus (9 mm), S. agalactiae (7 mm) and S. sonnei (7 mm) was also moderately inhibited. The extract exhibited effectiveness against 7 different species of bacteria out of 16. Cytotoxic effect was determined in lethality bioassay of brine shrimp species Artemia salina. The plant extracts exhibited significant cytotoxic property which was reflected in LC50 and LC90values of 20.42µg/ml and 229.09 µg/ml respectively. Cytotoxic property was found as dose dependent manner. Conclusion: These results suggest that, Ammania multiflora can effectively be used for its significant microbicidal action. It is also effective as cytotoxic agent and thus, could justify its use in traditional medicine

Hematological Indices of Sickle Cell Anaemia Patients with Pulmonary Tuberculosis in Northern Nigeria.

Nigeria has the fourth highest prevalence of TB and the highest prevalence of Sickle cell anaemia (SCA) in the world. SCA patients have impaired immunity and are vulnerable to TB. Hence, we studied the haematological indices of SCA patients with TB in Nigeria. A total of 23 SCA patients with TB were studied in parallel with equal number of age and sex matched SCA patients without TB. SCA patients with TB had significantly lower haematocrit, higher level of circulating sickle cells (CSCs) and similar level of reticulocyte count in comparison to patients without TB. SCA patients with TB had significantly higher mean WBC count associated with higher frequency of neutrophilia in comparison to those without TB. Monocytosis and eosinopenia were exclusively found in SCA patients with TB at frequencies of 52% and 65% respectively. Lymphocyte and basophil counts were normal in all patients with and without TB. Mean platelet counts were high in both patient groups but the frequency of thrombocytosis was significantly higher in patients with TB. SCA patients with TB had significantly higher mean ESR than their counterparts without the infection. The findings of this study revealed that TB in SCA patients was associated with rising level of CSCs, falling level of haematocrit, sub-optimal reticulocytosis, neutrophilia, monocytosis, thrombocytosis, eosinopenia and rising level of ESR. Hence, SCA patients presenting with these haematological indices should be investigated for TB

Wireless capsule endoscopy for the detection of small bowel diseases in HIV-1-infected patients

<p>Abstract</p> <p>Background and Aims</p> <p>In HIV-infected patients, manifestations of the disease are common in the gastrointestinal tract. The objective of our study was to evaluate the diagnostic yield of the Given^®Video Capsule System (Given Imaging, Yoqneam, Israel) in these patients.</p> <p>Methods</p> <p>After exclusion of GI-tract stenosis by anamnestic exploration, 49 patients were included into the study. Stratification: Group A (n = 19): HIV-positive, CD₄cell count < 200/μl, gastrointestinal symptoms present. Group B: HIV-positive, CD₄< 200/μl, without gastrointestinal symptoms (n = 19 Group) C: healthy volunteers (n = 11).</p> <p>Results</p> <p>In group A there was a total of 30 pathological findings, 15 of which with therapeutic implications. In group B, there was a total of 22 pathological findings, 5 relevant for therapy. In group C there was a total of 13 pathological findings, 3 with therapeutic relevance. In 89% (group A) vs. 26% (group B), pathological findings were detected distal the ligament of Treitz (p = 0.001). All capsules were recovered without complications after 12 to 96 h from the stool.</p> <p>Conclusion</p> <p>Wireless capsule endoscopy of the small intestine should be considered for HIV-infected patients with marked immunosuppression and gastrointestinal symptoms.</p

Comparative Study of Maximum Power Point Tracking with a Modified DC DC Converter

Maximum power points are used to find the voltages and currents at which a photovoltaic (PV) panel should operate to obtain maximum power. In order to deliver highest power, an efficient DC DC converter and a reliable tracking algorithm are used. There is also the need to continuously find the maximum power under any environmental conditions at all times. This research is intended to study a comparative performance of maximum power point (MPP) which is presented under uniform irradiance condition. The algorithm employed is an improved cuckoo search algorithm and the DC-DC Converter( switched mode power supply) has been modified by including a synchronous rectifier connected to a load, the performance of the system is validated using MATLAB/Simulink and practical implementation for this work. A comparison of the MATLAB Simulation with the practical implementation of MPP is presented using maximum power and percentage tracking efficiency as performance metric. From the MATLAB results obtained, maximum extracted power is 26.81W and the hardware implementation gives a maximum power of 28.71W. Tracking efficiency improves by 6.62%. The results show the practical MPP gives a better maximum power, which consequently improves the Photovoltaic systems efficiency and conversely mitigates the power consumption and the cost of the system than the simulation result obtained in MATLAB

Obstructed labour at Usmanu Danfodiyo university teaching hospital Sokoto: a five-year review

Background: Obstructed labour is an obstetric emergency and one of the major causes of maternal and perinatal morbidity and mortality in the developing countries, Nigeria inclusive. The aim of this study was to determine the prevalence, causes and feto-maternal outcome of cases of obstructed labour managed at Usmanu Danfodiyo University Teaching Hospital Sokoto from 1st January, 2014 to 31st December, 2018.Methods: This was a retrospective review of all cases of obstructed labour managed at Usmanu Danfodiyo University Teaching Hospital Sokoto over 5 years. List of cases managed during the study period was obtained and case notes were retrieved. Relevant information such as age, booking status, parity, educational status, address, causes, mode of delivery and both maternal and foetal outcomes were obtained from the case notes. Data analysis was done using statistical package for social sciences version 22 (SPSS Inc, Chicago, IL, USA).Results: A total two hundred and seventy-six cases of obstructed labour were managed out of the 15,452 total deliveries during the study period. This gives an obstructed labour prevalence of 1.79%. The major cause of obstructed labour identified in this study was Cephalopelvic disproportion (74.6%) and majority of the patients were delivered by emergency lower segment caesarean section (70.6%). Up to 32.3% of the patients had no maternal complications and also 42.3% of them had live birth with no fetal complication. However, 20.2% of these patients had ruptured uterus and 37.9% of them had still birth, while 19.8% had live birth complicated by birth asphyxia.Conclusions: This study has found that obstructed labour resulted in adverse maternal and perinatal outcome. Hence, there is need to prevent obstructed labour in order to avert this consequence

Low Cost Constant – Head Drip Irrigation Emitter for Climate Change Adaptation in Nigeria: Engineering Design and Calibration

A low cost constant – head emitter for drip irrigation was developed using cheap and readily available materials as a substitute for the imported drip emitters which deter the adoption of drip irrigation in sub – Saharan Africa (SSA). The emitter was calibrated at both laboratory scale and on the field. The drip system comprises of abarrel, sub-main line, lateral lines, tubes and emitters, it can irrigate140 crop stands and can be extended to 560 stands. The emitters produced a mean discharge and emission uniformity (Eu) of 1.60l/hr. and 74 % respectively; while the calibrated manufacturer’s coefficient of variation and distribution uniformity of discharge were 0.098 and 86.3% respectively. The system operates under low pressure (87.9 mbar) and can deliver the daily crop water requirement of a crop like maize in 20 minutes; the overall system performance based on field calibration is generally satisfactory and show potential for improvement when compared with global standards for drip systems. The system’s low cost of N15, 870 ($79) gives it an edge over existing locally developed drip systems, the low technology and the use of locally available materials coupled with the water savings will enable famers to adapt to the impact of climate change in sub-Saharan Africa through the production of high value crops in the dry season.http://dx.doi.org/10.4314/njt.v34i4.3