Digital Commons Network^™

The Role Of Glutaminase And Extracellular Vesicles In Macrophages And Microglia, Beiqing Wu

Theses & Dissertations

Glutamate serves as a crucial excitatory neurotransmitter that is essential for the proper functioning of the brain. However, excess levels of glutamate are neurotoxic and contribute to the pathogenesis of various neurodegenerative diseases, inducing HIV-1 associated neurocognitive disorders (HAND). Glutaminase 1 (GLS1) is an important mitochondrial enzyme responsible for producing glutamate from glutamine. GLS1 is upregulated during HAND and released from mitochondria to cytosol and extracellular space. However, why and how GLS1 is released remains unknown. In chapter II, we demonstrated that extracellular vesicles (EVs) carry GLS1 as cargos from cytosol to extracellular space during HIV infection and innate immune …

Changes To Echocardiography-Derived Left Ventricular Filling Pressures And Cardiac Output In Response To Fluid Boluses In Elderly Patients With Left Ventricular Diastolic Dysfunction Undergoing Vascular Surgery, Sasha K. Shillcutt

Theses & Dissertations

Left ventricular diastolic dysfunction (LVDD) of the heart is a condition where the heart does not relax properly. This condition is important during times of stress, as LVDD is associated with significant morbidity of elderly surgical patients. LVDD is often asymptomatic and unrecognized as many of these patients have normal ejection fractions. However, LVDD may lead to heart failure in patients with preserved systolic function, with the incidence being as high as 50% in hospitalized elderly patients. The diagnosis of LVDD is an independent risk factor for postoperative major adverse cardiac events (MACE) and negatively impacts post-surgery readmission rates. Anesthesiologists …

Ehd1 As A Positive Regulator Of Macrophage Colony-Stimulating Factor-1 Receptor, Luke R. Cypher

Theses & Dissertations

The master regulator of the macrophage development, differentiation, proliferation, survival, phagocytosis, cytokine secretion, motility, adhesion, migration, and spreading is the receptor tyrosine kinase (RTK) colony stimulating factor-1 receptor (CSF-1R). Aberrant CSF-1R signaling is present amongst a variety of highly prevalent and devastating human diseases in the United States such as atherosclerosis, cancer, inflammatory bowel disease, arthritis, and neuro-demyelination/neuro-degeneration. A better understanding of basic mechanisms that govern macrophage development and function is of vital importance in treating patients afflicted with these conditions/diseases. CSF-1R presentation on the macrophage cell surface is a required precursor for CSF1- induced RTK dimerization (activation) and downstream …

Mutations Affecting Epigenetic Regulators And Their Role In Peripheral T-Cell Lymphomas, Chao Wang

Theses & Dissertations

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of generally aggressive lymphoid malignancies, accounting for 10-15% of all non-Hodgkin lymphomas. Angioimmunoblastic T-cell lymphoma (AITL) represents approximately 20% of all PTCLs and is recognized as a distinct entity. Accurate diagnosis and classification of PTCL remain challenging. With the exception of ALK+ ALCL, patients with PTCL generally have a poor prognosis with standard chemotherapy and even with the availability of many novel drugs, including HDAC inhibitor (romidepsin and belinostat), gemcitabine, and bortezomib. Therefore, deciphering the pathogenesis of this group of diseases is needed to identify novel treatable targets for better therapeutic intervention. …

Risk Factors, Clinico-Pathologic Characteristics And Outcomes In Young Kenyan Female Patients With Breast Cancer In Akuh-N, Gilford Mutwiri Mwikamba

Theses & Dissertations

Background: Breast cancer in the young refers to a diagnosis of breast cancer in a female under the age of forty years. This is considered a distinct disease with different risk factors, biology, and prognosis. Young age at breast cancer diagnosis is reportedly more common among African-Americans. The highest proportion of breast cancer in the young has been reported in Africa. Early detection of breast cancer in Africa is hampered by lack of access to health care services, appropriate screening tools, and high cost of magnetic resonance imaging for the high risk groups. Despite a worse prognosis, management of breast …

Effect Of Laryngeal Mask Airway Manometry On Post-Operative Sore Throat In Spontaneously Breathing Adult Patients Presenting For Surgery At Aga Khan University Hospital, Nairobi, David Njoroge Waruingi

Theses & Dissertations

Background: Laryngeal mask airways (LMAs) are widely used in anaesthesia and are considered to be generally safe. Postoperative sore throat (POST) is a frequent complication following LMA use and can be very distressing to patients. The use of an LMA cuff pressure of between 30 and 32cm of H20 in alleviating postoperative sore throat has not been investigated.

Primary objective: To compare the occurrence of POST between the intervention group in which LMA cuff pressures will be adjusted to 30-32cm of H20 and the control group in which only monitoring of LMA cuff pressures will be done.

Secondary Objectives: To …

The Association Between Asymptomatic And Mild Neurocognitive Impairment And Adherence To Antiretroviral Therapy Amongst People Living With Hiv, Violet Maloba Awori

Theses & Dissertations

Background: HIV disease is associated with neurocognitive impairment which is one of the neurological complications of the viral infection. The spectrum of HIV Associated neurocognitive impairment has significantly changed since the advent of ART. The inclusion of the asymptomatic but cognitively impaired population of patients has changed the dynamics of this population, and requires further research to identify the impact it has on the progression of the disease as well as on any other aspects. Poor adherence to ART is one of the main causes of treatment failure and studies done previously point towards the milder forms of Neurocognitive Impairment …

Factors That Influence Advance Directives Completion Amongst Terminally Ill Patients At Akuhn, Stephen Omondi Otieno

Theses & Dissertations

Background: An advance directive is a written or verbal document that legally stipulates a person’s health care preference while they are competent to make decisions for themselves, and which is then used to guide decisions on life-sustaining treatment in the event that they become incapacitated. Advance directives can take one of four forms: a living will, a limitation of care document, a do-not-resuscitate order, and an appointment of a surrogate by durable power of attorney. The completion rate of advance directives varies from region to region, and it is influenced by different patient, caregiver, legal, institutional, cultural, and religious factors. …

Effect Of Low-Dose Ketamine Versus Fentanyl On Attenuating The Haemodynamic Response To Laryngoscopy And Endotracheal Intubation In Patients Undergoing General Anaesthesia At The Aga Khan University Hospital, Nairobi, Angela Ongewe

Theses & Dissertations

Background: The use of drugs to attenuate the haemodynamic response to laryngoscopy and endotracheal intubation is the standard of care during elective surgery. Current evidence is conflicting concerning the best agent and optimal dose for this purpose. In the majority of cases, Fentanyl is widely utilized to attenuate haemodynamic responses. Ketamine, an established available drug, has been scarcely studied in this regard at low doses and against varying doses of other common agents.

Objective: The primary objective was to compare the overall occurrence of hypertension and tachycardia immediately pre-intubation (post-induction) until 10 minutes post intubation between the study group receiving …

Prevalence Of Hepatic Steatosis As Diagnosed On Unenhanced Abdominal Ct, Naushad H. Karim Sokwalla

Theses & Dissertations

Background: Hepatic steatosis is the accumulation of triglycerides within hepatocytes. It may be broadly classified into alcoholic and non-alcoholic fatty liver disease, whereby non-alcoholic fatty liver disease is steatosis secondary to causes such as steatogenic medication. Liver biopsy remains the gold standard for diagnosis of hepatic steatosis. However, it is invasive and may potentially suffer from sampling errors. Hepatic steatosis may be diagnosed on unenhanced CT if the hepatic attenuation is less than 40 HU, or if the attenuation of the liver is at least 10 HU less than the spleen. Over the past three decades, non-alcoholic fatty liver disease …

Residents’ Perception On The Need For Clinical Leadership Training At The Aga Khan University, Nairobi, Lance Mayabi

Theses & Dissertations

Background:The healthcare environment is becoming increasingly complex with physicians undertaking more leadership roles. The majority of physicians are not prepared to take up these roles, despite evolving evidence that good clinical leadership yields better clinical outcomes for both patients and healthcare organizations. Further, few residency programs explicitly embed leadership training for their students despite their positions at the forefront of healthcare delivery. This deficit ultimately leaves a multilevel healthcare “leadership” gap in a sector that depends heavily on the education process to improve clinical outcomes.

A pre-study survey of residency graduates at the Aga Khan University, Nairobi (AKU,N) undertaken …

Outcomes In Patients With Acute Coronary Syndromes At The Aga Khan University Hospital, Nairobi, Mohamed Hasham Varwani

Theses & Dissertations

Background: As the prevalence of cardiovascular diseases in Sub-Saharan Africa rises, coronary artery disease, with its acute presentations, is being increasingly recognized in Kenyans and treated at tertiary level hospitals. It is just over a decade since the introduction and wide availability of modern cardiology services, including interventional cardiology in Kenya.

Following an acute coronary syndrome (ACS), patients remain at high risk of death and other adverse events such as heart failure, recurrent myocardial infarction, stroke, and bleeding. Local and regional data on long-term outcomes following ACS are lacking. These data are important to clinicians for prognostication and to health …

Maternal Inflammatory Markers In The Diagnosis Of Chorioamnionitis And Prediction Of Neonatal Sepsis In Preterm Pre-Labour Rupture Of Membranes: A Systematic Review, Angela Koech Etyang

Theses & Dissertations

Background: There is no consensus on the potential role of inflammatory markers in identifying chorioamnionitis in women with Preterm Pre-labour Rupture of Membranes (PPROM) or in predicting Early Onset Neonatal Sepsis (EONS) in their neonates.

Objectives: To perform a quantitative review on the accuracy of maternal C reactive protein (CRP), Procalcitonin (PCT) and Interleukin 6 (IL6) in the diagnosis of Histological Chorioamnionitis and/or Funisitis (HCA/Funisitis) and their role in the prediction of EONS in PPROM.

Methods: MEDLINE, EMBASE and The Cochrane Library databases were searched from inception to October 2015, for studies where these markers were assessed against a reference …

Prevalence Of Bladder Dysfunction In Children With Primary Nocturnal Enuresis Presenting To The Hospital, Nikita Pravin Jethwa

Theses & Dissertations

Introduction: Bladder dysfunction is thought to be a common cause of nocturnal enuresis. It can either be overactive, underactive or dysfunctional. Currently, there is a paucity of data on what proportions of children with nocturnal enuresis have bladder dysfunction. Studies have shown the prevalence of bladder dysfunction to be as high as 77-94.5% (28), and children with bladder dysfunction have poor response to treatment. There are currently no protocols for investigating and managing children with nocturnal enuresis. The decision for bladder ultrasound is usually made by the primary physician, and at times after the child has been on treatment for …

Comparison Of Weight Adjusted Dose Versus Fixed Dose Ondansetron In Preventing Shivering Following Spinal Anesthesia For Cesarean Deliveries, Moses Kimuri Gicheru

Theses & Dissertations

Background: Spinal anesthesia is an effective regional anesthesia technique, which is preferred in almost 86% of cesarean sections in the United States and United Kingdom. Eighty percent of cesarean sections done at the Aga Khan University hospital are under spinal anesthesia. Shivering is a common complication of spinal anesthesia, it occurs in 40%-64% of patients after neuraxial anesthesia. Shivering may cause maternal and fetal hypoxemia, maternal discomfort and a problem to the anesthesiologists when it comes to monitoring the patient during cesarean sections.

Ondansetron a 5-HT3 receptor antagonist is effective in treatment and prevention of post spinal anesthesia shivering. In …

Effect Of Additional Lumbosacral Corset On The Outcome Of Patients With Non-Specific Acute Low Back Pain At The Aga Khan University Hospital, Nairobi, Stanley Aruyaru Mwenda

Theses & Dissertations

Introduction: Low back pain (LBP) is a common problem world over affecting 60-90% of the population in their lifetime. It is a leading reason for hospital admission, healthcare spending, workplace absenteeism and years lived with disability.

Up to 90% of patients suffering from low back pain do not have a serious pathology warranting imaging or further intervention besides symptom relief. These are categorized as having non- specific low back pain. This has a good prognosis running a short course of 3 to 6 weeks.

The management of non-specific acute LBP entails analgesia and non-pharmacologic interventions (back school and physical therapy). …

Association Of 24-32wk Maternal Triglyceride Levels And Neonatal Birth Weight At The Aga Khan University Hospital, Demetrius Mududa Omondi

Theses & Dissertations

Introduction: The association of neonatal birth weight and mid-term maternal lipid levels has been demonstrated in several studies with elevated serum triglyceride levels shown to be a strong predictor of the large for gestational age baby/ fetal macrosomia. Maternal diabetes remains the strongest risk factor for developing a LGA/macrosomic baby explained by the Pederson hypothesis. However non-diabetic macrosomia is still an obstetric dilemma with the attendant fetal and maternal complications. This phenomenon could be explained by altered maternal lipid metabolism as lipids have been shown to be important for normal fetal growth and development.

Objective: Our primary objective was to …

Sonographic Estimation Of The Prevalence Of Hepatic Steatosis In Hiv Monoinfected Patients At Aga Khan University Nairobi., Bernadette Wambui Muthee

Theses & Dissertations

Introduction: Human immunodeficiency virus disease (HIV) is a worldwide health problem. It is estimated that 38.6 million people are infected with HIV globally. It has remained endemic in the African continent for close to 20 years and is a long term developmental challenge in Africa which bears 69 % of the HIV/AIDS global burden.

The introduction of highly active antiretroviral therapy (HAART) has caused dramatic improvement in prognosis of HIV disease. Consequently, this has resulted in substantial reduction in Acquired Immune Deficiency Syndrome (AIDS) related morbidity and mortality. In contrast, this has been accompanied by an upsurge in liver- related …

Modifiable Barriers To Optimal Outcomes In Gout Management, Brian W. Coburn

Theses & Dissertations

Improving patient outcomes in chronic disease is of critical importance to the future of health care. Gout, affecting 4% of the US population, is a highly treatable chronic disease from which patients experience unnecessarily suboptimal outcomes. In this dissertation, I demonstrate how interrelated patient and provider factors affect patient outcomes in gout. First, I describe how only 14% of gout patients know their serum urate (SU) goal for urate lowering therapy (ULT) despite otherwise being knowledgeable about gout and its treatment. I then demonstrate the importance of multiple patient and provider factors in achieving SU goal. Specifically, I demonstrate that …

Recurrent Mutations Of T-Cell Receptor And Co-Stimulatory Signaling Proteins In Peripheral T-Cell Lymphomas, Joseph Rohr

Theses & Dissertations

Peripheral T-cell lymphomas (PTCLs) comprise a heterogeneous group of mature T-cell neoplasms with a poor prognosis. Recently, mutations in TET2 and other epigenetic modifiers as well as RHOA have been identified in these diseases, particularly in angioimmunoblastic T-cell lymphoma (AITL). CD28 is the major co-stimulatory receptor in T-cells which, upon binding ligand, induces sustained T-cell proliferation and cytokine production when combined with T-cell receptor stimulation, through many signaling molecules including VAV1. This thesis identifies recurrent mutations in CD28 in PTCLs, as well as mutations in VAV1. Two residues of CD28 – D124 and T195 – were recurrently mutated in 11.3% …

Factors And Outcomes Associated With Potentially Inappropriate Medication Use In Rural Community-Dwelling Older Adults, Marcia Y. Shade

Theses & Dissertations

Potentially inappropriate medications (PIMs) use in older adults is a significant public health concern. The use of PIMs to avoid may lead to negative outcomes such as adverse drug events. Prior conceptual analysis of PIMs use and observation of health-related factors in rural adults led to the design of this dissertation study. A sample was recruited from a population of rural community-dwelling older adults to examine the following specific aims: 1) Describe the use of PIMs to avoid, 2) Explore individual demographic characteristics (age, gender, income, education, and rural home location), health experience (comorbidity, number of medications and health providers), …

The Impact Of The Introduction Of The Pecarn Head Ct Rules On The Utilisation Of Head Ct Scans For Children With Mild Head Injury At The Aga Khan University Hospital, Nairobi., Isaac Oluoch Kobe

Theses & Dissertations

Background: Head injury is the most common cause of childhood morbidity and mortality worldwide. Mild head injury comprises 90% of cases of head injury in children. Head CT scans are few, expensive and have the side effect of ionizing radiation whose effect is potentiated in children and also associated risk of sedation that is often required when doing CT scans in young children. The decision to order CT scans of the head is thus made on the basis of clinical decision rules of which the PECARN CT head rule has been found to be most sensitive and useful.

Objectives: Primary: …

The Diagnostic Accuracy Of Determine™ Tb Lam Antigen In Detection Of Extra Pulmonary Tuberculosis (Eptb), Fatimah Osman Juma

Theses & Dissertations

Background: TB remains a key global health challenge; particularly Extra pulmonary Tuberculosis (EPTB) and is also a major cause of morbidity and mortality in sub-Saharan Africa. The increasing incidence of EPTB compounded by difficulties in making a timely diagnosis portends to poor prognosis and increased mortality. Delays in diagnosis and misdiagnosis of EPTB in suspected patients account for mortality as well. Challenges in diagnosis of EPTB are mainly due to disease related factors, the paucibacillary nature of disease and challenges with sample collection and processing. Reference standard test such as TB culture, geneXpert and histology which are used in the …

Vitamin D Levels In Black African Adults At The Aga Khan University Hospital Nairobi, Elizabeth Muringa Kagotho

Theses & Dissertations

Introduction: Vitamin D has been known for centuries for its benefits in bone health. Recent observational studies have however demonstrated its benefits in infectious diseases such as tuberculosis and non-communicable diseases such as diabetes mellitus, cardiovascular diseases and cancer. This has led to a dramatic increase in testing among adults. The cut-offs for vitamin D deficiency have been debated for decades and the current cut off is derived from a Caucasian population. Studies done among black African adults in Africa are few and have shown that vitamin D deficiency ranges from 5-91%. In view of the difference in skin colour, …

Association Between Immediate Postnatal Anaemia And Risk Of Developing Postpartum Depression At The Aga Khan University Hospital: A Cohort Study, John Ndungu Kimani

Theses & Dissertations

Introduction: Postpartum depression has significant burden on obstetric psychopathology. While risk factors for the same have been extensively studied, most of this studies have focused on the role of psychosocial factors. Data on the role of physiological variables such as anaemia and role of obstetric complications in postpartum depression is now emerging. There are still gaps in literature regarding the same in developing countries and in Africa.

Primary Objective: To determine the association between low postnatal hemoglobin and postpartum depression

Secondary Objective: To determine the association between obstetric complication specifically postpartum hemorrhage, operative delivery and NICU/NHDU admission and postpartum depression. …