Medical Specialties Commons^™

Population Pharmacokinetics Of Ciprofloxacin In Neonates And Young Infants Less Than 3 Months Age, Wei Zhao, Helen Hill, Chantal Le Guellec, Tim Neal, Sarah Mahoney, Stephanie Paulus, Charlotte Castellan, Behrouz Kassai, John N. Van Den Anker, Gregory L. Kearns, Mark A. Turner, Evelyne Jacqz-Aigrain

Pediatrics Faculty Publications

Ciprofloxacin is used in neonates with suspected or documented Gram-negative serious infections. Currently, its use is off-label partly because of lack of pharmacokinetic studies. Within the FP7 EU project TINN (Treat Infection in NeoNates), our aim was to evaluate the population pharmacokinetics of ciprofloxacin in neonates and young infants <3 months of age and define the appropriate dose in order to optimize ciprofloxacin treatment in this vulnerable population. Blood samples were collected from neonates treated with ciprofloxacin and concentrations were quantified by high-pressure liquid chromatography-mass spectrometry. Population pharmacokinetic analysis was performed using NONMEM software. The data from 60 newborn infants (postmenstrual age [PMA] range, 24.9 to 47.9 weeks) were available for population pharmacokinetic analysis. A two-compartment model with first-order elimination showed the best fit with the data. A covariate analysis identified that gestational age, postnatal age, current weight, serum creatinine concentration, and use of inotropes had a significant impact on ciprofloxacin pharmacokinetics. Monte Carlo simulation demonstrated that 90% of hypothetical newborns with a PMA of <34 weeks treated with 7.5 mg/kg twice daily and 84% of newborns with a PMA ≥34 weeks and young infants receiving 12.5 mg/kg twice daily would reach the AUC/MIC target of 125, using the standard EUCAST MIC susceptibility breakpoint of 0.5 mg/liter. The associated risks of overdose for the proposed dosing regimen were <8%. The population pharmacokinetics of ciprofloxacin was evaluated in neonates and young infants <3 months old, and a dosing regimen was established based on simulation.

Cerebral Pressure Passivity In Newborns With Encephalopathy Undergoing Therapeutic Hypothermia, Rathinaswamy B. Govindan, An Nguyen Massaro, Nickie N. Andescavage, Taeun Chang, Adre J. Du Plessis

Neurology Faculty Publications

We extended our recent modification of the power spectral estimation approach to quantify spectral coherence. We tested both the standard and the modified approaches on simulated data, which showed that the modified approach was highly specific and sensitive to the coupling introduced in the simulation while the standard approach lacked these features. We also applied the modified and standard approaches to quantify the pressure passivity in 4 infants receiving therapeutic hypothermia. This was done by measuring the coupling between continuous cerebral hemoglobin differences and mean arterial blood pressure. Our results showed that the modified approach identified a lower pressure passivity …

Lysosomal Abnormalities In Hereditary Spastic Paraplegia Types Spg15 And Spg11, Benoit Renvoise, Jaerak Chang, Rajat Singh, Sayuri Yonekawa, Edmond J. Fitzgibbon, Ami Mankodi, Adeline Vanderver, Alice B. Schindler, Camilo Toro, William A. Gahl, Don J. Mahuran, Craig Blackstone, Tyler Pierson

Neurology Faculty Publications

Objective

Hereditary spastic paraplegias (HSPs) are among the most genetically diverse inherited neurological disorders, with over 70 disease loci identified (SPG1-71) to date. SPG15 and SPG11 are clinically similar, autosomal recessive disorders characterized by progressive spastic paraplegia along with thin corpus callosum, white matter abnormalities, cognitive impairment, and ophthalmologic abnormalities. Furthermore, both have been linked to early-onset parkinsonism.

Methods

We describe two new cases of SPG15 and investigate cellular changes in SPG15 and SPG11 patient-derived fibroblasts, seeking to identify shared pathogenic themes. Cells were evaluated for any abnormalities in cell division, DNA repair, endoplasmic reticulum, endosomes, and lysosomes.

Results

Fibroblasts …

Implicit Sequence Learning In People With Parkinson's Disease, Katherine R. Gamble, Thomas J. Cummings, Steven E. Lo, Pritha T. Ghosh, James H. Howard, Darlene V. Howard

Neurology Faculty Publications

Implicit sequence learning involves learning about dependencies in sequences of events without intent to learn or awareness of what has been learned. Sequence learning is related to striatal dopamine levels, striatal activation, and integrity of white matter connections. People with Parkinson’s disease (PD) have degeneration of dopamine-producing neurons, leading to dopamine deficiency and therefore striatal deficits, and they have difficulties with sequencing, including complex language comprehension and postural stability. Most research on implicit sequence learning in PD has used motor-based tasks. However, because PD presents with motor deficits, it is difficult to assess whether learning itself is impaired in these …

Concurrent Non-Ketotic Hyperglycinemia And Propionic Acidemia In An Eight Year Old Boy, Paul Kruszka, Brian Kirmse, Dina Zand, Kristina Cusmano-Ozog, Elaine Spector, John Hove, Kimberly A. Chapman

Pathology Faculty Publications

This is the first reported case of a patient with both non-ketotic hyperglycinemia and propionic acidemia. At 2 years of age, the patient was diagnosed with non-ketotic hyperglycinemia by elevated glycine levels and mutations in the GLDC gene (paternal allele: c.1576_1577insC delT and c.1580delGinsCAA; p.S527Tfs*13, and maternal allele: c.1819G>A; p.G607S). At 8 years of age after having been placed on ketogenic diet, he became lethargic and had severe metabolic acidosis with ketonuria. Urine organic acid analysis and plasma acylcarnitine profile were consistent with propionic acidemia. He was found to have an apparently homozygous mutation in the PCCB gene: c.49C …

Differential Expression Of The Nuclear-Encoded Mitochondrial Transcriptome In Pediatric Septic Shock., Scott L Weiss, Natalie Z Cvijanovich, Geoffrey L Allen, Neal J Thomas, Robert J. Freishtat, Nick Anas, +11 Additional Authors

Pediatrics Faculty Publications

INTRODUCTION: Increasing evidence supports a role for mitochondrial dysfunction in organ injury and immune dysregulation in sepsis. Although differential expression of mitochondrial genes in blood cells has been reported for several diseases in which bioenergetic failure is a postulated mechanism, there are no data about the blood cell mitochondrial transcriptome in pediatric sepsis.

METHODS: We conducted a focused analysis using a multicenter genome-wide expression database of 180 children ≤ 10 years of age with septic shock and 53 healthy controls. Using total RNA isolated from whole blood within 24 hours of PICU admission for septic shock, we evaluated 296 nuclear-encoded …

Hemorrhagic Stroke In An Adolescent Female With Hiv-Associated Thrombotic Thrombocytopenic Purpura, Natella Rakhmanina, Edward C.C. Wong, Jeremiah C. Davis, Patricio E. Ray

Pediatrics Faculty Publications

HIV-1 infection can trigger acute episodes of Idiopathic Thrombocytoponic Purpura (ITP), and Thrombotic Thrombocytopenic Purpura (TTP), particularly in populations with advanced disease and poor adherence to antiretroviral therapy (ART). These diseases should be distinguished because they respond to different treatments. Previous studies done in adults with HIV-TTP have recommended the prompt initiation or re-initiation of ART in parallel with plasma exchange therapy to improve the clinical outcome of these patients. Here, we describe a case of HIVTTP resulting in an acute hemorrhagic stroke in a 16 year old female with perinatally acquired HIV infection and non-adherence to ART, who presented …

Assessing Function And Endurance In Adults With Spinal And Bulbar Muscular Atrophy: Validity Of The Adult Myopathy Assessment Tool., Michael O. Harris-Love, Lindsay Fernandez-Rhodes, Galen Joe, Joseph A. Shrader, Angela Kokkinis, Alison La Pean Kirschner, Sungyoung Auh, Cheunju Chen, Li Li, Ellen Levy, Todd E. Davenport, Nicholas A. Di Prospero, Kenneth H. Fischbeck

Exercise and Nutrition Sciences Faculty Publications

Purpose. The adult myopathy assessment tool (AMAT) is a performance-based battery comprised of functional and endurance subscales that can be completed in approximately 30 minutes without the use of specialized equipment. The purpose of this study was to determine the construct validity and internal consistency of the AMAT with a sample of adults with spinal and bulbar muscular atrophy (SBMA).

Methods. AMAT validity was assessed in 56-male participants with genetically confirmed SBMA (mean age, 53 ± 10 years). The participants completed the AMAT and assessments for disease status, strength, and functional status. Results. Lower AMAT scores were associated with longer …

Medical Tourism: Comparing Coronary Bypass Surgery In The U.S. And Abroad, William K. Willis, Alberto Coustasse

Management Faculty Research

Rising health care costs have employers searching for remedies to the increasing rates they pay for employee health insurance. The development of U.S. health insurance policies, with the option of utilizing medical tourism as a low cost care provider for treatment of cardiac coronary bypass surgery provides a method for receiving treatment. The medical tourism approach to providing treatment for bypass surgery has prompted hospitals in India, Thailand, and Singapore to seek U.S. patients. A comparison of costs for bypass treatment between the U.S. and these countries illustrates some of the issues and concerns that arise when making such comparisons. …

Benzyl Isothiocyanate As An Adjuvant Chemotherapy Option For Head And Neck Squamous Cell Carcinoma, Mary Allison Wolf

Theses, Dissertations and Capstones

Isothiocyanates (ITCs) are natural phytochemicals produced by cruciferous vegetables. Recent evidence supports that, in addition to cancer prevention, ITCs can use various mechanisms to target malignant cells. Current therapies for cancer often provoke detrimental side effects, however clinical evidence supports that ITCs have little to no side effects in patients. Consequently, ITCs may be a promising treatment option for cancer patients, especially patients suffering from head and neck squamous cell carcinoma (HNSCC).

Despite recent improvements in cancer treatment, overall survival of advanced HNSCC has not improved in the past three decades. Metastasis and chemoresistance represent two detrimental events that greatly …

Menarche, Stephanie Stockburger, Hatim A. Omar

Pediatrics Faculty Publications

Menarche is a female’s first menstrual period and a landmark event for females during puberty. Historically, menarche has been thought of as a time when women were “unclean.” However, cultural acceptance and scientific knowledge of menarche has greatly increased. Menarche occurs as part of the typical progression of puberty caused by rises in luteinizing hormone (LH), follicle stimulating hormone (FSH), and estrogen. The achievement of menstruation is associated with reproductive capability. Menarche that occurs earlier or later than expected should be evaluated by an experienced clinician and may signal a serious underlying problem. Currently, researchers are evaluating whether menarche is …

The Importance Of Early Identification And Treatment Of Childhood Onset Bipolar Disorder: Creating Specialty Care, Robert M. Post

Psychiatry and Behavioral Sciences Faculty Publications

No abstract provided.

Synthesizing Data And Models For The Spread Of Mers-Cov, 2013: Key Role Of Index Cases And Hospital Transmission, Gerardo Chowell, Seth Blumberg, Lone Simonsen, Mark A. Miller, Cecile Viboud

Global Health Faculty Publications

The outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) has caused 209 deaths and 699 laboratory-confirmed cases in the Arabian Peninsula as of June 11, 2014. Preparedness efforts are hampered by considerable uncertainty about the nature and intensity of human-to-human transmission, with previous reproduction number estimates ranging from 0.4 to 1.5. Here we synthesize epidemiological data and transmission models for the MERS-CoV outbreak during April–October 2013 to resolve uncertainties in epidemic risk, while considering the impact of observation bias. We match the progression of MERS-CoV cases in 2013 to a dynamic transmission model that incorporates community and hospital compartments, and …

Conversion Of Autoimmune Hypothyroidism To Hyperthyroidism, Saira Furqan, Naeem-Ul Haque, Najmul Islam

Section of Diabetes, Endocrinology and Metabolism

Background: Graves' disease and Hashimoto's thyroiditis are the two autoimmune spectrum of thyroid disease. Cases of conversion from hyperthyroidism to hypothyroidism have been reported but conversion from hypothyroidism to hyperthyroidism is very rare. Although such cases have been reported rarely in the past we are now seeing such conversions from hypothyroidism to hyperthyroidism more frequently in clinical practice.

Case Presentation: We are reporting three cases of middle aged Asian females who presented with classical symptoms of hypothyroidism and the investigations showed elevated thyroid stimulating hormone with positive thyroid antibodies. Diagnosis of autoimmune hypothyroidism was made and thyroxine replacement therapy …

Pituitary Stalk Interruption Syndrome Presenting As Short Stature: A Case Report, Nanik Ram, Syed Ahsan Ali, Syed Zubair Hussain

Section of Diabetes, Endocrinology and Metabolism

Introduction: Pituitary stalk interruption syndrome is a rare congenital abnormality of the pituitary that is responsible for anterior pituitary deficiency. It is characterized by a classic triad of interrupted pituitary stalk, absent or ectopic posterior pituitary, and anterior pituitary hypoplasia or aplasia. Clinical presentation varies according to age. In adults it presents as short stature and anterior pituitary deficiency. Without early diagnosis and treatment, mortality and morbidity in these patients is high. Early diagnosis and treatment of this rare disease can prevent permanent short statue of the patient. We report the first case of pituitary stalk interruption syndrome from …

Preablation Stimulated Thyroglobulin/Tsh Ratio As A Predictor Of Successful I(131)Remnant Ablation In Patients With Differentiated Thyroid Cancer Following Total Thyroidectomy, Syed Zubair Hussain, Maseeh Uz Zaman, Sarwar Malik, Nanik Ram, Ali Asghar, Unaib Rabbani, Nida Aftab, Najmul Islam

Section of Diabetes, Endocrinology and Metabolism

Background. About 90% of thyroid cancers are differentiated thyroid cancers. Standard treatment is total thyroidectomy followed by radioactive I(131)remnant ablation and TSH suppression with thyroxine. Unsuccessful ablation drastically affects the prognosis of patients with DTC particularly high risk individuals; therefore, identifying the factors that affect the success of ablation is important in the management of patients with DTC. sTg is a good predictor of successful ablation in DTC. Its levels can be influenced by tumor staging and TSH values, as well as other factors. Therefore, we did this study using TSH to correct the predictive value of sTg in …

Role Of Complementary And Alternative Medicine In Controlling Dyslipidemia, Waris Qidwai, Firdous Jahan, Kashmira Nanji

Department of Family Medicine

No abstract provided.

Examining A Link Between Paraquat, Alpha-Synuclein Fibrillation And Neurodegeneration: A Review, Nikhil Ailaney

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Parkinson’s disease is a chronic and progressive motor system disorder that is caused by the degeneration of dopaminergic neurons in the central nervous system. At the molecular level, Parkinson’s disease works by decreasing the concentrations of the neurotransmitter dopamine, a chemical messenger involved in motor messaging, within the central nervous system. Low levels of dopamine in the central nervous system causes motor system dysfunction because the insufficient levels of dopamine lead to an inability for neurons to successfully transmit motor messages. At the organismal level, Parkinson’s disease causes tremors, Bradykinesia, and rigidity. These symptoms ultimately lead to a diminished quality …

Perceived Barriers Among Pregnant Women Towards Cervical Cancer Screening, Visavilwa Vincent Lamuka

Master of Medicine in Family Medicine

Background: Cervical cancer remains the most common cancer in women in Eastern Africa in general and Tanzania in particular. However, to a large extent cervical cancer is preventable by effective screening programmes as has been demonstrated in many developed countries. Developing countries lack formal national screening programmes. Screening is usually mainly done opportunistically. Objective: To assess the perceived barriers to uptake of cervical cancer screening among pregnant women attending antenatal clinics in two hospitals in Dar es Salaam. Methodology: This was a qualitative study, conducted at two hospitals in Dar es salaam, a government facility (Amana District Hospital) and a …

An Assessment Of Whether Medical Doctors Have The Knowledge That Would Enable Them To Competently Deliver Tobacco Cessation Services, Miriam Miima Khamonya

Master of Medicine in Family Medicine

Background: Tobacco use is the leading cause of preventable morbidity and mortality globally. The international community recognizes this epidemic and compelling evidence exists on the significant contribution of the health care provider in propagating the success of tobacco cessation. The World Health Organization highlights minimal implementation of tobacco control policies by Tanzania despite a rise in tobacco use prevalence. Medical doctors’ competence is a reflection on our commitment to tobacco cessation service delivery. Main Objectives: To assess whether medical doctors have the knowledge that would enable them to competently deliver tobacco cessation services. Specific Objectives 1. To assess medical doctors’ …

Understanding And Managing Complications In Neurosurgery, Raza Sayyed, M Shahzad Shamim

Pakistan Journal of Neurological Sciences (PJNS)

It is a well-known surgical maxim that only two types of surgeons do not have surgical complications; those who do not operate, and those who lie. Surgical complications in other words, are unwanted but undeniable part of surgery. There is not one operation with a 0% complication rate and therefore statistically, if a surgeon does not have complications, he probably has not operated enough. Despite their inevitability, complications convey a sense of gravity to the public, health professionals, and the policy makers alike.

Delay In Diagnosis Of Motor Neuron Disease. A Tertiary Care Experience, Hazim Brohi, Naveed Uddin Ahmed, Rajesh Khatri, Ishaq Asghar

Pakistan Journal of Neurological Sciences (PJNS)

Motor Neuron Disease is a progressive neurological disorder with poor prognosis. Inability to correctly recognize the disease, leads to undue agony and diagnostic dilemma. Studies have been done to look at the average duration taken to diagnose the disease from the onset of symptoms. The literature shows that latency from symptom onset to diagnosis range from 10.6–17.5 months. No such study has been conducted in our region. We reviewed 62 patients referred to the neurophysiology lab from year 2009 to 2013 with quarry of MND. Only 40 patients were identified to fulfill the El Escorial criteria for MND. The median …

Assessing Interprofessional Continuing Education And Planning Ahead, Farhan Vakani, Mughis Sheerani

Pakistan Journal of Neurological Sciences (PJNS)

The purpose of this survey is to check the concept of Interprofessional education (IPE) to continuing education among working physicians.It assessed 150 randomly selected working physicians of the Aga Khan University Hospital. One -best type questionnaire was designed and piloted to check its completion within 90 seconds.Four quick questions were dedicated at C1 & C2 level focused to check the knowledge and understanding of the physicians to IPE. The results showed 100% response rate. Majority (i.e. > 80%) of the respondents were familiar with the term IPE.The next three items tested physicians understanding regarding the IPE ability to improve communication, teamwork, …

Crossed Cerebellar Diaschisis In Partial Status Epilepticus, Sahrish Aieshah Kazi, Rehmani Aniqah Jawad, Rashed Nazir, Shahid Ahmed Shah, Arsalan Ahmad

Pakistan Journal of Neurological Sciences (PJNS)

Crossed cerebellar diaschisis is a phenomena described as decrease in metabolism in the cerebellar hemisphere contralateral to the supratentorial lesion. A 61 year old man presented with status epilepticus. CT Brain showed small acute hemorrhage in left parietal lobe.MRI revealed diffusion restriction in right cerebral and left cerebellar hemispheres with hyperintensities on T2WI and FLAIR. However, CT perfusion was suggestive of increased perfusion in these areas. Periictal EEG showed frequent bursts of higher voltage spike and wave discharges over the right hemisphere. He was treated with IV antiepileptics. But he continued to deteriorate, and expired at 10th day of admission.

Neurostimulation For Refractory Primary Chronic Headache Disorders: A Review, Bindu Yoga, Modar Khalil, Hassan Zafar, Fayyaz Ahmed

Pakistan Journal of Neurological Sciences (PJNS)

Headache is the commonest symptom seen in both primary and secondary care. Vast majority are primary i.e. for which no underlying cause has been detected. Tension Headaches, Migraine and Cluster Headaches are the most common primary headache disorders in the population. Although most of the primary headache disorders can be satisfactorily treated with both acute and preventive medications, those that are refractory to conventional treatment pose a great challenge to the headache physician. Moreover some patients are not able to use traditional treatment due to intolerance and co-morbidities. Neurostimulation is a treatment modality that has been used in other neurological …

Gossypiboma Diagnosed Fifteen Years After A Cesarean Section: A Case Report, Abdul Rehman, Noor Ul-Ain Baloch, Muhammad Awais

Department of Biological & Biomedical Sciences

Gossypiboma, a retained surgical sponge, is a rare complication following any surgical procedure and is primarily a result of human error. Such patients often have vague clinical presentations and the diagnosis often comes as a surprise. We present the case of a 40-year-old woman who had a long-standing history of lower abdominal discomfort. She was diagnosed with a gossypiboma fifteen years after a cesarean section. All general physicians, surgeons and radiologists must be aware of this rare but clinically significant entity.

Racecadotril For The Treatment Of Severe Acute Watery Diarrhoea In Children Admitted To The Kenyatta National Hospital - A Randomised Double Blinded Placebo Controlled Trial, Jaspreet Singh Gharial

Master of Medicine in Paediatrics and Child Health

Background: Diarrhoeal disease is the second most common cause of death in children under 5 years of age in Kenya. Treatment with Oral Rehydration Solution (ORS), elemental zinc and continued feeding (as recommended by the World Health Organisation) led to a significant reduction in mortality in the 1970s and 1980s, which has slowed since then. Adjunctive treatments have however, not gained much popularity either due to modest improvements in morbidity and mortality or unacceptable adverse effect profiles. Racecadotril, an enkephalinase inhibitor, has been used for over 2 decades in parts of Europe but is only recently gaining recognition in other …

Hospital-Acquired Malnutrition In Children In A Tertiary Care Hospital, Del-Rossi Sean Quadros

Master of Medicine in Paediatrics and Child Health

Introduction: Hospital-acquired Malnutrition occurs as a result of reduction in food intake, increased dietary loss and/or increased calorie requirements as a result of disease-induced high catabolic state. A child's nutritional status often deteriorates after admission to the hospital resulting in longer duration of hospital stay and increased risk of complications, which also increases treatment cost. Hospital-acquired Malnutrition is usually assessed using anthropometric measurements and/or serum pre-albumin. Objectives: This study sought to investigate the incidence of Hospital-acquired Malnutrition using anthropometric measurements and to determine diagnostic utility of serum pre-albumin in predicting weight change. A secondary objective was to identify factors associated …

Prevalence And Outcomes Of Acute Kidney Injury In Term Neonates With Perinatal Asphyxia, Dan Alaro, Bashir Admani, Lucy Wainaina, Rachel Musoke

Paediatrics and Child Health, East Africa

Background: The kidney is the most damaged organ in asphyxiated full-term infants. The severity of its damage is corre­lated with the severity of neurological damage. We determined the prevalence of perinatal asphyxia-associated acute kidney injury (AKI).

Methods: We conducted a prospective cohort study including 60 full-term neonates admitted at the Kenyatta National Hospital newborn unit (NBU) in Nairobi with hypoxic ischaemic encephalopathy (HIE) from June 2012 to November 2012. Renal function was assessed by measuring serum creatinine on day 3 of life. AKI was defined by a level of creatinine above 133 μmol/l. The degree of neurological impairment was determined …

Pediatric Cerebral Palsy In Africa: Where Are We?, Kirsten A. Donald, Angelina M. Kakooza, Robinson D. Wammanda, Macpherson Mallewa, Pauline Samia, Haydar Babakir, David Bearden, Annette Majnemer, Darcy Fehlings, Michael Shevell, Harry Chugani, Jo M. Wilmshurst

Paediatrics and Child Health, East Africa

Cerebral palsy is the most common cause of physical disability in children worldwide. However, little is reported on this condition in the African context. Doctors from 22 countries in Africa, and representatives from a further 5 countries outside Africa, met to discuss the challenges in the evaluation and management of children with cerebral palsy in Africa and to propose service needs and further research. Basic care is limited by the poor availability of diagnostic facilities or medical personnel with experience and expertise in managing cerebral palsy, exacerbated by lack of available interventions such as medications, surgical procedures, or even regular …