Atypical presentation of tuberous sclerosis and obsessive compulsive disorder in an adult male

Tuberous Sclerosis (TSC) is clinically marked by a triad of adenoma sebaceum, epilepsy and mental retardation. It can however manifest as various neuropsychiatric disorders. We report a patient who presented with TSC and co-morbid Obsessive Compulsive Disorder.     

Pharmacokinetics of Artesunate Alone and in Combination with Sulfadoxine/Pyrimethamine in Healthy Sudanese Volunteers

Artesunate (AS) in combination with sulfadoxine/pyrimethamine (SP) is the first-line therapy for management of uncomplicated Plasmodium falciparum malaria in Sudan. The objective of this study was to assess the potential impact of SP on the pharmacokinetics of AS and its active metabolite, dihydroartemisinin (DHA), in healthy adults. A single-dose, randomized, open-label, crossover study design with a washout period of three weeks was performed with 16 volunteers. After oral administration of AS alone or in combination with SP, T_max values of AS and DHA were significantly prolonged in the combination group (P < 0.05). However, there was no significant effect on the other pharmacokinetic parameters (P > 0.05). The t_1/2 values of AS and DHA were significantly higher in females than in males (P < 0.05). The present findings suggest that co-administration of SP with AS has no clinically relevant impact on the pharmacokinetics of AS or DHA in healthy persons.     

Myiasis in Kuwait: nosocomial infections caused by lucilia sericata and Megaselia scalaris

Myiasis, the invasion of live human tissue by larvae of Diptera, is reported in the nasopharynx and a leg wound in two patients who were hospitalized for more than 72 hours in Mubarak Al-Kabeer Teaching Hospital in Kuwait City, Kuwait. On the fourth and fifth days after a 10-year-old Kuwaiti boy was admitted to the hospital intensive care unit in a bloodied and comatose state following a traffic accident, 'worms' that came out of his nostrils were fixed, cleared, and identified as second and third instar of Lucilia sericata (Diptera: Calliphoridae). After 14 days, 'worms' were seen in the original dressing of a 35-year-old Iranian man admitted to the Orthopedic Unit of the hospital with multiple lacerations and fractures. The larvae, in various stages of development, were identified as those of Megaselia scalaris (Diptera: Phoridae). Since the presence of larvae in both patients was recorded after a stay of at least 3-4 days in the hospital, by definition, these infestations are considered nosocomial.     

Post-transplant infections: single center experience from the developing world.

OBJECTIVE: To describe our experience of post-transplant infections in allogeneic stem cell transplants at the Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan. METHODS: From July 2001 to September 2006, patients with malignant and non-malignant hematological disorders having human leukocyte antigen (HLA)-matched sibling donors were selected for transplant. Pre-transplant infection surveillance was carried out, and strict prophylaxis against infection was observed. After admission to the hospital, patients were kept in protective isolation rooms, equipped with a HEPA filter positive-pressure laminar airflow ventilation system. Bone marrow and/or peripheral blood stem cells were used as the stem cell source. Cyclosporin and prednisolone were used as prophylaxis against graft-versus-host disease (GVHD). The engraftment was monitored with cytogenetic/molecular analysis and change of blood group. Survival was calculated from the date of transplant to death or last follow-up. RESULTS: One hundred and fifty-four patients received allogeneic stem cell transplants from HLA-matched siblings for various hematological disorders at the Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan between July 2001 and September 2006. Indications for transplant included aplastic anemia (n=66), beta-thalassemia major (n=40), chronic myeloid leukemia (n=33), acute leukemia (n=8), and miscellaneous disorders (n=7). One hundred and twenty patients were male and 34 were female. The median age of the patient cohort was 14 years (range 1 1/4-54 years). One hundred and thirty-six patients and 135 donors were cytomegalovirus (CMV) IgG-positive. One hundred and forty patients (90.9%) developed febrile episodes in different phases of post-transplant recovery. Infective organisms were isolated in 150 microbiological culture specimens out of 651 specimens from different sites of infections (23.0% culture positivity). Post-transplant infections were confirmed in 120 patients (77.9%) on the basis of clinical assessment and microbiological, virological, and histopathological examination. Mortality related to infections was 13.0%. Fatal infections included CMV disease (100% mortality, 6/6), disseminated aspergillosis (66.7% mortality, 4/6), pseudomonas septicemia (42.9% mortality, 9/21), and tuberculosis (25% mortality, 1/4). CONCLUSIONS: More than 90% of our patients developed febrile episodes with relatively low culture yield. The majority of infections were treated effectively, however CMV, aspergillosis, and pseudomonas infections remained problematic with high mortality.     

Platelet glycoprotein IIb/IIIa inhibition using eptifibatide with primary coronary stenting for acute myocardial infarction: a 30-day follow-up study.

The results of primary coronary stenting for acute myocardial infarction (AMI) have been reported to improve significantly with the concomitant administration of platelet glycoprotein IIb/IIIa inhibitor abciximab. There are, however, no data available with the use of eptifibatide, a more cost-effective, small-molecule GP IIb/IIIa blocker with a shorter half-life. In a prospective multicenter feasibility and efficacy study, we assigned 55 consecutive patients with AMI being taken up for primary stenting to receive eptifibatide just before the procedure (two boluses of 180 microg/kg 10 min apart and a 24-hr infusion of 2 microg/kg/min). Clinical outcomes were evaluated at 30 days after the procedure. The angiographic patency of the vessel with TIMI flow rates, TIMI myocardial perfusion (TMP) grade, and corrected TIMI frame counts were assessed at the end of procedure and before hospital discharge. At 30 days, the primary endpoint, a composite of death, myocardial infarction, and urgent target vessel revascularization (TVR) was seen in 12.7% of patients. The TIMI 3 and TMP grade 3 flow, which was seen in 93% and 86% of patient, respectively, at the end of the procedure, declined to 86% and 78%, respectively (P < 0.05) before hospital discharge. Corrected TIMI frame counts also decreased from 25.7 +/- 7.2 to 22.9 +/- 6.8 (P < 0.05). There were five (9.1%) instances of subacute thrombosis (SAT) presenting as AMI, needing urgent TVR in all, within 3-5 days of the primary procedure. No excessive bleeding complication, directly attributable to the use of eptifibatide, was observed. The study was terminated prematurely because of an unacceptable SAT rate. Administration of eptifibatide along with primary stenting for AMI is associated with a high TIMI 3 and TMP grade 3 flow acutely. However, these flows decline significantly before hospital discharge and lead to a high rate of SAT. The dosage and duration of infusion of eptifibatide in this setting needs further evaluation.     

Population pharmacokinetic analysis of oseltamivir and oseltamivir carboxylate following intravenous and oral administration to patients with and without renal impairment

This work characterizes the pharmacokinetics (PK) of oseltamivir phosphate (OP) and its active metabolite, oseltamivir carboxylate (OC), and investigates oseltamivir i.v. dosing regimens for treatment of influenza in patients with normal renal function and with various degrees of renal impairment. Initially, data collected from 149 subjects with normal renal function and mild to severe renal impairment who were administered 40–200 mg oseltamivir i.v. were described by a four-compartment model. Two compartments described OP, one compartment described OC and one compartment described OP to OC metabolism. Then, data of 128 subjects administered 20–1,000 mg oseltamivir orally were added. The absorption model included three first-order processes with direct (via first-pass) input in the OC compartment and two (direct and delayed) inputs in the OP compartment. Simulations and PK bridging were used to recommend i.v. dosing regimens. The analysis demonstrated that renal function had a major effect on OC clearance (CL _M ) and exposure. CL _M for subjects with mild, moderate and severe renal impairment was 18, 50, and 84 % lower than for subjects with normal renal function. Simulations were used to select i.v. dosing regimens that provide OC C_min coverage and exposures comparable to those achieved in subjects with normal renal function administered 75 mg b.i.d. orally. The oseltamivir dose depended on the degree of renal impairment and was independent of route of administration. Specifically, 75 mg b.i.d. is recommended for subjects with normal renal function or mild renal impairment, 30 mg b.i.d. for subjects with moderate renal impairment, and 30 mg q.d. for subjects with severe renal impairment. Recommended i.v. doses were the same as those recommended for oral administration in corresponding renal impairment groups.     

Peroral Endoscopic Myotomy Is a Safe and Feasible Option in Management of Esophageal Diverticula: Systematic Review and Meta-Analysis

Digestive Diseases and Sciences - Esophageal diverticula can cause significant symptoms and affect the quality of life. There has been recent interest in the use of peroral endoscopic myotomy in...     

Type II Achalasia Is Increasing in Prevalence

Background

Three manometric subtypes of achalasia were defined in the Chicago Classification approximately 10 years ago: type I (aperistalsis), type II (pan-pressurization), and type III (spastic). Since the widespread use of this classification scheme, the evolving prevalence of these subtypes has not been elucidated. We aim to determine the prevalence of each subtype a decade after the adoption of the Chicago Classification.

Methods

This is a retrospective cohort analysis of patients diagnosed with achalasia on high-resolution manometry (HRM) at two major academic medical centers between 2015 and 2018. Patients were excluded if they had a diagnosis of another esophageal motility disorder, previously treated achalasia, or foregut surgery. Demographic data, manometric subtype, and esophageal dilatation grade on endoscopy were obtained. Prevalence of achalasia subtypes was compared with a published historical control population (2004–2007). Fischer’s exact and t tests were used for analysis.

Results

Of 147 patients in the contemporary cohort and 99 in the historical control cohort, the prevalence of type I achalasia was 8% versus 21%, type II 63% versus 50%, and type III 29% versus 29%, respectively (p?=?0.01). The mean age in our population was 58 years compared to 57 years in the historical control, and the proportion of men 48% versus 47%, respectively (p?=?0.78). Mean endoscopic dilatation grade in the contemporary cohort was 1.5 for type I patients, 0.9 for type II, and 0.4 for type III, compared with 1.5, 0.6, and 0.4, respectively. Overall mean dilatation grade was 0.8 in our cohort versus 0.7 in the historical control (p?=?0.58).

Conclusion

The prevalence of type II achalasia was significantly greater and prevalence of type I significantly less in our patient population compared to our predefined historical control. Other characteristics such as age and sex did not appear to contribute to these differences. Histopathological evidence has suggested that type II achalasia may be an earlier form of type I; thus, the increased prevalence of type II achalasia may be related to earlier detection of the disease. The adoption of HRM, widespread use of the Chicago Classification, and increased disease awareness in the past decade may be contributing to these changes in epidemiology.