Hemoperfusion for Clinically Suspected Organophosphate and Carbamate Poisoning in Critically Ill Patients: A Randomized Trial.

INTRODUCTION: Organophosphate poisoning occurs frequently, and despite treatment, increased severity and intensive care unit (ICU) admissions have been observed. We hypothesized that early hemoperfusion/hemadsorption (HA) therapy would change the clinical course of the disease. METHODS: We performed a prospective, open, randomized controlled study at an academic ICU. Adult patients referred for an acute cholinergic toxidrome were screened. Patients meeting inclusion and exclusion criteria were randomized to standard of care (SoC) or HA therapy plus SoC, which included 2 6-h cycles of HA 12 h apart beginning within the first 24 h of ICU admission. The primary outcome was a comparison of ICU length of stay (LOS). RESULTS: There were no significant baseline differences between the groups. The median ICU LOS was 6.5 days (IQR 4.5-10) in the HA group compared to 8 days (IQR 3.5-17) for the control group, p = 0.58. Among patients with an excess ICU LOS ≥7 days, the median ICU LOS was significantly shorter for the HA group, 10 days (IQR 8-12) compared to 17 days (IQR 14-22) for the control group, p = 0.001, resulting in a cost saving of EUR 7308 per patient. Duration (8 days vs. 13.5 days) and cumulative dosage (316 mg vs. 887 mg) of atropine among patients with excess ICU LOS were significantly lower in the HA group compared to the SoC group, respectively. A similar reduction in the duration of mechanical ventilation (HA = 6 days vs. SoC = 15 days, p = 0.001) was found. The combination of day 28 mortality and severe complications was lower in the HA group (10%, n = 2/20) compared to the SoC group (42%, 14/33) p = 0.01. CONCLUSION: HA therapy resulted in significant cost savings driven by a reduced LOS among patients with excess ICU LOS ≥7 days. This therapy was also associated with a significant reduction in the combination of day 28 mortality and severe complications including cardiac arrest, organ dysfunction, reintubation, and tracheostomy.

Clinical and Radiological Outcomes Following Arthroscopic Dual Tibial Tunnel Double Sutures Knot-bump Fixation Technique for Acute Displaced Posterior Cruciate Ligament Avulsion Fractures.

BACKGROUND: Many fixation options (Open and arthroscopic) are described for Posterior Cruciate Ligament avulsion (PCL) fractures. In this retrospective series, we evaluated functional and radiographic outcomes following arthroscopic dual tunnel double sutures knot bump technique for acute PCL tibial end avulsion fractures. METHODS: 23 patients with acute PCL avulsion fractures who were operated between 2009 and 2016 by Arthroscopic dual tunnel double sutures technique at a minimum of two years of follow-up were included in the study. Clinical outcomes were measured by Lysholm and International Knee Documentation Committee (IKDC) scores. The radiographic assessment included union status of fracture, the grade of osteoarthritis, and knee laxity. RESULTS: The mean age of patients was 34.43 years (range, 18-54 years) with a mean follow up of 52.8 months (36-94 months). At the final follow-up, mean subjective IKDC and Lysholm scores were 82.71 (range, 65.5-100) and 95.82 (range, 81-100), respectively. On the IKDC objective scale, ten patients (43.47%) were graded as A, 11 patients [47.82%] as grade B, and two patients as grade C [8.7%]. On kneeling stress view, knee laxity in 21 patients (91.3%) was graded 0, and the remaining two as grade I and II. The fracture had united in all cases by the end of 12 weeks except one which had non-union. 21 patients had no evidence of osteoarthritis at the final follow up. CONCLUSION: Arthroscopic dual tibial tunnel double suture knot bump technique for acute PCL avulsion fractures is a safe and reliable technique that restores the stability and function of the knee.

Extra-articular Extra-synovial Solitary Osteochondromatosis of the Ankle

ABSTRACT Synovial chondromatosis or osteochondromatosis is a benign neoplastic condition arising from synovial tissue of joints, tendon sheath and bursa. The commonly involved joints are the knee, hip, shoulder, elbow and ankle. According to the author's knowledge, only four cases have been reported in the English literature, describing the extra-articular synovial chondro-matosis around the ankle joint. The peculiarity of the index case lies in its subtle clinical and radiological presentations which can create a diagnostic dilemma.

mRNA induced expression of human angiotensin-converting enzyme 2 in mice for the study of the adaptive immune response to severe acute respiratory syndrome coronavirus 2.

The novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic. Critical to the rapid evaluation of vaccines and antivirals against SARS-CoV-2 is the development of tractable animal models to understand the adaptive immune response to the virus. To this end, the use of common laboratory strains of mice is hindered by significant divergence of the angiotensin-converting enzyme 2 (ACE2), which is the receptor required for entry of SARS-CoV-2. In the current study, we designed and utilized an mRNA-based transfection system to induce expression of the hACE2 receptor in order to confer entry of SARS-CoV-2 in otherwise non-permissive cells. By employing this expression system in an in vivo setting, we were able to interrogate the adaptive immune response to SARS-CoV-2 in type 1 interferon receptor deficient mice. In doing so, we showed that the T cell response to SARS-CoV-2 is enhanced when hACE2 is expressed during infection. Moreover, we demonstrated that these responses are preserved in memory and are boosted upon secondary infection. Importantly, using this system, we functionally identified the CD4+ and CD8+ structural peptide epitopes targeted during SARS-CoV-2 infection in H2b restricted mice and confirmed their existence in an established model of SARS-CoV-2 pathogenesis. We demonstrated that, identical to what has been seen in humans, the antigen-specific CD8+ T cells in mice primarily target peptides of the spike and membrane proteins, while the antigen-specific CD4+ T cells target peptides of the nucleocapsid, membrane, and spike proteins. As the focus of the immune response in mice is highly similar to that of the humans, the identification of functional murine SARS-CoV-2-specific T cell epitopes provided in this study will be critical for evaluation of vaccine efficacy in murine models of SARS-CoV-2 infection.

mRNA induced expression of human angiotensin-converting enzyme 2 in mice for the study of the adaptive immune response to severe acute respiratory syndrome coronavirus 2.

The novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic resulting in nearly 20 million infections across the globe, as of August 2020. Critical to the rapid evaluation of vaccines and antivirals is the development of tractable animal models of infection. The use of common laboratory strains of mice to this end is hindered by significant divergence of the angiotensin-converting enzyme 2 (ACE2), which is the receptor required for entry of SARS-CoV-2. In the current study, we designed and utilized an mRNA-based transfection system to induce expression of the hACE2 receptor in order to confer entry of SARS-CoV-2 in otherwise non-permissive cells. By employing this expression system in an in vivo setting, we were able to interrogate the adaptive immune response to SARS-CoV-2 in type 1 interferon receptor deficient mice. In doing so, we showed that the T cell response to SARS-CoV-2 is enhanced when hACE2 is expressed during infection. Moreover, we demonstrated that these responses are preserved in memory and are boosted upon secondary infection. Interestingly, we did not observe an enhancement of SARS-CoV-2 specific antibody responses with hACE2 induction. Importantly, using this system, we functionally identified the CD4+ and CD8+ peptide epitopes targeted during SARS-CoV-2 infection in H2b restricted mice. Antigen-specific CD8+ T cells in mice of this MHC haplotype primarily target peptides of the spike and membrane proteins, while the antigen-specific CD4+ T cells target peptides of the nucleocapsid, membrane, and spike proteins. The functional identification of these T cell epitopes will be critical for evaluation of vaccine efficacy in murine models of SARS-CoV-2. The use of this tractable expression system has the potential to be used in other instances of emerging infections in which the rapid development of an animal model is hindered by a lack of host susceptibility factors.

mRNA induced expression of human angiotensin-converting enzyme 2 in mice for the study of the adaptive immune response to severe acute respiratory syndrome coronavirus 2

The novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic resulting in nearly 20 million infections across the globe, as of August 2020. Critical to the rapid evaluation of vaccines and antivirals is the development of tractable animal models of infection. The use of common laboratory strains of mice to this end is hindered by significant divergence of the angiotensin-converting enzyme 2 (ACE2), which is the receptor required for entry of SARS-CoV-2. In the current study, we designed and utilized an mRNA-based transfection system to induce expression of the hACE2 receptor in order to confer entry of SARS-CoV-2 in otherwise non-permissive cells. By employing this expression system in an in vivo setting, we were able to interrogate the adaptive immune response to SARS-CoV-2 in type 1 interferon receptor deficient mice. In doing so, we showed that the T cell response to SARS-CoV-2 is enhanced when hACE2 is expressed during infection. Moreover, we demonstrated that these responses are preserved in memory and are boosted upon secondary infection. Interestingly, we did not observe an enhancement of SARS-CoV-2 specific antibody responses with hACE2 induction. Importantly, using this system, we functionally identified the CD4+ and CD8+ peptide epitopes targeted during SARS-CoV-2 infection in H2b restricted mice. Antigen-specific CD8+ T cells in mice of this MHC haplotype primarily target peptides of the spike and membrane proteins, while the antigen-specific CD4+ T cells target peptides of the nucleocapsid, membrane, and spike proteins. The functional identification of these T cell epitopes will be critical for evaluation of vaccine efficacy in murine models of SARS-CoV-2. The use of this tractable expression system has the potential to be used in other instances of emerging infections in which the rapid development of an animal model is hindered by a lack of host susceptibility factors.

'Getting out of the dark': Implications of load shedding on healthcare in South Africa and strategies to enhance preparedness.

Power failures and the lack of a robust contingency plan could prove catastrophic in any healthcare environment, with varied and far-reaching consequences. In 2003, a 28% rise in both accidental and non-accidental deaths was recorded in the USA as a result of mass power outages. For every day with a power outage lasting longer than 2 hours, hospital mortality has been estimated to increase by 43%.

Pigmented onychomatricoma may originate from a childhood trauma: A case report.

Pigmented onychomatricoma (OM) is a very rare benign fibroepithelial tumor of the nail matrix. We report the case of a 23-year-old Lebanese man with 15-year history of nail plate dystrophy with longitudinal ridging, yellowish discoloration, excessive transverse curvature and late-onset melanonychia along the medial third of the right thumb nail. Excisional biopsy was performed and confirmed OM. We outline the clinical history, radiological and histopathological findings as well as the surgical and reconstructive technique of this unusual case of OM. The age group, history of crush injury, and pigmentation of the nail plate make of this rare form of ungual tumor an interesting case report.

Audit of defibrillators at an urban public sector hospital.

INTRODUCTION: Life-threatening emergencies are not limited to the emergency department. Any delay in intervention during an emergency often culminates into a poor outcome. Early electrical defibrillation is one of the most important interventions in patients with cardiac arrest. This study aimed to conduct a clinical audit of defibrillator devices at an urban public sector hospital in Johannesburg. METHODS: All defibrillator devices within various areas of the hospital were assessed. Device characteristics were recorded into a data collection sheet and subjected to further analysis. RESULTS: This study assessed 112 out of 123 areas in the hospital with a total of 143 defibrillators comprising 139(97.2%) manual external defibrillators (MED) and four(2.8%) automated external defibrillators (AED). MEDs were located in the general wards (n=52, 37.4%), theatre complex (n=25, 17.9%), high dependency areas (n=27, 19.4%) and non-sleepover areas (n=35, 25.2%). Daily checklist books were available for 101 (72.7%) MEDs, 26 (18.7%) had at least once daily documented checks over a 5-day period while 57 (41.0%) had been serviced in the last 12 months. Seven MEDs (4.9%) and one AED (0.7%) had critical problems. CONCLUSION: Compliance with regard to the availability of defibrillator checklist books, conducting and recording of daily defibrillator checks, timely service maintenance of defibrillators and identification of critical device problems was suboptimal in this study. There is a need for ongoing training of hospital staff as well as the establishment of systems to prevent potential adverse consequences due to device failure.

Profile of major congenital malformations in neonates in Al-Jahra region of Kuwait.

We investigated major congenital abnormalities in babies born in Al Jahra Hospital, Kuwait from January 2000 to December 2001. Of 7739 live and still births born over this period, 97 babies had major congenital malformations (12.5/1000 births): 49 (50.6%) babies had multiple system malformations, while 48 (49.4%) had single system anomalies. Of the 49 babies with multiple malformations, 21 (42.8%) had recognized syndromes, most of which were autosomal recessive and 17 had chromosomal aberrations. Isolated systems anomalies included central nervous system (12 cases), cardiovascular system (9 cases), skeletal system (7 cases) and gastrointestinal system (6 cases). Of the parents, 68% were consanguineous. Genetic factors were implicated in 79% of cases. Genetic services need to be provided as an effective means for the prevention of these disorders.

Profile of major congenital malformations in neonates in Al-Jahra region of Kuwait

We investigated major congenital abnormalities in babies born in Al Jahra Hospital, Kuwait from January 2000 to December 2001. Of 7739 live and still births born over this period, 97 babies had major congenital malformations [12.5/1000 births]: 49 [50.6%] babies had multiple system malformations, while 48 [49.4%] had single system anomalies. Of the 49 babies with multiple malformations, 21 [42.8%] had recognized syndromes, most of which were autosomal recessive and 17 had chromosomal aberrations. Isolated systems anomalies included central nervous system [12 cases], cardiovascular system [9 cases], skeletal system [7 cases] and gastrointestinal system [6 cases]. Of the parents, 68% were consanguineous. Genetic factors were implicated in 79% of cases. Genetic services need to be provided as an effective means for the prevention of these disorders

Differential brain responses when applying criterion attribute versus family resemblance rule learning.

Subsystems of category learning have been identified on the basis of general domains of content (e.g., tools, faces). The present study examined categories from the standpoint of internal structure and determined brain topography associated with expressing two fundamentally different category rule structures (criterion attribute, CA, and family resemblance, FR). CA category learning involves processing stimuli by isolated features and classifying by properties held by all members. FR learning involves processing stimuli by integral wholes and classifying on overall similarity among members without sharing identical features. fMRI BOLD response to CA and FR categorization was measured with pseudowords as stimuli. Category knowledge for both tasks was mastered prior to brain imaging. Areas of activation emerged unique to the structure of each category and followed from the nature of the rule abstraction procedure. CA categorization was implemented by strong target monitoring and expectation (medial parietal), rule maintenance in working memory, feature selection processes (inferior frontal), and a sensitivity to high frequency components of the stimulus such as isolated features (anterior temporal). FR categorization, consistent with its multi-featural nature, involved word-level processing (left extrastriate) that evoked articulatory rehearsal (medial cerebellar). The data suggest category structure is an important determinant of brain response during categorization. For instance, anterior temporal structures may help attune visual processing systems to high frequency components to support the learning of criterial, highly predictive rules.

Cerebellar mediation of the complexity of bimanual compared to unimanual movements.

OBJECTIVE: To study rapidly alternating movements under fMRI in order to identify the brain regions that mediate increased complexity in bimanual vs unimanual movements and to verify the localization of a clinical test of limb ataxia (diadochokinesis). METHODS: Unimanual and bimanual movements, that is, palm(s) pronated then supinated, served as stimulation in a block design fMRI investigation at 1.5 T. Analyses compared bimanual movements and rest for each hand separately and the unimanual conditions combined. A pronation/supination task was chosen as it provides the same objective motor output during unimanual and bimanual formats. The increased coordination demand of the bimanual format (phase/antiphase movements) was expected to result in distinct activation in supplementary motor, primary motor, prefrontal, and cerebellar regions. RESULTS: The bimanual task uniquely elicited responses in specific anterior medial and posterior (vermal) cerebellar regions. CONCLUSIONS: The study corroborated clinical use of diadochokinesis tasks to test for aspects of cerebellar integrity. The data do not support the literature emphasizing basal ganglia mediation of this type of coordinated movement. Cerebellar medial and vermal regions (in connection with central nuclei) are proposed as the locus within the cerebellum for mediating complexity, that is, the effective integration of separate limb movements that proceed in an asynchronous but systematic fashion.

The in vitro antitumor assay of 5-(Z)-arylidene-4-imidazolidinones in screens of AIDS-related leukemia and lymphomas.

Thirty-one different 5-(Z)-arylidene-4-imidazolidinones were tested on six AIDS-related lymphoma (ARL) tumor cell lines, one leukemia CCRF-CEM cell culture and five different lymphoma cell lines: RL, KD-488, AS283, PA682 and SU-DHL-7. The investigated compounds showed remarkable activity against ARL, compounds 3d and 5c proved to inhibit AS283 and SU-DHL-7 cell lines, respectively, both at a GI50 value of 0.03 microM. The 2-(2-carboxyphenylamino) series proved to be the most active members in this investigation. Compounds 6b and 6d showed GI50 (MGMID) values of 6.1 and 8.7 microM, respectively, against the studied six ARL.

Functional MR imaging of the human cervical spinal cord.

BACKGROUND AND PURPOSE: Although research with functional MR imaging of the brain has proliferated over the past 5 years, technical limitations, such as motion, chemical shift, and susceptibility artifacts, have impeded such research in the human spinal cord. The purpose of this investigation was to determine whether a reliable functional MR imaging signal can be elicited from the cervical spinal cord during simple motor activity. METHODS: Subjects performed three different motor tasks that activate different segments of the spinal cord. Gradient-echo-planar imaging on a 1.5-T clinical unit was used to image cervical spinal cords of human subjects. Another group of subjects was imaged while performing isometric exercise to study the relationship between the blood oxygenation level-dependent (BOLD) signal and applied force. RESULTS: Task-dependent BOLD activity was detected in all subjects. Signal amplitude varied between 0.5% and 7%. Moreover, a linear relationship was found between the applied force and the signal amplitude during isometric exercise. While regions of activation were distributed throughout the spinal cord, concentrated activity was found in the anatomic locations of expected motor innervation. CONCLUSION: The functional MR imaging signal can be reliably detected with motor activity in the human cervical spinal cord on a 1.5-T clinical unit. The location of neural activation has an anatomic correspondence to the myotome in use. The strength of the BOLD signal is directly proportional to the level of muscular activity.

Evaluation of parental knowledge of Pediatric Rheumatic Diseases.

OBJECTIVE: To investigate the parental knowledge of pediatric rheumatic diseases in general, and in particular information regarding their children's diseases. To focus on the important role of health education in understanding these chronic diseases, and formulate a future plan for establishing a general public education program. METHODS: One hundred sets of parents, of children with established rheumatic diseases with mean duration of illness, (4.1 +/- 2.83), a mean child age (9.9 +/- 3.15) years, were given a 20 multiple choice questionnaire during their routine visit to the Pediatric Rheumatology Clinic and Physiotherapy Department or to the pediatric ward at King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia, over a 6-month period between December 1998 and June 1999. The questionnaire addressed 4 main areas: 1. parental awareness regarding their children's diagnosis and duration, 2. source of information and parental satisfaction, 3. general knowledge about rheumatic diseases and 4. knowledge about medical and physical therapy. The total possible score is 23. RESULTS: The overall mean score is 11.6. The mean total score is not affected by the parental education level. The majority of parents have wrong beliefs, regarding rheumatic diseases. The treating physician is the main source of parental information and in the majority of the parents, this information is satisfactory. CONCLUSION: The questionnaire is a simple and easy test to investigate parental knowledge regarding pediatric rheumatic diseases. The survey shows the need for health education programs and a future general public health education plan to improve awareness of pediatric rheumatic diseases and maybe other chronic illness.

Determination of the antiepileptics vigabatrin and gabapentin in dosage forms and biological fluids using Hantzsch reaction.

A selective and sensitive method was developed for the determination of the anticonvulsants vigabatrin (I) (CAS 60643-86-9) and gabapentin (II) (CAS 60142-96-3). The method is based on the condensation of the drugs through their amino groups with acetylacetone and formaldehyde according to Hantzsch reaction yeilding the highly fluorescent dihydropyridine derivatives. The yellowish-orange color was also measured spectrophotometrically at 410 nm and 415 nm for I and II, respectively. The absorbance-concentration plots were rectilinear over the ranges 10-70 micrograms/ml and 20-140 micrograms/ml for I and II, respectively. As for the fluorescence-concentration plots, they were linear over the ranges 0.5-10 micrograms/ml and 2.5-20 micrograms/ml with minimum detection limits (S/N = 2) of 0.05 microgram/ml (approximately 2.1 x 10(-8) mol/l) and 0.1 microgram/ml (approximately 5.8 x 10(-7) mol/l) for I and II, respectively. The spectrophotometric method was applied to the determination of I and II in their tablets. The percentage recoveries +/- SD (n = 6) were 99.45 +/- 0.13 and 98.05 +/- 0.53, respectively. The spectrofluorimetric method was successfully applied to the determination of I and II in spiked human urine and plasma. The % recoveries +/- SD (n = 5) were 98.77 +/- 0.29 and 98.39 +/- 0.53 for urine and 99.32 +/- 0.74 and 98.90 +/- 0.96 for plasma, for I and II, respectively. No interference was encountered with the co-administered drugs: valproic acid (CAS 99-66-1), diphenylhydantoin (CAS 57-41-0), phenobarbital (CAS 50-06-6), carbamazepine (CAS 298-46-4), clonazepam (CAS 1622-61-3), clobazam (CAS 22316-47-8) or cimetidine (CAS 51481-61-9). A proposal of the reaction pathway is suggested. The advantages of the proposed methods over existing method are discussed.

An epidemiologic, clinical, and therapeutic study of childhood Guillain-Barré syndrome in Kuwait: is it related to the oral polio vaccine?

We studied Guillain-Barré syndrome, affecting children 12 years old or less, throughout Kuwait, in the period between January 1, 1992, and March 31, 1997. Nineteen children had the diagnostic criteria of Guillain-Barré syndrome, with an overall annual incidence rate of 0.95/100,000 population at risk. Female patients outnumbered male patients with a sex ratio of 1.4:1. There was a clustering of cases in winter and spring and in the year 1996. The disease symptoms were relatively severe in our patients because only 16% (3 of 19) of them were able to walk at the height of their illness, whereas the rest were bed or chair bound or needed assisted ventilation. Two patients had the electrodiagnostic features of axonal neuropathy and both had residual deficits on follow-up, whereas the rest recovered fully. All the patients received intravenous immunoglobulin. The mean time to walk unaided was 23.5 days (range, 2-84 days) after intravenous immunoglobulin and excluding the two patients with axonal neuropathy, and full recovery was achieved in a mean time of 103 days (range, 30-300 days). Contrary to previous studies, we found no correlation between oral polio vaccine administration and Guillain-Barré syndrome in 2 successive years (1995 and 1996) during a nationwide campaign targeting children less than 5 years old.