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AMR is a major public health concern that calls for extensive work and a multidisciplinary team approach. The high prevalence of infectious diseases in African nations leads to widespread antibiotic usage and eventual antimicrobial resistance, which has significant negative effects on people's health, the economy, and society. Additionally, inadequate or nonexistent antimicrobial drug regulations, inappropriate prescription practices, and restrictions on public health prevention initiatives such as immunization, water and sanitation, and sexual health may all contribute to the emergence of AMR. Despite the need for laboratory quality assurance, many African laboratories confront substantial difficulties in implementing efficient quality assurance programs. AMR surveillance in Africa is hampered by a lack of laboratory capacity, insufficient data collection and analysis, and poor stakeholder collaboration. Several initiatives and programs, including the World Health Organization's Global Antimicrobial Resistance and Use Surveillance System (GLASS), the Africa Centres for Disease Control and Prevention (Africa CDC) Antimicrobial Resistance Surveillance Network (AMRSNET), and the Fleming Fund, a UK government initiative aimed at tackling AMR in low- and middle-income countries, have been established to strengthen AMR surveillance in Africa and globally.

Numeric sex chromosome abnormalities are commonly associated with an increased cancer risk. Here, we report a 14-year-old boy with a rare mosaic 45, X/48, XYYY karyotype presenting with subtle dysmorphic features and relative height deficiency, requiring growth hormone therapy. As only 12 postnatal cases have been described so far with very limited follow-up data, to assess the proband's long-term prognosis, including cancer risk, we performed high-throughput single-cell RNA sequencing (scRNA-seq) analysis. Although comprehensive cytogenetic analysis showed seemingly near perfect balance between 45, X and 48, XYYY cell populations, scRNA-seq revealed widespread differences in genotype distribution among immune cell fractions, specifically in monocytes, B- and T-cells. These results were confirmed at DNA level by digital-droplet PCR on flow-sorted immune cell types. Furthermore, deregulation of predominantly autosomal genes was observed, including TCL1A overexpression in 45, X B-lymphocytes and other known genes associated with hematological malignancies. Together with the standard hematological results, showing increased fractions of monocytes and CD4+/CD8+T lymphocytes ratio, long-term personalized hemato-oncological surveillance was recommended in the reported patient., (© 2022. The Author(s).)

Mucopolysaccharidosis type IIIB (MPS IIIB or Sanfilippo syndrome type B) is an inherited metabolic disease caused by mutations in the NAGLU gene, encoding α-N-acetylglucosaminidase. Accumulation of undegraded heparan sulfate (one of glycosaminoglycans) arises from deficiency in this enzyme and leads to severe symptoms, especially related to dysfunctions of the central nervous system. Here, we describe a case of two siblings with highly diverse phenotypes, despite carrying the same mutations (c.1189 T > G/c.1211G > A (p.Phe397Val/p.Trp404Ter)) and similar residual activities of α-N-acetylglucosaminidase; the younger patient reveals more severe phenotype; thus, these differences cannot be explained by the age and progression of the disease. Surprisingly, the whole exome sequencing analysis indicated the presence of an additional mutation in one allele of the AUTS2 gene (c.157G > A (p.Ala53Thr)) in the younger patient but not in the older one. Since mutations in this gene are usually dominant and cause delayed development and intellectual disability, it is likely that the observed differences between the MPS IIIB siblings are due to the potentially pathogenic AUTS2 variant, present in one of them. This case confirms also that simultaneous occurrence of two ultra-rare diseases in one patient is actual, despite a low probability of such a combination. Moreover, it is worth noting that apart from the genotype-phenotype correlation and the importance of the residual activity of the deficient enzyme, efficiency of glycosaminoglycan synthesis and global secondary changes in expression of hundreds of genes may considerably modulate the course and severity of MPS, especially Sanfilippo disease., (© 2022. The Author(s), under exclusive licence to Institute of Plant Genetics Polish Academy of Sciences.)

A cross-sectional study was employed from March 2021 to October 2021 to isolate and identify Klebsiella species found in the gut of honey bees collected from worker of honey bee ( Apis mellifera ) from hives in Haramaya University bee farm, Damota and Finqile's, managed under traditional and modern beekeeping apiculture. From the selected farm, a total of 60 samples of live adult honey bees were collected purposively. The live adult worker of the honey bee was individually surface-sterilized and complete alimentary canals of the worker bee were dissected and processed for Klebsiella isolation. Descriptive statistics were used to describe the occurrence of Klebsiella species and the proportion of Klebsiella found in the gut was analyzed for the association with study variables by the Pearson chi-square test. The overall prevalence of Klebsiella spp. was 50% from samples. The prevalence of Klebsiella pneumoniae was 26.7% and that of Klebsiella oxytoca was 23.3% from isolated using bacteriological examined samples. The isolates were characterized for the antimicrobial susceptibility test using the disc diffusion method. Among the isolated colonies, Klebsiella pneumoniae had the highest resistance to ampicillin (84.2%) and showed less resistance to gentamycin and trimethoprim sulfamethoxazole (26.3%). Klebsiella oxytoca was highly resistant to ampicillin (54.5%) and erythromycin (54.5%) and showed low and equal resistance to gentamycin and amoxicillin (18.2%). Molecular characterization should be conducted to identify Klebsiella spp. from honey bees. Monitoring antimicrobial effectiveness is recommended to tackle the existing problem in apiculture farms, and its possible public health threat should be noted for community by public health professionals., Competing Interests: The authors declare that they have no conflicts of interest in publishing this manuscript., (Copyright © 2022 Abdallahi Abdurehman Damissie and Kedir Abdurahman Musa.)

There is a need to synthesize eco-friendly nanoparticles with more effective and potent antibacterial activities. A green and cost-effective method for the synthesis of silver nanoparticles (AgNPs) using Thymus vulgaris , Mentha piperita , and Zingiber officinale extracts was developed. The analytical instrumentation, namely, UV/Vis, absorption spectroscopy, FTIR, and scanning electron microscopy (SEM), was used to determine the developed AgNPs, confirming the functional groups involved in their reduction. Acidic molybdate, DPPH, and FRAP regents were reacted with AgNPs extract to evaluate their antioxidant, scavenging, and oxidative activities. The agar well diffusion method was used to determine the antibacterial potential of AgNPs extracts using clinical isolates. The developed AgNPs showed peaks at 25 cum\Diff, 50 cum\Diff, and 75 cum\Diff, respectively, of 16.59 ± 0.78, 45.94 ± 1.07, and 81.04 ± 0.98 nm, for Thymus vulgaris , Mentha piperita , and Zingiber officinale . SEM revealed uniform prepared and encapsulated AgNPs by plant extracts matrix. The FTIR shows the involvement of amide (-CO-NH 2 ), carbonyl (-CO), and hydroxyl (-OH), which resulted in the reduction of AgNPs. The AgNPs extract showed significantly higher TAA, DPPH, and FRAP values than free AgNPs and plant extract ( p < 0.05). Antibacterial of AgNPs extracts revealed various degrees of inhibition zones against Escherichia coli , Acinetobacter baumannii , and Staphylococcus aureus . The developed AgNPs extract showed acceptable antioxidant activities and noticeable antibacterial potential. The prepared green synthesized AgNPs showed a promising antibacterial activity against four multidrug-resistant clinical isolates, Escherichia coli , Acinetobacter baumannii , and Staphylococcus aureus . Further, fractionated extracts other than crude extracts will be utilized in the preparation of AgNPs to get more efficient antibacterial activities for future work., Competing Interests: The authors declare that they have no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Ahmed A. H. Abdellatif et al.)

Patients with acute myocardial infarction (AMI) or ischaemic heart disease are at risk of developing anxiety and depression. This systematic review aims to identify the various risk factors and the role of cardiac rehabilitation in reducing the risk of depression in patients after AMI. In this review, we included data on the prevalence of depression in patients post-AMI for the years 2016-2017 from a cardiac rehabilitation unit at Morriston Hospital, Swansea, a primary coronary angioplasty centre. Results from our meta-analysis were compared with the findings of previous studies. Our data showed the prevalence of depression to be 14% pre-cardiac rehabilitation and 3% post-cardiac rehabilitation. A meta-analysis of seven studies showed the prevalence to be approximately 20-35% depending on the type of questionnaire or screening method used. Gender, marital status, age, and sedentary lifestyle were found to be risk factors for depression post-acute coronary syndrome (ACS). Females, patients aged >65 years, and those who were single, lived alone, or widowed were at a higher risk of depression, and patients with sedentary lifestyles were more likely to have post-ACS depression. Depression in patients post-myocardial infarction was also associated with increased mortality and morbidity risk as well as higher hospital re-admission and future cardiac events. The meta-analysis showed significant publication bias, studies with negative results were less likely to be published, and the study data were heterogeneous. The pooled estimate for depression estimated using the random-effects model was 1.78 (95% confidence interval = 1.58-2.01)., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Khan et al.)

Haematology inpatients are subject to extensive blood testing and many of these tests could be deemed inappropriate as they are not indicated for monitoring or clinical symptoms. Unnecessary testing exposes the patient to the risks of phlebotomy and adds resources' strain to the NHS.Our aim was to reduce the number of inappropriate blood tests performed on haematology inpatient wards.Quality improvement projects (QIPs) were performed in four haematology units introducing inpatient blood testing schedules (BTS) or providing staff education on current schedules.A reduction in inappropriate or overall blood testing was achieved at every site where a BTS was implemented, with a median reduction in inappropriate blood testing of 24.7% and estimated cost savings of up to £38,438 per annum.This QIP can be safely adapted to a variety of inpatient settings and is associated with cost savings. This initiative could be extended to other inpatient departments throughout the NHS., (© Royal College of Physicians 2021. All rights reserved.)

Background: Urinary tract infections (UTIs) in pregnant women contribute about 25% of all infections and are among the most frequent clinical bacterial infections. Pregnancy changes in women that include anatomical, physiological and hormonal make them susceptible to develop UTI. Left untreated, UTI in pregnancy is associated with grave complications to the mother and fetus. These complications can be decreased by prompt and proper diagnosis and appropriate treatment that also reduces the emergency of drug resistance. Antimicrobial resistance is a major health problem in the treatment of UTI. We determined the prevalence, bacteriology and antimicrobial susceptibility of symptomatic urinary tract infection among pregnant women at Mbarara Regional Referral Hospital., Methods: We conducted a cross-sectional study from November 2019 to February 2020 involving 400 pregnant women with symptomatic UTI. Patient information was obtained using a structured questionnaire. We collected clean-catch midstream urine specimens for culture and performed antimicrobial susceptibility testing following Clinical and Laboratory Standards Institute standards. Data was entered into RED-cap Version 8.2 software and then exported to Stata Version 14.1 for analysis., Results: The proportion of culture-positive UTI was 140/400 (35%). Gram-negative bacteria were more prevalent (73%): Klebsiella pneumoniae 52(37.41%), Escherichia coli 40(28.78%), Pseudomonas aeruginosa and Proteus mirabilis 7(5.04% each), Citrobacter freundii 1(1%). Staphylococcus aureus 33(23.57%) was the only gram-positive isolate. All the isolates were resistant to ampicillin, amoxicillin, amoxicillin/clavulanic acid and ceftazidime/clavulanic acid (95.7, 95.0, 72.9 and 50.7% respectively). Prevalence of extended-spectrum beta-lactamases producing Enterobacteriaceae was 29.0% while that of methicillin-resistant Staphylococcus aureus was 33.3%. All cultures demonstrated resistance to more than one drug. Majority of the bacterial isolates were sensitive to ciprofloxacin, ceftriaxone, nitrofurantoin, cefotaxime and gentamicin at 82.9, 81.4, 79.3, 78.6, 66.4 and 65.7% respectively., Conclusions: Klebsiella pneumoniae was the most prevalent isolate followed by E. coli. These two organisms were highly resistant to the commonly used antibiotics. Our study recorded a higher prevalence of culture-positive UTI in pregnancy than all the studies in Uganda. Empirical treatment of UTI should be minimized as sensitivity varies for each organism, for each drug and over time.

Insurgency in the Northeastern Nigeria has left millions of adolescents internally displaced, with deplorable living conditions that affect adolescents' sexual and reproductive health (SRH). The aim of the study was to identify SRH needs and problems of Internally Displaced Adolescents (IDAs) and ways of improving their SRH. The study used cross-sectional design. Data were collected from 396 IDAs using questionnaire and focus group discussions. Descriptive and Chi square statistics were used to analyze data from the questionnaire, using Statistical Package for the Social Sciences (SPSS) version 20.0 while qualitative data were thematically analyzed. Results showed that sexuality education (83.2%), safe motherhood services (81.6%) and family planning services (71.9%) were important SRH needs while complications of pregnancy (83.1%), early sex experimentation (81.8%), unsafe sex (80.1%) were among the SRH problems. Gender, educational attainment, age, religion, and marital status differed significantly (≤ .05) with sexuality education and family planning needs of IDAs. Suggested ways of improving IDAs' SRH include making SRH services accessible in internally displaced persons' (IDPs) camps.

Background: Diabetes and dyslipidemia are significantly associated with stroke recurrence, yet the evidence for this relationship is conflicting. Consequently, the parameters in the glucose and lipid profiles may inform us regarding their relationship with stroke recurrence, thus enhancing the physicians' clinical decision-making., Aim: This study sought to investigate whether glucose and lipid profiles could prognosticate stroke recurrence in Malaysia., Methods: We conducted a retrospective hospital-based study where we analyzed the first-ever stroke cases regarding about which the Malaysia National Stroke Registry was informed between 2009 and 2017, that fulfilled this study's criteria, and that were followed for stroke recurrence. Using the Cox proportional hazard regression analysis, we estimated the adjusted hazard ratios (HRs), which reflected the prognostic effect of the primary variables (i.e., glucose and lipid profiles on the first-stroke admission) on stroke recurrence., Results: Among the 8,576 first-ever stroke patients, 394 (4.6%) experienced a subsequent first stroke recurrence event. The prognostic effect measured by univariable Cox regression showed that, when unadjusted, ten variables have prognostic value with regards to stroke recurrence. A multivariable regression analysis revealed that glucose was not a significant prognostic factor (adjusted HR 1.28; 95% CI [1.00-1.65]), while triglyceride level was the only parameter in the lipid profile found to have an independent prognostication concerning stroke recurrence (adjusted HR: 1.28 to 1.36)., Conclusions: Triglyceride could independently prognosticate stroke recurrence, which suggests the role of physicians in intervening hypertriglyceridemia. In line with previous recommendations, we call for further investigations in first-ever stroke patients with impaired glucose and lipid profiles and suggest a need for interventions in these patients., Competing Interests: The authors declare there are no competing interests., (©2020 Chen et al.)

Therapies to reduce liver fibrosis and stimulate organ regeneration are urgently needed. We conducted a first-in-human, phase 1 dose-escalation trial of autologous macrophage therapy in nine adults with cirrhosis and a Model for End-Stage Liver Disease (MELD) score of 10-16 (ISRCTN 10368050). Groups of three participants received a single peripheral infusion of 10 7 , 10 8 or up to 10 9 cells. Leukapheresis and macrophage infusion were well tolerated with no transfusion reactions, dose-limiting toxicities or macrophage activation syndrome. All participants were alive and transplant-free at one year, with only one clinical event recorded, the occurrence of minimal ascites. The primary outcomes of safety and feasibility were met. This study informs and provides a rationale for efficacy studies in cirrhosis and other fibrotic diseases.

Background: Children with cerebral palsy require effective, accessible and affordable medical and rehabilitation care., Objective: The aim of this study was to evaluate the direct monthly cost of outpatient hospital-based care for children with cerebral palsy (CP) in Kano City, Nigeria., Methods: The study was a cross-sectional survey. Consenting participants were recruited using the purposive sampling technique. Data on cost of medical and physiotherapy consultations, number of consultations per month, cost of diagnostic investigations, and out-of-pocket expenditures were captured using a researcher-designed questionnaire. Data were analyzed with descriptive statistics using Microsoft Excel and SPSS version 20., Results: A total of 106 children with CP and their caregivers participated in this study. The mean age of the children was 3.18 ± 1.90 years and that of their caregivers was 27.32 ± 4.63 years. The average direct cost of outpatient care per month was ₦14 295.38 (Nigerian naira) ($46.87) ± ₦13 211.52 ($43.32). The average monthly cost of physiotherapy was ₦503.77 ($1.65) ± ₦220.79 ($0.72), whereas those for transportation and radiological investigations were ₦1861.49 ($6.10) ± ₦1435.06 ($4.71) and ₦3771.46 ($12.37) ± ₦5135.32 ($16.84), respectively., Conclusion: The average direct monthly cost of providing outpatient hospital-based care for children with CP in Kano City, Nigeria may not be affordable because most of the participants earned very meager monthly incomes. The highest medical cost was incurred from radiological investigation, whereas transportation was the most important out-of-pocket cost. The Nigerian government should make a policy decision for the automatic enrollment of all children diagnosed with CP into the National Health Insurance Scheme., (Copyright © 2019 ISPOR–The professional society for health economics and outcomes research. Published by Elsevier Inc. All rights reserved.)

Background: Maternal and child health workers (MCHWs) are often the first point of contact with pregnant women, children, and caregivers. Therefore, they can play a significant role in early detection of causes of childhood blindness, facilitate prompt referral to specialized centers and provide health education to caregivers for preventive eye care., Methods: This is a pre-test, post-test, single group, quasi-experimental study to evaluate the outcome of training MCHWs on common blinding childhood diseases. All MCHWs in Ifo Local Government Area were selected to participate in the study. Pre-training, qualitative data was obtained from two focus group discussions while quantitative data was obtained using a self-administered questionnaire. Three months post-training, quantitative data was obtained using the same self-administered questionnaire as was used pre-training. Total and percentage scores on the pre- and post-tests were calculated for each participant. A score of ≥70% was regarded as sufficient while < 70% score was regarded as insufficient. McNemar's test was used to determine differences in proportions between pre- and post-training quantitative measurements., Results: Of the 65 MCHWs in the Local Government Area, 61 participated in the study giving a response rate of 93.8%. The age range of study participants was from 28 to 57 years with a mean age of 41 ± 8.3 years. The male: female ratio was 1:7.7. During the focus group discussions, measles was the most commonly mentioned cause of childhood blindness however, participants showed more knowledge of the signs and symptoms of new-born conjunctivitis. Based on a sufficient knowledge score of ≥70%, only one participant (1.6%) demonstrated sufficient knowledge on quantitative survey pre-training. Post-training, there was a statistically significant increase (20, 32.8%) in the proportion of participants with sufficient knowledge (McNemar's test p = .000)., Conclusions: This study demonstrated that the training of MCHWs on common childhood blinding diseases (such as congenital cataract and congenital glaucoma) had the potential to improve knowledge regarding prevention, prompt recognition and early referral of common treatable potentially blinding diseases.

Background: Biomarkers of rheumatoid arthritis (RA) disease activity typically measure inflammation or autoimmunity (e.g. CRP, RF). C1M and C3M, metabolites of type I and III collagen, are markers reflecting tissue metabolism. These markers have been documented to provide additional prognostic and predictive value compared to commonly used biomarkers. We investigated the relationship of high serum levels of C1M or C3M to radiographic progression, and benchmarked them to CRP and RF., Methods: Placebo treated patients of the OSK1, 2 and 3 studies (Phase III clinical trials testing efficacy of fostamatinib) with baseline serum biomarkers C1M, C3M, CRP and RF were included (n BL  = 474). Van der Heijde mTSS was calculated at baseline and 24-week (n 24  = 261). Progression was defined as moderate or rapid by ΔmTSS ≥0.5 or ≥ 5 units/year. Patients were divided into subgroups; low (L), high (H) or very high (V) C1M, C3M and CRP, or RF negative, positive and high positive. Difference in clinical parameters were analyzed by Mann-Whitney or χ 2 tests, and modelling for prediction of progression by logistic regression including covariates (age, gender, BMI, and clinical assessment scores)., Results: Levels of C1M, C3M, CRP and RF were significantly ( p  < 0.05) associated with measures of disease activity and mTSS at baseline. For prognostic measures, there were 2.5 and 4-fold as many rapid progressors in the C1M H and CRP H (p < 0.05), and in the C1M V and CRP V groups ( p  < 0.001) compared C1M L and CRP L , respectively. C1M and CRP performed similarly in the predictive analysis, where high levels predicted moderate and rapid progression with odds ratio of 2.1 to 3.8 and 3.7 to 13.1 after adjustment for covariates. C3M and RF did not provide prognostic value alone., Discussion: Serum C1M and CRP showed prognostic value and may be tools for enrichment of clinical trials with structural progressor. The two markers reflect two different aspect of disease pathogenesis (tissue turnover vs. inflammation), thus may provide individual and supplementary information., Competing Interests: The clinical trial included in this post hoc biomarker analysis was conducted in accordance with the Declaration of Helsinki [16, 17]. The studies were approved by the relevant institutional ethical committees or review bodies at Stanford University Panel on Human subjects in Medical research or Brigham and Women’s hospital and were conducted in accordance with good clinical practice and the Astra Zeneca Policy on Bioethics.All authors approved the manuscript. No personal or patient specific data were available for the researcher of current work, neither are any person sensitive data reported in the manuscript.ACBJ, MAK, IB and KM are full time employees and shareholders in Nordic Bioscience, a privately-owned biotech company focused on the development of biomarkers for inflammatory diseases. AP and MAJ are full time employees and shareholders of Astra Zeneca. MEW and MCG have nothing to declare for the context of current manuscript.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Objective: Rheumatoid arthritis (RA) is a chronic and degenerative autoimmune joint disease that leads to disability, reduced quality of life, and increased mortality. Although several synthetic and biologic disease-modifying antirheumatic drugs are available, there is still a medical need for novel drugs that control disease progression. As only 10% of experimental drug candidates for treatment of RA that enter phase I trials are eventually registered by the Food and Drug Administration, there is an immediate need for translational tools to facilitate early decision-making in drug development. In this study, we aimed to determine if the inability of fostamatinib (a small molecule inhibitor of Syk) to demonstrate sufficient efficacy in phase III of a previous clinical study could have been predicted earlier in the development process., Methods: Biomarkers of bone, cartilage, and interstitial matrix turnover (C-telopeptide of type I collagen [CTX-I], matrix metalloproteinase-derived types I, II, and III collagen neoepitopes [C1M, C2M, and C3M]) were measured in 450 serum samples from the Oral Syk Inhibition in Rheumatoid Arthritis 1 study (OSKIRA-1, a phase III clinical study of the efficacy of fostamatinib in RA) at baseline and follow-up. Additionally, the same biomarkers were subsequently measured in conditioned media from osteoclast, cartilage, and synovial membrane cultured with the active metabolite of fostamatinib, R406, to assess the level of suppression induced by the drug., Results: In OSKIRA-1 serum samples and osteoclast and cartilage cultures, fostamatinib suppressed the levels of CTX-I and C2M. In OSKIRA-1 serum samples and synovial membrane cultures, fostamatinib did not mediate any clinical or preclinical effect on either C1M or C3M, which have previously been associated with disease response and efficacy., Conclusion: These data demonstrate that translational biomarkers are a potential tool for early assessment and decision-making in drug development for RA treatment., (© 2018 The Authors Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.)

Background: Circulatory abnormalities of retrobulbar vessels are increasingly being linked to the aetiopathogenesis of primary open angle glaucoma. These abnormalities can be assessed with a colour Doppler Imaging of retrobulbar vessels., Aims and Objectives: To compare the Doppler ultrasound patterns of central retinal artery and ophthalmic artery in new patients with primary open angle glaucoma (POAG) diagnosis with those of non-glaucomatous group., Design of the Study: A hospital-based, comparative, cross-sectional study., Setting: Department of Ophthalmology (Guinness Eye Centre) and Department of Radiology, Lagos University Teaching Hospital, Idi-Araba, Lagos, Nigeria., Materials and Methods: End diastolic velocity (EDV), Peak systolic velocity (PSV) and resistivity index (RI) were measured in the central retinal artery (CRA) and ophthalmic artery (OA) of both eyes of newly diagnosed POAG patients. The CDI values of newly diagnosed POAG patients were compared with age-gender matched non-glaucomatous group. The Doppler values of the better and worse eye of patients with asymmetrical POAG were also compared., Results: One hundred subjects (200 eyes) comprising of 50 POAG patients and 50 non-glaucomatous healthy subjects were recruited for this study. The male to female ratio was 1:1.1(24 males and 26 females) for POAG patients and 1:1 (25 males and 25 females) for non-glaucomatous subjects. The CRA and OA in both eyes of POAG patients had a significantly lower mean EDV and PSV compared with those of non-glaucomatous group (p< 0.001). The CRA and OA in both eyes of POAG patients had a significantly higher mean RI compared with those of non-glaucomatous group (p< 0.001). A significant positive Pearson correlation was seen between the IOP and the RI in the CRA and OA in both eyes. Also, statistically significant negative Pearson correlations were seen between the IOP and the PSV and EDV in the OA and CRA in both eyes., Conclusion: This study demonstrated a significant reduction in EDV and PSV as well as an increase in RI of the CRA and OA in both eyes among POAG patients compared to the non-glaucomatous group., (© 2010 - 2018 JWACS-JCOAC. ALL RIGHTS RESERVED.)

We present a new surgical modification to allow propeller perforator flaps to cover pressure sores at various locations. We used a propeller perforator flap concept based on the detection of newly formed perforator vessels located 1 cm from the wound margin and stimulated by the chronic inflammation process. Between January 2009 and January 2017, 33 wound edge-based propeller perforator flaps were used to cover pressure sores at various locations in 28 patients. In four cases more than one flap was used on the same patient. The patients comprised 18 males and 10 females with a mean age of 41·25 (range, 16-70) years. All patients underwent follow-up for 0-12 months. The mean follow-up duration was 5·03 months. Venous congestion was observed in three flaps that were rotated by 180° (9·1%). However, there was a significant difference between flaps rotated by 90° and 180° according to the complication rate (P = 0·034). Out of 33 flaps, 29 flaps healed uneventfully. Patients were able to sit and lie on their flaps three weeks after surgery. In our study, we were able to obtain satisfying final results using these novel flaps., (© 2017 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Objective: To determine the pattern of presentation of uveitis at the Guinness Eye Centre of the Lagos University Teaching Hospital, Lagos, Nigeria., Materials and Methods: The case files of all patients with the diagnosis of uveitis who presented at the center from January 2006 to December 2010 were reviewed. Data on age, sex, ethnicity, symptoms, duration of symptoms before presentation, eye affected, anatomical type of uveitis and clinical type of uveitis were extracted onto a form for analysis., Results: A total of 68 cases of uveitis were reviewed. There were 38(60.3%) males and 25 (39.7%) females. The range was from 12 to 90 years. The peak incidence occurred within the age range 21-40 years inclusive. Anterior uveitis and posterior uveitis occurred in 34(54.0%) and 17(27%) patients respectively. While reduction in vision was reported as a symptom by 54(85.7%) patients, only 41(65.1%) patients presented within 4 weeks of onset of symptoms., Conclusion: Anterior uveitis was the most common clinical type in this study. The highest incidence of uveitis occurred in the third and fourth decades of life.

Background and Aim: Alkaptonuria (AKU) clinical manifestations resemble severe arthritis. The Suitability of Nitisinone in Alkaptonuria 1 (SONIA 1) study is a dose-finding trial for nitisinone treatment of AKU patients. We tested a panel of serum and urinary biomarkers reflecting extracellular matrix remodelling (ECMR) of cartilage, bone and connective tissue in SONIA 1 patients to identify non-invasive and diagnostic biomarkers of tissue turnover in AKU., Methods: Fasted serum and urine were retrieved from 40 SONIA 1 patients and 44 healthy controls. Established biomarkers of bone remodelling (CTX-I, P1NP, OC), cartilage remodelling (CTX-II, C2M, AGNx1) and inflammation (CRPM) as well as exploratory biomarkers of ECMR (C6M, VCANM, MIM, TIM) were measured at baseline in serum and urine by means of enzyme-linked immunosorbent assays (ELISAs) or automated systems (Elecsys 2010)., Results: The levels of bone resorption (CTX-I) and cartilage degradation (C2M) were elevated in AKU patients as compared to controls (p > 0.0001 and p = 0.03, respectively). Also tissue inflammation (CRPM) was elevated in AKU patients (p = 0.01). In addition all four exploratory biomarkers of ECMR (C6M, VCANM, MIM, TIM) were elevated in AKU patients compared to healthy controls. CTX-II was the only biomarker to be reduced in AKU patients. TIM was the only marker that showed a higher concentration than the normal assay range in AKU patients., Conclusions: We have identified new potential biomarkers for assessment of cartilage, bone and cardiovascular remodelling in AKU and demonstrated the robustness of the assays used to measure the biomarker concentration in biological fluids.

Background: Very little has been published about acute transfusion reactions (ATRs) in developing countries. This study was undertaken to determine the incidence, type, imputability, severity, and possible associated factors of ATRs observed in a university-affiliated hospital in Uganda., Study Design and Methods: We prospectively followed the transfusion of blood units issued over a 7-week period from the hospital blood bank during regular working hours to nonbleeding patients. For each transfusion, we recorded the patient's status before, during, at the end of, and 4 hours after transfusion. Three physicians independently reviewed all reports of suspected ATRs and related hospital charts. Using predefined criteria, the presence, type, imputability, and severity of ATRs were adjudicated by consensus of two of three physicians. Factors potentially associated with ATRs were analyzed for statistical significance., Results: A total of 507 transfusions were analyzed. Fifty-three acute transfusion events were recorded and 49 of 53 or 9.6% of the 507 transfusions were confirmed to be ATRs by physician consensus: 24 febrile, seven allergic, five hypertensive, three hypotensive, three transfusion-associated circulatory overload, two acute hemolytic, and five others. Imputability of ATRs was definite, probable, or possible in 45 of 49 ATRs (92% of ATRs or 8.9% of transfusions) and judged to be severe in nine of 45. No significant associated factors were identified., Conclusions: Our findings suggest that ATRs may occur more commonly in resource-limited settings than in high-income countries. Although some reactions are unavoidable, improved surveillance of transfusions and implementation of transfusion guidelines could improve the safety of transfusions in these settings., (© 2014 AABB.)

Background: Diagnosis and treatment of neuropathic pain is an important clinical problem., Objectives: A self report version of the Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) score provides identification of neuropathic pain without the help and need of a clinician. We targeted validation of the S-LANSS score in the northern Turkish population in this study., Material and Methods: For the linguistic validation of S-LANSS, translation and back-translation method was used to adapt S-LANSS into Turkish and a cognitive-debriefing test was performed. A total of 148 patients were enrolled in the present study. S-LANSS, The Leeds Assessment of Neuropathic Symptoms and Signs (LANSS), Visual Annalogue Score (VAS) and Neuropathic Pain Questionnaire (NPQ) were performed twice for every patient. The patients were examined and diagnosed as having nociceptive or neuropathic pain by neurologists, who were blind for S-LANSS, LANSS and NPQ scores of the patients., Results: Results of the McNemar test indicated that S-LANSS scores were reliable when the first and the second scores were compared. The sensitivity and specificity of the scale were found to be 98% and 97% respectively., Conclusions: We believe that using S-LANSS scores for the diagnosis of neuropathic pain may help our colleagues as a tool for a quicker differential diagnosis of pain in daily practice.

Background: The aim of this study was to present our experience with six cases of fetal intracranial hemorrhage (ICH) in terms of prenatal diagnostic features, and postnatal outcome., Methods: The database of prenatal diagnosis unit was searched for antenatally diagnosed ICH cases. Maternal characteristics, ultrasound (US), and magnetic resonance imaging (MRI) findings, clinical course, and postnatal outcome were noted., Results: We evaluated six consecutive cases of fetal ICH. One case was terminated at 24 weeks, and remaining five cases were delivered between 34 and 38 weeks. Five cases (5/6) had intraventricular, and one (1/6) had intraparenchymal hemorrhage. Hemorrhages were right sided in five cases (5/6), left sided in one case (1/6). Dilated and echogenic ventricular wall were the common US findings. No predisposing factor was detected in four of the cases, and intrauterine growth restriction was an underlying factor in two fetuses. Intrauterine progression of the hydrocephaly, and parenchymal thinning was seen in four cases (4/6). In three of four cases (3/4) with progressive grade 3-4 hemorrhage and hydrocephaly, postnatal outcome were dismal, and one case had mild neurological impairment at three months. In one case which had non-progressive mild ventriculomegaly, the lesion regressed after 4 weeks, and had normal short-term outcome, Conclusion: Fetal ICH can be accurately identified and categorized by antenatal sonography, and fetal MRI. Although intrauterine regression or normal short-term postnatal outcome is possible, the outcome is usually poor for fetuses with high grade and/or progressive lesions. Therefore, further studies assessing long-term postnatal outcome are needed.

Crude saponin extracts of five medicinal plants used in the treatment of inflammatory diseases like rheumatoid arthritis, gout and haemorrhoids were screened for anti-inflammatory activity using carrageenan-induced rat paw oedema test. These plants were the whole plant of Schwenkia americana Linn (WSA), the rhizomes of Asparagus africanus Lam (RAA), the leaves of Dichrostachys cinerea Linn (LDC), the stem bark of Ficus iteophylla Miq (BFI) and the leaves of Indigofera pulchra Willd (LIP). A modify traditional method of crude saponins extraction was used to give the following percentage yields: WSA-2.74%, RAA-3.59%, LDC-1.62%, BFI-0.81% and LIP-1.57% respectively. Thin-layer chromatography was used to identify the type of saponins present in the extracts. The acute toxicity study of the crude saponin extracts in mice gave the following intraperitoneal LD50: WSA-471.2mg/kg, RAA- 1264.9mg/kg, LDC-1264.9 mg/kg, BFI-118.3mg/kg and LIP-1264.9 mg/kg respectively. The anti-inflammatory study of the extracts showed statistically significant (P<0.05) decreases in the rat paw-oedema as compared to the control. The percentage inhibitions of the extracts after four hours were as follow: WSA-61%, RAA-55%, LDC-72%, BFI-66% and LIP-40% respectively. These values were found to be comparable to that of ketoprofen-63%. The study showed that the anti-inflammatory properties attributable to these plants may be due to their saponins contents.

Background: Urethral calculi are rare and usually encountered in males with urethral pathology., Objective: To present our experience managing urethral calculi in a resource limited centre and review the literature., Methods: We did a chart review of management of patients with urethral calculi between January and April 2009, at Federal Medical Centre (FMC) Azare, Nigeria. We also reviewed the literature on this rare condition., Results: Four young adult male Nigerians between the ages of 17 and 27 years presented with varying degrees of urethral pain and palpable calculi in the anterior urethra. Two presented with acute retention of urine, but none had haematuria. The calculi were radio-opaque, located in the anterior urethra with no associated urethral pathology. Three were solitary and one multiple. The composition of the urethral calculi was a mixture of calcium oxalate calcium carbonate, magnesium phosphate, one has additional cystine but none had struvite or uric acid. Their sizes ranged between 1cm ×1.5cm and 1.5cm × 5.5cm. External urethrotomy was the method of treatment., Conclusion: Urethral calculi are rare in our setting, with no clear identifiable aetiological factors which suggests urinary schistosomiasisbeing associsted. The occurrence of urethral calculi appears to have a relationship with childhood urinary schistosomasis.

Objective: To investigate the safety of laparoscopic intervention for diagnosis and treatment at 8 mm Hg pressure in one-hour period on acute peritonitis related intra-abdominal sepsis model., Methods: In this study, we included 32 female Wistar-Albino rats, weighing 250 +/- 20 g, and divided them into 4 groups. This study was conducted in Istanbul University Experimental Medical Research Institution (DETAE) laboratory from April to May 2009. Intra-abdominal sepsis was created with intraperitoneal (i.p.) one mL (109 CFU/mL) Escherichia coli (E. coli) injection, and pneumoperitoneum was formed with CO2 insufflation at 8 mm Hg pressure for one hour i.p. The rats were administered with: Group 1 - one mL i.p. isotonic saline; Group 2 - one mL i.p. isotonic saline + pneumoperitoneum; Group 3 - i.p E. coli; and Group 4 - i.p. E.coli + pneumoperitoneum. Data were analyzed using the Statistical Package for Social Sciences version 15 for Windows (SPSS Inc, Chicago, IL, USA)., Results: Fever and leukocyte values were considered high in Groups 3 and 4 compared with Groups 1 and 2 (p=0.001). The administered reproduction ratio of the E. coli strain was determined as 0% in Groups 1 and 2, and 100% in Groups 3 and 4., Conclusion: In this study, as pneumoperitoneum was formed for one hour at 8 mm Hg pressure, in case of intra-abdominal derived sepsis where emergency intervention is needed, we consider that laparoscopic approaches with low pressure may be used safely for diagnosis and treatment.

Nosocomial blood stream infection (or nosocomial bacteremia) is a common problem in hospitals worldwide, including Malaysia. A three-year prospective cohort study (October 2003-March 2007) of the incidences, risk factors, and patterns of the microorganisms causing bacteremia was conducted using a validated surveillance form in three intensive care units (ICUs) in Malaysia. Center for Disease Control criteria were used to diagnose bacteremia. Patients were monitored from admission until the end point of study, which was the first detection of bacteremia in the blood in each patient. The frequency of occurrence of bacteremia with clinical symptoms was 10.7% (n=23). Bacteremia was observed to occur within a mean length of stay of 10 days in ICU. The rate of device-related infection was 10.4% per device utilization days with a device utilization rate of 95.9%/1000 patient days. The total number of patient days was 2309 and the period of device utilization was 2211 days. The common bacteria detected were extended-spectrum beta-lactamases (ESBLs) Klebsiella pneumoniae (n=6); Pseudomonas aeruginosa (n=6); Acinetobacter species (n=5); Methicillin-resistant Staphylococcus aureus (MRSA)(n=3); and (non- ESBL) Klebsiella pneumoniae (n=2). Multivariable analysis using Cox Proportional Hazard Model showed that the predictors for developing bacteremia were cancer, MRSA carriage, duration of central venous catheter (CVC) infusion, frequency change of CVC, and the administration of hydrocortisone drugs. These results indicate that a combination of nursing and medical interventions as well as patients' severity of illness could lead to bacteremia in ICU. Strategic implementation of quality assurance measures in ICUs could help to control this problem.

Background: The outcome indicator of nosocomial infection (NI) in the intensive care unit (ICU) is used to benchmark the quality of patient care in Malaysia. We conducted a three-year prospective study on the incidences of ventilator-associated pneumonia (VAP), risk factors, and patterns of the microorganisms isolated in three ICUs., Methodology: A follow-up in prospective cohort surveillance was conducted on patients admitted to an adult medical-surgical ICU of a university hospital and two governmental hospitals in Malaysia from October 2003 to December 2006. VAP was detected using CDC criteria which included clinical manifestation and confirmed endotracheal secretion culture results., Results: In total, 215 patients (2,306 patient-days) were enrolled into the study. The incidence of ICU-acquired device-related NI was 29.3 % (n = 63). The device-related VAP infection rate was 27.0 % (n = 58), with a mechanical ventilator utilization rate of 88.7%. The death rate due to all ICU-acquired NI including sepsis was 6.5%. The most common causative pathogen was Klebsiella pneumoniae (n = 27). Multivariate analysis using Cox regression showed that the risk factors identified were aspiration pneumonia (HR = 4.09; 95% CI = 1.24, 13.51; P = 0.021), cancer (HR = 2.51; 95% CI = 1.27, 4.97; P = 0.008), leucocytosis (HR=3.43; 95% CI= 1.60, 7.37; P=0.002) and duration of mechanical ventilation (HR=1.04; 95% CI = 1.00, 1.08; P = 0.030). Age, gender and race were not identified as risk factors in the multivariable analysis performed., Conclusion: The incidence of VAP was comparable to that found in the National Nosocomial Infection Surveillance (NNIS) System report of June 1998. The incidence of VAP was considered high for the three hospitals studied.

Axillary neuropathy due to entrapment of the nerve in the quadrilateral space is seen rarely. Here, we describe a 24-year-old patient diagnosed with isolated axillary neuropathy that mimicked quadrilateral space syndrome. Quadrilateral or quadrangular space syndrome (QSS), first described by Cahill and Palmer in 1983, was defined as the entrapment of the distal branch of the axillary nerve and the posterior humeral circumflex artery (PHCA) in the quadrangular shaped anatomic space. We tracked the follow up of the patient for one year both clinically and electrophysiologically. Our aim in reporting this case is to stress the point that cases of such a nature usually represent situations of diagnostic and treatment challenges, where multidisciplinary approaches are required.

Behcet`s disease is characterized by small vessel vasculitis and involvement of multiple systems. In neuro-Behcet cases, spinal cord involvement is approximately 10-18%. Spinal cord lesions are often associated with cerebral or brainstem lesions, and isolated spinal cord involvement in Behcet`s disease is very rare. Here, we report a case with an isolated lesion of the cervical spine.

Objective: To ascertain the causative organisms of community acquired pneumonia (CAP) in Jordanian patients requiring hospital admission., Methods: A prospective study of both adults and children admitted to Princess Basma and Princess Rahma Teaching Hospitals in Irbid, Jordan with a diagnosis of CAP over a 6-month period from April to October 2002., Results: A total of 35 adult patients were admitted with a mean age of 47 years, and 63 children with a mean age of 3 years. A pathogen was isolated from 25 (71%) adults, and from 17 (27%) children, and sputum cultures gave the best diagnostic yield. In adults Streptococcus pneumoniae was the most common isolate (26%), followed by Chlamydia pneumoniae (23%), Haemophilus influenzae (17%), Mycoplasma pneumoniae (9%), and Legionella pneumophila and Klebsiella pneumoniae (6%) each. Seven of the 9 gram negative isolates were from patients with some co morbid illness. While in children, Chlamydia pneumoniae was the most common (14%), followed by Mycoplasma pneumoniae (6%), and Streptococcus pneumoniae, Haemophilus influenzae, and Pseudomonas aeruginosa (3%) each., Conclusion: Streptococcus pneumoniae and atypical microorganisms are the most common cause of CAP in previously healthy adults; while in those with associated co morbid illness, gram negative organisms are the likely cause. In children, the overall detection rate of causative organisms was low with atypical microorganisms being the most common.

This is a brief report evaluating a new single use endotracheal tube introducer (METTI) which has a soft curved atraumatic tip. The introducer was tried in 44 patients, whose direct laryngoscopic view was simulated to Cormack IIIb score, and in six patients with real Cormack III score. The overall success rate of railroading of the tracheal tube over the introducer was 94% from the first attempt.

An intervention study was carried out in Mymensingh Medical College during the second week of January, 2003 to compare knowledge and attitude of the faculty members of Mymensingh Medical College on PBL before and after exposure to a symposium. Pretest was done among 48 faculty members before and 45 faculty members after exposure to the symposium using a self-administered questionnaire. Before the symposium about 17% of faculty members had a sound knowledge on PBL, the figure rose significantly to about 61% after exposure to the symposium (P < 0.001). About 73 % of faculty members felt that PBL is effective in problem solving after exposure to the symposium, as compared to about 60% who felt that PBL is effective in problem solving before the symposium (P < 0.01). About 69% of faculty members stated that PBL is better than traditional ward teaching after exposure to the symposium, as compared to 51.1% who stated that PBL is better than traditional ward teaching before the symposium (P < 0.001). About 69% of faculty members stated that PBL enhances self-directed learning after exposure to the symposium, as compared to about 52% who stated PBL enhances self-directed learning before the symposium(P <0.005). About 64% of faculty members affirmed that they will welcome PBL in clinical teaching after exposure to the symposium, as compared to 62.5% of faculty members who would welcome PBL in clinical teaching before the symposium (P < 0.01). A total of 59% of faculty members asserted that they will recommend PBL to be included in Undergraduate Medical Curriculum after exposure to the symposium, as compared to 60.3% who would recommend PBL in Undergraduate Medical Curriculum before the symposium. About 51 % of faculty members agreed that practicing PBL will help students after graduation to continue independent learning before the symposium, as compared to 60% who agreed that practicing PBL will help students after graduation after exposure to the symposium (P < 0.05). It can be concluded that exposure to a symposium centered on PBL can improve knowledge and attitude of faculty members on PBL positively & significantly.

Epilepsy is a serious neurological disease that responds to two very different treatments involving lipids. Clinically, it responds to a state of ketosis induced by a very high-fat 'ketogenic' diet. Experimentally, in vitro and in vivo models demonstrate that injection or infusion of free (non-esterified) polyunsaturates such as arachidonate and docosahexaenoate also reduces seizure susceptibility. In our experience, rats on a very high-fat ketogenic diet not only have mild-to-moderate ketosis, but also have raised serum free fatty acids. Some polyunsaturates, particularly linoleate and alpha-linolenate, are relatively easily beta-oxidized and are therefore ketogenic. We conclude that raised levels of free plasma polyunsaturates could contribute to the beneficial effect of the ketogenic diet in refractory epilepsy not only by helping sustain ketosis, but also by their own direct (though poorly defined) antiseizure effects., (Copyright 2002 Elsevier Science Ltd.)

Background: The mechanism of a high-fat, low-carbohydrate ketogenic diet (KD) in alleviating drug-resistant epilepsy is unknown but may be related to systemic ketosis induced under this treatment. The need for frequent measurement of systemic ketosis, which is essential for improving maintenance of the KD in patients and for studying mechanism of the KD action, has prompted us to validate the breath acetone test as a fast, reliable, and noninvasive tool for ketosis assessment., Methods: A rat model of the KD that allowed frequent blood sampling was used to investigate how well breath acetone reflects plasma beta-hydroxybutyrate (beta-HBA), the most commonly measured ketone body. Rat pups (20 days of age) were introduced to and maintained on a KD or control diet for 33 days. During this period, breath acetone, plasma beta-HBA, blood glucose, and body weight were measured approximately every 4th day. A correlational analysis of breath acetone and plasma beta-HBA was conducted., Results: Breath acetone was found to be a significant predictor of plasma beta-HBA over a clinically relevant range of beta-HBA concentrations (r(2) = 0.75; P <0.001). We have proposed a general formula that allows the value of plasma beta-HBA to be estimated based on breath acetone measurement., Conclusions: Breath acetone is an accurate measure of mild to moderate systemic ketosis. The noninvasive nature of this test will be useful for day-to-day implementation of the KD, searching for better forms of this diet, and understanding the role of ketosis in the mechanism of the KD action.

High-fat ketogenic diets are used to treat intractable seizures in children, but little is known of the mechanism by which these diets work or whether fats rich in n-3 polyunsaturates might be beneficial. Tissue lipid and fatty acid profiles were determined in rats consuming very high fat (80 weight%), low-carbohydrate ketogenic diets containing either medium-chain triglyceride, flaxseed oil, butter, or an equal combination of these three fat sources. Ketogenic diets containing butter markedly raised liver triglyceride but had no effect on plasma cholesterol. Unlike the other fats, flaxseed oil in the ketogenic diet did not raise brain cholesterol. Brain total and free fatty acid profiles remained similar in all groups, but there was an increase in the proportion of arachidonate in brain total lipids in the medium-chain triglyceride group, while the two groups consuming flaxseed oil had significantly lower arachidonate in brain, liver, and plasma. The very high dietary intake of alpha-linolenate in the flaxseed group did not change docosahexaenoate levels in the brain. Our previous report based on these diets showed that although ketosis is higher in rats consuming a ketogenic diet based on medium-chain triglyceride oil, seizure resistance in the pentylenetetrazol model is not clearly related to the degree of ketosis achieved. In combination with our present data from the same seizure study, it appears that ketogenic diets with widely differing effects on tissue lipids and fatty acid profiles can confer a similar amount of seizure protection.

Purpose: Fat is the major component of the ketogenic diet (KD), yet no studies have examined whether the type of fat used in the diet can be optimized to provide additional benefits. The purpose of the present experiments was to compare the efficiency of different fats in inducing ketosis and affording seizure resistance., Methods: The effects of KDs that incorporate lard, butter, medium-chain triglycerides (MCT), or flaxseed oil or a mixture of the latter three fats were examined in rats fed KD for up to 98 days. The maximal electroshock (MES) or pentylenetetrazole (PTZ) threshold tests were used to assess seizure susceptibility in two separate experiments., Results: The rank order of induced ketosis was MCT > mixture > or = flaxseed oil > or = lard = butter > or = control. MES failed to reveal anticonvulsant effects, but the PTZ test indicated that up to 50% of rats fed the KD were seizure protected (p < 0.05). The measures of seizure protection, seizure incidence and score, did not correlate, however, with the level of ketosis in the range of 0. 7-5.2 mmol/L for beta-hydroxybutyrate. In the long-term study, flaxseed oil KD maintained stable ketosis throughout 98 days, whereas ketones declined with lard and butter KD to the control level., Conclusions: Seizure protection with the versions of the KD did not improve with the higher level of ketosis. The focus of the KD improvement, therefore, is not the achievement of higher ketosis per se but rather designing a diet that provides steady ketosis, exploits advantages of certain fats for neurological development or seizure protection via a nonketogenic mechanism, and is nutritionally balanced.

Male Wistar rat pups were weaned at 20 days of age and placed on either a control diet or a ketogenic diet containing medium-chain triglyceride (MCT) oil. After 10 days on the diets, they were subjected to one of four seizure tests-maximal electric shock, threshold electroconvulsive shock, threshold pentylenetetrazol, or maximal pentylenetetrazol. After testing, subjects were sacrificed and blood samples were analyzed for beta-hydroxybutyrate concentration. It was found that the MCT diet produced blood levels of beta-hydroxybutyrate that were comparable to or higher than those commonly reported in clinical studies. However, no anticonvulsant effects were seen in any of the seizure tests. In fact, the tests involving maximal seizures actually showed proconvulsant effects. It appears that clinical levels of ketones may be present in the bloodstream without suppressing seizures., (Copyright 2000 Academic Press.)

Substituted 2,2'-dithiobisbenzamides and 2-benzisothiazolones were prepared and shown to possess low microM activity with high therapeutic indices against HIV-1, HIV-2 and SIV in cell culture. The mechanism of antiviral action was determined to be directed toward the nucleocapsid protein (NCp7), which contains two zinc fingers and plays vital roles in the viral life cycle. The "active sulfides" of this study cause the extrusion of zinc from these zinc fingers. Structure-activity relationships of the 2,2'-dithiobisbenzamides reveal that the disulfide bond and the ortho benzamide functional groups are essential for activity, with the best compounds having a carboxylic acid, carboxamide, or sulfonamide substituent. The 2-benzisothiazolones are formed from the disulfides both chemically and in vivo and their SAR mimics that of the 2,2'-dithiobisbenzamides. The antiviral activity of the disulfides may require cyclization to the isothiazolones. Two agents, PD 159206 and PD 161374, which showed good antiviral activity, physical properties, and excellent pharmacokinetics in mice, were selected for advanced studies.

A sensitive and specific double antibody radioimmunoassay has been developed capable of measuring LH-RH in extracted human plasma. Thyrotropin releasing hormone, lysine vasopressin and most of LH-RH analogues did not appear to affect the assay. Hypothalamic extract and some of the LH-RH analogues produced displacement curves which were parallel to that obtained with the synthetic LH-RH. Sensitivity of the radioimmunoassay was about 3 pg per assay tube. The coefficient of variation of intraassay was 6.4%, while that of interassay was 9.6%. Exogenous LH-RH could be quantitatively extracted by acidic ethanol when varying amounts of synthetic LH-RH were added to plasma. Immunoreactivity of LH-RH was preserved in plasma until 2 hr in the cold and gradually reduced thereafter. The plasma levels in LH-RH were 20 pg/ml or less in normal adults and not detectable in children. The aged males over 60 yr and postmenopausal women showed a tendency to have higher levels of plasma LH-RH. Plasma LH-RH level was significantly higher in midcycle than in follicular and luteal stages. The disappearance rate of LH-RH from the circulation after intravenous injection could be represented as half times of 4-6 min. Between 0.2-0.4% of the injected dose was excreted into urine within 1 hr. These results indicate that the determination of LH-RH might be a useful tool for elucidating hypothalamic-pituitary-gonad interactions.

A sensitive and specific radioimmunoassay has been developed capable of measuring thyrotropin releasing hormone (TRH) in extracted human plasma and urine. All of three TRH analogues tested had little cross-reactivity to antibody. Luteinizing hormone releasing hormone, lysine vasopressin, rat growth hormone and bovine albumin were without effect, but rat hypothalamic extract produced a displacement curve which was parallel to that obtained with the synthetic TRH. Sensitivity of the radioimmunoassay was 4 pg per tube with intraassay coefficient of variation of 6.2-9.7%. Synthetic TRH could be quantitatively extracted by methanol when added to human plasma in concentration of 25, 50 and 100 pg/ml. TRH immunoreactivity was rapidly reduced in plasma at 20 degrees C than at 0 degrees C, but addition of peptidase inhibitors, FOY-007 and BAL, prevented the inactivation of TRH for 3 hr at 0 degrees C. The TRH in urine was more stable at 0 degrees C than 20 degrees C, and recovered 75 +/- 4.6% hr after being added. The plasma levels of TRH were 19 pg/ml or less in normal adults and no sex difference was observed. The rate of disappearance of TRH administered i.v. from the blood could be represented as half-times of 4-12 min. Between 5.3-12.3% of the injected dose was excreted into urine within 1 hr as an immunoreactive TRH. These results indicate the usefulness of TRH radioimmunoassay for clinical investigation.