Health sciences educator's simulation debriefing practice needs: A mixed methods study.

BACKGROUND: Simulation debriefing influences learning from healthcare simulation activities. Health sciences educators must be competent in conducting simulation debriefing for healthcare students. A structured faculty development intervention for health sciences educators must be informed by educator needs to enhance its utility. This paper describes the needs of health sciences educators regarding simulation debriefing at a faculty of health sciences. MATERIALS AND METHODS: A parallel convergent mixed methods study design was applied on a selected population of 30 health sciences educators at the University (x) who integrate immersive simulation for first- to final-year students in their undergraduate programs. The Objective Structured Assessment of Debriefing tool underpinned observations which informed the quantitative strand of the study, while semi-structured interviews were conducted as part of the qualitative strand. Descriptive statistics and thematic analysis were used to analyze the data. RESULTS: Health sciences educators struggled to establish the learning environment for simulation (median 1), facilitate learning (median 3), and evaluate their debriefing activities. However, they were able to apply an appropriate approach toward simulation (median 4). They identified the need to be educated on the fundamentals of simulation-based education. CONCLUSION: A continuing professional development program must be developed aimed at transforming approaches toward facilitating learning, explaining the fundamentals of simulation-based education, modeling of best-practices related to debriefing, and applying appropriate strategies for evaluating debriefing activities.

Diversity of the gut, vaginal and oral microbiome among pregnant women in South Africa with and without pre-eclampsia.

Background: Changes in microbial communities are a known characteristic of various inflammatory diseases and have been linked to adverse pregnancy outcomes, such as preterm birth. However, there is a paucity of information regarding the taxonomic composition and/or diversity of microbial communities in pre-eclampsia. The aim of this study was to determine the diversity of the gut, vaginal and oral microbiome in a cohort of South African pregnant women with and without pre-eclampsia. The diversity of the gut, vaginal and oral microbiome was determined by targeted next generation sequencing (NGS) of the V3 and V4 region of the 16S rRNA gene on the Illumina MiSeq platform. Results: In this study population, pre-eclampsia was associated with a significantly higher alpha diversity (P = 0.0472; indicated by the Shannon index) in the vaginal microbiome accompanied with a significant reduction in Lactobacillus spp. (P = 0.0275), compared to normotensive pregnant women. Lactobacillus iners was identified as the predominant species of the vaginal microbiome in both cohorts. High inter-individual variation in alpha diversity was observed in the gut and oral microbiome in both cohorts. Although differences in the relative abundance of bacteria at all phylogenetic levels were observed, overall microbial composition of the gut, oral and vaginal microbiome was not significantly different in the pre-eclampsia cohort compared to the normotensive cohort. Conclusion: Collectively, a reduction of Lactobacillus spp., and predominance of L. iners in pregnant women with pre-eclampsia could suggest an unstable vaginal microbiome that might predispose pregnant women to develop pre-eclampsia. The lack of significant structural changes in the gut, oral and vaginal microbiome does not suggest that the characterized communities play a role in pre-eclampsia, but could indicate a characteristic unique to the study population. The current study provided novel information on the diversity of the gut, oral and vaginal microbiome among pregnant women in South Africa with and without pre-eclampsia. The current study provides a baseline for further investigations on the potential role of microbial communities in pre-eclampsia.

A comparison of the effectiveness of QCPR and conventional CPR training in final-year medical students at a South African university.

INTRODUCTION: High-quality cardiopulmonary resuscitation (CPR) saves lives. Training on basic first aid manikins allows students to practice manoeuvres and provides realistic resistance to chest compressions. Conventional CPR has no real-time feedback to observe the quality of CPR. Quality cardiopulmonary resuscitation (QCPR) is technology using wireless sensors embedded in the manikin to measure the effectiveness of core CPR components. This study compared the effectiveness of CPR training of final-year undergraduate medical students using electronic-feedback QCPR adult manikins and conventional adult manikins. The effectiveness of compressions was compared and return on investment was investigated. METHODS: In an experimental study, 53 students were divided into two groups using simple random sampling. The QCPR group practised CPR on the QCPR manikins. The CPR group practised on conventional CPR manikins. Both groups were allowed to practice for approximately 10 minutes. After the training session, both groups were tested using the QCPR manikin. Only chest compression performance in adult-sized manikins were measured, recorded and compared. RESULTS: The median flow fraction for the QCPR group was 78.0% (interquartile range (IQR) 63-89%) and for the CPR group 80.0% (IQR 74-85%). The median number of compressions for the QCPR group was 104 (IQR 101-109) and for the CPR group 107 (IQR 79-124). Both groups achieved a 100% compression rate with adequate depth. The maximum total effectiveness of both groups was 99%. No statistically significant difference was seen for the overall percentage of compression effectiveness between the groups. CONCLUSION: Participants achieved acceptable scores on most CPR compression metrics and complied with CPR guidelines in most cases. Efficacy of CPR training on conventional and QCPR manikins was comparable. CPR training in low resource settings can be just as effective on conventional manikins. Immediate feedback technology adds value to the training experience, allowing for individuals to adjust for deviations to set standards.

Bacterial Vaginosis: Current Diagnostic Avenues and Future Opportunities.

A healthy female genital tract harbors a microbiome dominated by lactic acid and hydrogen peroxide producing bacteria, which provide protection against infections by maintaining a low pH. Changes in the bacterial compositions of the vaginal microbiome can lead to bacterial vaginosis (BV), which is often associated with vaginal inflammation. Bacterial vaginosis increases the risk of acquiring sexually transmitted infections (STIs) like human immunodeficiency virus (HIV) and affects women's reproductive health negatively. In pregnant women, BV can lead to chorioamnionitis and adverse pregnancy outcomes, including preterm premature rupture of the membranes and preterm birth. In order to manage BV effectively, good diagnostic procedures are required. Traditionally clinical and microscopic methods have been used to diagnose BV; however, these methods require skilled staff and time and suffer from reduced sensitivity and specificity. New diagnostics, including highly sensitive and specific point-of-care (POC) tests, treatment modalities and vaccines can be developed based on the identification of biomarkers from the growing pool of vaginal microbiome and vaginal metabolome data. In this review the current and future diagnostic avenues will be discussed.

Growth Forms of Gardnerella spp. and Lactobacillus spp. on Vaginal Cells.

Bacterial vaginosis (BV) is a common vaginal condition in women of reproductive age. During BV development, BV-associated bacteria may form a polymicrobial biofilm, which predispose women to recurrent BV. The aim of the study was to investigate the growth forms of Gardnerella spp. and Lactobacillus spp. and to determine the association between the bacterial growth forms and clinical characteristics [urinary tract infection (UTI) symptoms, human immunodeficiency virus (HIV) infection and abnormal vaginal discharge] in women attending a tertiary hospital in Pretoria, South Africa. A first-void urine specimen was collected from 196 women and BV was diagnosed using the Nugent scoring and the Ison-Hay criteria (vaginal smear microscopy). Fluorescence in situ hybridisation (FISH) was performed to classify the growth forms ["dispersed" or "biofilm"]. Bacterial cells were categorized as "dispersed" if cells were scattered separately and as "biofilm" if bacterial aggregates on the vaginal epithelial cells were observed. BV was detected in 52 women (52/196; 27%) and in these women, Gardnerella spp. were predominantly present in biofilms (46/52; 88% for Nugent scoring; and 45/50; 90% for Ison-Hay criteria), whereas Lactobacillus spp. were predominantly present in a dispersed form (38/52; 73% for Nugent scoring; and 37/50; 74% for Ison-Hay criteria). The odds of having BV increased when Gardnerella biofilms were present (p < 0.001), whereas the opposite was observed for Lactobacillus biofilms (p = 0.001). Neither Gardnerella spp. or Lactobacillus spp. (both dispersed or biofilms) had an association with the presence of UTI symptoms, HIV coinfection or abnormal vaginal discharge. In conclusion, this study demonstrated and confirmed that Gardnerella biofilms are associated with BV and that Lactobacillus spp. may form biofilms to protect against BV.

Prevalence of eye pathology in a group of diabetic patients at National District Hospital Outpatient Department in Bloemfontein, South Africa.

BACKGROUND: Diabetic retinopathy is the third most common cause of blindness after cataracts and glaucoma in South Africa. Primary healthcare interventions providing eye care services play an important role in preventing complications. AIM: To determine the prevalence of eye pathology in a group of diabetic patients at National District Hospital by screening for diabetes-associated ocular pathology. SETTING: Outpatients Department run by Department of Family Medicine at National District Hospital in Bloemfontein from June to July 2014. METHODS: Interviews were used to collect information regarding diabetic patients' history of diabetes mellitus and if and when previous diabetic retinopathy screening was performed. Visual acuity was assessed, intra-ocular pressure measured and a non-mydriatic digital fundus camera used to screen for retinal pathology. RESULTS: During the last year, only 4.5% of patients had their vision checked with a Snellen chart, and 16.5% were examined with an ophthalmoscope. Since diagnosis of diabetes, only 15.5% of patients were referred to an ophthalmologist. Patient referral was needed for 87 (42.9%) cases for refractive disorders, 37 (18.2%) for suspected glaucoma, 30 (14.8%) for cataracts, and 22 (10.8%) for diabetic retinopathy. CONCLUSION: This study confirms that glaucoma, cataracts and diabetic retinopathy are prevalent eye conditions among diabetic patients. Offering eye screening at primary healthcare level may contribute to early detection of eye pathology and timeous referral for sight-saving treatment.

Chlamydia trachomatis Biovar L2 Infection in Women in South Africa.

We detected Chlamydia trachomatis biovar L2 in vaginal swab specimens of 7 women with vaginal discharge in South Africa. Whole-genome sequencing directly from clinical specimens identified a closely related cluster of strains. The clinical role of this infection in the context of syndromic management should be clarified.

Etiology of bacterial vaginosis and polymicrobial biofilm formation.

Microorganisms in nature rarely exist in a planktonic form, but in the form of biofilms. Biofilms have been identified as the cause of many chronic and persistent infections and have been implicated in the etiology of bacterial vaginosis (BV). Bacterial vaginosis is the most common form of vaginal infection in women of reproductive age. Similar to other biofilm infections, BV biofilms protect the BV-related bacteria against antibiotics and cause recurrent BV. In this review, an overview of BV-related bacteria, conceptual models and the stages involved in the polymicrobial BV biofilm formation will be discussed.

A cross-sectional study on the relationship of age, gestational age and HIV infection to bacterial vaginosis and genital mycoplasma infection.

OBJECTIVES: Pregnant women are especially at risk of developing complications when infected with reproductive tract infections (RTIs). The objective of this study was to determine the prevalence of bacterial vaginosis (BV) and genital mycoplasmas in pregnant women and investigate the associations between BV, genital mycoplasmas, HIV infection, age and gestational age. DESIGN: Cross-sectional study with descriptive and analytical components. SETTING: Antenatal clinic of a tertiary academic hospital in South Africa. PARTICIPANTS: 220 pregnant women older than 18 were included in the study and provided self-collected vaginal swabs. PRIMARY AND SECONDARY OUTCOMES: BV and genital mycoplasma colonisation and/or infection in women of differing age, gestational period and HIV status. RESULTS: The prevalence of BV was 17.7% (39/220) (95% CI 12.9 to 23.4), intermediate vaginal flora (IVF) 15% (33/220) (95% CI 10.56 to 20.42), and the overall prevalence of genital mycoplasmas was 84% (185/220) (95% CI 78.47 to 88.58). BV was significantly associated with HIV infection with an OR of 2.84 (95% CI 1.08 to 7.46 and p value=0.034). However, BV was inversely associated with gestational age with an OR of 0.08 (95% CI 0.01 to 0.42 and p value=0.003) for second trimester pregnancies and an OR of 0.03 (95% CI 0.01 to 0.17 and p value<0.001) for third trimester pregnancies using the first trimester as reference. IVF was significantly associated with HIV infection with an OR of 2.7 (95% CI 1.07 to 6.79 and p value=0.035) but not with age or gestational age. Genital mycoplasmas were not significantly associated with age, gestational age, HIV status, BV flora or IVF. CONCLUSIONS: The high infection rate of genital mycoplasmas and the association of BV with HIV found in this study reiterate the importance of screening for these RTIs in high-risk groups such as pregnant women.

Antimicrobial susceptibility patterns of Ureaplasma species and Mycoplasma hominis in pregnant women.

BACKGROUND: Genital mycoplasmas colonise up to 80% of sexually mature women and may invade the amniotic cavity during pregnancy and cause complications. Tetracyclines and fluoroquinolones are contraindicated in pregnancy and erythromycin is often used to treat patients. However, increasing resistance to common antimicrobial agents is widely reported. The purpose of this study was to investigate antimicrobial susceptibility patterns of genital mycoplasmas in pregnant women. METHODS: Self-collected vaginal swabs were obtained from 96 pregnant women attending an antenatal clinic in Gauteng, South Africa. Specimens were screened with the Mycofast Revolution assay for the presence of Ureaplasma species and Mycoplasma hominis. The antimicrobial susceptibility to levofloxacin, moxifloxacin, erythromycin, clindamycin and tetracycline were determined at various breakpoints. A multiplex polymerase chain reaction assay was used to speciate Ureaplasma positive specimens as either U. parvum or U. urealyticum. RESULTS: Seventy-six percent (73/96) of specimens contained Ureaplasma spp., while 39.7% (29/73) of Ureaplasma positive specimens were also positive for M. hominis. Susceptibilities of Ureaplasma spp. to levofloxacin and moxifloxacin were 59% (26/44) and 98% (43/44) respectively. Mixed isolates (Ureaplasma species and M. hominis) were highly resistant to erythromycin and tetracycline (both 97% resistance). Resistance of Ureaplasma spp. to erythromycin was 80% (35/44) and tetracycline resistance was detected in 73% (32/44) of Ureaplasma spp. Speciation indicated that U. parvum was the predominant Ureaplasma spp. conferring antimicrobial resistance. CONCLUSIONS: Treatment options for genital mycoplasma infections are becoming limited. More elaborative studies are needed to elucidate the diverse antimicrobial susceptibility patterns found in this study when compared to similar studies. To prevent complications in pregnant women, the foetus and the neonate, routine screening for the presence of genital mycoplasmas is recommended. In addition, it is recommended that antimicrobial susceptibility patterns are determined.

Comparison of the new Mycofast Revolution assay with a molecular assay for the detection of genital mycoplasmas from clinical specimens.

BACKGROUND: Genital mycoplasmas are opportunistic bacteria that are associated with undesirable gynaecologic and reproductive events. Mycoplasmas are fastidious bacteria with increasing resistance to routine antimicrobials and often fail to grow on conventional culture methods. The commercial Mycofast Revolution assay permits the phenotypic detection and identification of genital mycoplasmas. Antimicrobial susceptibility testing against five antimicrobial agents with MICs corresponding to the CLSI guidelines can also be performed. This study aimed to compare the new commercially available Mycofast Revolution assay with a multiplex PCR assay. METHODS: Self-collected swabs were obtained from pregnant women attending the antenatal clinic of a tertiary academic hospital in Pretoria, South Africa from October 2012 to November 2012. These swabs were used to seed UMMt and modified Amies transport media. The seeded UMMt transported medium was used to inoculate the Mycofast Revolution assay for the identification, enumeration and antimicrobial susceptibility testing of genital mycoplasmas. Following DNA extraction from the modified Amies transport medium, specimens were subjected to a multiplex PCR assay for the detection of genital mycoplasmas. RESULTS: The Mycofast Revolution kit had a sensitivity and specificity of 77.3% (95% CI: 62.15% to 88.51%) and 80% (95% CI: 28.81% to 96.70%), respectively, against the PCR assay. The positive and negative predictive values were 97.1% (95% CI: 85.03% to 99.52%) and 28.6% (95% CI: 8.57% to 58.08%). Genital mycoplasmas were detected in 71.4% (35/49) of samples with the Mycofast Revolution assay with 49% (24/49) being Ureaplasma spp. and 22.4% (11/49) mixed strains. The multiplex PCR assay had a positivity rate of 89.8% (44/49) for genital mycoplasmas; mixed strains were present in 51% (25/49) of samples, Ureaplasma spp. in 16.3% (8/49) and M. hominis in 22.4% (11/49) of samples. CONCLUSIONS: There was a fair agreement (κ = 0.319) between the Mycofast Revolution assay and the mPCR assay. With the high prevalence rates of genital mycoplasmas, fast and efficient diagnostic methods are imperative to treat infections and minimise complications. The Mycofast Revolution assay is simple to use, has a short turn-around time and interpretation of results are straightforward. This assay circumvents common problems experienced with conventional culture and molecular methods in diagnostic laboratories where skilled personnel are limited and can be used as an alternative diagnostic assay.

Microparticles and their emerging role in cancer multidrug resistance.

Drug resistance is a major obstacle to the successful treatment of cancer as tumor cells either fail to reduce in size following chemotherapy or the cancer recurs after an initial response. The phenomenon of multidrug resistance (MDR) is particularly problematic as it involves the simultaneous resistance to numerous chemotherapeutics of different classes. MDR is predominantly attributed to the overexpression of efflux transporters such as P-glycoprotein (P-gp) and the Multidrug Resistance-Associated Protein 1 (MRP1). P-gp and MRP1 are members of the ATP Binding Cassette (ABC) superfamily of transporters and are capable of effluxing many chemotherapeutics out of cancer cells, allowing them to survive the toxic insult. Numerous strategies have been developed over the years to circumvent MDR. Of these, the discovery and implementation of P-gp and MRP1 inhibitors have been most extensively studied. However, these inhibitors have not been able to be used clinically. While research continues in this area, it must also be acknowledged that other avenues must be explored. Recently, the novel 'non-genetic' acquisition of P-gp-mediated MDR by microparticles (MPs) has been reported. MPs are vesicles 0.1-1µm in diameter that are released via plasma membrane blebbing. They are important mediators of inflammation, coagulation and vascular homeostasis. In addition to surface P-gp protein, MPs also carry various nucleic acid species as cargo. This 'non-genetic' intercellular transfer provides an alternative pathway for the cellular acquisition and dissemination of traits and implicates MPs as important mediators in the spread of MDR and provides a novel pathway for the circumvention of MDR.

[Orthostatic headache with tachycardia]. / Orthostatische Kopfschmerzen und Tachykardie.

We report the case of a 17 year old male patient who presented with a history of orthostatic headache (present in the upright position only) for several months. The diagnostic investigations (MRI of the head and of the spine, lumbar puncture) revealed no signs of an intracranial hypotension or a CSF leak. In standing position, a significant raise of the heart rate (>40 bpm) without fall of the blood pressure occurred together with a bilateral, pressure-like headache. A diagnosis of postural tachycardia syndrome was made. Treatment with increase of fluid and salt intake, elastic compression stockings and regular exercise was successful.

Evaluation of the vector space representation in text-based gene clustering.

Thanks to its increasing availability, electronic literature can now be a major source of information when developing complex statistical models where data is scarce or contains much noise. This raises the question of how to deeply integrate information from domain literature with experimental data. Evaluating what kind of statistical text representations can integrate literature knowledge in clustering still remains an unsufficiently explored topic. In this work we discuss how the bag-of-words representation can be used successfully to represent genetic annotation and free-text information coming from different databases. We demonstrate the effect of various weighting schemes and information sources in a functional clustering setup. As a quantitative evaluation, we contrast for different parameter settings the functional groupings obtained from text with those obtained from expert assessments and link each of the results to a biological discussion.

Liver regeneration is an angiogenesis- associated phenomenon.

OBJECTIVE: To investigate whether liver regeneration is an angiogenesis-associated phenomenon. SUMMARY BACKGROUND DATA: Angiogenesis is predominantly known for its pivotal role in tumor growth. However, angiogenesis could also play a role in physiologic processes involving tissue repair, such as liver regeneration. METHODS: Mice subjected to 70% partial hepatectomy were treated with human angiostatin (100 mg/kg body weight). Regeneration-induced hepatic angiogenesis was determined by assessing intrahepatic microvascular density using CD31 staining of frozen liver sections. Liver regeneration was evaluated by assessing wet liver weights and BrdU incorporation in DNA at regular intervals after partial hepatectomy. Possible direct effects of angiostatin on hepatocytes were studied by assessment of liver enzymes (ASAT, ALAT, bilirubin, lactate dehydrogenase), MTT assay (cytotoxicity), aminophenol production (metabolic function), and TUNEL (apoptosis). RESULTS: In a regenerating liver, microvascular density increased by 38%. Angiostatin significantly inhibited this response by 60%. In addition, angiostatin inhibited liver regeneration by 50.4% and 24.9% on postoperative days 7 and 14, respectively. In control mice liver weights regained normalcy in 8 days, whereas those in angiostatin-treated mice normalized after 21 days. In angiostatin-treated mice, the maximal BrdU incorporation was decreased and delayed. Direct adverse effects of angiostatin on cultured and in vivo hepatocytes were not observed. Angiostatin neither induced necrosis on hematoxylin and eosin staining nor affected serum levels of liver enzymes. CONCLUSIONS: Liver regeneration is accompanied by intrahepatic angiogenesis. Antiangiogenic treatment using angiostatin inhibits both phenomena. The authors conclude that liver regeneration is, at least in part, an angiogenesis-dependent phenomenon.

[Evaluation of an internet site on evidence-based medicine]. / Evaluation eines Internetangebotes über Evidence-based Medicine.

The present study evaluated a Swiss internet provider of Evidence-based Medicine (EBM) with regard to its utilization and function for medical practitioners. The internet provider under study (www.evimed.ch) primarily provides abstracts of original articles relevant to medical practice that are presented according to the criteria of EBM and includes information about EBM itself. In March 1999 a survey was conducted to better appraise the benefits gained from the information provided from the website visitors' point of view. Around 400 persons who had entered their names in the homepage guest book were informed about the survey by e-mail. A total of 167 questionnaires were filled in online, which is equivalent to the reply rate of close to 42%. The majority of the replies (63.5%) were from private-practice physicians, 22.2% from hospital-based physicians. The average age ranged between 40 and 49 years. 67.7% of the 167 respondents had internet access at their workplace, 72.5% had private internet access. For their own practical work, 61.1% of the respondents rated the information provided by www.evimed.ch as generally useful. The clinical relevance of the studies presented in the Journal Club was rated as good by 55.7% and as very good by 26.9%. The reliability of the information provided was rated as good by 56.3% and as very good by 35.3%. The majority regarded the following homepage sites as personally important: Journal Club (55.7%), articles about EBM (46.1%), MEDLINE access (37.7%) and article citations/links (41.3%). The homepage was visited at an average frequency of 1-3 times a month. 50.3% preferred electronic media (40.1% using various internet providers, 10.2% www.evimed.ch) and 44.3% preferred print media to search for specialist information on a specific medical subject. With regard to new medical findings, 44.9% of the respondents stated that they used print media, 17.4% the www.evimed.ch homepage and 28.7% other internet sources as their primary information medium. Based on this survey, the majority of the respondents gave a positive rating of the www.evimed.ch homepage. Information about EBM and critically appraised studies were evaluated as particularly useful.

NF-kappa B modulates TNF-alpha production by alveolar macrophages in asymptomatic HIV-seropositive individuals.

Local TNF-alpha production in different organs may affect HIV replication and pathogenesis. Alveolar macrophages (AMs) obtained by bronchoalveolar lavage from asymptomatic HIV-seropositive and HIV-seronegative individuals did not spontaneously release TNF-alpha, but LPS stimulation of these cells significantly increased TNF-alpha production. We tested whether NF-kappa B affects TNF-alpha production by AMs using N-tosyl-l -phenylalanine chloromethylketone (TPCK) or N-benzoyl-l -tyrosine ethyl ester (BTEE), which inhibit the degradation of I kappa B, or tricyclodecan-9-yl-xanthogenate-potassium (D609), which inhibits phospholipase C. Alveolar macrophages were exposed to LPS alone and with the chemical protease inhibitors TPCK, BTEE, and D609. NF-kappa B DNA binding induced by LPS treatment of AMs was inhibited by TPCK, BTEE, and D609. These agents also inhibited TNF-alpha mRNA and TNF-alpha protein production. After 24 h, the levels of TNF-alpha mRNA reached equilibrium, as assessed by RT-PCR. The levels of NF-kappa B mRNA remained constant under all conditions. The levels of I kappa B-alpha mRNA were similar after 30, 60, and 180 min, but the I kappa B-beta mRNA concentration was initially low and increased over time under all conditions. I kappa B-alpha and I kappa B-beta protein production was not affected by the chemical protease inhibitors. Our data show that TNF-alpha production by LPS-stimulated AMs from asymptomatic HIV-seropositive and -seronegative individuals is regulated via the phospholipase C pathway and by NF-kappa B DNA binding activity without obvious changes in I kappa B-alpha or I kappa B-beta protein concentrations.

Systemic administration of the iron chelator deferiprone attenuates subarachnoid hemorrhage-induced cerebral vasospasm in the rabbit.

OBJECTIVE: Iron catalyzed generation of injurious free radicals has been implicated in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). The present study assessed the effects of the iron chelator deferiprone on cerebral vasospasm in an in vivo rabbit model of SAH. METHODS: Twenty-four rabbits were assigned to three groups as follows: SAH plus placebo (n = 8), SAH plus deferiprone (n = 8), or control plus placebo (n = 8). Deferiprone was administered to an additional group of three rabbits that were not subjected to SAH. Drug administration was initiated 8 hours after SAH was induced and was repeated at 8-hour intervals. The animals were killed using perfusion-fixation 48 hours after SAH. Cross-sectional areas of basilar artery histological sections were measured by an investigator blinded to the treatment groups. RESULTS: In placebo-treated animals, the average luminal cross-sectional area of the basilar artery was reduced by 54% after SAH compared to controls (i.e., from 0.272 to 0.125 mm2). The vasospastic response after SAH was attenuated significantly in animals treated with deferiprone (0.208 mm2, representing a 24% reduction). CONCLUSION: Previous experimental studies suggested that iron chelation can be effective in attenuating cerebral vasospasm after SAH. Deferiprone is a recently developed iron chelator that has been extensively evaluated for the treatment of patients requiring chronic blood transfusions. The present study demonstrates that deferiprone is effective in attenuating experimental cerebral vasospasm. Because of its stability, lipophilicity, and ability to penetrate the blood-brain barrier, deferiprone represents an attractive candidate for the treatment of cerebral vasospasm.

The sequence of 23 kb surrounding the SNF3 locus on the left arm of yeast chromosome IV reveals the location of five known genes and characterizes at least six new open reading frames including putative genes for ribosomal protein L35 and a sugar transport protein.

The nucleotide sequence of 22,846 bp of the left arm of chromosome IV is described. Twelve open reading frames (ORFs) greater than 100 triplets were detected, one of which extends into an adjacent cosmid. Two of the ORFs may contain an intron. One of these is an L35 ribosomal protein gene. Five ORFs (D1204, D1214, D1219, D1234 and D1244) encode previously sequenced genes (MGT1, SHM1, ASF2, SNF3 and ARF2, respectively). The nucleotide sequence of a sixth ORF (D1229) is quite similar to the WEB1 gene, which appeared in the DNA databases shortly after finishing the sequence reported here. It is not clear whether or not WEB1 and D1229 represent one and the same gene. The co-linearity of the reported DNA sequences with the genome of strains from Saccharomyces cerevisiae subspecies carlsbergensis, sake and diastaticus was assessed by comparative PCR with overlapping primer sets.