Syphilis: mimicking yet another disease!
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Biomedical subjects
Publications and source records attributed to M Fisher.
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The utility of diagnostic imaging during the critical first few hours after stroke onset has many important applications. First and foremost, imaging technologies that can reliably detect and quantify the location of acute stroke will greatly enhance the clinician's ability to accurately diagnose individual stroke patients. Secondly, if imaging technology could provide information about the likely severity of the ischemic injury, patient prognosis and management would be enhanced. The possibility of potentially distinguishing severely injured and likely irreversible ischemic brain tissue from ischemic tissue likely not yet irreversibly injured may soon be attainable. The ability of imaging technology to reliably distinguish the status of focally ischemic brain will presumably dramatically impact upon patient management. This information, along with the data about the severity and extent of blood flow and tissue perfusion abnormalities, will help acute stroke care evolve beyond rigid time windows to individualized, pathophysiologically based treatment decisions. Not only will decisions to treat or not be made based upon imaging-derived status, but also the most appropriate type of therapy to be employed, i.e. thrombolysis, neuroprotection, therapy to reduce secondary reperfusion-related injury or combinations of these modalities. In this brief and necessarily incomplete overview of acute stroke imaging, the focus will be on new developments in CT and MRI.
BACKGROUND AND PURPOSE: The apparent diffusion coefficient of water (ADC) rapidly drops in ischemic tissue after cerebral artery occlusion. This acute drop is thought to be caused by the loss of extracellular fluid and the gain of intracellular fluid. To test the latter possibility, changes in ADC and the size of several cellular compartments were assessed in 3 regions of rat brain at the end of 90 minutes of focal cerebral ischemia. METHODS: One middle cerebral artery was permanently occluded in 8 Sprague-Dawley rats; sham occlusions were performed in 2 other rats. ADC maps were generated 90 minutes later, and the brains were immediately perfusion fixed. Three regions of interest (ROIs) were defined on the basis of ADC range. Various neuronal, astrocytic, and capillary compartments in each ROI were quantified with light and electron microscopy. RESULTS: At the end of 90 minutes of ischemia, mean ADC was normal in the cortex of sham-operated rats and the contralateral cortex of ischemic rats (ROI-a), 25% lower in the ipsilateral frontoparietal cortex (ROI-b), and 45% lower in the ischemic lateral caudoputamen (ROI-c). At this time, the frequency of swollen astrocytic cell bodies and volume of swollen dendrites and astrocytic processes in neuropil were ROI-a<ROI-b<ROI-c. In ROI-b and ROI-c, 40% and 60% of the neurons, respectively, were shrunken; the shrunken neurons were approximately 25% smaller in ROI-c than in ROI-b. In these areas, many capillary endothelial cells, pericytes, and perivascular foot processes were swollen. CONCLUSIONS: The initial lowering of ADC during focal ischemia probably is the result of not only the acute loss of extracellular fluid and concomitant swelling of various cellular compartments but also concurrent neuronal shrinkage.
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UNLABELLED: Emergency contraception (EC) is the use of a method of contraception after unprotected intercourse to prevent unintended pregnancy. Although first described over 20 years ago, physician awareness of EC has been limited and many feel uncomfortable prescribing it. OBJECTIVE: To assess the knowledge, attitudes, and opinions of practicing pediatricians regarding the use of EC in adolescents. METHODS: An anonymous questionnaire was mailed to all 954 active members of New York Chapter 2, District II of the American Academy of Pediatrics. The questionnaire assessed basic knowledge, attitudes, and opinions regarding EC in adolescents. Data were analyzed by physician age, gender, year completed residency, and practice type. RESULTS: Two hundred thirty-three practicing pediatricians (24.4%) completed the survey. Of the respondents, 23.7% had been asked to prescribe EC to an adolescent and 49% of these cases involved a rape victim. Only 16.7% of pediatricians routinely counsel adolescent patients about the availability of EC, with female pediatricians more likely to do so. Most respondents (72.9%) were unable to identify any of the Food and Drug Administration-approved methods of EC. Only 27.9% correctly identified the timing for its initiation and only 31.6% of respondents felt comfortable prescribing EC. Inexperience with use was cited as the primary reason for not prescribing EC by 70% of respondents. Twelve percent cited moral or religious reasons and 17% were concerned about teratogenic effects. There were no differences in comfort level based on age, gender, or practice type. Twenty-two percent of respondents believed that providing EC encourages adolescent risk-taking behavior and 52.4% would restrict the number of times they would dispense EC to an individual patient. A minority of respondents (17%) believed that adolescents should have EC available at home to use if necessary and only 19.6% believed that EC should be available without a prescription. The vast majority (87.5%) were interested in learning more about EC. CONCLUSIONS: Despite the safety and efficacy of EC, the low rate of use is of concern. Pediatricians are being confronted with the decision to prescribe EC but do not feel comfortable prescribing it because of inadequate training in its use. Practicing pediatricians are aware of their lack of experience and are interested in improving their knowledge base.
Eprinomectin has been approved for use as a topically applied endectocide for beef and dairy cattle. To determine if eprinomectin has utility as an injectable anthelmintic, it was titrated at 0.05, 0.1, and 0.2 mg/kg s.c. against adult (Trial 1) and at 0.05, 0.1, 0.14, and 0.2 mg/kg s.c. against immature (Trial 2) stages of lung and gastrointestinal nematodes in cattle. In Trial 1, every dose of subcutaneously delivered eprinomectin showed maximal or near-maximal (> or = 99%) efficacy against Haemonchus placei, Ostertagia ostertagi, Trichostrongylus axei, T colubriformis, Cooperia punctata, Nematodirus helvetianus, Oesophagostomum radiatum, and Dictyocaulus viviparus. Adult C. oncophora was the only exception. However, even against this species, the lowest dose of 0.05 mg/kg showed 93% efficacy, and the efficacious dose necessary to kill 95% (ED95) of adults was 0.056 mg/kg. In Trial 2, every dose of subcutaneously delivered eprinomectin showed maximal or near-maximal (> or = 99%) efficacy against the immature stages of all of the above species of endoparasites. As a result, ED95 values could not be calculated. Consequently, the exquisite potency against endoparasites through parenteral administration suggests that eprinomectin may also have potential utility as an injectable product for cattle.
This prospective single-blinded study aimed to compare the types of medication errors and medication error rates of two medication delivery systems. The setting was a 30 bed surgical ward that was divided into two identical areas. In one area medications were stored and issued in a ward bay workstation immediately outside the patients' rooms. The alternate area used a medication trolley at the patients' bedside. Three hundred and forty opportunities for errors were observed using five nurse educators. Twenty administration errors (5.8% error rate) and two dispensing errors (0.6% error rate) were detected. A statistically significant difference was found between the two systems, where four errors occurred from the medication trolley (2.6% error rate), and fifteen errors occurred from the ward bay (9.2% error rate). These results suggest that medications were less likely to be omitted and more likely to be given on time when they were issued at the patient's bedside using the medication trolley.
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The utility of diagnostic imaging during the critical first few hours after stroke onset has many important applications. First and foremost, imaging technologies that can reliably detect and quantify the location of acute stroke will greatly enhance the clinician's ability to accurately diagnose individual stroke patients. Secondly, if imaging technology could provide information about the likely severity of the ischemic injury, patient prognosis and management would be enhanced. The possibility of potentially distinguishing severely injured and likely irreversible ischemic brain tissue from ischemic tissue likely not yet irreversibly injured may soon be attainable. The ability of imaging technology to reliably distinguish the status of focally ischemic brain will presumably dramatically impact upon patient management. This information, along with the data about the severity and extent of blood flow and tissue perfusion abnormalities, will help acute stroke care evolve beyond rigid time windows to individualized, pathophysiological-based treatment decisions. Not only will decisions to treat or not be made based upon imaging-derived status, but also the most appropriate type of therapy to be employed, i.e., thrombolysis, neuroprotection, therapy to reduce secondary reperfusion-related injury or combinations of these modalities. In this brief and necessarily incomplete overview of acute stroke imaging, the focus will be on new developments in CT and MRI.
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Cation channels conduct calcium, sodium and potassium, cations that are likely deleterious in the evolution of focal ischemic injury. We studied the effects of a novel, broad-spectrum inhibitor of several cation channels, LOE 908 MS, on acute ischemic lesion development with diffusion-weighted magnetic resonance imaging (DWI) and on cerebral perfusion with perfusion imaging (PI) in vivo and on cerebral infarct size using 2,3,5-triphenyltetrazolium chloride (TTC) staining postmortem. A total of 18 male Sprague-Dawley rats underwent 90 min of middle cerebral artery occlusion (MCAO) and were randomly and blindly assigned to either LOE 908 MS or vehicle starting 30 min after inducing focal ischemia and continuing for 4 h. Whole-brain DWI and multislice PI were done before initiation of treatment and repeated frequently for the next 3.5 h. DWI-derived lesion volume at 4 h showed a significant difference in favor of the drug treated group (P=0.03), whereas PI-derived perfusion deficit volumes did not significantly differ between the groups. The postmortem infarct volume at 24 h was significantly attenuated in the treated group in comparison to controls (P=0.0001) and neurological score was significantly better in the treated group (P<0.02). Blocking several distinct cation channels with LOE 908 MS significantly reduced infarct size and improved neurological outcome without observable adverse effects in this focal ischemia model.
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Antisense oligonucleotides are potentially a powerful tool for the therapeutic manipulation of genes associated with cancer. However, pharmacological applications of oligonucleotides have been hindered by the inability to effectively deliver these compounds to their sites of action within cells. In this study, we have prepared peptide-oligonucleotide conjugates with the intent of improving intracellular delivery. The phosphorothioate oligonucleotide component of the conjugates was complementary to a site flanking the AUG of the message for P-glycoprotein, a membrane ATPase associated with multidrug resistance in tumor cells. Two types of peptide-antisense oligonucleotide conjugates, but not mismatched control conjugates, provided substantial inhibition of cell surface expression of P-glycoprotein. Surprisingly, the peptide-oligonucleotide conjugates were more potent in the presence of serum than when used under serum-free conditions; this is in striking contrast to most other approaches for intracellular delivery of nucleic acids. Effective inhibition of P-glycoprotein expression was attained with submicromolar concentrations of antisense conjugates under serum-replete conditions. The combination of relatively modest molecular size and good efficacy in the presence of serum proteins suggests that peptide-antisense oligonucleotide conjugates may have significant promise for in vivo therapeutic applications.
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Based on Silverman and Eals' hunter-gatherer theory of the origin of sex-specific spatial attributes, the present research sought to identify the evolved mechanisms involved in hunting that contribute to the dimorphism. The focus of these studies was the relationship between three-dimensional mental rotations, the spatial test showing the largest and most reliable sex difference favoring males, and wayfinding in the woods. Space constancy was presumed to be the evolved mechanism fundamental to both of these abilities. Measures of wayfinding were derived by leading subjects individually on a circuitous route through a wooded area, during which they were stopped at prescribed places and required to set an arrow pointing in the direction the walk began. As well, subjects were eventually required to lead the experimenters back to the starting point by the most direct route. In support of the hypotheses, males excelled on the various measures of wayfinding, and wayfinding was significantly related across sexes to mental rotations scores but not to nonrotational spatial abilities or general intelligence.