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1.
Science ; 371(6533): 1038-1041, 2021 03 05.
Article En | MEDLINE | ID: mdl-33674491

Spectroscopy of transiting exoplanets can be used to investigate their atmospheric properties and habitability. Combining radial velocity (RV) and transit data provides additional information on exoplanet physical properties. We detect a transiting rocky planet with an orbital period of 1.467 days around the nearby red dwarf star Gliese 486. The planet Gliese 486 b is 2.81 Earth masses and 1.31 Earth radii, with uncertainties of 5%, as determined from RV data and photometric light curves. The host star is at a distance of ~8.1 parsecs, has a J-band magnitude of ~7.2, and is observable from both hemispheres of Earth. On the basis of these properties and the planet's short orbital period and high equilibrium temperature, we show that this terrestrial planet is suitable for emission and transit spectroscopy.

2.
BMJ Support Palliat Care ; 6(3): 377-80, 2016 Sep.
Article En | MEDLINE | ID: mdl-25563336

OBJECTIVES: To determine the views and experiences of health and social care professionals on using integrated care pathways (ICPs)for caring for people in the last days to hours of life. METHODS: Online cross-sectional questionnaire survey of UK professionals working in UK primary and secondary care settings. RESULTS: 1331 professionals returned completed questionnaires. Ninety-three per cent (1138/1228) of respondents used the Liverpool Care Pathway (LCP) or local variant. Eighty-eight (1089/1234) felt ICPs enabled professionals to provide better care for individuals and their families/carers. ICPs were viewed as promoting patient-centred holistic care, improving pain and symptom control, providing guidance and standards and improving communication with patients/families. Sixty-two per cent (770/1234) had no concerns regarding the use of ICPs. Areas of concern included incorrect use and implementation of the ICP, poor communication with families, junior level staff making decisions and insufficient education and support. CONCLUSIONS: There was strong support for using ICPs for caring for people in the last days to hours of life. ICPs were viewed as supporting high-quality patient-centred holistic care. Given the recommendations of the More Care Less Pathway report, those that develop the guidance and support that replace the LCP need to incorporate the aspects of this that have resulted in the benefits seen by professionals within this survey, but also learn from the instances where ICPs have failed to prevent poor care, or worse, have contributed to it.


Attitude of Health Personnel , Caregivers , Delivery of Health Care, Integrated/standards , Needs Assessment , Terminal Care/standards , Cross-Sectional Studies , Delivery of Health Care, Integrated/statistics & numerical data , Humans , Surveys and Questionnaires , Terminal Care/statistics & numerical data
3.
Psychol Med ; 45(16): 3571-80, 2015 Dec.
Article En | MEDLINE | ID: mdl-26266877

BACKGROUND: Suicide is a devastating public health problem and very few biological treatments have been found to be effective for quickly reducing the intensity of suicidal ideation (SI). We have previously shown that a single dose of ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, is associated with a rapid reduction in depressive symptom severity and SI in patients with treatment-resistant depression. METHOD: We conducted a randomized, controlled trial of ketamine in patients with mood and anxiety spectrum disorders who presented with clinically significant SI (n = 24). Patients received a single infusion of ketamine or midazolam (as an active placebo) in addition to standard of care. SI measured using the Beck Scale for Suicidal Ideation (BSI) 24 h post-treatment represented the primary outcome. Secondary outcomes included the Montgomery-Asberg Depression Rating Scale--Suicidal Ideation (MADRS-SI) score at 24 h and additional measures beyond the 24-h time-point. RESULTS: The intervention was well tolerated and no dropouts occurred during the primary 7-day assessment period. BSI score was not different between the treatment groups at 24 h (p = 0.32); however, a significant difference emerged at 48 h (p = 0.047). MADRS-SI score was lower in the ketamine group compared to midazolam group at 24 h (p = 0.05). The treatment effect was no longer significant at the end of the 7-day assessment period. CONCLUSIONS: The current findings provide initial support for the safety and tolerability of ketamine as an intervention for SI in patients who are at elevated risk for suicidal behavior. Larger, well-powered studies are warranted.


Depression/drug therapy , Excitatory Amino Acid Antagonists/administration & dosage , Ketamine/administration & dosage , Suicidal Ideation , Adult , Bipolar Disorder/epidemiology , Depressive Disorder, Major/epidemiology , Double-Blind Method , Excitatory Amino Acid Antagonists/therapeutic use , Female , Humans , Ketamine/therapeutic use , Male , Middle Aged , Psychiatric Status Rating Scales , Stress Disorders, Post-Traumatic/epidemiology , Treatment Outcome
4.
Transl Psychiatry ; 5: e509, 2015 Feb 17.
Article En | MEDLINE | ID: mdl-25689570

The glutamate N-methyl-D-aspartate receptor antagonist ketamine has demonstrated antidepressant effects in individuals with treatment-resistant major depressive disorder (TRD) within 24 h of a single dose. The current study utilized functional magnetic resonance imaging (fMRI) and two separate emotion perception tasks to examine the neural effects of ketamine in patients with TRD. One task used happy and neutral facial expressions; the other used sad and neutral facial expressions. Twenty patients with TRD free of concomitant antidepressant medication underwent fMRI at baseline and 24 h following administration of a single intravenous dose of ketamine (0.5 mg kg(-1)). Adequate data were available for 18 patients for each task. Twenty age- and sex-matched healthy volunteers were scanned at one time point for baseline comparison. Whole-brain, voxel-wise analyses were conducted controlling for a family-wise error rate (FWE) of P<0.05. Compared with healthy volunteers, TRD patients showed reduced neural responses to positive faces within the right caudate. Following ketamine, neural responses to positive faces were selectively increased within a similar region of right caudate. Connectivity analyses showed that greater connectivity of the right caudate during positive emotion perception was associated with improvement in depression severity following ketamine. No main effect of group was observed for the sad faces task. Our results indicate that ketamine specifically enhances neural responses to positive emotion within the right caudate in depressed individuals in a pattern that appears to reverse baseline deficits and that connectivity of this region may be important for the antidepressant effects of ketamine.


Caudate Nucleus/drug effects , Depressive Disorder, Major/physiopathology , Depressive Disorder, Treatment-Resistant/physiopathology , Emotions , Excitatory Amino Acid Antagonists/pharmacology , Ketamine/pharmacology , Social Perception , Adult , Brain/drug effects , Brain/physiopathology , Case-Control Studies , Caudate Nucleus/physiopathology , Depressive Disorder, Major/drug therapy , Depressive Disorder, Treatment-Resistant/drug therapy , Excitatory Amino Acid Antagonists/therapeutic use , Facial Expression , Female , Functional Neuroimaging , Humans , Ketamine/therapeutic use , Magnetic Resonance Imaging , Male , Middle Aged , Neural Pathways/drug effects , Neural Pathways/physiopathology , Pattern Recognition, Visual , Young Adult
5.
Br J Cancer ; 104(10): 1551-7, 2011 May 10.
Article En | MEDLINE | ID: mdl-21559024

BACKGROUND: Hospital mastectomy rates vary. This study explores the relationship between mastectomy rates and breast cancer patients' consultation and decision-making experiences with specialist clinicians. METHODS: Qualitative semi-structured interviews were conducted with 65 patients from three purposively selected breast units from a single UK region. Patients provided with a choice of breast cancer surgery (breast conservation therapy (BCT) or mastectomy) were purposively recruited from high, medium and low case-mix-adjusted mastectomy rate units. RESULTS: Low mastectomy rate unit patients' consultation and decision-making experiences were markedly different to those of the medium and high mastectomy rate breast units. Treatment variation was associated with patients' perception of the most reassuring and least disruptive treatment; the content and style of information provision (equipoise or directed); level of patient participation in decision making; the time and process of decision making and patient autonomy in decision making. The provision of more comprehensive less directive information and greater autonomy, time and support of independent decision making were associated with a lower uptake of BCT. CONCLUSION: Variation in hospital mastectomy rates was associated with differences in the consultation and decision-making experiences of breast cancer patients. Higher mastectomy rates were associated with the facilitation of more informed autonomous patient decision making.


Breast Neoplasms/surgery , Decision Making , Mastectomy/statistics & numerical data , Adult , Aged , Female , Hospitals , Humans , Middle Aged , Patient Participation , Patient Satisfaction , Referral and Consultation
6.
Mol Cell Biol ; 21(19): 6574-84, 2001 Oct.
Article En | MEDLINE | ID: mdl-11533245

The assembly of newly synthesized DNA into chromatin is essential for normal growth, development, and differentiation. To gain a better understanding of the assembly of chromatin during DNA synthesis, we identified, cloned, and characterized the 180- and 105-kDa polypeptides of Drosophila chromatin assembly factor 1 (dCAF-1). The purified recombinant p180+p105+p55 dCAF-1 complex is active for DNA replication-coupled chromatin assembly. Furthermore, we have established that the putative 75-kDa polypeptide of dCAF-1 is a C-terminally truncated form of p105 that does not coexist in dCAF-1 complexes containing the p105 subunit. The analysis of native and recombinant dCAF-1 revealed an interaction between dCAF-1 and the Drosophila anti-silencing function 1 (dASF1) component of replication-coupling assembly factor (RCAF). The binding of dASF1 to dCAF-1 is mediated through the p105 subunit of dCAF-1. Consistent with the interaction between dCAF-1 p105 and dASF1 in vitro, we observed that dASF1 and dCAF-1 p105 colocalized in vivo in Drosophila polytene chromosomes. This interaction between dCAF-1 and dASF1 may be a key component of the functional synergy observed between RCAF and dCAF-1 during the assembly of newly synthesized DNA into chromatin.


Cell Cycle Proteins/metabolism , Chromatin/chemistry , Chromosomal Proteins, Non-Histone , DNA-Binding Proteins/metabolism , Drosophila Proteins , Drosophila/genetics , Molecular Chaperones , Nuclear Proteins , Peptides/metabolism , Animals , Chromatin Assembly Factor-1 , Cloning, Molecular , DNA-Binding Proteins/genetics , DNA-Binding Proteins/physiology , Drosophila/metabolism , Microscopy, Fluorescence , Molecular Sequence Data , Peptides/genetics , Peptides/physiology , Protein Subunits , Retinoblastoma-Binding Protein 4 , Sequence Homology, Amino Acid , Spodoptera/genetics , Transfection
7.
Am J Forensic Med Pathol ; 22(3): 228-32, 2001 Sep.
Article En | MEDLINE | ID: mdl-11563728

The survival of spermatozoa and the persistence of prostatic acid phosphatase has been an area of interest for investigators of sexual assault. However, not much documentation exists concerning the examination of a deceased individual with regard to the postmortem interval and presence of such evidence. The authors reviewed cases referred to the medical examiner's office during a 10-year period. During this time, 199 cases were both autopsied and examined for sexual assault. In particular, these examinations included procurement of swabs for Papanicolaou staining of smears and for quantitation of prostatic acid phosphatase. Most of the victims were female, although a few were male. In the majority of cases, the swabs for smears and prostatic acid phosphatase were taken from oral, vaginal, and anorectal areas in females and oral and anorectal areas in males. The smears all were stained with the routine Papanicolaou stain, and intact spermatozoa and spermatozoan heads were sought. The prostatic acid phosphatase was analyzed by the microparticle enzyme immunoassay method and reported as ng/ml. A level of greater than 100 ng/ml was considered positive. The cases were analyzed with respect to postmortem interval; presence or absence of intact spermatozoa or spermatozoan heads; presence of an elevated prostatic acid phosphatase; body location of the specimen; the time of year; location of the victim; and physical injury (anogenital) of sexual assault. The authors hope that by examining the laboratory evidence of sexual assault, a correlation can be drawn between the presence or absence of such evidence and the aforementioned variables.


Homicide , Protein Tyrosine Phosphatases/analysis , Rape , Spermatozoa/physiology , Acid Phosphatase , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Double-Blind Method , Female , Forensic Anthropology , Humans , Male , Middle Aged , Mouth/pathology , Postmortem Changes , Rectum/pathology , Retrospective Studies , Sensitivity and Specificity , Specimen Handling/standards , Time Factors , Vagina/pathology
8.
Am J Forensic Med Pathol ; 22(3): 261-5, 2001 Sep.
Article En | MEDLINE | ID: mdl-11563736

Fetal death has been defined by the World Health Organization as death before complete expulsion or extraction from its mother of a product of conception, irrespective of the duration of pregnancy. Certain causes of fetal death, including syphilis, Rh isoimmunization, toxemia, and diabetes, have shown significant declines over the past several decades. However, many fetal losses continue to occur from intrauterine infections, lethal malformations, fetal growth retardation, and abruptio placentae. Fetal death with no identifiable specific cause is another consideration when dealing with these cases. Other risk factors can include maternal, sociodemographic, and medical care factors. The authors reviewed all forensic cases referred for autopsy to the Forensic Section of the Medical University of South Carolina, Medical Examiners' Office over the 10-year period 1990-1999. All cases listed as fetal death or stillbirth were included. The 42 cases were analyzed as to fetus' gestational age, sex, race, weight, location of delivery, history of prenatal care, maternal drug use, chromosomal abnormalities, cause and manner of death, and autopsy findings. The black:white ratio was approximately 2:1, and the male:female ratio was virtually 1:1. Most fetuses were older than 20 weeks' gestational age, with one third between 20 and 29 weeks. The majority were externally normal aside from maceration. Only 7.5% had congenital anomalies. Twenty-one of 38 placentas were grossly and microscopically normal. Of cases with toxicologic analysis, 21% were positive for drugs, and 17% were positive for cocaine/benzoylecgonine. The manner of death was classified as natural (28), accident (2), and undetermined (12). Few studies have reported the specific causes of fetal death, and the lack of uniformity in data collection and classification of causes of fetal death has made comparisons difficult. The authors present this retrospective study to better determine the factors leading to fetal demise in the hope of assisting death investigators in this challenging arena.


Fetal Death/epidemiology , Adolescent , Adult , Female , Fetal Death/etiology , Forensic Anthropology , Gestational Age , Humans , Male , Medical Records , Pregnancy , Retrospective Studies , Risk Factors , Socioeconomic Factors , South Carolina/epidemiology
9.
Am J Forensic Med Pathol ; 22(3): 292-5, 2001 Sep.
Article En | MEDLINE | ID: mdl-11563743

Anaphylactic reactions involve contact with an antigen that evokes an immune reaction that is harmful. This type of reaction is a rapidly developing immunologic reaction termed a type I hypersensitivity reaction. The antigen complexes with an IgE antibody that is bound to mast cells and basophils in a previously sensitized individual. Upon re-exposure, vasoactive and spasmogenic substances are released that act on vessels and smooth muscle. The reaction can be local or systemic and may be fatal. The authors report the death of a 19-year-old white male who had a history of "multiple allergies," including pets, molds, and penicillin. One morning, he and his friends made pancakes with a packaged mix that had been opened and in the cabinet for approximately 2 years. The friends stopped eating the pancakes because they said that they tasted like "rubbing alcohol." The decedent continued to eat the pancakes and suddenly became short of breath. He was taken to a nearby clinic, where he became unresponsive and died. At autopsy, laryngeal edema and hyperinflated lungs with mucous plugging were identified. Microscopically, edema and numerous degranulating mast cells were identified in the larynx. The smaller airways contained mucus, and findings of chronic asthma were noted. Serum tryptase was elevated at 14.0 ng/ml. The pancake mix was analyzed and found to contain a total mold count of 700/g of mix as follows: Penicillium, Fusarium, Mucor, and Aspergillus. Witness statements indicate that the decedent ate two pancakes; thus he consumed an approximate mold count of 21,000. The decedent had a history of allergies to molds and penicillin, and thus was allergic to the molds in the pancake mix. The authors present this unusual case of anaphylaxis and a review of the literature.


Anaphylaxis/pathology , Food Contamination , Mitosporic Fungi/isolation & purification , Adult , Anaphylaxis/etiology , Aspergillus/isolation & purification , Autopsy , Fusarium/isolation & purification , Humans , Male , Mucor/isolation & purification , Penicillium/isolation & purification
10.
Circulation ; 104(3): 352-7, 2001 Jul 17.
Article En | MEDLINE | ID: mdl-11457757

BACKGROUND: Echocardiographic contrast media have been used to assess myocardial perfusion and to enhance endocardial definition for improved assessment of left ventricular (LV) function. These methodologies, however, have been qualitative or have required extensive offline image analysis. Power modulation is a recently developed imaging technique that provides selective enhancement of microbubble-generated reflections. Our goal was to test the feasibility of using power modulation for combined quantitative assessment of myocardial perfusion and regional LV function in an animal model of acute ischemia. METHODS AND RESULTS: Coronary balloon occlusions were performed in 18 anesthetized pigs. Transthoracic power modulation images (Agilent 5500) were obtained during continuous intravenous infusion of the contrast agent Definity (DuPont) at baseline and during brief coronary occlusion and reperfusion and were analyzed with custom software. At each phase, myocardial perfusion was assessed by calculation, in 6 myocardial regions of interest, of mean pixel intensity and the rate of contrast replenishment after high-power ultrasound impulses. LV function was assessed by calculation of regional fractional area change from semiautomatically detected endocardial borders. All ischemic episodes caused detectable and reversible changes in perfusion and function. Perfusion defects, validated with fluorescent microspheres, were visualized in real time and confirmed by a significant decrease in pixel intensity in the left anterior descending coronary artery territory after balloon inflation and reduced rate of contrast replenishment. Fractional area change decreased significantly in ischemic segments and was restored with reperfusion. CONCLUSIONS: Power modulation allows simultaneous online assessment of myocardial perfusion and regional LV wall motion, which may improve the echocardiographic diagnosis of myocardial ischemia.


Coronary Circulation , Echocardiography/methods , Image Processing, Computer-Assisted , Myocardial Ischemia/diagnostic imaging , Ventricular Function, Left , Animals , Balloon Occlusion , Contrast Media , Disease Models, Animal , Echocardiography/instrumentation , Feasibility Studies , Fluorocarbons , In Vitro Techniques , Male , Microspheres , Myocardial Ischemia/physiopathology , Predictive Value of Tests , Reproducibility of Results , Swine , Ventricular Function, Left/physiology
11.
Am J Forensic Med Pathol ; 22(2): 155-9, 2001 Jun.
Article En | MEDLINE | ID: mdl-11394749

Overlaying, the accidental death by smothering caused by a larger individual sleeping on top of an infant, is a cause of death that has been documented for centuries. The hazard of death has been reported to be greater in infants less than 5 months of age but may occur in children up to the age of 2 years. When an adult or older child rolls on top of an infant, mechanical asphyxia results. The face may be pressed into the mattress or into the body of the sleeping adult or older child. The infant's air may be expressed, and he or she is unable to cry due to pressure on the thorax and the inability to inhale. Some pathologists and investigators believe that the victims of overlaying have no pertinent physical findings at autopsy and that any injury is indicative of inflicted trauma. Others believe that one may see contusions and abrasions from overlaying in and of itself. Wedging is another form of accidental mechanical asphyxia that may have negative autopsy findings. The prevalence of bruising, contusions, or facial and ocular petechiae is not clear. The author reviewed all pediatric forensic cases referred for autopsy to the Forensic Section of the Medical University of South Carolina/Medical Examiners' Office over the past 15 years, from 1985 to 1999. Of these, all cases of overlaying, cases listed as undetermined sudden infant death syndrome versus overlaying, and wedging were included. The cases were analyzed as to victims' age, sex, race, location/bedding, bed-sharer, and whether the bed-sharer was known to have ingested drugs or alcohol before sleep. Postmortem physical findings were also reviewed, particularly for documentation of contusions, abrasions, or facial or ocular petechiae. By clarifying not only the victim, bed-sharer, and scenario but also the presence or absence of physical findings in cases of overlaying, wedging, and other accidental asphyxia, we can better categorize these cases.


Accidents, Home/statistics & numerical data , Asphyxia/pathology , Sudden Infant Death/pathology , Asphyxia/epidemiology , Autopsy , Female , Humans , Infant , Infant, Newborn , Male , Medical Records , North Carolina/epidemiology , Retrospective Studies , Sudden Infant Death/epidemiology
12.
Am J Forensic Med Pathol ; 22(2): 169-72, 2001 Jun.
Article En | MEDLINE | ID: mdl-11394752

The suicide rate in the 65-year and older age group has been increasing since 1980. The elderly attempt suicide less often than younger people but are successful more often. The authors retrospectively reviewed all cases referred to the Forensic Pathology Section of the Medical Examiners' Office at the Medical University of South Carolina (Charleston, SC) from January 1988 through December 1997. The cases of suicide in victims 65 years and older totaled 78, accounting for 11.5% of all suicides reviewed. Of these 78 cases, 41% were autopsied and 59% were externally examined. All of the cases were initially analyzed as to age, race, sex, and method of suicide. Files also were reviewed to determine time of year of the suicide, toxicology results, psychiatric history, social history, medical history, and whether a suicide note was left. The ages of these suicide victims ranged from 65 to 94 years; men comprised 85% of the victims, and whites, 94%. The male-to-female and white-to-black ratios were 6:1 and 15: 1, respectively. The average age of the victim was 73 years. Gunshot wound was the most common method of suicide, accounting for 80.7% of the cases. Other methods included overdose (6.4%), hanging (3.8%), fall from height (2.6%), incised wounds (2.6%), drowning (2.6%), and carbon monoxide poisoning (1.3%).


Suicide/statistics & numerical data , Aged , Aged, 80 and over , Female , Humans , Male , Medical Records , Retrospective Studies , South Carolina/epidemiology
13.
Am J Forensic Med Pathol ; 22(2): 173-6, 2001 Jun.
Article En | MEDLINE | ID: mdl-11394753

Postmortem examination may be useful in establishing the cause of sudden unexpected death. In many instances, however, limitations of staffing, budget, and time may force the pathologist to triage cases to external examination rather than autopsy. A rapid assay for cardiac troponin T (cTnT) to document suspected cardiac-related deaths may optimize the use of the time and resources of the autopsy pathologist. Peripheral blood was sampled percutaneously before each of 40 autopsies and placed in the well of the Cardiac T Rapid Assay unit in accordance with the included instructions, and the results were read after 15 minutes. The assay result, decedent age, postmortem interval, and evidence of cardiopulmonary resuscitation were tabulated and subsequently correlated with the cause of death. On final sign-out of each of the autopsies, the cause of death was determined to be cardiac-related (n = 20) versus the cause in non-cardiac control subjects (n = 20). This determination was made while the investigators were blinded to the cTnT assay result. Of the 20 cardiac deaths, 17 (85%) showed positive results for cTnT compared with 6 (30%) false-positive results among the 20 control cases; this result was statistically significant according to the chi-square test. In the over-50 age group, the sensitivity of this assay in detecting cardiac-related death was 91%, with a specificity of 86%. Perimortem cardiopulmonary resuscitation did not appear to result in false-positive results. In the appropriate setting, this rapid assay for cTnT can provide valuable data supportive of a cardiac-related death. This inexpensive test may best be used in triaging sudden deaths in persons over 50 to external examination versus complete autopsy.


Death, Sudden, Cardiac/pathology , Troponin T/blood , Adult , Autopsy , Cause of Death , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Sensitivity and Specificity
14.
Am J Forensic Med Pathol ; 22(2): 184-7, 2001 Jun.
Article En | MEDLINE | ID: mdl-11394756

A 10-year retrospective study of pediatric toxicologic deaths was performed at the Medical University of South Carolina (Charleston, SC) from January 1989 to December 1998. During this time, 709 pediatric forensic autopsies were performed on children younger than 18 years of age. Eleven deaths were determined to be secondary to toxic exposures (excluding carbon monoxide poisonings secondary to fires). The remaining deaths were reviewed for the presence of alcohol or illicit drugs. The 11 toxicologic deaths were analyzed for age, sex, race, type of toxic exposure, cause and manner of death, location of incident, witness, and, in the younger age group, the primary caregiver at the time of exposure. The deaths had a bimodal age distribution (6 deaths in victims ages 15 to 17 and 5 deaths in victims ages 4 or younger), involving a wide range of toxins. The teenage group was composed of five males and one female, all white. The preschool group had three females and three males, all black. The manner of death ranged from accidental to suicidal to homicidal. In addition, in eight neonatal and fetal deaths, the victims tested positive for maternal cocaine use, and five of these victims tested positive for cocaine or benzoylecgonine. However, the cause of death was not stated to be cocaine in any of these neonatal and fetal cases.


Poisoning/epidemiology , Accidents/statistics & numerical data , Adolescent , Autopsy , Child, Preschool , Female , Fetal Death/epidemiology , Homicide/statistics & numerical data , Humans , Infant , Male , Medical Records , Poisoning/pathology , Pregnancy , Retrospective Studies , South Carolina/epidemiology , Suicide/statistics & numerical data
15.
Neuropsychopharmacology ; 25(1): 149-56, 2001 Jul.
Article En | MEDLINE | ID: mdl-11377928

Tyrosine availability can influence dopamine (DA) synthesis in highly electrophysiologically active DAergic neurons, such as those innervating the medial prefrontal cortex (MPFC). Whether tyrosine concentrations can also affect MPFC extracellular DA concentrations, measured in vivo, is not known. Since clozapine preferentially activates mesocortical DA neurons, we posited that tyrosine administration to a clozapine-pretreated rat would enhance the clozapine-induced augmentation of MPFC extracellular DA concentrations. Tyrosine alone (25-50mg/kg IP) did not affect mesocortical or striatal extracellular DA concentrations measured by in vivo microdialysis. Given 30 minutes after clozapine (10 mg/kg), tyrosine (50 mg/kg) significantly prolonged the clozapine-induced increase in MPFC extracellular DA concentrations but had no effect in the striatum. In contrast, tyrosine (50 mg/kg) significantly prolonged the haloperidol (1 mg/kg) induced increase in striatal extracellular DA concentrations but had no effect in the MPFC. These data constitute the first in vivo evidence that administration of tyrosine can selectively potentiate the clozapine-evoked increase in mesocortical extracellular DA concentrations.


Antipsychotic Agents/pharmacology , Clozapine/pharmacology , Dopamine Antagonists/pharmacology , Dopamine/biosynthesis , Haloperidol/pharmacology , Prefrontal Cortex/drug effects , Tyrosine/pharmacology , Animals , Dose-Response Relationship, Drug , Drug Combinations , Drug Interactions/physiology , Extracellular Space/drug effects , Extracellular Space/metabolism , Male , Microdialysis , Neostriatum/drug effects , Neostriatum/metabolism , Neural Pathways/drug effects , Neural Pathways/metabolism , Neurons/drug effects , Neurons/metabolism , Prefrontal Cortex/metabolism , Rats , Rats, Sprague-Dawley , Substantia Nigra/drug effects , Substantia Nigra/metabolism , Time Factors , Tyrosine/metabolism
16.
Am J Physiol Heart Circ Physiol ; 280(5): H1954-62, 2001 May.
Article En | MEDLINE | ID: mdl-11299194

Genetically modified mice have created the need for accurate noninvasive left ventricular mass (LVM) measurements. Recent technical advances provide two-dimensional images adequate for LVM calculation using the area-length method, which in humans is more accurate than M-mode methods. We compared the standard M-mode and area-length methods in mice over a wide range of LV sizes and weights (62-210 mg). Ninety-one CD-1 mice (38 normal, 44 aortic banded, and 9 inherited dilated cardiomyopathy) were imaged transthoracically (15 MHz linear transducer, 120 Hz). Compared with necropsy weights, area-length measurements showed higher correlation than the M-mode method (r = 0.92 vs. 0.81), increased accuracy (bias +/- SD: 1.4 +/- 27.1% vs. 36.7 +/- 51.6%), and improved reproducibility. There was no significant difference between end-systolic and end-diastolic estimates. The truncated ellipsoid estimation produced results similar in accuracy to the area-length method. Whereas current echocardiographic technology can accurately and reproducibly estimate LVM with the two-dimensional, area-length formula in a variety of mouse models, additional technological improvements, rather than refinement of geometric models, will likely improve the accuracy of this methodology.


Echocardiography/standards , Hypertrophy, Left Ventricular/diagnostic imaging , Hypertrophy, Left Ventricular/pathology , Myocardium/pathology , Animals , Aorta , Cardiomyopathy, Dilated/diagnostic imaging , Cardiomyopathy, Dilated/pathology , Chronic Disease , Disease Models, Animal , Echocardiography/methods , Echocardiography/statistics & numerical data , Female , Heart Ventricles/pathology , Male , Mice , Mice, Inbred Strains , Mice, Transgenic , Observer Variation , Reproducibility of Results
17.
Am J Physiol Heart Circ Physiol ; 280(4): H1770-81, 2001 Apr.
Article En | MEDLINE | ID: mdl-11247791

Echocardiographic diagnosis of myocardial ischemia is based on visualizing hypokinesis, which occurs late in the ischemic cascade. We hypothesized that temporal changes in endocardial motion may constitute sensitive early markers of ischemia. Two protocols were performed in 19 anesthetized pigs. Protocol 1 included 54 intracoronary balloon occlusions. Transthoracic images were acquired at baseline and every 15 s during 5 min of occlusion and reperfusion. In protocol 2, ischemia was induced in 12 animals by use of graded dobutamine infusion, after creating significant partial occlusions without a resting wall motion abnormality. Systolic and diastolic endocardial motion was color encoded using color kinesis and analyzed using custom software. All ischemic episodes caused detectable and reversible changes. The earliest sign of ischemia was tardokinesis in 31/54 occlusions, whereas hypokinesis appeared first in 23/54 cases. Dobutamine-induced ischemia caused tardokinesis first in 9/12 and hypokinesis in 3/12 animals. Reversible ischemic changes in regional left ventricular performance can be objectively detected using analysis of echocardiographic images and will likely improve the early noninvasive diagnosis of acute ischemia.


Hemodynamics/physiology , Myocardial Ischemia/physiopathology , Ventricular Dysfunction, Left/physiopathology , Ventricular Function, Left/physiology , Animals , Coronary Circulation/drug effects , Coronary Circulation/physiology , Coronary Vessels , Diastole , Dobutamine/pharmacology , Echocardiography , Electrocardiography , Endocardium/physiology , Endocardium/physiopathology , Heart Rate , Hemodynamics/drug effects , Image Processing, Computer-Assisted , Male , Myocardial Ischemia/complications , Myocardial Reperfusion , Swine , Systole , Time Factors , Ventricular Dysfunction, Left/etiology
19.
J Forensic Sci ; 45(6): 1256-8, 2000 Nov.
Article En | MEDLINE | ID: mdl-11110178

Suicide is a complex phenomenon associated with psychological, biological, and social factors, claiming approximately 30,000 lives each year in the United States. We retrospectively reviewed all cases referred to the Medical Examiners' Office/Forensic Pathology Section at the Medical University of South Carolina from January 1988 to December 1997. The cases of suicide totaled 678. All of the cases were analyzed as to age/race/sex, method of suicide, time of year, and toxicological results. Files were also reviewed to determine if the victim left behind a suicide note. The ages ranged from 12 to 94 years; males comprised 79.5% of the victims, and whites 78.3%. The male to female and white to black ratios were both 3.9:1. The most common methods were gunshot wounds, accounting for 64.6% of the cases. No correlation existed with time of year, and the number of cases was not increased around major holidays. The group of victims 65 years and older and the pediatric group under the age of 18 were also examined separately.


Suicide/statistics & numerical data , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Child , Female , Forensic Medicine , Humans , Incidence , Male , Middle Aged , Retrospective Studies , Seasons , Sex Factors
20.
Arch Pathol Lab Med ; 124(7): 1080-2, 2000 Jul.
Article En | MEDLINE | ID: mdl-10888788

Traditionally, the finding of semen, that is, spermatozoa and acid phosphatase, in cervicovaginal specimens has been considered the laboratory evidence needed to prove recent sexual contact. Recent research with fluorescence in situ hybridization (FISH) has shown that in the absence of semen, male epithelial and inflammatory cells can be found within the female genital tract. A striking paucity of literature exists pertaining to the examination of the penis of an alleged assailant for potential evidence indicative of sexual assault. The current study uses FISH to analyzepostcoital swabs of the penis for such laboratory evidence. A male and female volunteer couple consented to participate in this study. Following coitus, the male partner presented to one of the investigators for penile swabbing. Swabs were taken at varying postcoital intervals (1-24 hours) subsequent to 10 coital episodes. The male participant was instructed not to shower following coitus, but to otherwise go about daily activities until specimen collection. To obtain each sample, 4 sterile cotton-tipped applicators were slightly moistened in sterile saline and swabbed along the length of the penile shaft and around the base of the penis. From the swabs, 3 air-dried slides were prepared, coded, and blinded. As controls, swabs were taken from the buccal surfaces of both volunteers. Multicolor FISH was performed using dual X- and Y-chromosome probes, and slides were counterstained with 4'-6-diamidino-2-phenylindole (DAPI). Cells were easily visualized under a fluorescent microscope, but only cells with 2 nonoverlapping fluorescent signals were counted. Fluorescence in situ hybridization is highly sensitive and specific, and the dual probes easily distinguished between male and female cells. Female cells were identified on smears from every penile swab over the entire 1- to 24-hour postcoital interval. The FISH technique, previously successful in identifying male cells within the female genital tract, may also be employed on penile swabs. Once the presence of female cells is confirmed by FISH, the identity of the female can be confirmed by DNA analysis. Potentially, with such current molecular analyses, both the assailant and the victim can be positively identified.


Coitus , In Situ Hybridization, Fluorescence , Penis/cytology , Rape/diagnosis , Cytodiagnosis/methods , Female , Forensic Medicine/methods , Humans , Male , X Chromosome/genetics , Y Chromosome/genetics
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