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Biomedical subjects

K A Collins

Publications and source records attributed to K A Collins.

At least 19 recordsLinked to original sources

Combined assessment of myocardial perfusion and regional left ventricular function by analysis of contrast-enhanced power modulation images.

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.

Animals↗

Tyrosine augments acute clozapine- but not haloperidol-induced dopamine release in the medial prefrontal cortex of the rat: an in vivo microdialysis study.

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.

Animals↗

Death by overlaying and wedging: a 15-year retrospective study.

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↗

Elderly suicide: a 10-year retrospective study.

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%).

Aged↗

A rapid postmortem cardiac troponin T assay: laboratory evidence of sudden cardiac death.

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.

Adult↗

Pediatric toxicologic deaths: a 10-year retrospective study.

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.

Accidents↗

Persistence of spermatozoa and prostatic acid phosphatase in specimens from deceased individuals during varied postmortem intervals.

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.

Acid Phosphatase↗

Fetal death. A 10-year retrospective study.

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.

Adolescent↗

An unusual case of anaphylaxis. Mold in pancake mix.

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.

Adult↗

Interaction between the Drosophila CAF-1 and ASF1 chromatin assembly factors.

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.

Animals↗

Detection of regional temporal abnormalities in left ventricular function during acute myocardial ischemia.

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.

Animals↗

Accuracy of echocardiographic estimates of left ventricular mass in mice.

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.

Animals↗

Phenotypic manifestation in a child with 46,X,der(X)t(X;1)(q24;q31.1).

We report on a 5-year-old girl with multiple congenital anomalies, developmental delay, and a de novo unbalanced translocation between chromosomes X and 1[46,X,der(X)-t(X;1)(q24;q31.1)] resulting in partial trisomy 1q and partial monosomy Xq. The karyotype shows inactivation of the abnormal X chromosome. The translocated portion of 1q remains active in the tissues studied. This is the third case report with partial trisomy 1q and partial monosomy Xq. However, it is the first with specific breakpoints at 1q31.1 and Xq24.

Abnormalities, Multiple↗

Formation of charge-transfer complexes from neutral bis(porphyrin) sandwiches.

Lanthanide(III) bis(porphyrin) sandwich complexes of octaethyltetraazaporphyrin (OETAP) were synthesized and characterized by UV-vis, IR, and NMR spectroscopies. Cyclic voltammetry results indicate that these neutral sandwich complexes are very easily reduced. Charge-transfer reactions were performed in solution with Ln-(OETAP)2 sandwiches and zirconium(IV) bis(porphyrin) sandwiches. The lanthanide sandwiches partially oxidize the zirconium sandwiches in solution, and a solvent dependence of the charge-transfer reaction was observed. The solid-state properties of these charge-transfer materials were also studied. Magnetic susceptibility results suggest weak intermolecular interactions between the sandwiches. The conductivities of the charge-transfer species are greatly improved relative to those of the insulating undoped sandwiches, but the conductivities are in the lower semiconducting region. The low conductivity values are thought to be due to poor intermolecular overlap.

Journal Article↗

Isolation and identification of female DNA on postcoital penile swabs.

After sexual assault, cells originating from the assailant may be recovered from the victim. Through polymerase chain reaction (PCR)-based technology, positive scientific identification of the assailant may be made from these cells. Described is a prospective study describing a method for positively identifying cells from a female sex partner obtained from postcoital swabs of the penis of the male sex partner. Swabs were taken from the penis of a man at 1- to 24-hour intervals after coitus. DNA was isolated from each swab through standard organic extraction methods. The presence of female DNA was detected using the gender-specific amelogenin marker. Extracted DNA was amplified for eight different genetic loci using the Promega PowerPlex kit (Promega) and Amplitaq Gold (Perkin Elmer). Amplified samples were electrophoresed on precast sequencing gels (Hitachi) and were analyzed fluorescently using Hitachi's FMBIO 2 fluorescent scanner and software. Each sample obtained from a penile swab or condom was compared to male and female buccal controls. Female DNA was isolated from all postcoital penile swabs as determined by exclusive amplification of the X-chromosome specific 212 base pair amelogenin marker. In all cases, scientific identification of the female DNA from the swabs was determined by coamplification of eight STR loci (PowerPlex) and was compared to female and male control profiles. Cells shed from a female victim during sexual intercourse can be retrieved from the penis of a male offender after sexual intercourse during a 1- to 24-hour postcoital interval. DNA can be extracted from these cells and can be used to scientifically identify the female sexual participant through PCR-based technology. It is suggested that penile swabs be taken from alleged perpetrators of sexual assaults to associate them with a female victim.

Amelogenin↗

Identification of female cells in postcoital penile swabs using fluorescence in situ hybridization.

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↗

Isolation and identification of male and female DNA on a postcoital condom.

BACKGROUND: Identification of male perpetrators of sexual assault may be made from cells and fluids recovered from postcoital condoms. To date, the focus has been on identifying the person who had worn the condom. OBJECTIVE: To describe a method for scientifically identifying both the male and female participants in a sex act by employing polymerase chain reaction-based technology on swabs taken from the internal and external surfaces of a condom. Fluorescence in situ hybridization may be used to screen for the presence of female cells on a condom. METHODS: Swabs were taken from the internal and external surfaces of a condom 8 hours postcoitus. DNA was isolated from each swab through standard organic extraction. Extracted DNA was amplified for 8 different genetic loci using the Promega PowerPlex kit and the sex identification amelogenin marker. Amplified samples were electrophoresed on precast sequencing gels and analyzed fluorescently using a Hitachi FMBIO 2 fluorescent scanner and software. Each DNA sample obtained from the condom was compared with male and female buccal controls. At the time of collection, air-dried slides were prepared from the swabs for subsequent multicolor fluorescence in situ hybridization using dual X- and Y-chromosome probes with 4'-6-diamidino-2-phenylindole (DAPI) counterstaining. RESULTS: A pure sample of female DNA was isolated from the external surface of the condom as determined by exclusive amplification of the X-chromosome-specific 212-base pair amelogenin marker. Swabs taken from the internal surface yielded DNA originating from the male participant. Identification was conclusive at 8 of 8 genetic loci. Fluorescence in situ hybridization identified pure populations of male epithelial cells from the internal surface of the condom and female cells from the external surface. CONCLUSIONS: Cells shed from a female during sexual intercourse can be retrieved from the external surface of a condom following sexual intercourse. Fluorescence in situ hybridization can be used to screen for the presence of female cells, and positive identification of the female sexual partner can then be made using polymerase chain reaction-based methods. We suggest that swabs taken from both surfaces of a condom used during sexual assault may be used to provide information that will definitively link the victim to the suspect.

Coitus↗