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Modulation of voltage-gated potassium (Kv) channels by protein phosphorylation plays an essential role in the regulation of the membrane properties of cells. Protein-protein binding domains, such as Src homology 3 (SH3) domains, direct ion channel modulation by coupling the channels with intracellular signaling enzymes. The conventional view is that protein kinase binding to ion channels leads to modulation by bringing the channel substrate into physical proximity to the enzyme, thereby fostering covalent modification of the channel. The SH3 domain binding-dependent functional suppression of Kv1.5 currents by Src family protein tyrosine kinases (PTKs) is considered a canonical example of this type of mechanism. In the present study we address whether the SH3-dependent binding of Src family PTKs to Shaker family Kvs mediates modulatory events that are independent of and/or dependent on Src-catalyzed tyrosine phosphorylation of the channel. We find that Src binding and tyrosine phosphorylation are each able to modulate Kv1 family macroscopic channel currents independently. SH3-dependent binding of Src leads to the suppression of both Kv1.5 and Kv1.4 (modified to contain proline-rich SH3 domain binding sites) macroscopic currents even in the absence of Src-catalyzed tyrosine phosphorylation, whereas binding-independent tyrosine phosphorylation by Src leads to the suppression of Kv1.5 macroscopic currents and the modulation of Kv1.4 inactivation kinetics.

Background: Conventional echocardiographic assessment of left ventricular wall motion is based on visual interpretation of dynamic images, which depends on readers' experience. We tested the feasibility of evaluating endocardial motion using still-frame parametric images., Methods and Results: In protocol 1, integrated backscatter images were obtained in 8 anesthetized pigs at baseline, 5, and 60 seconds after left anterior descending coronary occlusion and during reperfusion. Images from 1 cardiac cycle were analyzed offline to create a parametric image of local video intensity oscillations. Ischemia-induced changes were quantified by segmenting the parametric images and calculating regional pixel-intensity profiles. In protocol 2, parametric images were obtained from contrast-enhanced echocardiograms in 30 patients (18 with wall-motion abnormalities; 12 control subjects). "Gold standard" for wall motion was determined from independent interpretations of dynamic images made by 3 experienced reviewers. Dynamic images were independently classified by 3 inexperienced and 3 intermediate-level readers. Interpretation was then repeated in combination with parametric images. Parametric images showed a bright band in the area spanned by endocardial motion, which gradually decreased in brightness and thickness in the left anterior descending territory during coronary occlusion in all animals. In patients, the agreement with the gold standard correlated with the readers' experience (68% inexperienced, 87% intermediate) and significantly improved by adding parametric images (83% and 91%, respectively)., Conclusion: Parametric imaging provides a still-frame display of regional endocardial motion, sensitive to track ischemia-induced abnormalities. When combined with dynamic images, this technique improves the accuracy of the interpretation of wall motion, especially by less experienced echocardiographers.

There is no method to objectively evaluate left ventricular (LV) function from contrast-enhanced images. We tested the feasibility of evaluating regional LV function by using power modulation imaging. In protocol 1, 9 anesthetized closed-chest pigs were studied. Images were obtained during contrast infusion at baseline, during LAD occlusion and reperfusion. In protocol 2, images were obtained in 20 patients (14 wall-motion abnormalities; 6 controls) during contrast enhancement. Off-line, frame-by-frame, semiautomated endocardial border detection was followed by color encoding of endocardial motion, followed by segmentation and calculation of regional fractional area changes. In all animals, coronary occlusions resulted in hypokinesis and decreased fractional area changes in LAD-related segments only, which were reversed during reperfusion. In patients, wall-motion analysis was in agreement with an expert reader of dynamic images in 92.5% segments, with interobserver variability of 12.5%. Color encoding of endocardial motion from contrast-enhanced power modulation images allows accurate quantitative assessment of regional LV function.

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.

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.

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.

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.

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.

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.

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.

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%).

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.

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.

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.

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.

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.

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.

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.

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.

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., (Copyright 2000 Wiley-Liss, Inc.)

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.

The assessment of the patient with peripheral vascular disease encompasses a thorough history and physical examination with the adjunctive use of the noninvasive vascular laboratory to confirm, localize, and grade lesions. The need for additional vascular testing depends upon the clinical scenario and urgency with which intervention must be undertaken with contrast angiography reserved for planning surgical intervention. While multiple noninvasive and invasive methods are available to assess the peripheral vasculature, it should be obvious that not every patient requires an exhaustive battery of tests in order to evaluate their vascular status. In general, only those tests that are likely to provide information which will alter the course of action should be performed. Differing clinical syndromes mandate the extent of peripheral vascular testing. Table 5 lists distinct clinical syndromes and presentations and the peripheral vascular testing that is likely to yield timely and cost efficient results.

More than 3 million children are abused and/or neglected each year in the United States. Unfortunately, a significant percentage of these cases result in homicide by child abuse or child neglect. Causes of death range from blunt force trauma and shaking to asphyxia to immolation. We retrospectively reviewed all pediatric forensic cases referred to the Medical University of South Carolina Forensic Pathology Section over the past 10 years, from January 1986 to December 1995. Of these, we looked only at children < or =5 years of age. The majority (342 cases, 69%) of these deaths were classified as natural, 96 (19%) as accident, and 60 (12%) as homicide. Of the homicides, we examined the cause of death; age, gender, and race of the victim; relationship to the perpetrator; time interval between injury and death; and the initial history given as to the cause of the injury. The cause of death fell into nine categories, the number one category being head trauma. Forty-five percent of the homicides were by head trauma, 12% by abdominal or body trauma, 25% by asphyxia (with half of these due to drowning), 10% by carbon monoxide poisoning or thermal injury, and the remaining 8% involving cases of neglect, stabbing, and poisoning. The majority of the homicide victims were male (67%) and black (67%). Forty-six percent were < or =1 year of age. Approximately 25% of the homicide cases were designated as shaken baby syndrome (SBS). In 97% of the cases, the assailant was known to the victim and was a family relative in 77%. Sixty-three percent of the assailants were female and 45% of the assailants were male; in 12%, the assailants were both parents, and in 1 case, the assailant remains unknown. Of the asphyxia deaths, 87% of the assailants were female. The time interval between injury and death ranged from minutes to hours in most cases to months in cases of repeated abuse and chronic injury and sequelae. The time interval between injury and the onset of symptoms remains unknown in most cases due to inconsistencies in the history and lack of credibility of the caretaker. The most common initial history given was "a fall" (20%). We report our findings of a decade of pediatric homicides to increase awareness of the common scenarios and case histories, demographics of the victims, causes of death, and perpetrators of pediatric homicide.

The number of suicides in the pediatric age group is rising, and death investigators need to be aware of the common scenarios, risk factors, and victims as they investigate such cases to properly assign the cause and manner of death. We reviewed all pediatric cases referred to the Medical University of South Carolina, Forensic Section, from January 1988 through January 1998. Thirty-one cases of pediatric suicide were analyzed with regards to age, gender, race, cause of death, surrounding circumstances, and past history. Sixty-eight percent of victims were aged 16 or 17 years, 84% were male, 68% were white, 78% used firearms to commit suicide, 81% were found within close vicinity of their home, and 26% had a documented history of mental illness. Suicide is a manner of death that is often difficult for the public to accept, especially in pediatric cases. We report our findings in this 10-year retrospective study to better understand this entity and work toward the prevention of future cases.

Foreign-body embolization is not an uncommon occurrence. However, to our knowledge, there are only ten reported cases of needle embolization associated with intravenous drug use. We report the sudden death of a 49-year-old white male with a known history of crack cocaine abuse. At autopsy, suspicious needle marks were noted on the right lower extremity. The lungs were of increased weight at 1000 and 1090 g and appeared edematous. The heart weighed 520 g and had a normal red-brown myocardium. Upon sectioning, a broken hypodermic needle of very small caliber was identified in the right ventricular myocardium protruding into the right ventricular chamber. This needle apparently traveled from the injection site to the right ventricle. The right ventricle was dilated and hypertrophied, and microscopic examination showed hyperemic myocardium surrounding the needle. Sections of lung showed numerous foreign-body type giant cells containing polarizable foreign material consistent with intravenous drug use. Toxicological analysis revealed the presence of ethanol (36 mg/dL), cocaine (0.098 mg/L), benzoylecgonine (2.16 mg/L), and morphine (0.841 mg/L). Urine and blood were positive for the presence of 6-monoacetylmorphine. Based on the toxicological analysis, the cause of death was determined to be cocaine and heroin toxicity, and the manner accidental. The needle embolus was considered an incidental finding.

Objectives: To establish the relative cost effectiveness of community leg ulcer clinics that use four layer compression bandaging versus usual care provided by district nurses., Design: Randomised controlled trial with 1 year of follow up., Setting: Eight community based research clinics in four trusts in Trent., Subjects: 233 patients with venous leg ulcers allocated at random to intervention (120) or control (113) group., Interventions: Weekly treatment with four layer bandaging in a leg ulcer clinic (clinic group) or usual care at home by the district nursing service (control group)., Main Outcome Measures: Time to complete ulcer healing, patient health status, and recurrence of ulcers. Satisfaction with care, use of services, and personal costs were also monitored., Results: The ulcers of patients in the clinic group tended to heal sooner than those in the control group over the whole 12 month follow up (log rank P=0.03). At 12 weeks, 34% of patients in the clinic group were healed compared with 24% in the control. The crude initial healing rate of ulcers in intervention compared with control patients was 1.45 (95% confidence interval 1.04 to 2. 03). No significant differences were found between the groups in health status. Mean total NHS costs were 878.06 pounds per year for the clinic group and 859.34 pounds for the control (P=0.89)., Conclusions: Community based leg ulcer clinics with trained nurses using four layer bandaging is more effective than traditional home based treatment. This benefit is achieved at a small additional cost and could be delivered at reduced cost if certain service configurations were used.

We present a case of sudden death in a 24-year-old, healthy white female who was physically active and participated in sports, including soccer. Two weeks prior to her death, an insurance physical examination revealed an abnormal electrocardiogram which demonstrated flipped T waves in the anterior leads. There was no other remarkable medical history. At autopsy, only one coronary ostium was demonstrated and it originated from the right aortic sinus. Approximately 0.8 cm from this right coronary artery (RCA) ostium, a left coronary artery (LCA) branched off the RCA at a 90-degree angle. The LCA had luminal diameter of 0.4 m but the LCA had a luminal diameter of only 0.1 cm. The LCA coursed anterior to the base of the pulmonary artery and down the anterior ventricular septum reflecting the usual course of the left anterior descending (LAD) coronary artery. The LCA and RCA paths appeared to merge or terminate at the anterior left ventricular myocardium which was discolored gray, a process that involved the inner and middle thirds of the myocardium. Based on the autopsy findings, we certified the cause of death as a probable arrhythmia due to myocardial fibrosis and dystrophic calcification resulting from complications of an anomalous hypoplastic left coronary artery. Anomalies of coronary arteries have been classified and studied at autopsy and by clinical angiography. Coronary artery anomalies can be divided into minor and major forms with major anomalies often resulting in cardiac dysfunction that may cause failure and death. Minor anomalies, in general, have no pathophysiological significance and are compatible with life. Minor anomalies include variations in number and location of coronary ostia. A single coronary ostia is exceedingly rare in hearts with no other congenital malformations. The prognostic significance can be unpredictable. A single coronary artery has the potential to be dangerous if obstructed at its main stem, or if it branches at an acute angle. Additionally, hypoplasia of one or more coronary arteries has been found to be associated with sudden death.

The experiments were designed to determine the role of pertussis toxin-(PTX) sensitive G-proteins Gi/Go in the brain and spinal cord in antinociception induced by epsilon-opioid receptor agonist beta-endorphin (beta-EP) and mu-opioid receptor agonist morphine. The effects of intracerebroventricular (i.c.v.) or intrathecal (i.t.) pretreatment with PTX on antinociception induced by morphine, beta-endorphin (beta-EP) and other selective opioid receptor agonists given i.c.v. or i.t. were studied in male ICR mice. Antinociception was assessed by the tail-flick and hot-plate tests. An i.c.v. pretreatment with PTX (0.5 microgram) caused a time- and dose-dependent attenuation of the tail-flick and hot-plate inhibition induced by i.c.v.-challenged morphine-induced antinociception. However, the same pretreatment with PTX did not affect the antinociception induced by i.c.v.-administered beta-EP. The tail-flick and hot-plate inhibition induced by selective mu-, delta- and kappa-opioid receptor agonist, DAMGO, [D-Ala2]deltorphin II and U50,488H, respectively, given i.c.v. was also attenuated by the i.c.v. pretreatment with PTX. An i.t. pretreatment with PTX (0.5 microgram) blocked markedly the tail-flick inhibition induced by morphine and beta-EP given i.c.v. However, the same treatment did not affect the hot-plate inhibition induced by beta-EP and attenuated, to a lesser degree, the hot-plate inhibition induced by morphine given i.c.v. An i.t. pretreatment with PTX blocked the tail-flick inhibition induced by selective delta 2-, alpha 2 and 5-HT receptor agonist [D-Ala2]deltorphin, norepinephrine and 5-HT, respectively, given i.t. Our results indicate that the antinociception induced by mu-, delta-, kappa-opioid receptor agonists given supraspinally is mediated by respectively opioid receptors that are coupled to PTX-sensitive Gi/Go proteins at the supraspinal sites and subsequently mediated by the activation of PTX-sensitive Gi/Go coupled receptors in the spinal cord. However, the antinociception induced by beta-EP given supraspinally is mediated by the PTX-resistant epsilon-opioid receptors at the supraspinal sites and subsequently activation of the delta 2-opioid receptors in the spinal cord that is sensitive to the pretreatment with PTX.

Although hyperkinesis is expressed in several neurological disorders, the biological basis of this phenotype is unknown. The mouse mutant coloboma (Cml+) exhibits profound spontaneous locomotor hyperactivity resulting from a deletion mutation. This deletion encompasses several genes including Snap, which encodes SNAP-25, a nerve terminal protein involved in neurotransmitter release. Administration of amphetamine, a drug that acts presynaptically, markedly reduced the locomotor activity in coloboma mice but increased the activity of control mice implicating presynaptic function in the behavioral abnormality. In contrast, the psychostimulant methylphenidate increased locomotor activity in both coloboma and control mice. When a transgene encoding SNAP-25 was bred into the coloboma strain to complement the Snap deletion, the hyperactivity expressed by these mice was rescued, returning these corrected mice to normal levels of locomotor activity. These results demonstrate that the hyperactivity exhibited by these mice is the result of abnormalities in presynaptic function specifically attributable to deficits in SNAP-25 expression.

Huntington's disease is a hereditary neurodegenerative disorder characterized by involuntary choreiform movements and progressive dementia. Although controversy exists regarding the exact risk of suicide in patients with Huntington's chorea, the literature supports an increased risk of suicide, especially in the early stages of this disease. We describe a case of homicide-suicide involving a father and son. The 60-year-old father, the homicide victim, suffered from advanced Huntington's disease; his 30-year-old son, the assailant, had a history of depression but had not been diagnosed with Huntington's disease at the time of his suicide. The psychiatric implications of this dementing disease, including the risk of suicide, are discussed. The gross, histologic, and molecular genetic features of this neurodegenerative disease are also described. The recognition of this autosomal dominantly inherited disorder at autopsy can make a profound impact on the lives of surviving family members.

Objective: The utility of fine needle aspiration biopsy (FNAB) for the diagnosis of epithelial hepatic neoplasms is now widely recognized. The liver may also play host to malignant nonepithelial stromal and lymphoreticular neoplasms, both metastatic and rarely primary. The cytomorphology of these hepatic tumors in aspiration smears is much less well known. In the current study, we examined FNAB material from hepatic lymphomas, including ancillary studies., Study Design: We collected 16 cases of lymphoma involving the liver and diagnosed by FNAB. The patients included seven women and nine men, with ages ranging from 34 to 84 years. Nine patients did not have a diagnosis of lymphoma prior to FNAB. In all cases, aspiration smears were stained by both Diff-Quik and Papanicolaou stain., Results: Dispersed, monomorphic lymphoid cells were usually numerous, whereas benign hepatocytes were scanty. In addition to the lymphoid appearances of individual cells, helpful clues included the presence of lymphoglandular bodies and the absence of true intercellular cohesion. There were 6 large cell, 3 immunoblastic, 2 small cell, 1 small cell cleaved, 2 mixed cell and 2 unclassified lymphomas in our FNAB series. Immunocytochemical studies were performed on 9 aspirated specimens, flow cytometry on 4 and gene rearrangement on 1. All these ancillary studies supported the cytomorphologic diagnosis of lymphoma, with approximately 90% classified as of B-cell lineage. All seven subsequent histologic examinations were confirmatory., Conclusion: Other entities that must be considered in the FNAB differential diagnosis of hepatic lesions are nonlymphoreticular small cell neoplasms, inflammatory processes and sinusoidal hematopoietic cells. FNAB with ancillary studies can successfully establish the diagnosis of involvement of the liver by lymphoma.

We have previously demonstrated that the antinociception induced by morphine and beta-endorphin given intracerebroventricularly (i.c.v.) is mediated by the stimulation of respective mu- and epsilon-opioid receptors. The effects of i.c.v. pretreatment with pertussis toxin on the antinociception induced by morphine and beta-endorphin given i.c.v. were studied in male ICR mice. Antinociception was assessed by the tail-flick and hot-plate tests. Pretreatment with pertussis toxin (0.5 microgram) given i.c.v. 96 h earlier blocks the antinociception induced by i.c.v. administered morphine in both tail-flick and hot-plate tests. The same pretreatment did not affect the antinociception induced by i.c.v. administered beta-endorphin. Our results indicate that morphine-, but not beta-endorphin-induced antinociception is mediated by pertussis toxin sensitive G-proteins.

The expression of intercellular adhesion molecule 1 (ICAM-1), a molecule pivotal in many inflammatory and immune paracrine interactions, has been highly correlated with malignant melanoma (MM) progression. Because numerous parallels exist between tissues of neural crest origin and the immune system in the regulation of postmitotic cell survival, ICAM-1 expression was studied in MM and compared with that of B-cell lymphoma/leukemia 2 protein (bcl-2 oncoprotein), an important regulator in prolonging lymphoid cell survival by blocking programmed cell death. Frozen sections from 33 cases were studied by immunoperoxidase techniques: 14 primary MM (five in situ), nine metastatic MM (one epidermotropic), four melanocytic nevi, and six normal skin controls. The percentages of the cells that stained and their intensities (0-4+) were graded. Both ICAM-1 (90%, 3-4+) and bcl-2 (95%, 2-4+) were strongly expressed in all nine metastases, including the epidermotropic disease extension. Bcl-2 strongly decorated the tumor cells in all 14 cases of primary MM (80%, 2-4+); in the five in situ MM, bcl-2 stained the atypical melanocytes at the dermal-epidermal junction (DEJ) and throughout the epidermis (75%, 1-2+). In contrast, ICAM-1 was negative in the in situ MM. ICAM-1 expression became strong (85%, 2-4+) in the dermal component of early invasive disease. Both ICAM-1 and bcl-2 were expressed in melanocytic nevi, decreasing in intensity deep within the dermis as the nevus cells senesced ("matured"). Only bcl-2 was expressed in the normal melanocytes of the six skin controls. These data show that bcl-2 is constitutively expressed in normal melanocytes and melanocytic nevi and persists in the transformed cells of early and late MM. ICAM-1 is expressed only after dermal involvement occurs, both in melanocytic nevi and in invasive MM; it persists in metastatic disease. The coexpression of bcl-2 and ICAM-1 demonstrates another similarity between the immune and neural crest systems, but it does not define or necessarily imply any functional interaction between the two proteins. The intercellular relationship of these two molecules, if any, remains to be investigated.

In a prospective blinded controlled study, the efficacy of fluorescence in situ hybridization (FISH) to detect non-sperm male cells verifying sexual contact was examined. Cervicovaginal smears (CVS) from 40 women with reported post-coital intervals were examined for sperm by cytology and for sperm and non-sperm male cells by FISH using X and Y chromosome specific DNA probes. Fluorescence in situ hybridization identified sperm and/or non-sperm male cells in all specimens from women with positive coital histories, including when the partner had a vasectomy. Male cells were also detectable by FISH in CVS up to 3 weeks after coitus. In comparison, cytology identified sperm in 41% of the positive coital history cases, and none beyond 2 weeks. Fluorescence in situ hybridization is highly sensitive and specific in detecting male cells, and can be performed rapidly on routine CVS. Application of this technique can provide new and additional evidence of sexual contact when current tests are inconclusive.

The antinociception induced by beta-endorphin given supraspinally has been previously demonstrated to be mediated by the stimulation of epsilon-, but not mu-, delta- or kappa-opioid receptors in rats and mice. The present study was designed to determine what types of opioid receptors in the spinal cord are involved in the antinociception induced by intrathecally (i.t.) administered beta-endorphin. Antinociception was assessed by the tail-flick test in male Sprague-Dawley rats. CTOP (0.9-6.6 nmol), a selective mu-opioid receptor antagonist, or nor-BNI(13.6-95.3 nmol), a selective kappa-opioid receptor antagonist, given i.t. dose-dependently reversed i.t. administered beta-endorphin-induced inhibition of the tail-flick response. On the other hand, naltrindole (6.6-44.4 nmol), a selective delta-opioid receptor antagonist, or beta-endorphin (1-27) (1-6.7 nmol), a selective epsilon-opioid receptor antagonist given i.t., did not antagonize the inhibition of the tail-flick response induced by i.t. administered beta-endorphin. The results are consistent with the previous study in mice [Tseng LF and Collins KA (1992) Eur J Pharmacol 214: 59-65] that the antinociception induced by beta-endorphin given i.t. is mediated by the stimulation of mu- and kappa-, but not delta- and epsilon-opioid receptors.

Germ cell tumors (GCT) are neoplasms that originate predominately in the ovary and testis. Tumors of germ cell origin only very uncommonly arise in extragonadal sites. We have diagnosed ten primary malignant extragonadal GCT arising in the mediastinum, retroperitoneum, liver, and sacrococcygeal region by fine-needle aspiration biopsy (FNAB). Patient ages ranged from 1 to 54 years; the majority were males. Our series included three seminomas, three yolk sac tumors (YST), one choriocarcinoma, one embryonal carcinoma, and two mixed, poorly differentiated GCT. In aspirates, seminomatous elements are dissociated with uniform mononucleate cells having large vesicular nuclei and prominent nucleoli. A tigroid background is produced with Diff-Quik-stained smears. YST yields cohesive clusters of cells with large nuclei, vacuolated cytoplasm, and extracellular hyaline matrix (spheres or hyaline globules). Giant multinucleate tumor cells are seen in choriocarcinoma. Embryonal carcinoma yields cellular smears of hyperchromatic cells with scant cytoplasm arranged predominantly in glandular or papillary formations. Ultrastructural (four cases) and immunocytochemical (seven cases) studies of aspirated material corroborated our cytologic interpretations. Aneuploid tumor cells were found by flow cytometry in aspirated material from a YST. Subsequent histologic examinations were performed on eight, and all were confirmatory. Although extragonadal GCT are relatively uncommon, they need to be considered in FNAB material from midline mass lesions. Ancillary studies were useful in confirming their diagnosis.

The antinociception induced by beta-endorphin given supraspinally has been previously demonstrated to be mediated by the release of [Met5]enkephalin acting on delta-opioid receptors in the spinal cord. The present study was designed to determine what type of opioid receptors in the spinal cord is involved in beta-endorphin-induced antinociception in the rat. Antinociception was induced by beta-endorphin (0.6 nmol) given into nucleus raphe obscurus and was assessed by the tail-flick test in pentobarbital-anesthesized rats. Naltriben (0.6-6.0 nmol), a selective delta 2-opioid receptor antagonist, given intrathecally dose-dependently attenuated beta-endorphin-induced inhibition of the tail-flick response. On the other hand, 7-benzylidene naltrexone (2.1-64.3 nmol), CTOP (D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2, 0.09-2.8 nmol), or nor-binaltorphimine (1.4-40.8 nmol), selective delta 1-, mu-, and kappa-opioid receptor antagonists, respectively, did not block beta-endorphin-induced antinociception. The results of present study in rats are consistent with previous experiments in mice indicating that spinal delta 2-, but not delta 1-, mu- or kappa-opioid receptors are involved in beta-endorphin-induced inhibition of the tail-flick response.

The antinociceptive effects induced by beta-endorphin and morphine given supraspinally have been previously demonstrated to be mediated by the activation of different neural mechanisms. The present experiments were to examine the effects of intraventricular administration of beta-endorphin and morphine in mechanical paw-withdrawal and thermal tail-flick nociceptive tests in rats of 2-28 days of age. 2-4-day-old neonates were not responsive to i.c.v. injection of beta-endorphin or morphine for the inhibition of the tail-flick response. The thermal antinociceptive responses induced by beta-endorphin and morphine started to develop in 7-14-day-old rats and continued to increase at 21-28 days. The inhibition of the mechanical paw-withdrawal response to beta-endorphin was already present in 2-day-old rats and morphine in 4-day-old rats. The mechanical antinociception progressively increased and reached a plateau at 7 days of age for beta-endorphin and 28 days of age for morphine. beta-Endorphin was found to be more efficacious than morphine in producing mechanical antinociception. The results demonstrate that beta-endorphin- and morphine-induced antinociception to mechanical and thermal stimuli develops differently and are consistent with the hypothesis that two descending pain inhibitory systems activated by beta-endorphin and morphine are differentially developed.

Impulsive killers often use whatever instrument is close at hand in the perpetration of their deed. We describe a homicidal death, first thought to be accidental, in a rural sawmill where the assailant manipulated a large board of wood into a machine known as a bull-edger (which cuts logs into rough boards) in such a fashion as to cause the death of his work partner. The physics of the events at the scene as well as the subsequent investigation are discussed.

Gastroesophageal reflux with aspiration of feedings in infants and young children may be involved in the development of chronic lung damage. Our laboratory has utilized tracheal aspirates stained with oil red O to identify and quantitate lipid-laden alveolar macrophages as a marker of such aspiration. During the last 10 years, we have evaluated 244 tracheal aspiration smears in children. Although a few patients were up to 3 years old, the vast majority were infants. The cytologist looked for the presence of and the number of oil red O-positive macrophages on tracheal aspirate smears. The specimens were easily assigned grades of absent (grade = 0), low positive (grade 1: 1-25 lipid-laden macrophages), moderate positive (grade 2: 26-50 lipid-laden macrophages), and high positive (grade 3: > 50 lipid-laden macrophages). The grade was then correlated with the positive or negative clinical diagnosis of gastroesophageal reflux with aspiration. We believe the cytologic evaluation and grading of oil red O-stained tracheal aspirates for lipid-laden macrophages is valuable in identifying these patients with gastroesophageal reflux and aspiration.

Lymphomas are malignant neoplasms of cells native to lymphoid tissue that can arise anywhere in the body. Angiotropic large cell lymphoma (ALCL) is characterized by a proliferation of neoplastic mononuclear cells within the lumina of small blood vessels. The clinical manifestations are usually neurologic, including progressive dementia and nonlocalizing deficits, cutaneous infiltration, adrenal masses, or fever of unknown origin. The diagnosis is made at autopsy or on skin biopsy, brain biopsy, or other surgical resection. Differential diagnoses include metastatic malignant neoplasms and vascular tumors. We report the case of a 63-year-old white man who had neurologic signs and symptoms as well as dyspnea. Autopsy revealed ALCL involving multiple organ systems, including the central nervous system. Diagnostic techniques currently used to confirm the nature of this malignant neoplasm include immunohistochemistry, ultrastructural analysis, cytogenetics, and molecular biologic studies.

Air embolism secondary to vaginal insufflation has been documented as a cause of death in pregnant women. Under pressure, the air enters the uterus, causing air emboli within the uterine venous drainage and subsequently the systemic circulation. Death is usually sudden as the air obstructs the normal flow of circulation. Acute cocaine toxicity is also a well-known cause of sudden death. Cocaine use is prevalent in our society, even among pregnant women. We report the sudden death of a 31-year-old gravid female and 39-week gestational age male fetus. The cause of death was air embolism secondary to oral-vaginal insufflation of cocaine smoke.

The identification of spermatozoa or constituents of seminal fluid is critical in the evaluation of alleged sexual assault victims. However, failure to identify sperm and/or elevated levels of acid phosphatase can occur for a variety of reasons. Molecular techniques, such as molecular cytogenetic analysis offers new approaches to improve on the identification of male cells in alleged sexual assault cases. Fluorescence in situ hybridization (FISH) with a Y chromosome specific DNA probe was applied to archival cervicovaginal smears from 41 alleged sexual assault cases to identify Y-bearing (male) cells. FISH identified Y-bearing sperm and non-sperm cells in 78% of the cases previously confirmed to have sperm. FISH also identified Y-bearing non-sperm male cells in 39% of the cases in which cytology did not detect spermatozoa; in one of these instances, it also detected sperm. Cervicovaginal acid phosphatase levels, determined at the time of the cervicovaginal smears, were also compared with the presence or absence of Y-positive cells. Application of this technique can detect non-spermatozoic male cells in routine cervicovaginal smears of sexual assault victims.