Antecedents of euthanasia and suicide among older women.

OBJECTIVES: To identify the characteristics of older women who sought Jack Kevorkian's assistance in dying and to compare them with those of an age-matched sample who committed suicide. METHOD: This retrospective case-control study compared all 18 women age 55 and older who died with the assistance of Jack Kevorkian and whose deaths were investigated in Oakland County, Michigan from 1995 to 1997 with all 15 women age 55 and older who committed suicide in the same county during the same time period. We coded 203 variables in 7 domains from medical examiner files, including autopsy findings. RESULTS: Significantly more of Kevorkian's cases had amyotrophic lateral sclerosis or multiple sclerosis (p = .018), a recent decline in health (p = .031), or inadequately controlled pain (p = .041). Women who committed suicide had more prevalent chronic illnesses and were more likely to have been diagnosed with clinically significant depression or other psychiatric disorders (p = .023). Both groups were significantly less likely to be married (p < .001) and more likely to be divorced (p < .001) than US Census data would predict. CONCLUSIONS: The different vulnerabilities of older women who want to die and either commit suicide or seek assistance deserve continued careful research. Poorly controlled pain was a factor in seeking assistance in dying, and depression and psychiatric disorders characterized older women who committed suicide in our study. Not having a spouse may increase isolation and reinforce the hopelessness of women who are living with catastrophic illness.

A comparison of characteristics of Kevorkian euthanasia cases and physician-assisted suicides in Oregon.

PURPOSE: The sociodemographic and clinical characteristics of Kevorkian euthanasia cases were compared with Oregon physician-assisted suicide (PAS) cases and U.S. mortality data. DESIGN AND METHODS: Two hundred variables were coded from medical examiner reports on all 69 Kevorkian euthanasia cases who died and were autopsied by the Oakland County Medical Examiner. Data on the 43 Oregon PAS cases in the first two years and U.S. mortality data were obtained from published sources. RESULTS: Only 25% of patients euthanized by Kevorkian were terminally ill as compared to 100% of Oregon PAS cases. PAS cases were significantly more likely to have cancer (72%) than euthanasia cases (29%). Women and those who were divorced or had never married were significantly more likely to seek euthanasia than would have been predicted by national mortality statistics. IMPLICATIONS: Gender and marital status appeared to influence decisions to seek an assisted death, and research on the role of these factors in end-of-life decision making is merited.

An update on the Kevorkian-Reding 93 physician-assisted deaths in Michigan: is Kevorkian a savior, serial-killer or suicidal martyr?

This report presents an update of the Kevorkian-Reding physician-assisted (or physician-aided) deaths to include the ninety-three publicly acknowledged cases as of November 25, 1998. These deaths are divided into ten distinct time phases. The following trends emerge. Over two-thirds of the decedents are women, the ratio of females to males varying widely with phase. The proportion of women seems to be the highest when Kevorkian is free to act as he wants and lowest when he seems to be acting under legal or political restraints. Based on autopsy results, only 29.0 percent of the cases are terminal, this percentage being higher among men (37.9%) than among women (25.4%). However, 66.7% of the decedents were disabled, no significant difference emerging between men and women. Further, five out of the six decedents showing no apparent anatomical sign of disease at autopsy were women. Over 80 percent of the physician-assisted deaths are cremated, approximately twice as high a proportion as that emerging for suicides in Michigan and four times as high as cremations occurring with regard to overall deaths. Finally, death by carbon monoxide decreases dramatically with time phase while the use of the contraption dubbed the "suicide machine" increases, suggesting an increasing routinization over time. Finally, during the ninth and tenth phases, Kevorkian's aims and his own suicidality emerge more clearly involving 1) harvesting organs and 2) threat of starving himself in prison if he is convicted. Phase 10 can be seen as an escalation from assisted death to overt euthanasia, repeating the same need for a demonstration (Thomas Youk) that was first exhibited in Phase I (Janet Adkins).

Acute coronary artery thrombosis in a postpartum woman receiving bromocriptine.

A 35-year-old postpartum woman who was receiving bromocriptine (Parlodel) for only several days to suppress lactation experienced an episode of a seizure, complained of chest pains, and died in the emergency department. At autopsy, acute coronary thrombosis of the left main, left anterior descending, and circumflex arteries was found. Cases of reported cardiac-related complications associated with bromocriptine use in the puerperium are extremely rare. The mechanism of bromocriptine-related acute coronary thrombosis is poorly understood and warrants further scrutiny, because the synthetic brominated ergopeptide is generally regarded as safe. The updated review of reports available in literature mandates the acknowledgment of possible serious and even lethal cardiac events as a result of untoward effects of bromocriptine.

Expression of immunologically relevant endothelial cell activation antigens on isolated central nervous system microvessels from patients with multiple sclerosis.

Activation of the vascular endothelium is thought to be an important facet of inflammation, thrombosis, and vasculitis. Activated endothelial cells express a number of immunologically relevant surface markers not expressed by normal endothelial cells. Many of these surface antigens are thought to augment adhesion reactions and migration. Our results show that endothelial activation may play a central role in the pathogenesis of multiple sclerosis (MS). Normal human central nervous system microvessels isolated from autopsy material do not express endothelial cell activation markers, including the adhesion proteins vascular cell adhesion molecule-1 (VCAM-1) and endothelial cell leukocyte adhesion molecule-1 (E-selectin/ELAM-1). They exhibit little to no constitutive expression of immunoreactive intercellular adhesion molecule-1 (ICAM-1) or the urokinase plasminogen activator receptor. Control microvessels exhibit no major histocompatibility complex (MHC) class II antigen. MS microvessels express significant levels of MHC class II antigens, ICAM-1, VCAM-1, and urokinase plasminogen activator receptor. E-selectin was expressed by 3 of 5 MS brains tested. Histologically unaffected areas of MS brain expressed less VCAM-1, ICAM-1, and E-selectin than did microvessels from periplaque zones. However, MHC class II antigens and urokinase plasminogen activator receptor were increased in areas exhibiting little to no evidence of leukocyte infiltration. When microvessels were examined for dual expression of activation markers, we found that in periplaque areas, 50% of microvessels coexpressed HLA-DR and VCAM-1, 28% of microvessels coexpressed HLA-DR and urokinase plasminogen activator receptor, and 43% of microvessels coexpressed HLA-DR and ICAM-1.

Expression of endothelial cell activation antigens in microvessels from patients with multiple sclerosis.

Although the mechanisms governing EC activation are not well understood, evidence points to a role for locally released cytokines from activated leukocytes. We propose that the sequence of events that result in EC activation are important in perivascular leukocyte infiltration into the CNS seen in MS. In the present study we examined expression of EC activation antigens on cerebral microvessels from patients with MS using immunofluorescence staining and quantitation by laser cytometry. Normal human microvessels do not express MHC class II antigens (Ags), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), or the urokinase plasminogen activator receptor (uPA-R). They express low levels of transferrin receptors and express factor VIII. Microvessels prepared from MS brain with plaque involvement expressed decreased factor VIII and increased transferrin receptors (tfR). Expression of the adhesion molecules VCAM-1, and ICAM-1 were found on 80% of isolated microvessels. HLA-DR Ags were expressed on 40-60% of microvessels, and the uPA-R was expressed on 50% of MS microvessels examined. MHC class II Ags co-express with VCAM-1 and ICAM-1 more frequently than with the uPA-R. Results indicate that activation of EC in MS is likely to be an important factor in disease pathology.

Variability of the territories of the major cerebral arteries.

Recent morphological and functional studies on the circle of Willis suggest that the areas of supply of the six major cerebral arteries show a considerable variation in distribution, in contrast to the relatively consistent pattern generally accepted; therefore, the cortical and intracerebral distribution of the territories of these arteries was investigated in 25 unfixed human brains obtained at routine autopsy. The six major cerebral arteries were simultaneously injected under the same pressure with different-colored Araldite F mixtures under standardized conditions to obtain the most realistic territorial distribution. The cortical boundaries were examined and recorded in relation to the cerebral gyri and sulci, and the territories of the anterior, middle, and posterior cerebral arteries were analyzed and compared. The intracerebral distribution of these territories was investigated after the injected brains were cut in parallel slices. The variability of the territories of these arteries was much larger than generally described in the literature. Twenty-six variations in the territory of the anterior cerebral artery, 17 variations in the area of the middle cerebral artery, and 22 variations in the area of the posterior cerebral artery were found in the cortex of 50 hemispheres. Intracerebrally, the anterior, middle, and posterior cerebral arteries contributed in varying degrees to the blood supply of the lobar white matter, the internal capsule, the caudate nucleus, and the lentiform nucleus. The large variation in the area in which the cortical and intracerebral boundaries between these territories was located was demonstrated by illustrating the minimum and maximum extent of each. The results are compared with prior findings, and their implications for both experimental model studies and clinical practice are discussed.

Microsurgical anatomy of the lower basilar artery.

This study was designed to study the microvascular anatomy of the basilar artery between the superior cerebellar artery and the vertebrobasilar junction (i.e. the lower basilar artery). Twenty unfixed brains were injected with silicone rubber solution and studied with a Zeiss OPMI microscope. The length of this segment of the basilar artery was 28.1 + 1.35 mm and its course was straight in 9 (45%) brains, curved in 7 (35%) and tortuous in 4 (20%). The total number of perforators found in 20 brains was 340 with an average of 17 per brain. Of these, 118 (34.7%) were median and 222 (65.2%) were lateral. Median branches had a mean length of 5.8 + 1.25 mm, whereas left and right lateral branches had a mean length of 16 + 1.25 mm and 16 + 1.58 mm respectively.

Preprotachykinin gene expression in the human basal ganglia: characterization of mRNAs and pre-mRNAs produced by alternate RNA splicing.

The nature and distribution of preprotachykinin (PPT, i.e. substance P/neurokinin A-encoding) gene expression in human basal ganglia was determined. Northern blot analysis visualized a single band of approximately 1300 bases, confirming the postmortem stability of PPT mRNA. Gross anatomical analysis indicated that PPT gene expression was relatively evenly distributed throughout the human caudate and putamen, but absent in the globus pallidus and substantia nigra. Nuclease protection analysis of these tissues established that human PPT mRNA consisted of approximately 80-85% beta-PPT (exon 1-7 derived) mRNA and 15-20% gamma-PPT (minus exon 4), with no alpha-PPT (minus exon 6) mRNA detected; these data contrast with the proportions of PPT mRNAs seen in non-human species. The incompletely spliced PPT RNA species detected in basal ganglia accounted for approximately 8% of total human PPT RNA and suggested a fixed order of exon splicing. Since various PPT mRNAs encode different combinations of tachykinin peptides with distinct biological activities, the markedly different proportions of PPT mRNAs seen in human basal ganglia compared to non-human tissues may be of physiological significance.

Selective deep hypothermia of the spinal cord prevents paraplegia after aortic cross-clamping in the dog model.

We tested, in the dog, the hypothesis that selective deep hypothermia (19 degrees to 12 degrees C) of the spinal cord protects it from the ischemia that follows double aortic cross-clamping. The extracorporal perfusion system consisted of heat exchanger and a pump, infusing saline solution at 5 degrees C into the subarachnoid space (L-6) and draining it through the cisterna magna. After 30 minutes this system cools a normally perfused spinal cord to a stable temperature gradient of 13 degrees C (inflow) to 18 degrees C (outflow). Proximal and distal intrathecal, proximal and distal aortic, and central venous pressures were continuously recorded. Rectal temperature was maintained between 36.5 degrees C and 38.5 degrees C. Eight control dogs had cross-clamping of the aorta below the left subclavian artery and above the diaphragm without cord hypothermia. Nine experimental dogs had cord hypothermia initiated 50 minutes before systemic heparinization (100 U/kg) and double cross-clamping of the aorta. Cross-clamping was maintained for 45 minutes. The aorta was then unclamped, heparin was reversed, cord cooling was discontinued, and the dura was closed. Hindlimb function of animals was graded by use of Tarlov's scale at recovery and 24 hours later. The dogs were then killed, and the cords were removed and fixed for microscopy. All control animals were paraplegic and had histologic confirmation of spinal cord infarction. All experimental animals had intact hindlimb function and normal appearing cords on histologic examination. A two-tailed Fisher's exact test (chi square) shows this difference to be significant to p = 0.00004. In the dog selective deep hypothermia of the cord avoids the ischemic injury induced by aortic cross-clamping that results in paraplegia. The implications of these findings in thoracoabdominal aortic clamping in humans is discussed.

Anatomy of the sympathetic pathways in the carotid canal.

The sympathetic fibers in the carotid canal were studied in 30 unfixed specimens from human cadavers. Thirty petrous internal carotid arteries were injected with red silicone rubber, and the course of the sympathetic fibers was examined after removal of the inferior and superior wall of the carotid canal. The internal carotid artery was removed completely, leaving the sympathetic fibers intact as much as possible. Instead of a plexus-like configuration of the sympathetic fibers around the petrous carotid artery in all specimens, an anterosuperior group and a posteroinferior group of sympathetic fibers were found together, and both closed on the inferior-anterior side of the terminal portion of the horizontal part of the carotid canal. Seventy-three percent of the anterosuperior group of sympathetic fibers consisted of one large bundle, and 27% consisted of two smaller bundles. The majority of the posteroinferior group of sympathetic fibers consisted only of one bundle (93%). In 60% of the specimens, the majority of sympathetic fibers in the carotid canal were found in the anterosuperior group, 20% were found in the posteroinferior group, and in 20%, there was an equal distribution. The formation of the petrous bone and the related structures of the skull base play an important role in the configuration of these groups of sympathetic fibers. This study shows that, in cases of operative intervention in the carotid canal, the anterosuperior group of sympathetic fibers may be encountered. Damage to this bundle may result in sympathicoparesis, as it often contains the most sympathetic fibers. This group of sympathetic fibers can be easily separated from the internal carotid artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Microvascular anatomy of foramen caecum medullae oblongatae.

The foramen caecum (FC) is a triangular-shaped fossa situated in the midline on the base of the brain stem, at the pontomedullary junction. Although this area is known to have a very high concentration of brainstem perforating vessels, its microvascular anatomy has not been studied in detail. The purpose of this study was to detail the microvasculature of this territory. Twenty unfixed brains were injected with silicone rubber solution and dissected under a microscope equipped with a camera. The origin, course, outer diameter, and branching pattern of the perforators were examined. The total number of perforators found in the 20 brains was 287, with an average (+/- standard deviation) of 14.35 +/- 1.24 perforators per brain (range seven to 28). Their origin was as follows: right vertebral artery in 52 perforators (18.11%); left vertebral artery in 35 (12.19%); basilar artery below the anterior inferior cerebellar artery (AICA) in 139 (48.43%); basilar artery above the AICA in 46 (16.02%); AICA in 10 (3.48%); and anterior spinal artery in five (1.74%). Most of the perforators arose as sub-branches of larger trunks; their average outer diameter was 0.16 +/- 0.006 mm while that of trunks was 0.35 +/- 0.02 mm. These anatomical data are important for those wishing 1) to study the pathophysiology of vascular insults to this area caused by atheromas, thrombi, and emboli; 2) to plan vertebrobasilar aneurysm surgery; 3) to plan surgery for vertebrobasilar insufficiency; and 4) to study foramen magnum neoplasms.

Effect of aging on tyrosine hydroxylase protein content and the relative number of dopamine nerve terminals in human caudate.

This study examined the effect of aging on the relative number of dopamine (DA) nerve terminals in human caudate nucleus, their content of tyrosine hydroxylase (TH) protein, and the relative abundance of TH monomers with different molecular weights. Preliminary studies on brain tissue cryopreservation, performed with rat striatum, indicated that intact synaptosomes can be prepared from fresh tissue slowly frozen in 0.32 M sucrose with 5% dimethyl sulfoxide and then thawed rapidly prior to synaptosome preparation. Synaptosomes were prepared in this manner from postmortem caudate nucleus tissue obtained from normal humans 1 month to 63 years of age. To determine the relative number of DA nerve terminals for each individual, dopaminergic synaptosomes were selectively labeled with a monoclonal antibody to TH and quantified by fluorescence-activated cell sorting. To determine the relative amount of TH protein for each individual, the concentration of TH protein in the same synaptosomal preparations was determined using immunoblots. Our results suggest that caudate TH levels plateau soon after birth and tend to remain relatively stable during aging, since no changes in either the relative number of TH-containing nerve terminals or the concentration of TH protein were found in subjects 15-63 years of age. In light of previous studies showing an age-related loss of DA cell bodies, these findings suggest that remaining DA neurons compensate to maintain caudate levels of TH protein and TH-containing nerve terminals. Immunoblot studies identified three forms of TH monomer (60.6, 61.7, and 65.1 kDa), indicating that mRNAs coding for high molecular mass forms of TH may be actively translated in human brain. No age-related differences in the relative abundance of these forms were found.

Heterogeneity of the T-cell receptor beta gene rearrangements generated in myelin basic protein-specific T-cell clones isolated from a patient with multiple sclerosis.

Seventeen T-cell clones derived from the peripheral blood of a patient with multiple sclerosis and reactive with a synthetic peptide corresponding to residues 152-170 of the human myelin basic protein molecule were previously shown to be cytotoxic for myelin basic protein-coated target cells. Genetic restriction studies have now demonstrated that these clones recognize myelin basic protein in association with human leukocyte antigen DRw13. Studies of the T-cell receptor beta gene rearrangements generated by these clones demonstrated 12 different patterns, as evaluated by Southern blot analysis. Thus, the human T-cell response to myelin basic protein is exceedingly heterogeneous, even among T cells that recognize the same small fragment of the molecule in association with the same class II restriction element.

The anterior cavernous sinus space.

The anterior cavernous sinus space is the venous space anterior to the cavernous carotid artery. It is tetrahedral in shape with the anterior apex at the superior orbital fissure. The superomedial wall is formed by the base of the anterior clinoid process. The inferomedial wall is formed by the sphenoid bone. The lateral wall consists of two layers of dura with the oculomotor, trochlear, ophthalmic and abducens nerves in the inner layer. Medially, the posterior wall consists of the cavernous carotid artery. Laterally, it communicates with the lateral cavernous sinus space. Paraclinoid and carotid cave aneurysms may occupy this space and its microanatomy is important in the surgery of these aneurysms.

Characterization of herpes simplex virus type 2 latency-associated transcription in human sacral ganglia and in cell culture.

The ability of herpes simplex virus type 2 (HSV-2) to establish latency in and reactivate from sacral dorsal root sensory ganglia is the basis for recurrent genital herpes. The expression of HSV-2 genes in latently infected human sacral ganglia was investigated by in situ hybridization. Hybridizations with a probe from the long repeat region of HSV-2 revealed strong nuclear signals overlying neurons in sacral ganglia from five of nine individuals. The RNA detected overlaps with the transcript for infected cell protein O but in the opposite, or "anti-sense," orientation. These observations mimic those made previously with HSV-1 in human trigeminal ganglia and confirm the recent findings during latency in HSV-2-infected mice and guinea pigs. Northern hybridization of RNA from infected Vero cells showed that an HSV-2 latency-associated transcript was similar in size to the larger (1.85 kb) latency transcript of HSV-1. Thus, HSV-1 and HSV-2 latency in human sensory ganglia are similar, if not identical, in terms of their cellular localization and pattern of transcription.

Effect of cocaine on rat pineal melatonin synthesis in vivo and in vitro.

Moderate concentrations (10 microM) of cocaine increased melatonin content and N-acetylserotonin and serotonin-N-acetyltransferase activity in rat pineal glands freshly placed in organ culture. Pineals cultured for 48 hours or taken from ganglionectomized animals did not respond to cocaine. Both procedures markedly reduced pineal noradrenalin (NA). Cocaine (5, 10, 20 mg/kg) given to adult intact rats stimulated pineal melatonin synthesis but only in animals exposed to constant light for 24 hours. Pineal denervation and/or adrenal demedullation neither completely eliminated NA from blood nor prevented cocaine-induced stimulation of melatonin synthesis in these light-primed animals.