Recent advances in atypical antipsychotics.
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Biomedical subjects
Publications and source records attributed to D J Miller.
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Unexpectedly low levels of mitochondrial DNA (mtDNA) cytochrome b sequence divergence are found between species of the scleractinian coral genus Acropora. Comparison of 964 positions of the cytochrome b gene of two out of the three Caribbean Acropora species with seven of their Pacific congeners shows only 0.3-0.8% sequence difference. Species in these biogeographic regions have been evolving independently for at least three million years (since the rise of the Isthmus of Panama) and this geological date is used to estimate nucleotide divergence rates. The results indicate that the Acropora cytochrome b gene is evolving at least 10-20 times slower than the 'standard' vertebrate mtDNA clock and is one of the most slowly evolving animal mitochondrial genes described to date. The possibility is discussed that, unlike higher animals, cnidarians may have a functional mtDNA mismatch repair system.
Liver transplantation for patients with a history of substance abuse remains controversial. Resumption of heavy alcohol use postoperatively is a threat to long-term survival, but recidivism among transplanted alcoholics is reportedly low. An argument against psychological evaluation prior to transplantation revolves around the speculation that candidates will attempt to portray themselves as more desirable prior to listing with UNOS (United Network for Organ Sharing). This study measured psychological distress, coping styles, optimism, selected personality features, and perception of family environment among 73 U.S. military veterans who were candidates for liver transplantation. Candidates with positive histories of substance abuse revealed significantly more distress, less adaptive coping styles, and more character pathology than their counterparts. The only significant difference according to UNOS listing was on one measure of family environment. Results support preoperative psychological assessment and intervention on a more extensive level for substance abusers and raise questions for future research.
The acrosome reaction is an exocytotic process that enables a sperm to penetrate the zona pellucida and fertilize an egg. The process involves the fenestration and vesiculation of the sperm plasma membrane and outer acrosomal membrane releasing the acro somal contents. Many different methods have been devel oped to detect the acrosomal status of sperm. These techniques are sometimes complicated, costly, and can be used on only a few species. The aim of this study was to develop an efficient and inexpensive method to assess the acrosomal status of sperm from a variety of species. We prepared and fixed sperm from humans, cattle, swine, rabbits, guinea pigs, and mice and stained them with Coomassie G250. The acrosomes were stained intensely blue in color. Following capacitation, some sperm were incubated for 1 hr with 10 microM calcium ionophore A23187 to induce the acrosome reaction. They were also stained with Coomassie G-250. Ionophore-treated sperm lacked Coomassie staining over the acrosomal region. Differential interference contrast (DIC), bright field microscopy or Pisum sativum agglutinin staining confirmed that the acrosomes of sperm from these species were reacted in response to calcium ionophore treatment and the acrosome reaction frequencies matched results with Coomassie staining. These results demonstrate that the acrosomal status of mammalian sperm from several species can be determined easily and reliably using this simple Coomassie Blue G-250 staining method.
The binding of sperm to the zona pellucida is an integral part of the mammalian fertilization process, investigated most extensively in the mouse. Several sperm receptors for the murine zona pellucida have been studied (Snell WJ, White JM. 1996. Cell 85:629-637; Wassarman PM. 1999. Cell 96:175-183), but the most compelling evidence exists for beta-1,4-galactosyltransferase (GalTase). Considering that GalTase is present on the surface of porcine sperm (Larson JL, Miller DJ. 1997. Biol Reprod 57:442-453), we investigated the role of GalTase in porcine sperm-zona binding. Sperm surface GalTase catalyzed the addition of uridine diphosphate-[(3)H]galactose to the 55 kDa group of the porcine zona pellucida proteins implicated in sperm binding, demonstrating that GalTase binds the porcine zona. The functional importance of GalTase-zona pellucida binding was tested. Addition of uridine diphosphate galactose, a substrate that completes the GalTase enzymatic reaction and disrupts GalTase mediated adhesion, had no effect on binding of sperm to porcine oocytes. Furthermore, removal of the GalTase zona ligand by incubation of oocytes with N-acetylglucosaminidase had no effect on binding of sperm to oocytes. These results suggest that GalTase is not necessary for sperm to bind to the zona pellucida. Digestion of isolated porcine zona proteins with N-acetylglucosaminidase did not affect the biological activity of soluble porcine zona proteins in competitive sperm-zona binding assays, suggesting that GalTase alone is not sufficient to mediate sperm-zona attachment. From these results, it appears that, although GalTase is able to bind porcine zona proteins, its function in porcine sperm-zona binding is not necessary or sufficient for sperm-zona binding. This supports the contention that porcine sperm-zona binding requires redundant gamete receptors.
This study uses the 1988 National Health Interview Survey (NHIS) data to examine the effects of both heavy and problem drinking as well as moderate or light parental alcohol use on children's behaviour problems. The analysis is formulated within Becker's household production function framework. The production of child behavioural health is estimated using items from the Behavior Problems Index, a battery of 32 questions about behaviour problems which is derived from the Child Behavior Checklist (CBCL), a widely-used parent report instrument. Measures of parents' alcohol consumption are constructed from the NHIS Alcohol Supplement that was administered to one randomly selected adult in each household in 1988. Ordinary least squares (OLS) and two-stage least squares (TSLS) results are presented. The results provide consistent evidence that parental alcohol use is an input with negative marginal product in the production of child behavioural health, regardless of which parent drinks. The magnitude of the effect is generally larger in the TSLS specification. There is also strong evidence of relationships between some family structure variables and child behavioural health and between parental physical health and child behavioural health.
This study aimed to determine structural alterations occurring in cardiac myofilaments after exogenous application of oxidants and the effects of oxidants on contractile protein function in a rabbit coronary artery ligation model of heart failure. Myocardial "stiffness" was higher in the ligated animals (Lig) than sham-operated controls (Sh, 4.9+/-1.5 versus 1.6+/-0.8 mN.mm-1). Superoxide anion (O2-) exposure decreased active stiffness in both groups, whereas hypochlorous acid (HOCl) had no effect in Lig but increased stiffness in Sh. Resting stiffness was higher in Lig than Sh (0.6+/-0.2 versus 0.2+/-0.1 mN.mm-1), remaining unchanged after O2- exposure but increasing after HOCl in both groups. The frequency at minimum stiffness was lower in Lig than Sh (0.9+/-0.2 versus 1. 7+/-0.6 Hz) and was reduced in both groups after oxidant exposure. Myofilament calcium sensitivity (pCa50) was not altered by O2- in Sh but increased in Lig (pCa50 increased from 5.41+/-0.05 to 5.56+/-0. 06). Protease contamination in the xanthine oxidase used to generate O2- did not affect myofilament ultrastructure at the concentrations used here. These data demonstrate that contractile proteins from "failed" myocardium have a similar response to exogenously applied oxidants as controls and that application of protease-contaminated xanthine oxidase system does not degrade the contractile protein structure.
Barriers to high blood pressure (HBP) care and control have been reported in the literature for > 30 years. Few reports on barriers, however, have focused on the young black man with HBP, the age/sex/race group with the highest rates of early severe and complicated HBP and the lowest rates of awareness, treatment, and control. In a randomized clinical trial of comprehensive care for hypertensive young urban black men, factors potentially associated with care and control were assessed at baseline for the 309 enrolled men. A majority of the men encountered a variety of barriers including economic, social, and lifestyle obstacles to adequate BP care and control, including no current HBP care (49%), risk of alcoholism (62%), use of illicit drugs (45%), social isolation (47%), unemployment (40%), and lack of health insurance (51%). Having health insurance (odds ratio = 7.20, P = .00) and a negative urine drug screen (odds ratio = .56, P = .04) were significant predictors of being in HBP care. Low alcoholism risk and employment were identified as significant predictors of compliance with HBP medication-taking behavior. Men currently using illicit drugs were 2.64 times less likely to have controlled BP compared with their counterparts who did not use illicit drugs, and men currently taking HBP medication were 63 times more likely have controlled BP compared with men not taking HBP medication. Comprehensive interventions are needed to address socioeconomic and lifestyle issues as well as other barriers to care and treatment, if HBP care is to be salient and effective in this high risk group.
An issue in the design of trials in traumatic brain injury is whether variation amongst centres in 'conventional' management could mask the impact of a powerful new pharmacological agent. We report the results of an observational study of 988 patients admitted to one of four British neurosurgical units between 1986 and 1988 within 3 days of a severe head injury. The centres fell into two pairs on the basis of the 'intensity' of management. In Edinburgh and Southampton, more frequent use of intracranial pressure monitoring, ventilation and osmotic diuretics was made than in Glasgow and Liverpool. The odds ratio for an independent outcome at 6 months in Edinburgh or Southampton, relative to Glasgow or Liverpool, controlling for case mix, was 1.43 (95% CI, 1.03-1.98, p = 0.033). Thus, there is weak evidence of an association between the approach to management and clinical outcome at 6 months.
Activation of mitogen-activated protein kinase (MAPK) results in pleiotropic effects such as modulation of the transcription and activation of enzymes involved in signal transduction. One such enzyme is the cytoplasmic phospholipase A(2) (cPLA(2)), which releases arachidonic acid (AA). AA is the precursor of prostaglandins and leukotrienes, two inflammatory mediators, which regulate gene expression and protein kinase (PK) activity. Fumonisin B(1) (FB(1)) was shown to increase PKC translocation and stimulate MAPK. We have investigated the effect of FB(1) on the AA cascade in a human epithelial cell line and the signal transduction pathway regulating PLA(2) activation. We observed that FB(1) stimulated cPLA(2) activity and increased AA release by a mechanism independent of PKC activation and that the activation of cPLA(2) is a two-step process: the first is phosphorylation of cPLA(2) by MAPK; the second is a consequence of the increase in sphingosine inside and outside the cells after 2 h, which is known to induce a rise in intracellular free calcium. Overall, this suggests that the effect of FB(1) on cells is partially dependent on the action of FB(1) on the enzymes involved in the cell cycle, such as MAPK and PKA, and on bioactive fatty acids, such as the prostaglandins and leukotrienes, and also on disruption of sphingolipid metabolism. In addition, we have observed down-regulation of cPLA(2) activity and AA metabolism by a mechanism involving prostaglandin production, cAMP synthesis and PKA activation.
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OBJECTIVE AND IMPORTANCE: Vertex epidural hematomas may be underestimated or overlooked altogether when computed tomographic scans alone are used for diagnosis. Such hematomas can be resolved with active intervention and sometimes with conservative treatment. CLINICAL PRESENTATION: Two cases of successfully treated vertex epidural hematomas, in a 33-year-old man who presented with seizures and an 11-year-old girl who presented with headache and vomiting, are described. Both hematomas were traumatic in origin and were associated with cranial fractures. In each, coronal images (computed tomographic or magnetic resonance imaging scans) showed the extent of the hematoma much more clearly than did axial images. INTERVENTION: One case was treated surgically and the other conservatively. CONCLUSION: Magnetic resonance imaging is not usually indicated for trauma patients, but it is an appropriate diagnostic modality for these rare lesions, to supplement standard axial computed tomographic scans. Because vertex epidural hematomas may resolve spontaneously with time, conservative treatment should be considered on a case-by-case basis.
BACKGROUND: Dispositional optimism and adaptive coping styles have been shown to correlate with each other and with physical and psychological well-being in a number of studies with medical patients. Few studies in the transplant literature evaluate psychological characteristics of patients across medical diagnoses. A comparison of optimism and coping styles among candidates for liver and lung transplantation is presented. METHOD: Subjects were 73 candidates for lung transplantation at the University of Pittsburgh Medical Center and 76 candidates for liver transplantation at the Pittsburgh VA Healthcare System. All candidates were classified according to medical diagnosis and history of substance abuse (alcohol/drugs or smoking). There were no significant between- or within-group differences on optimism. RESULTS: There was a significant difference within both groups, according to history of substance abuse on the coping style 'acceptance'. There were also significant between-group differences on a number of coping styles. CONCLUSIONS: This preliminary study is intended to suggest direction for future research; studying psychological variables known to impact on health apart from medical diagnosis may provide data pertinent to selection criteria and the design of interventions to more effectively maximize the benefit of transplantation for all concerned.
As the number of nonagenarians increases yearly in the United States, surgeons will be asked more often to evaluate the possibility of intervention for coronary artery disease in this age group. The purpose of this study is to document experience with patients 90 years of age or older in order to determine whether coronary artery bypass grafting surgery is justified. Eleven patients aged 90 years or more underwent cardiac surgery for symptomatic coronary artery disease refractory to medical management between January 1, 1987, and December 31, 1996. All patients were in NYHA Class IV preoperatively. In-hospital death occurred in two patients (18%). In-hospital morbidity occurred in all patients (100%) including seven cardiac, four respiratory, two neurologic, and one infectious. All survivors left the hospital symptomatically improved. The mean length of stay was 28 days. Four patients died at a mean of 2 years and 2 months postoperatively. Five patients remain alive at a mean of 1 year and 7 months. Coronary artery bypass grafting in nonagenarians can be performed successfully in selected cases. However, increased mortality and morbidity rates and length of stay are associated with this age group. For survivors, the quality of life is improved and the projected life expectancy restored.
While clinical healthcare systems may have lagged behind computer applications in other fields in the shift from mainframes to client-server architectures, the rapid deployment of newer applications is closing that gap. Organizations considering the transition to client-server must identify and position themselves to provide the resources necessary to implement and support the infrastructure requirements of client-server architectures and to manage the accelerated complexity at the desktop, including hardware and software deployment, training, and maintenance needs. This paper describes an information resources assessment of the recently aligned Pennsylvania regional Veterans Administration Stars and Stripes Health Network (VISN4), in anticipation of the shift from a predominantly mainframe to a client-server information systems architecture in its well-established VistA clinical information system. The multimethod assessment study is described here to demonstrate this approach and its value to regional healthcare networks undergoing organizational integration and/or significant information technology transformations.
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Adjusting the pH of water samples before performing solid-phase microextraction (SPME) analysis can be used to selectively extract organic acids (at pH 2) and bases (at pH 12). Sorption behavior of test organics is predictable based on the acid dissociation constant in water. In general, polyacrylate (PA) and Carbowax-divinylbenzene (CW-DVB) show substantially higher fiber/water sorption coefficients (Kd values) than a polydimethylsiloxane (PDMS) coated fiber. Gas chromatography-flame ionization detection (GC-FID) detection limits with the CW-DVB sorbent are approximately 0.5 to 10 ng/ml in a 2-ml water sample for a variety of aromatic amines, phenols, and chlorinated phenols, and are approximately 1 to 50 ng/ml for the same solutes using the PA sorbent. However, the PA fiber is more selective (depending on the water pH) for the acid or base components than the CW-DVB fiber. With proper pH adjustment, the recovery of spiked aromatic amines and phenols from a surface wetlands water ranged from 73 to 118% of the known values, with a precision (R.S.D.) of approximately 5 to 20%. SPME quantitation of phenols in a coal gasification wastewater using a PA fiber also gave excellent agreement with conventional methylene chloride extraction, although continued use of a single fiber with this wastewater led to poorer precision.