Antifibrinolytic agents make alpha1- and beta2-microglobulinuria poor markers of postcardiac surgery renal dysfunction.
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Publications and source records attributed to M S Smith.
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UNLABELLED: Although the Internet has been described as "ubiquitous," little is known about the extent to which physicians have access to the Internet while providing clinical care. OBJECTIVE: To assess the extent of Internet connectivity within the clinical area of every ED within the state of Illinois. METHODS: This was a prospective observational study. Each Illinois ED listed in a published directory was called by telephone, and a responsible party was identified to provide information regarding the type and size of the ED, patient demographics, the types of personal computers (PCs) available in the ED (if any), the types of operating systems used, the availability of access to the World Wide Web (Web), and the highest speed at which an Internet connection could be established. Responses regarding the presence and types of PCs and the types of operating systems used were assessed using one-factor chi-square. Univariate and multivariate predictors of the type of PC used, the presence or absence of Web access, and the highest speed of Internet access were evaluated using optimal discriminant analysis and nonlinear classification tree analysis, respectively. RESULTS: One hundred ninety-eight of the 199 EDs in the state of Illinois (99.5%) completed the survey. Of the responding EDs, 50.5% had PCs, but only 17.6% had Web access. When Web access was available, it was most often available through a high-speed Internet connection that was faster than a dial-up modem. Most departments (68.1%) with PCs used the Windows 95 or Windows 98 operating systems. A majority (62.5%) used the Netscape browser exclusively. Larger EDs (more than six ED beds) in rural or suburban areas were more likely to have a PC compared with smaller EDs (six or fewer beds). Large EDs (more than 12 ED beds) in private tertiary care or academic hospitals were most likely to have Web access. CONCLUSIONS: Although half of Illinois EDs have PCs, only one in six has access to the Internet; thus, most emergency physicians do not have ready access to the Web from the site where they deliver clinical care.
During lactation there are many dramatic alterations in the hypothalamic-pituitary (HP) axis, as well as an increased demand for food and water. The renin-angiotensin system (RAS) is one of the major mediators of the HP axis. This study examined the receptors for ANG II in the rat brain during lactation and diestrus. Compared with diestrus, lactating rats had significant decreases in ANG II receptor binding in several forebrain regions, most notably in the arcuate nucleus/median eminence, dorsomedial hypothalamic nucleus (DMH), and lateral hypothalamic area (LHA). In contrast, there was an increase in ANG II receptor binding in the preoptic area during lactation. These significant changes in ANG II binding in the brain during lactation support the hypothesis that changes in the RAS may contribute to the dramatic changes in the HP axis during lactation. In addition, the significant reduction in ANG II binding in the DMH and LHA may be indicative of a role in the regulation of food intake, a function only recently associated with the RAS.
During lactation the suckling stimulus increases the activity of two populations of neuropeptide Y (NPY) neurons in the hypothalamus, the caudal portion of the arcuate nucleus (ARH) and the dorsomedial hypothalamus (DMH), and suppresses the activity of TIDA neurons in the ARH. In the present study, an acute resuckling model was used to examine the role of suckling-induced hyperprolactinemia in modulating the activity of these systems. Lactating rats were deprived of their eight-pup litters on day 9 postpartum, and 48 h later, the animals served either as nonsuckled controls (0 pups) or were suckled for 24 h. In addition, some of the resuckled animals received two s.c. injections of bromocriptine (0.5 mg/rat x injection), a dopamine D2 agonist, to inhibit suckling-induced PRL secretion. In situ hybridization was performed for rat NPY messenger RNA (mRNA) and tyrosine hydroxylase (TH) mRNA to provide an index for NPY and TIDA neuronal activities, respectively. Resuckling for 24 h induced a significant increase in NPY mRNA levels in the caudal portion of the ARH and in the DMH. Bromocriptine treatment did not alter the increase in NPY mRNA levels in the ARH, whereas the treatment greatly attenuated the increase in NPY mRNA in the DMH. TH mRNA levels in the rostral ARH area returned to basal levels in the nonsuckled control animals, and 24 h of resuckling significantly suppressed TH mRNA expression in this area. Bromocriptine treatment caused a significant increase in TH mRNA levels compared with those in the eight-pup suckled group. Thus, the results from the present study demonstrate that the suckling stimulus activated the two populations of NPY neurons and suppressed TIDA activity. Suckling-induced hyperprolactinemia did not participate in the increase in ARH NPY activity, whereas it played a major stimulatory role in suckling-induced activation of NPY neurons in the DMH and an inhibitory role in suckling-induced suppression of TIDA activity. The increase in TIDA activity after bromocriptine treatment was unexpected and suggests that the role of PRL in the regulation of TIDA activity is significantly altered during lactation.
Neuropeptide Y (NPY) neurons in the arcuate nucleus of the hypothalamus (ARH) have been shown to play an important role in modulating LH secretion. One mechanism by which the ARH NPY system may regulate LH secretion is by modulating GnRH neuronal function. Thus, the present study examined whether the ARH NPY system provided direct input to GnRH cell bodies in the preoptic area (POA), as well as to their nerve terminals in the median eminence (ME). The possible involvement of the NPY Y1 receptor subtype in mediating the effects of NPY was also investigated. Lactating rats were used in these studies because they have increased hypothalamic NPY content, especially in the ARH/ME areas, making it easier to detect NPY fibers and terminals. The anterograde tracer, Phaseolus vulgaris leucoagglutinin (PHA-L), was iontophoresed into the ARH of lactating rats; and triple-label immunofluorescence was performed, with the aid of confocal microscopy, to visualize NPY, PHA-L, and GnRH. GnRH cell bodies were found scattered throughout the organum vasculosum laminae terminalis (OVLT)/POA region, and NPY/ PHA-L double-labeled fibers were found in very close proximity to numerous GnRH perikarya. In the ME, double-labeled NPY/PHA-L fibers were found in the inner and external zones, and they were found in close proximity to GnRH neuronal fibers. Using a NPY Y1 specific antibody, double-label immunofluorescence was performed to examine whether the Y1 receptor subtype was expressed in GnRH neurons. No convincing Y1-positive staining was found in GnRH cell bodies in the OVLT/POA region. However, abundant Y1-positive fiber and cell staining were observed throughout the region, and Y1-positive fibers were found in close apposition to GnRH cell bodies. In contrast, numerous GnRH nerve fibers and terminals in both the OVLT and ME were colocalized with Y1-positive staining. The results of this study suggest that ARH NPY neurons come in close contact with GnRH neurons and may provide direct input to both GnRH cell bodies in the POA region and to their nerve terminals in the ME. The Y1 receptor subtype may be directly involved in NPY modulation of GnRH secretion from its nerve terminals.
Agouti-related protein (AGRP) is a recently described homolog of the skin agouti protein. AGRP is transcribed primarily in the adrenal and hypothalamus and is a high affinity antagonist of the neural melanocortin-3 and melanocortin-4 receptors. The perikarya expressing AGRP messenger RNA are found in the arcuate nucleus of the rat and rhesus monkey. Using a polyclonal antibody against the pharmacologically active domain of AGRP (amino acids 83-132), we have also characterized the distribution of AGRP-immunoreactive neurons in both species. The major fiber tracts are conserved in both species, with dense projections originating in the arcuate nucleus and proceeding along the third ventricle. Dense fiber bundles are also visible in the paraventricular, dorsomedial, and posterior nuclei in the hypothalamus, in the bed nucleus of the stria terminalis, and in the lateral septal nucleus of the septal region. AGRP-containing neurons are not visualized in a number of areas, including portions of the amygdala, thalamus, and brain stem, that express MC3-R and MC4-R messenger RNA and receive innervation from POMC neurons that serve as the source of melanocortin agonists. Thus, AGRP is most likely to be involved in modulating a conserved subset of the physiological functions of central melanocortin peptides. Based on the particular distribution of AGRP neurons, those functions are likely to include the central control of energy homeostasis.
Lactation in the rat is characterized by the suppression of pulsatile LH secretion, a large increase in food intake, and changes in energy balance due to the metabolic drain of milk production. The change in energy balance may be a major component in altering reproductive function. A number of factors may contribute to changing energy balance of a lactating animal; one is leptin, the product of adipose tissue, which is known to act partly as a satiety factor to decrease food intake. The aims of the present study were to determine whether there are changes in leptin levels during lactation, a state of high energy demand, and during periods of acute suckling in the presence or absence of changes in energy demand. Our goals were to determine whether lactation and the suckling stimulus influenced serum leptin levels and whether there was a potential role for leptin in the suppression of LH secretion during lactation. The first experiment was performed during diestrus of the estrous cycle, and chronic lactation, (day 9 post partum) in animals suckling 8 pups. The results showed that leptin levels were significantly decreased in both ovarian intact or ovariectomized lactators; this decrease parallels the suppression of pulsatile LH secretion. Serum insulin levels were not altered in the lactating animals. The second experiment was performed in ovariectomized lactators whose 8 pup litters were removed for 48 h, starting on day 9. On day 11, mothers received no pups or pups that were either nonfostered (resulting in no milk production) or fostered (resulting in milk production). The pups were allowed to suckle for 24 h. Following 24 h of acute suckling, serum leptin, and insulin levels correlated with the energy drain on the mother. The levels of leptin were normal and of insulin were elevated in mothers producing no milk. Conversely, leptin levels were suppressed and insulin levels normal in mothers producing milk. The third experiment used the same groups as described for the second experiment except that serial blood samples were collected for measurement of pulsatile LH secretion following 24 h of acute suckling. The results showed that regardless of whether leptin levels remained normal or were suppressed in response to acute suckling, pulsatile LH secretion was significantly inhibited compared with the nonsuckled control animals. In summary, these data suggest that the metabolic drain of milk production, and not the suckling stimulus itself, is the most likely factor responsible for the suppression of leptin secretion during lactation. Furthermore, although the decreased levels of leptin may be causally related to the inhibition of pulsatile LH secretion during chronic lactation, changes in leptin are not a prerequisite for the suppression of LH secretion in response to suckling.
During lactation, the levels of neuropeptide Y (NPY), which plays an important role in mediating food intake, are significantly elevated in a number of hypothalamic areas, including the arcuate nucleus (ARH). To identify additional hypothalamic systems that might be important in mediating the increase in food intake and alterations in energy homeostasis during lactation, the present studies examined the expression of agouti-related protein (AGRP), a recently described homologue of the skin agouti protein. AGRP is found in the hypothalamus and has been suggested to play an important role in the regulation of food intake. In the first experiment, animals were studied during diestrus of the estrous cycle, a stage of the cycle when estrogen levels are basal and similar to lactation, or during days 12-13 postpartum. Lactating animals had their litters adjusted to eight pups on day 2 postpartum. Brain tissue sections were used to measure AGRP messenger RNA (mRNA) levels by in situ hybridization. AGRP mRNA signal was found mostly in the ventromedial portion of the ARH, which has been shown to contain a high density of NPY neurons. A significant increase in AGRP mRNA content was observed in the mid- to caudal portion of the ARH of lactating animals compared with diestrous females. No difference was found in the rostral portion of the ARH. In the second experiment, double-label in situ hybridization for AGRP and NPY was performed in lactating animals to determine the extent of colocalization of the two peptides in the ARH, using 35S-labeled and digoxigenin-labeled antisense complementary RNA probes. It was found that almost all of the NPY-positive neurons throughout the ARH also expressed AGRP mRNA signal. Furthermore, AGRP expression was confined almost exclusively to NPY-positive neurons. Thus, the present study showed that during lactation, AGRP gene expression was significantly elevated in a subset of the AGRP neurons in the ARH. The high degree of colocalization of AGRP and NPY, coupled with previous reports from our laboratory demonstrating increased NPY expression in the ARH in response to suckling, suggests that AGRP and NPY are coordinately regulated and may be involved in the increase in food intake during lactation.
The orexigenic role of central neuropeptide Y (NPY) in nonhuman primates has been questioned. Therefore, we have studied the effect of central NPY on feeding in ad libitum-fed male rhesus macaques. NPY dose-dependently increased food intake, with the maximal effect obtained by 50 microg (960 min food intake +/- SEM, 104 +/- 5 to 188 +/- 11 g; vehicle vs. NPY; n = 6). Blood glucose levels were unaffected by intracerebroventricular administration of NPY, but animals receiving either 20 or 50 microg displayed increased plasma levels of insulin and cortisol at few time points. To assess the pharmacological specificity of this response, a novel Y1 antagonist, [(Ile,Glu,Pro,Daba,Tyr,Arg,Leu,Arg,Tyr-NH2)2 cyclic (2,4'),(2',4)-diamide] (Y1ANT), was synthesized. Receptor binding experiments demonstrated that Y1ANT preferentially binds to Y1 and Y4 receptors (pKi 10.12 +/- 0.06 and 9.11 +/- 0.05 nmol/L, respectively). Functional analysis revealed that Y1ANT is a Y1 antagonist and a partial Y4 agonist. Central administration of Y1ANT blocked NPY-induced feeding. In food-deprived monkeys, Y1ANT attenuated the feeding response. However, Y1ANT had no effect on food intake in satiated monkeys. Thus, endogenous NPY is likely to be involved in the regulation of food intake in the nonhuman primate, and this effect is at least partially mediated via Y1-like receptors.
The effectiveness of a new examination gown, as a stimulus control intervention designed to reduce distress during the pelvic exam, was investigated in a sample of sexual abuse survivors and women without abuse histories. Sixty-nine participants from a women's health ambulatory center and a private practice in gynecology were randomly assigned to the experimental gown condition or the paper drape control group. One-third of the sample reported a history of childhood sexual abuse. Survivors reported higher anxiety during exams than did women without abuse histories. Women who wore the experimental gown reported more positive emotional and physical experiences of the exam. Further research is required to examine the trend showing that survivors who wore the experimental gown reported less anxiety during the examination than survivors who wore the control drape.
The lactating rat has been shown to lack a behavioral response and immediate early gene expression (cFos) in the hippocampus (Hipc) following intravenous or intracerebroventricular administration of an N-methyl-d-aspartate (NMDA) receptor agonist. The purpose of this study is to determine whether neurons in the Hipc have an intact postsynaptic NMDA receptor system. The presence of NMDA receptor protein was determined by Western blot analysis for the NR1, NR2A, and NR2B subunits. The presence of functional NMDA receptors in the Hipc was determined by behavioral responses and the expression of cFos immunoreactivity (-ir) in response to microinjection of an NMDA receptor agonist into the hilus of the dentate gyrus. No difference in NR1 and NR2A subunit protein in the Hipc was detected between the lactating and nonlactating rats. However, there was a 26% decrease in NR2B subunit protein in this region in the lactating rat. Lactating rats receiving NMA injections displayed hyperactive behavior, similar to that observed in the nonlactating animals receiving the same treatment. The lactating rat and the nonlactating rat also displayed equivalent bilateral cFos-ir in the dentate gyrus (DG), CA1 and CA3 regions of the Hipc in response to unilateral NMA injections into the Hipc. These data indicate that the lactating rat has an intact postsynaptic NMDA receptor system. Thus, Hipc refractoriness to peripheral and third ventricular injections of an NMDA receptor agonist may reflect inhibition of presynaptic input and glutamate release.
Lactation induces an increase in NPY activity in two neuronal populations in the hypothalamus: the arcuate nucleus (ARH) and the dorsomedial nucleus (DMH) area. To determine if NPY neurons from these areas project to the paraventricular nucleus of the hypothalamus (PVH), the retrograde tracer, fluorogold (FG), was injected into the PVH of lactating females. FG-labeled NPY cells (identified by in situ hybridization for NPY mRNA) were observed throughout the ARH; however, a greater number of double-labeled cells were found in the caudal portion than the rostral portion of the ARH. Thus, NPY neurons in the caudal portion of the ARH provide the major ARH NPY input into the PVH area. If these results are combined with our previous data showing that activation of NPY neurons in the ARH during lactation is confined to the caudal portion, it is very likely that the lactation-activated NPY neurons project to the PVH. FG-labeled NPY cells were also identified in the DMH area, providing the first evidence that the NPY neurons in the DMH area activated during lactation also project to the PVH. Taken together, the increase in NPY activity may be important in modulating some of the physiological alterations occurring during lactation, such as the increase in food intake, in part through modulating PVH neuronal activity.
The reactivates of human sera with uninduced and phorbol ester (TPA)-induced human herpesvirus-8 (HHV-8)-infected BCBL-1 cells were examined by immunofluorescence assay (IFA) and by radioimmunoprecipitation reactions (RIP). The seroprevalence of HHV-8 infections is low in the United States general population and only low levels of HHV-8 antibodies were detected in the seropositive sera. In contrast, high levels of antibodies against HHV-8 lytic and latent antigens were detected by IFA in the sera from HIV+ Kaposi's sarcoma (KS)-positive individuals. These sera recognized several proteins and glycoproteins from BCBL-1 cells in RIP reactions. Two types of antibody responses were detected in the sera from HIV+ KS- homosexual men. In majority of the sera with and without detectable HHV-8 DNA in the peripheral blood mononuclear cells (PBMC), significantly low levels of HHV-8 antibodies were detected by IFA. These sera recognized only a subset of HHV-8 proteins and glycoproteins in RIP reactions. In contrast, in a subgroup of sera from HIV+ KS- homosexual men, higher levels of IFA antibodies against HHV-8 lytic and latent antigens were detected. These sera also recognized several viral proteins and glycoproteins in RIP reactions. These results suggest that antibody response profiles to HHV-8 infection vary significantly and serologic assays to detect antibody responses to a panel of both lytic and latent antibodies may be required for maximum sensitivity. Screening of a cDNA library from TPA-induced BCBL-1 cells with an HIV+ KS+ serum identified cDNAs encoding 12 HHV-8 proteins. Further characterization of these HHV-8 proteins would define the HHV-8 antigens useful for seroepidemiological studies and in discriminating lytic, latent, past, and/or reactivation infections.
Neural regeneration after grafting can be unpredictable. In an effort to enhance the return of function after cable grafting, we studied the effects of an angiogenic factor, endothelial cell growth factor (ECGF), on regenerating nerves. Cable grafts on the sciatic nerve were established in 18 rats and treated with ECGF or a control saline solution. At 5 weeks, nerve conduction studies were performed, and the animals were killed for histologic measurements of graft vascularity and axon counts. A significant increase in vascularity was noted in the treated group versus the control group; neither the axon counts nor the nerve conduction velocities differed significantly between the two groups, although the treated group appeared to show improved neural conduction compared with the control group.
The greatest advances in medicine over the next two decades will result from application of the tools and principles of informatics to the problems of clinical medicine. New developments in medical informatics will drive advances in clinical care administration, research, and education. Information flow in the emergency department a decade hence will be characterized by a transformation from a "hunter-gatherer" information model to a "publisher-subscriber" model in which the right information will always be available at the right time. In large part, information will be gathered automatically rather than manually. Computers will be ubiquitous and almost invisible. Invasive and attached monitoring and testing will yield to new remote and noninvasive technologies. Information will be shared and modified as needed, rather than recreated and reentered by each caregiver. Eventually, the use of information technologies in the emergency medicine workplace will enhance our traditional role as hands-on providers of direct patient care.
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BACKGROUND: Previously the authors showed that myocardial beta-adrenergic (betaAR) function is reduced after cardiopulmonary bypass (CPB) in a canine model Whether CPB results in similar effects on betaAR function in adult humans is not known. Therefore the current study tested two hypotheses: (1) That myocardial betaAR signaling is reduced in adult humans after CPB, and (2) that administration of long-term preoperative betaAR antagonists prevents this process. METHODS: After they gave informed consent, 52 patients undergoing aortocoronary surgery were enrolled. Atrial biopsies were obtained before CPB and immediately before discontinuation of CPB. Plasma catecholamine concentrations, myocardial betaAR density, and functional responsiveness (basal, isoproterenol, zinterol, sodium fluoride, and manganese-stimulated adenylyl cyclase activity) were assessed. RESULTS: Catecholamine levels increased significantly during CPB (P < 0.005). Myocardial betaAR adenylyl cyclase coupling decreased during CPB, as evidenced by a 21% decrease in isoproterenol-stimulated adenylyl cyclase activity (750 [430] pmol cyclic adenosine monophosphate per milligram total protein 15 min before CPB compared with 540 [390] at the end of CPB, P = 0.0062, medians [interquartile range]) despite constant betaAR density. Differential activation along the betaAR signal transduction cascade localized the defect to the adenylyl cyclase moiety. Administration of long-term preoperative betaAR antagonists did not prevent acute CPB-induced myocardial betaAR dysfunction. CONCLUSIONS: These data indicate that the myocardial adenylyl cyclase response to betaAR agonists decreases acutely in adults during aortocoronary surgery requiring CPB, regardless of whether long-term preoperative betaAR antagonists are administered. The mechanism underlying acute betaAR dysfunction appears to be direct impairment of the adenylyl cyclase moiety. Similar increases in manganese-stimulated activity before and at the end of CPB show preserved adenylyl cyclase catalytic activity, suggesting that other mechanisms (such as decreased protein levels or altered isoform expression or function) may be responsible for decreased adenylyl cyclase function.