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Biomedical subjects

L Schultz

Publications and source records attributed to L Schultz.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effects of propanolol in patients entered in the Beta-Blocker Heart Attack Trial with their first myocardial infarction and persistent electrocardiographic ST-segment depression.

OBJECTIVE/BACKGROUND: It has been shown that patients with an acute myocardial infarction and persistent electrocardiographic ST-segment depression are at high risk for subsequent cardiac events. The purpose of this retrospective analysis was to examine the long-term effects of propranolol therapy in patients with their first acute myocardial infarction and persistent electrocardiographic ST-segment depression. METHODS: The outcomes of 2877 patients enrolled in the Beta-Blocker Heart Attack Trial (BHAT) with their first myocardial infarction (75% of patients in BHAT) were reviewed. Patients were divided into three groups on the basis of presence or absence of > or =1 mm ST-segment depression in two contiguous leads of the 12-lead electrocardiogram obtained soon after admission or at the time of randomization, which occurred 10.1+/-3.5 days after the index myocardial infarction. Group 1 included 774 patients (392 randomly assigned to placebo and 382 to propranolol) with no ST-segment depression; group 2 included 1447 patients (713 placebo, 734 propranolol) with ST-segment depression at admission or at the time of randomization (labeled as transient); and group 3 included 656 patients (339 placebo and 317 propranolol) who had electrocardiographic ST-segment depression from the time of admission to the time of randomization (labeled as persistent). RESULTS: In group 3, patients with persistent electrocardiographic ST depression, the mortality rate in patients randomly assigned to placebo was 13.6% compared with 7.6% in patients with propranolol (p = 0.012; log rank test). Sudden death in the placebo arm was 9.7% compared with 4.7% in the propranolol group (p = 0.012, log rank test). The results of the Cox regression analysis, adjusting for all baseline variables with p values <0.25, showed the relative risk of overall mortality rate and the relative risk of sudden death were 2.13 ( 1.22, 3.70) and 2.56 (1.27, 5.26), respectively, for the placebo group compared with the propranolol group. Patients with persistent ST-segment depression had the greatest benefit from propranolol (47.2 fewer events [deaths/reinfarctions] per 1000 person-years compared with 78 and 2.1 fewer events in patients with transient and no ST-segment depression, respectively). CONCLUSIONS: It appears that the greatest benefit for beta-blocker therapy in patients after myocardial infarction is observed in patients with persistent ST-segment depression who are at greatest risk for death and reinfarction. Definitive conclusions regarding therapy with beta-adrenergic blocking agents in patients with persistent ST-segment depression cannot be made because our analysis, given its retrospective nature, is only hypothesis generating.

Adrenergic beta-Antagonists↗
PubMed1998

Simultaneous determination of phenytoin, carbamazepine, and 10,11-carbamazepine epoxide in human plasma by high-performance liquid chromatography with ultraviolet detection.

The Bioanalytical Chemistry Department at the Madison facility of Covance Laboratories, has developed and validated a simple and sensitive method for the simultaneous determination of phenytoin (PHT), carbamazepine (CBZ) and 10,11-carbamazepine epoxide (CBZ-E) in human plasma by high-performance liquid chromatography with 10,11 dihydrocarbamazepine as the internal standard. Acetonitrile was added to plasma samples containing PHT, CBZ and CBZ-E to precipitate the plasma proteins. After centrifugation, the acetonitrile supernatant was transferred to a clean tube and evaporated under N2. The dried sample extract was reconstituted in 0.4 ml of mobile phase and injected for analysis by high-performance liquid chromatography. Separation was achieved on a Spherisorb ODS2 analytical column with a mobile phase of 18:18:70 acetonitrile:methanol:potassium phosphate buffer. Detection was at 210 nm using an ultraviolet detector. The mean retention times of CBZ-E, PHT and CBZ were 5.8, 9.9 and 11.8 min, respectively. Peak height ratios were fit to a least squares linear regression algorithm with a 1/(concentration)2 weighting. The method produces acceptable linearity, precision and accuracy to a minimum concentration of 0.050 micrograms ml-1 in human plasma. It is also simple and convenient, with no observable matrix interferences.

Carbamazepine↗
PubMed1998

Specificity, isotype, and titer distribution of anticardiolipin antibodies in CNS diseases.

BACKGROUND AND PURPOSE: There is an association between anticardiolipin antibodies (aCL) and ischemic stroke. There are, however, also occasional reports linking aCL with other CNS diseases (OND), particularly with multiple sclerosis (MS). Hence, we studied the specificity of aCL for ischemic stroke. METHODS: Prospective, consecutively identified patients evaluated for aCL (immunoglobulin G [IgG] and immunoglobulin M [IgM] isotypes) were divided into two groups: ischemic stroke (first ever) and OND (stroke-free subjects affected by OND). RESULTS: The ischemic stroke group (n = 300) and the OND (n = 149) differed in the following risk factors: age (64 +/- 14 versus 58 +/- 15 years; p < 0.001) and proportions of African Americans (67% versus 29%; p < 0.001); current cigarette smoker (26% versus 17%; p = 0.028); hypertensive (69% versus 34%; p < 0.001); diabetic (18% versus 7%; p = 0.001); history of angina (16% versus 8%; p = 0.015) or myocardial infarction (15% versus 3%; p < 0.001). There were higher rates of aCL positivity (26% versus 17%; p = 0.050), IgG-aCL > 10 GPL (23% versus 11%; p = 0.003) or IgG aCL > 20 GPL (12% versus 4%; p = 0.012) among the stroke group than among the OND group. No differences in IgG-aCL positivity were found between the MS group and the rest of the OND group but the MS patients had a higher rate of IgM-aCL positivity than the other OND patients. CONCLUSION: IgG-aCL positivity does not appear to be a marker for CNS disease generally but of ischemic stroke.

Antibodies, Anticardiolipin↗
PubMed1997

Development neurobiology of the stress response: multilevel regulation of corticotropin-releasing hormone function.

The ability to respond to adverse environmental cues is present in the neonatal and infant rat, although in an immature form: A number of laboratories have demonstrated stress-induced elevations of plasma glucocorticoids during the first two postnatal weeks. The limbic and hypothalamic mechanisms controlling the hormonal stress-response during this period are not fully understood and are, therefore, the focus of this report. Both hypothalamic corticotropin-releasing hormone (CRH) and vasopressin contribute to the release of ACTH from the pituitary in the adult. The relative roles of these two peptides during the neonatal (first week) and infant (second week) developmental period, are controversial. Evidence is presented that argues strongly for a major role for CRH. Up-regulation of hypothalamic CRH synthesis is a major component in the mature stress response. CRH-mRNA levels in the hypothalamic PVN are increased with cold stress by ninth postnatal day, but not during the first postnatal week. Further, down-regulation of CRH gene expression by glucocorticoids (GC) constitutes a critical "shut-down" mechanism for the hormonal stress response. In vivo and in vitro experiments supporting the "immaturity" of GC feedback on CRH synthesis during the first postnatal week are described. CRH-mediated neurotransmission, in both the endocrine and neuronal effector arms of the response to stress may be modulated via alteration of receptor number. The first member of the CRH receptor family, CRF1, probably mediates the neuroendocrine effects of CRH. The developmental profile of CRF1-mRNA reveals several distinctive spatial and temporal patterns. In the hippocampal CA1, CA2, and CA3a peak (300-600% adult values) CRF1-mRNA is found on postnatal day 6. In the amygdala, CRH receptor mRNA levels are maximal on the ninth postnatal day (at 180% of adult values). In cortex, a steady decline from high postnatal day 2 levels results in adult levels by 12. These findings demonstrate distinct, regional, age-specific control of the synthesis of CRF1. Receptor expression profile may provide important information regarding modulation of the age-specific roles of CRH in different regions. For example, a high ratio of hippocampus/amygdala receptors may preferentially activate negative hippocampal input to the hypothalamus during the neonatal period. Additionally, increased CRH receptor mRNA in the infant compared with the adult provides a mechanism for enhanced excitatory effect of the peptide at this age. In conclusion, increasing evidence exists for multiple control points of the early postnatal response and adaptation to stress. CRH synthesis in hypothalamus and amygdala, its sensitivity to GC feedback, and the abundance and distribution of at least two distinct CRH receptors in the limbic central nervous system and the pituitary are developmentally regulated. All serve as control points permitting an effective endocrine, autonomic, and behavioral response to stressful environmental cues.

Age Factors↗
PubMed1997

Febrile seizures: an appropriate-aged model suitable for long-term studies.

Seizures induced by fever are the most prevalent age-specific seizures in infants and young children. Whether they result in long-term sequelae such as neuronal loss and temporal lobe epilepsy is controversial. Prospective studies of human febrile seizures have found no adverse effects on the developing brain. However, adults with temporal lobe epilepsy and associated limbic cell loss frequently have a history of prolonged febrile seizures in early life. These critical issues may be resolved using appropriate animal models. Published models of hyperthermic seizures have used 'adolescent' and older rats, have yielded a low percentage of animals with actual seizures, or have suffered from a high mortality, rendering them unsuitable for long-term studies. This article describes the establishment of a model of febrile seizures using the infant rat. Hyperthermia was induced by a regulated stream of mildly heated air, and the seizures were determined by both behavioral and electroencephalographic (EEG) criteria. Stereotyped seizures were generated in 93.6% of 10-11-day-old rats. EEG correlates of these seizures were not evident in cortical recordings, but were clearly present in depth recordings from the amygdala and hippocampus. Prolonged febrile seizures could be induced without burns, yielding a low mortality (11%) and long-term survival. In summary, in infant rat paradigm of EEG-confirmed, hyperthermia-induced seizures which is suitable for long-term studies is described. This model should be highly valuable for studying the mechanisms and sequelae of febrile seizures.

Aging↗
PubMed1997

Psychiatric sequelae of posttraumatic stress disorder in women.

BACKGROUND: The risk for first-onset major depression, anxiety, and substance use disorders associated with prior posttraumatic stress disorder (PTSD) was estimated in a sample of women. METHODS: The National Institute of Mental Health Diagnostic Interview Schedule, revised according to DSM-III-R, was used to measure lifetime psychiatric disorders in a stratified random sample of 801 mothers of children, who participated in a study of cognitive and psychiatric outcomes by level of birth weight. Cox proportional hazards models with time-dependent covariates were used to calculate the hazards ratios of first onset of other disorders following PTSD. RESULTS: The lifetime prevalence of traumatic events was 40% and of PTSD, 13.8%. Posttraumatic stress disorder signaled increased risks for first-onset major depression (hazards ratio, 2.1) and alcohol use disorder (hazards ratio, 3.0). The risk for major depression following PTSD was of the same magnitude as the risk for major depression following other anxiety disorders. Women with preexisting anxiety and PTSD had significantly increased risk for first-onset major depression. Additional analysis showed that preexisting major depression increased women's vulnerability to the PTSD-inducing effects of traumatic events and risk for exposure to traumatic events. CONCLUSIONS: Posttraumatic stress disorder influences the risk for first-onset major depression and alcohol use disorder. The causal explanation of these temporally secondary disorders is unclear and might involve the effect of PTSD or underlying vulnerabilities exposed by the traumatic experience.

Adult↗
PubMed1997

Not for resuscitation: two decades of challenge for nursing ethics and practice.

Since the 1970s, the designation of some patients as 'not for resuscitation' (NFR) has become standard practice in many health care facilities. Considerable disquiet has subsequently arisen about the way these decisions are implemented in practice. Nurses, in particular, often find themselves initiating or withholding cardiopulmonary resuscitation (CPR) in situations characterized by verbal orders, euphemistic documentation and poor communication, and when consultations with patients about their CPR choices often do not take place. These practices have developed in large part because a clear legal foundation for withdrawal of treatment decisions such as NFR is still lacking in many countries. The problems with NFR were identified in the 1970s and 1980s and are not new, but, as yet, we have not been able to bring about the necessary changes, in effect to translate broadly accepted ethical principles into clinical practice. This paper explores some of the reasons for this and provides a review and analysis of the main issues, including NFR guidelines and the nursing role in NFR decision-making.

Aged↗
PubMed1996

B cells are not essential for peripheral T-cell tolerance.

Some self-reactive T cells avoid thymic tolerance and become mature peripheral cells. Nevertheless, these cells do not usually attack their hosts because T cells can be inactivated or killed, even after they are mature, by various means. The details of these processes are not fully understood; however, a number of experiments have suggested that peripheral tolerance may be induced in mature mouse T cells by exposure to antigen on resting B cells, cells that can express antigen bound to major histocompatibility complex proteins but that lack critical costimulatory molecules such as B7-1 and B7-2. Conversely, previous experiments have indicated that mature T cells can be stimulated by exposure to antigen on cells such as dendritic cells, cells that are thought to express the essential costimulatory molecules. We tested this idea in vivo by using mice that lack B cells. Unexpectedly, T-cell tolerance and antigen-induced T-cell death occurred normally in mice free of B cells. On the other hand, antigen-specific T-cell expansion in the spleens of such mice was impaired. Finally, we have recently shown that T-cell death in mice can be prevented by exposure to antigen and an inflammatory agent such as bacterial lipopolysaccharide. This was also true in mice that lacked B cells. Overall, these data show that mature T cells can be tolerized and rescued from tolerance in the absence of B cells.

Animals↗
PubMed1996

Abnormal corticosterone regulation in an immature rat model of continuous chronic stress.

Neuroendocrine correlates of chronic stress in human infants have not been established. The goal of the present study was to create an animal model of continuous chronic stress using the immature rat to measure basal plasma corticosterone, and secretion of plasma corticosterone in response to an acute stress. This was achieved by modulation of the cage environment for rat pups and their mothers. During postnatal days 2-9, pups were maintained in three groups: (1) handled, (2) not handled and with ample bedding; and (3) not handled with limited bedding. On postnatal day 9, some pups from each group were subjected to acute cold-separation stress and were killed 90, 240, or 360 min later along with unstressed controls. The group not handled and with limited bedding manifested increased plasma corticosterone output even without cold exposure and a sustained increase of plasma corticosterone after cold-separation stress. Plasma corticosterone interanimal variability was increased and body weight was decreased in these pups, typical of a state of chronic stress. The first model of continuous stress in infant rats in which upregulation of hypothalamic-pituitary-adrenal axis is achieved without maternal separation is presented. This paradigm may more closely approximate the human situation of chronically stressed, neglected infants.

Animals↗
PubMed1996

Are smokers with alcohol disorders less likely to quit?

OBJECTIVES: This study examined the likelihood of smoking cessation in smokers with a prior history of alcoholism. METHODS: Data came from an epidemiologic study of 1007 young adults, randomly selected from those insured in a large health maintenance organization (HMO) in southeast Michigan. Cox proportional hazards models with time-dependent covariates were used to estimate the hazards ratios of quitting in smokers with current and past alcoholism, with smokers with no history of alcoholism as a reference. Sex, race, and education were controlled. RESULTS: Smokers with active alcoholism in the preceding year were 60% less likely to quit than were smokers with no history of alcoholism. In contrast, smokers whose alcoholism had remitted were at least as likely to quit as smokers with no history of alcoholism. Compared with persistent alcoholism, remission of alcoholism was associated with more than a threefold increase in the likelihood of subsequent smoking cessation. CONCLUSIONS: The findings suggest that discontinuation of alcoholism might increase the potential for successful smoking cessation.

Adult↗
PubMed1996

Isolation and structure elucidation of five new asterriquinones from Aspergillus, Humicola and Botryotrichum species.

Five new quinone pigments have been discovered from the fermentation broth of Aspergillus, Humicola and Botryotrichum species isolated from different soil samples. These compounds inhibit serine proteases of the coagulation pathway. Their structures which differ in the identity and position of a 5-carbon side chain on the indole moiety have been elucidated based on NMR and FAB-MS experiments.

Aspergillus↗
PubMed1996

The effect of 'Astressin', a novel antagonist of corticotropin releasing hormone (CRH), on CRH-induced seizures in the infant rat: comparison with two other antagonists.

Corticotropin releasing hormone (CRH) has both neuroendocrine effects, promoting ACTH release from the anterior pituitary, and neurotransmitter properties, acting on specific neuronal populations. A recently designed CRH analogue has been shown to be highly potent in preventing activation of pituitary CRH receptors. The efficacy of this compound, 'Astressin', in blocking the effects of CRH in the central nervous system (CNS) has not been determined. CRH induces prolonged amygdala-origin seizures in neonatal and infant rats. This model was used in the current study, to compare Astressin to alpha-helical CRH-(9-41), and to [D-Phe12, Nle21.38, C-MeLeu37]CRH-(12-41), i.e. D-Phe-CRH-(12-41). Astressin (3 or 10 micrograms) was infused into the cerebral ventricles of infant rats prior to CRH infusion. Both doses of the analogue significantly delayed the onset of CRH-induced seizures when given 15, but not 30 min before CRH. No effect of the lower Astressin dose on seizure duration was demonstrated; the higher dose prevented seizures in 2/12 rats, and delayed seizure onset in the others (22.7 +/- 5 min vs 10.1 +/- 1.3 min). In the same paradigm, 10 micrograms of alpha-helical CRH-(9-41) and 5 micrograms of D-Phe-CRH-(12-41) had comparable effects on seizure latency and duration. Electroencephalograms confirmed the behavioral effects of Astressin. Therefore, in a CNS model of CRH-mediated neurotransmission, the potency of Astressin is not substantially higher than that of alpha-helical CRH (9-41) and D-Phe-CRH-(12-41).

Animals↗
PubMed1995

Sex differences in depression: a role for preexisting anxiety.

The role of anxiety disorders in the development of sex differences in major depression is analyzed. Data come from a longitudinal epidemiologic study of young adults in the Detroit, Michigan area. The Diagnostic Interview Schedule, revised according to DSM-III-R, was used at baseline to measure lifetime psychiatric disorders and at follow-up to measure psychiatric disorders during the 3.5-year interval since baseline assessment. Consistent with previous reports, the lifetime prevalence of major depression was nearly two-fold higher in females than in males. The sex difference was primarily in major depression comorbid with anxiety disorders. Results from Cox-proportional hazards models, with time-dependent covariates, showed that prior anxiety disorder increased the risk for subsequent major depression in both sexes, with no evidence of an interaction. History of anxiety disorder, including number of prior anxiety disorders, accounted for a considerable part of the observed sex difference in major depression. Controlling for prior anxiety reduced by more than 50% the coefficient that estimates the association between gender and major depression. The results suggest that the higher occurrence of anxiety disorders in females than males beginning early in life might explain in large part the higher female risk for major depression. They emphasize the need for further research on sex differences in anxiety disorders.

Adult↗
PubMed1995

Reasons for early recurrence following laparoscopic hernioplasty.

The incidence and reasons for early recurrences following laparoscopic hernioplasty have not been studied. Because the incidence is small and the follow up is short, a multi-institutional study was performed among the pioneers in the field. The incidence figures were obtained by survey of surgeons who had significant experience (over 100 cases) and kept concurrent records. Fifty-four recurrences (1.7%) occurred after 3229 laparoscopic hernia repairs. There were 1944 transabdominal preperitoneal (TAPP) repairs with 19 recurrences (1%) and 578 preperitoneal repairs with no recurrences. There were 345 onlay mesh (IPOM) repairs with seven recurrences (2%), and 286 plug and patch repairs with 26 recurrences (9%). Simple closures were performed 76 times with two recurrences (2.6%). Fifty-seven patients (three cases were referred to the author without incidence data but complete records for analysis) had 60 recurrent hernias. Recurrences were noted, on average, 5.1 months postoperatively (range 0-30 months). The most common reason for recurrence was that the mesh was too small - 36 (60%). The mesh was never stapled in 19 instances (32%), and the hernia was never repaired in three cases (20%). The clips pulled through the tissue in six cases (8%), and in 10 cases (15%) the repair has not yet been undertaken because the etiology was unclear. There was more than one reason in 19 patients. Technical factors were responsible for nearly all recurrences.

Hernia↗
PubMed1995

ACTH does not control neonatal seizures induced by administration of exogenous corticotropin-releasing hormone.

ACTH has been used extensively for treatment of massive infantile spasms (MIS) and other intractable seizures. The mechanisms by which ACTH exerts anticonvulsant effects are unknown. ACTH is a neuropeptide with both endocrine and neuromodulatory properties; its efficacy against MIS could derive from intrinsic anticonvulsant properties or from hormonal effects, either directly or through glucocorticoids. We tested ACTH activity against exogenous corticotropin-releasing hormone (CRH)-induced seizures in the infant rat model. CRH was administered into the cerebral ventricles of 85 infant rats aged 5-13 days. ACTH was used either 20-60 min before CRH administration or "chronically" (pretreatment with four doses of ACTH every 6 h, before CRH administration). In a separate group of rat pups, we measured plasma corticosterone to ascertain ACTH availability. Administration of CRH, an age-specific endogenous convulsant, resulted in a prolonged series of seizures after 2- to 55-min latency. There was no difference in latency between controls (9.5 +/- 1.2 min) and ACTH-treated rats (12.4 +/- 2.8 min for combined acute and chronic groups). CRH-induced seizure duration (88.2 +/- 9 vs. 74.7 +/- 9.4 min) and severity of seizures was also unchanged by ACTH treatment. ACTH reached the circulation and caused significant increase in plasma glucocorticoids. ACTH does not block the convulsant action of exogenous CRH in infant rats. An alternative mechanism for the anticonvulsant effect of ACTH may be suppression of synthesis and secretion of an endogenous convulsant, i.e., CRH.

Adrenocorticotropic Hormone↗