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PubMed1990

Prevention of infection and graft-versus-host disease by suppression of intestinal microflora in children treated with allogeneic bone marrow transplantation.

The effect of suppression with antimicrobial agents of the intestinal microflora of paediatric bone marrow graft recipients on severe bacterial and fungal infections and on moderate to severe acute graft-versus-host disease was studied retrospectively. Data on 65 cases of bone marrow transplantation for either severe bone marrow failure or leukaemia, performed in a strict protective environment with either complete or selective gastrointestinal decontamination, were evaluated. All bone marrow grafts were from HLA-identical siblings and were not depleted of T-lymphocytes. Twenty percent of the recipients had one or more episodes of septicaemia during the granulocytopenic period after transplantation, mostly due to gram-positive bacteria. Only five children died due to infection, in each case caused by a microorganism originating from the endogenous flora. Complete gastrointestinal decontamination was superior to selective gastrointestinal decontamination in preventing infectious complications (p less than 0.001). The same was the case for the prevention of acute graft-versus-host disease of grade II or higher, which was observed in 7 of 40 (17.5%) completely decontaminated children versus 9 of 18 (50%) selectively decontaminated children evaluable for graft-versus-host disease (p less than 0.01). It is concluded that complete gastrointestinal decontamination in a strict protective environment is a feasible and very effective method for preventing severe infections and acute graft-versus-host disease after allogeneic bone marrow transplantation in children and adolescents; it resulted in a low transplantation-related mortality of 26% and a good quality of survival in 69% of the graft recipients.

Adolescent↗

PubMed1999

Frequency of oropharyngeal candidiasis in HIV-infected patients on protease inhibitor therapy.

OBJECTIVE: The purpose of this study was to investigate the effect of HIV-1 protease inhibitors on the frequency of oropharyngeal candidiasis in HIV-infected patients. STUDY DESIGN: A clinical and analytic follow-up was carried out to determine the number of episodes of oropharyngeal candidiasis during HIV-1 protease inhibitor therapy and the relation of this incidence to the CD4 lymphocyte count and circulating neutrophils level. Seventy-five HIV-positive patients were selected, and HIV-1 protease inhibitor therapy was administered to each patient over a minimum of 6 months. These patients did not receive long-term preventive antifungal therapy for oral candidiasis, even as secondary prophylaxis against cryptococcosis. Results were compared with those obtained during the previous 6 months, during which patients had been treated only with reverse transcriptase inhibitors. RESULTS: At least one episode of oropharyngeal candidiasis was seen in 56% (42/75) of patients during reverse transcriptase inhibitor therapy and in only 9.3% (7/75) of patients after the initiation of protease inhibitor therapy. The number of relapses decreased significantly when the 2 follow-up periods were compared (P<.0001). The CD4 and CD8 lymphocyte counts increased significantly with protease inhibitor therapy (P<.001 and P<.05, respectively). During reverse transcriptase inhibitor treatment, the probability of the presentation of oropharyngeal candidiasis correlated with falling CD4 counts (P<.0001). The HIV-1 protease inhibitor therapy was associated with a significant increase in the neutrophil count (P<.01). The probability of the occurrence of some episode of candidiasis correlated inversely with the circulating neutrophil level (P<.05). CONCLUSIONS: Protease inhibitor therapy decreases the frequency of HIV-related oropharyngeal candidiasis. The mechanism involved is unknown, but it can be speculated that a reduction of the viral load increases the number of intact T helper cells, which in turn enhances the number of circulating polymorphonuclear neutrophils and regulates their function by means of colony-stimulating factors.

Adult↗

PubMed2005

The fast is positive, now what? Derivation of a clinical decision rule to determine the need for therapeutic laparotomy in adults with blunt torso trauma and a positive trauma ultrasound.

INTRODUCTION: The object of this study was to derive a clinical decision rule for therapeutic laparotomy among adult blunt trauma patients with a positive abdominal ultrasound for trauma (FAST) examination. METHODS: We retrospectively reviewed the trauma registry and medical records of all critical trauma patients who underwent a FAST examination in the emergency department (ED) in a university Level I trauma center over a 3-year period. Blunt trauma patients aged >16 years who had a positive FAST examination (defined as the presence of intraperitoneal fluid) were eligible. We selected seven clinical and ultrasound variables available during ED resuscitation for analysis: age, presence of an episode of hypotension (systolic blood pressure <90 torr in the ED), presence of abdominal tenderness, chest injury, pelvic fracture, femur fracture, and FAST fluid location (right upper quadrant [RUQ] only; RUQ plus other location; other location only). The primary outcome variable was whether a laparotomy was performed and whether this laparotomy was needed to provide the definitive surgical intervention ("therapeutic laparotomy"). We analyzed the variables using binary recursive partitioning analysis to create a decision rule. RESULTS: There were 2336 FAST examinations performed during the study period, resulting in 230 (9.8%) positive examinations in patients meeting inclusion criteria. There were 135 patients who had therapeutic laparotomies and 95 who did not need laparotomy. The groups were similar in baseline characteristics. In the recursive partitioning analysis, the first node in the decision tree was the presence of fluid in the RUQ. Of the 144 patients with RUQ fluid, 105 (73%, 95% confidence interval [CI] 64%-80%) required therapeutic laparotomy. Of the 86 patients without RUQ fluid, 30 (35%, 95% CI 25%-46%) nevertheless required therapeutic laparotomies, and the variables blood pressure, femur fracture, abdominal tenderness, and age further divided these patient into high- and low-risk groups. Of the 12 patients without RUQ fluid who had normal blood pressures, no femur fractures, no abdominal tenderness, and were aged 60 years and younger, none (95% CI 0%-22%) required therapeutic laparotomy. In conclusion, given a positive FAST examination, the presence of fluid in the RUQ is an important predictor of the need for therapeutic laparotomy. CONCLUSION: In the absence of fluid in the RUQ, there are other clinical variables that may allow for the development of a clinical decision rule regarding the need for therapeutic laparotomy.

Abdominal Injuries↗

PubMed1987

On the overdispersed molecular clock.

Rates of molecular evolution at some loci are more irregular than described by simple Poisson processes. Three situations under which molecular evolution would not follow simple Poisson processes are reevaluated from the viewpoint of the neutrality hypothesis: concomitant or multiple substitutions in a gene, fluctuating substitution rates in time caused by coupled effects of deleterious mutations and bottlenecks, and changes in the degree of selective constraints against a gene (neutral space) caused by successive substitutions. The common underlying assumption that these causes are lineage nonspecific excludes the case where mutation rates themselves change systematically among lineages or taxonomic groups, and severely limits the extent of variation in the number of substitutions among lineages. Even under this stringent condition, however, the third hypothesis, the fluctuating neutral space model, can generate fairly large variation. This is described by a time-dependent renewal process, which does not exhibit any episodic nature of molecular evolution. It is argued that the observed elevated variances in the number of nucleotide or amino acid substitutions do not immediately call for positive Darwinian selection in molecular evolution.

Animals↗

PubMed1986

Morphology and electrophysiological properties of reticularis thalami neurons in cat: in vivo study of a thalamic pacemaker.

Reticularis thalami neurons (RE neurons) were identified morphologically, and their electrophysiological properties were studied in cat under barbiturate anesthesia. Intracellular HRP injections showed that RE neurons possessed very long dendrites bearing numerous filopodia-like appendages and that their axons were directed toward main thalamic nuclei. As a rule, small axonal branches were also emitted within the RE nucleus itself. At rest, the membrane potential of RE neurons displayed 2 types of oscillations: a slow 0.1-0.2 Hz oscillation and fast 7-12 Hz oscillations occurring on the positive phase of the former. Episodes of spindle (7-12 Hz) waves lasted for 2-3 sec and were characterized by rhythmic depolarizations and burst discharges. Intracellular injections of QX314 and current pulse analyses revealed the presence in RE cells of 2 distinct inward currents: a persistent current that promoted tonic firing and a low-threshold current deinactivated by hyperpolarization that generated burst discharges. The low-threshold current deinactivated with large somatic hyperpolarizations (up to 30 mV) and produced depolarizing responses that lasted for about 70 msec. In addition, low-threshold responses appeared rhythmically at intervals of about 150 msec after recovery of the membrane potential from hyperpolarization. Because of their duration, voltage dependence, and persistence after intracellular injections of QX314, it is suggested that these responses resulted from activation of a low-threshold Ca2+ current at the dendritic level. In QX314-injected cells, selective components of spontaneous oscillations were abolished, among them the positive phase of the slow oscillation and late depolarizing humps that followed burst discharges within spindle sequences. However, the rhythmic occurrence of spindle episodes at 0.1-0.2 Hz was never affected by DC currents or by QX314 or Cl- injections, suggesting that oscillations within a particular RE neuron partly reflected the oscillatory behavior of a network of cells. On the basis of these electrophysiological results and the known morphological and neurochemical features, a new hypothesis is proposed to account for the rhythmicity of RE neurons.

Animals↗

PubMed1983

Experience with the Nissen fundoplication for correction of gastroesophageal reflux in infants.

UNLABELLED: In the past 15 years at Children's Hospital in Washington, D.C., approximately 500 infants under 1 year of age have been evaluated because of symptomatic gastroesophageal reflux. A contrast esophagogram will demonstrate reflux in the majority of affected infants. However, this diagnostic method is not always reliable. Timed monitoring of esophageal pH, and extended radionuclide scan even in infants can document accurately the frequency and character of episodic reflux. Following diagnosis, most infants are treated by conservative therapy, which includes the upright position. Of the 500 patients, 72 infants (14%) were selected for operative correction using the Nissen fundoplication. The indications for surgery in these infants with gastroesophageal reflux were: (A) failure to thrive, (35); (B) chronic respiratory infection, (24); (C) apnea spells, (8); and (D) esophagitis. One infant was found to have a stricture. In these symptomatic patients, three had previous operative correction of esophageal atresia, and two had congenital gastric dislocation in the chest. RESULTS: 61 excellent; six recurrences, of whom five are satisfactory after a second operation; two lost to follow-up but doing well when last seen; three deaths from causes unrelated to reflux. The selection of infants with gastroesophageal reflux for surgical correlation is primarily based on life-threatening clinical effects. The Nissen fundoplication has worked well in this group of infants.

Apnea↗

PubMed2004

The bedding environment, sleep position, and frequent wheeze in childhood.

OBJECTIVE: Synthetic quilt use has been associated with increased childhood wheeze in previous studies. Our aim was to examine whether the adverse effect of synthetic quilt use on frequent wheeze differed by usual sleep position. DESIGN, SETTING, AND PARTICIPANTS: A population-based cross-sectional study of 6378 (92% of those eligible) 7-year-olds in Tasmania, Australia, was conducted in 1995. Exercise-challenge lung function was obtained on a subset of 414 children from randomly selected schools. EXPOSURE MEASURES: Child bedding including pillow and overbedding composition and usual sleep position by parental questionnaire. OUTCOME MEASURES: Frequent wheeze (>12 wheeze episodes over the past year), using the International Study of Asthma and Allergies in Childhood parental questionnaire, and baseline and postexercise forced expiratory volume in 1 second lung-function measures. RESULTS: Frequent wheeze (n = 117) was positively associated with synthetic quilts, synthetic pillows, electric blankets, and sleeping in a bottom bunk bed but did not vary by sleep position. In a nested case-control analysis, the association between synthetic quilt use and frequent wheeze differed by sleep position. Among children who slept supine, synthetic (versus feather) quilt use was associated with frequent wheeze (adjusted odds ratio: 2.37 [1.08, 5.23]). However, among nonsupine sleepers, overlying synthetic quilt use was not associated with frequent wheeze (adjusted odds ratio: 1.06 [0.60, 1.88]). This difference in quilt effect by sleep position was highly significant. Similarly, synthetic quilt use was associated with lower postexercise forced expiratory volume in 1 second measures among supine but not nonsupine sleeping children. CONCLUSION: An increasing focus on the bedding environment immediately adjacent to the nose and mouth is required for respiratory disorders provoked by bedding, such as child asthma characterized by frequent wheeze.

Asthma↗

PubMed2001

Novelty-elicited mismatch negativity in patients with schizophrenia on admission and discharge.

OBJECTIVE: Given recent reports of differences between mismatch negativity (MMN) elicited by always novel sounds (novelty-elicited MMN) and that elicited by repeated rare deviants (conventional MMN), we investigated novelty-elicited MMN and P3a in patients with schizophrenia before and after a nonstandardized inpatient treatment. DESIGN: Electrophysiological and clinical assessment of patients on admission and discharge from hospital. Assessment of control subjects on 2 sessions. SETTING: Inpatient treatment in a psychiatric university hospital. SUBJECTS: 20 patients with schizophrenia and 21 healthy control subjects of similar age and sex. Selection of patients with first- to third-episode schizophrenia. OUTCOME MEASURES: Early and late component MMN amplitudes and latencies, P3a amplitudes and latencies, Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning (GAF), Extrapyramidal Symptom Scale (EPS), Abnormal Involuntary Movement Scale (AIMS) and chlorpromazine equivalents. RESULTS: In patients with schizophrenia, novelty-elicited MMN was unimpaired on admission, and there was a statistically significant reduction of the late MMN component with treatment. Improvements in symptom expression were associated with increased latencies of the early MMN component. CONCLUSION: Results indicate differences in information processing between conventional and novelty-elicited MMN. Some components of the novelty-elicited MMN might be more state dependent than those of the conventional MMN.

Adult↗

PubMed2001

Aerobic bacterial and fungal infections in peripheral blood stem cell transplants.

Allogeneic and autologous peripheral blood stem cell transplants are frequently complicated by infections. This study was performed to evaluate early and late infections in 74 patients who underwent peripheral blood stem cell transplantation (PBSCT). Fifty-eight patients received allogeneic and 16 autologous PBSCT. All patients received fluconazole, ciprofloxacin and acyclovir prophylaxis. 93.1% of alloPBSCT patients and 87.5% of autoPBSCT patients developed fever. Febrile episodes were commonly seen in the week of transplantation (66%). There was a median of 3 days with fever in alloPBSCT, and 2 days in autoPBSCT. Period of neutropenia was 15 days for AlloPBSCT and 12 days for AutoPBSCT. The microbiological identification rate was 47% (32/68). Gram-positive infections dominated the early period (50%) and Gram-negative bacterial infections dominated the late period (50%). All our patients had Hickman-type catheters and 26 infections involving catheters were seen. Sixteen occurred in the early, and 10 in the late period. Ten of 14 (71.4%) late bacterial infections were catheter-related. The dominance of Gram-positive infections and high rates of methicillin resistance warranted the use of vancomycin extensively. Surveillance cultures were found to be useful in selected patients. Although slime factor is an important virulence factor, there was no difference between slime factor positive and negative coagulase-negative staphylococci isolated during infections. In conclusion, febrile episodes are the most frequent complication of PBSCT and Gram-positive microorganisms remain the main pathogen in these patients because of catheter use, mucositis and ciprofloxacin prophylaxis. Methicillin resistance is increasing and glycopeptides remain the only choice for treating such infections. Although the infection rate is high, measures taken to prevent and treat infections result in very low rates of mortality from infection in PBSCT patients.

Adolescent↗

PubMed2001

A randomized controlled trial of the accuracy of clinical record retrieval using SNOMED-RT as compared with ICD9-CM.

BACKGROUND: Concept-based Indexing is purported to provide more granular data representation for clinical records.1,2 This implies that a detailed clinical terminology should be able to provide improved access to clinical records. To date there is no data to show that a clinical reference terminology is superior to a precoordinated terminology in its ability to provide access to the clinical record. Today, ICD9-CM is the most commonly used method of retrieving clinical records. OBJECTIVE: In this study, we compare the sensitivity, specificity, positive likelihood ratio, positive predictive value and accuracy of SNOMED-RT vs. ICD9-CM in retrieving ten diagnoses from a random sample of 2,022 episodes of care. METHOD: We randomly selected 1,014 episodes of care from the inpatient setting and 1,008 episodes of care from the outpatient setting. Each record had associated with it, the free text final diagnoses from the Master Sheet Index at the Mayo Clinic and the ICD9-CM codes used to bill for the encounters within the episode of care. The free text diagnoses were coded by two expert indexers (disagreements were addressed by a Staff Clinician) as to whether queries regarding one of 5 common or 5 uncommon diagnoses should return this encounter. The free text entries were automatically coded using the Mayo Vocabulary Processor. Each of the ten diagnoses was exploded in both SNOMED-RT and ICD9-CM and using these entry points, a retrieval set was generated from the underlying corpus of records. Each retrieval set was compared with the Gold Standard created by the expert indexers. RESULTS: SNOMED-RT produced significantly greater specificity in its retrieval sets (99.8% vs. 98.3%, p<0.001 McNemar Test). The positive likelihood ratios were significantly better for SNOMED-RT retrieval sets (264.9 vs. 33.8, p<0.001 McNemar Test). The positive predictive value of a SNOMED-RT retrieval was also significantly better than ICD9-CM (92.9% vs. 62.4%, p<0.001 McNemar Test). The accuracy defined as 1 (the total error rate (FP+FN) / Total # episodes queried (20,220)) was significantly greater for SNOMED-RT (98.2% vs. 96.8%, p=0.002 McNemar Test). Interestingly, the sensitivity of the SNOMED-RT generated retrieval set was not significantly different from ICD9-CM, but there was a trend toward significance (60.4% vs. 57.6%, p=0.067 McNemar Test). However, if we examine only the outpatient practice SNOMED-RT produced a more sensitive retrieval set than ICD9-CM (54.8% vs. 46.4%, p=0.002 McNemar Test). CONCLUSIONS: Our data clearly shows that information regarding both common and rare disorders is more accurately identified with automated SNOMED-RT indexing using the Mayo Vocabulary Processor than it is with traditional hand picked constellations of codes using ICD9-CM. SNOMED-RT provided more sensitive retrievals of outpatient episodes of care than ICD9-CM.

Decision Support Systems, Management↗

PubMed1990

Selective deficits in cognition and memory in high-functioning parkinsonian patients.

To evaluate the profile and extent of cognitive deficits in Parkinson's disease, afflicted patients of exceptional professional distinction, who continue to function successfully in leadership positions, were compared neuropsychologically to neurologically normal individuals, matched for sex, age, education and professional standing. While patients showed relative preservation of verbal skills and higher executive function, they exhibited a significant reduction in episodic memory and visuospatial function. The observation of circumscribed impairment in this select group of Parkinsonian patients further implicates cognitive and memory deficits as consistent features of Parkinson's disease.

Adult↗

PubMed2004

Comparative analysis of individuals with and without chiropractic coverage: patient characteristics, utilization, and costs.

BACKGROUND: Back pain accounts for more than $100 billion in annual US health care costs and is the second leading cause of physician visits and hospitalizations. This study ascertains the effect of systematic access to chiropractic care on the overall and neuromusculoskeletal-specific consumption of health care resources within a large managed-care system. METHODS: A 4-year retrospective claims data analysis comparing more than 700 000 health plan members with an additional chiropractic coverage benefit and 1 million members of the same health plan without the chiropractic benefit. RESULTS: Members with chiropractic insurance coverage, compared with those without coverage, had lower annual total health care expenditures ($1463 vs $1671 per member per year, P<.001). Having chiropractic coverage was associated with a 1.6% decrease (P = .001) in total annual health care costs at the health plan level. Back pain patients with chiropractic coverage, compared with those without coverage, had lower utilization (per 1000 episodes) of plain radiographs (17.5 vs 22.7, P<.001), low back surgery (3.3 vs 4.8, P<.001), hospitalizations (9.3 vs 15.6, P<.001), and magnetic resonance imaging (43.2 vs 68.9, P<.001). Patients with chiropractic coverage, compared with those without coverage, also had lower average back pain episode-related costs ($289 vs $399, P<.001). CONCLUSIONS: Access to managed chiropractic care may reduce overall health care expenditures through several effects, including (1) positive risk selection; (2) substitution of chiropractic for traditional medical care, particularly for spine conditions; (3) more conservative, less invasive treatment profiles; and (4) lower health service costs associated with managed chiropractic care. Systematic access to managed chiropractic care not only may prove to be clinically beneficial but also may reduce overall health care costs.

Adolescent↗

PubMed1989

Closed-chest ablation of retrograde conduction in patients with atrioventricular nodal reentrant tachycardia.

We applied a new technique of catheter ablation to treat atrioventricular nodal reentrant tachycardia and preserve anterograde conduction, performing this procedure in 21 patients with repetitive episodes of tachycardia refractory to antiarrhythmic drugs. Using atrial activation in the His-bundle lead as a reference, we selected the optimal site of ablation by positioning an electrode catheter so that atrial activation occurred simultaneously with or earlier than the reference activation during tachycardia. At this site, the His-bundle deflection was completely absent or was present only at a low amplitude (less than 0.1 mV). In the majority of patients, these criteria could be met by withdrawing the catheter 5 to 10 mm from the site of the His-bundle recording (adjacent to the reference catheter). Shocks of 160 or 240 J were delivered at this site (cumulative energy [mean +/- SD], 689 +/- 442 J). Treatment resulted in preferential abolition or impairment of retrograde nodal conduction. Anterograde conduction, although modified, was preserved in 19 patients; complete heart block persisted in 2 patients. Sixteen patients remained free of arrhythmia, without medication or implantation of a pacemaker, for a mean follow-up period of 14 +/- 8 months (range, 7 to 42). Tachycardia was not inducible in 14 patients in a follow-up electrophysiologic study performed 3.6 +/- 6 months after the procedure. We conclude that catheter ablation is an effective alternative for the treatment of atrioventricular nodal tachycardia in patients with drug-resistant tachycardia.

Adult↗

PubMed1994

[Cardiac retransplantation: is it justified in childhood?].

A 7-year-old boy had undergone heart transplantation (HT) at 1 year of age. The immunosuppressive regimen consisted of cyclosporine and azathioprine (Cy+Aza). During the follow-up there were 7 episodes of moderate rejection: 4 of them occurred during the first 3 months. He had cytomegalovirus (CMV) seroconversion 4 years after HT. After 5 years since he underwent primary HT, cardiac catheterization and selective coronary angiography, performed on a yearly basis, showed triple vessel occlusive disease. The treadmill test was positive. During the following year, the patient's clinical condition deteriorated: in May '92 he underwent retransplantation. Cross-match was negative and there were no common HLA-DR antigens between the first and the second donor heart. Only 1 rejection episode occurred during the first 18 months of follow-up. Despite the shortage of donor hearts we feel that retransplantation is justified as an elective procedure in pediatric patients with cardiac allograft vasculopathy (CAV).

Biopsy↗

PubMed1987

Prediction of airway reactivity from responses to a standardized respiratory symptom questionnaire.

A standardized respiratory symptom questionnaire was administered to 200 male insulators who then underwent inhalational bronchial challenge to measure their airway reactivity. The results were analyzed to determine the value of questionnaire information in predicting airway reactivity measured objectively. Questionnaire information was grouped according to topic, scored according to severity, and then combined to create several airway reactivity indices by stepwise multivariate analysis. The final index selected for testing contained information on a history of "asthma," "wheeze," "episodes of cough with sputum," and "pneumonia." It had a sensitivity ranging from 5% to 67% and positive predictive value from 67% to 28% depending on the cutoff point chosen as indicative of increased airway reactivity. These results indicate that questionnaire information is not adequate for discriminating between those with and those without increased airway reactivity in population screening.

Adult↗

PubMed1993

Protein S deficiency in men with long-term human immunodeficiency virus infection.

Decreases in protein S levels have recently been reported in some human immunodeficiency virus (HIV)-infected patients. To examine predisposing factors, 25 men randomly selected from a long-term study of HIV-infected patients were studied. The minimum mean duration of HIV seropositivity in this group was 106.6 months (range 15 to 143 months). No patients were anticoagulated at the time of the study. Three of the 25 randomly selected patients gave a history of thrombosis, in each instance occurring after the onset of HIV positivity. Two of the 3 patients with thrombosis had more than one episode. Coagulation studies showed that 3 of 3 (100%) of the patients with thrombosis and 16 of 22 (72.7%) of those without previous thrombosis had decreased free protein S. Mean-free and total protein S levels were statistically lower for HIV-infected patients with and without previous thrombosis compared with healthy male controls. C4b-binding protein was not increased in study patients with decreased protein S levels. Decreases in protein S levels did not correlate with CD4+ cell levels, CDC class, p24 antigen positivity, zidovudine (AZT) use, or Pneumocystis carinii prophylaxis. The duration of disease statistically correlated with decreases in protein S levels (r = .37, P < .05). A linear correlation existed between increasing IgG anticardiolipin antibody levels and decreasing free protein S antigen (r = .67, P < .005). This study shows that protein S deficiency is common in long-term HIV-infected patients and is caused by a decrease in the free protein, rather than by changes in the bound complex. The data suggest that protein S deficiency is not correlated with HIV disease severity but may predispose patients to thromboembolic complications.

Adult↗

PubMed1993

Nicotine stimulates the expression of cFos protein in the parvocellular paraventricular nucleus and brainstem catecholaminergic regions.

The rapid secretion of ACTH in response to nicotine is mediated by a central mechanism involving brainstem catecholaminergic regions. To identify specific brainstem regions involved in activating the hypothalamo-pituitary-adrenal axis and other areas of the brain by iv nicotine, immunocytochemical detection of cFos protein was used as a marker for neuronal activation. Nicotine (0.05 mg/kg) stimulated cFos expression in the parvocellular paraventricular nucleus (pcPVN; containing CRH-positive neurons mediating ACTH secretion); this correlated with the expression of cFos in the A2 (norepinephrinergic) and C2 (epinephrinergic) regions of the brainstem nucleus tractus solitarius, which project directly to the pcPVN. The selectivity of this brainstem activation was shown by the absence of responses in the locus coeruleus (LC), A1, and C1 catecholaminergic regions to this low dose of nicotine. In contrast, a high dose of nicotine (0.1 mg/kg), which produced a brief episode of tremor, was required for expression of cFos in the LC. This was associated with a further increase in the number of cFos-positive cells in the PVN, primarily through recruitment in the magnocellular region, a known projection field of LC. The higher dose of nicotine also induced cFos in the vasopressinergic region of the supraoptic nucleus (SON), whereas the lower dose of nicotine exclusively induced cFos in the oxytocinergic region of the SON. Limbic regions that receive catecholaminergic inputs, such as the the central nucleus of the amygdala (involved in PVN regulation) and the cingulate gyrus of the cortex, showed a dose-dependent increase in the number of cFos-positive cells after nicotine, whereas the dentate gyrus of the hippocampus only responded to the high dose. Thus, nicotine is a potent and selective stimulus for neuronal activation in brainstem catecholaminergic regions and their projection fields in the pcPVN and SON, which regulate the hypothalamo-pituitary-adrenal axis and vasopressin/oxytocin secretion, respectively.

Adrenocorticotropic Hormone↗

PubMed1998

Selection of 'normal' control subjects for psychiatric research: update on a model for centralized recruitment.

A recruitment program for 'normal' control subjects is evaluated with regard to the yield of 'healthy' subjects, the degree to which subjects remain healthy over a number of years, and the rate of subject participation in research. Only 22.4% had no lifetime history of mental illness (Never Mentally III), 6.8% met the criteria for one episode of a minor mental disorder (MMD), 41.6% were currently healthy but had a more serious history of mental illness and 29.9% were currently mentally ill. Diagnostic follow-up found that subjects in the NMI and MMD categories did not differ with regard to the rate of interval episodes in themselves or in family members over an average of 27 months. However, subjects in the MMD category were more likely to have a positive family history of mental illness (chi2(1) = 21.34; P < 0.001). The longitudinal course of mental health in a combined group of NMI and MMD subjects was predicted by sex of the subject (chi2(1) = 4.04; P < 0.05), but not by age or family history of mental illness. These findings suggest that investigators selecting 'healthy' control subjects consider the probability that a currently healthy individual will have episodes of mental illness in the future.

Adult↗