Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a fatal autosomal recessive disorder seen in infants. It is characterized by lower motor neuron degeneration, progressive muscle paralysis and respiratory failure, for which no effective treatment exists. The phenotype of neuromuscular degeneration (nmd) mice closely resembles the human SMARD1. The identification of the mutated mouse gene in nmd mice, Ighmbp2, led to the discovery of mutations of the homologous gene in humans with SMARD1. We have studied the nmd mouse model with in vivo electrophysiological techniques and evaluated the efficacy of Mab2256, a monoclonal antibody with agonist effect on the tyrosine kinase receptor C, trkC, on disease progression in nmd mice. Treatment with Mab2256 resulted in a significant but transient improvement of muscle strength in nmd mice, as well as normalization of the neuromuscular depression during high-frequency nerve stimulation. These results suggest the potential of using monoclonal agonist antibodies for neurotrophin receptors in lower motor neuron diseases such as SMARD1.
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PMID:Treatment with trkC agonist antibodies delays disease progression in neuromuscular degeneration (nmd) mice. 1588 78

Pharmacotherapy in pregnant women is often necessary to treat chronic or relapsing depression or anxiety disorders. Studies that have evaluated the safety of selective serotonin reuptake inhibitors (SSRIs) in early pregnancy have not shown an enhanced risk of major congenital malformations and these results may have contributed to the increasing use of these agents during pregnancy. Fewer studies have assessed the safety of SSRIs in the third trimester of pregnancy. This article reviews available human data on the safety of SSRI treatment in the third trimester. The main purpose is to present and discuss the existing literature on the risks to the infant and to suggest treatment guidelines for the use of SSRIs in late pregnancy. The use of SSRIs in the third trimester has shown various perinatal complications, most frequently respiratory distress, irritability and feeding problems. Further studies are needed to evaluate the frequency of these complications and to elucidate whether the symptoms represent a direct serotonergic effect or are a drug withdrawal effect. Studies have shown conflicting results with respect to whether SSRI exposure decreases birthweight and increases the risk of premature delivery. A few case reports have described intracerebral haemorrhage in neonates after maternal SSRI treatment, but it is not known whether the frequency of such complications is higher than in unexposed neonates. Data on possible long-term effects of prenatal SSRI exposure on psychomotor and behavioural development are very sparse. Our interpretation of the current literature suggests that the risk of not receiving adequate antidepressant treatment in the third trimester when indicated outweighs the risks of adverse events in the infant. Thus, adequate pharmacological treatment should not be withheld from a depressed pregnant woman in late pregnancy. However, the neonate should be monitored for possible adverse effects after maternal use of an SSRI in the third trimester.
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PMID:Treatment with selective serotonin reuptake inhibitors in the third trimester of pregnancy: effects on the infant. 1596 5

The present study reports the clinical, virological and pathological findings observed in a natural outbreak of highly pathogenic avian influenza in farmed commercial ducks. The ducks developed clinical signs, including mild respiratory distress, depression, mild diarrhoea, loss of appetite and increasing mortality (up to 12%). At necropsy, multifocal mottled necrosis was commonly found in the pancreas with splenomegaly, hepatomegaly, and swollen kidneys. Microscopically, there was necrotized pancreatitis and hepatitis, and lymphocytic meningoencephalitis and myocarditis. Influenza viral antigen was demonstrated in areas closely associated with histopathological lesion. Avian influenza virus was isolated from the caecal tonsil, faeces, and kidney of the domestic ducks. The isolated virus was identified as a highly pathogenic H5N1, with a haemagglutinin proteolytic cleavage site deduced amino acid sequence of ... QREKRKKR/GLFGAIAG ... In order to determine the pathogenicity of the isolate, eight 6-week-old specific pathogen free chickens were inoculated intravenously with the virus, and all birds died within 24 h after inoculation. This is the first report of an outbreak of highly pathogenic avian influenza with clinical signs in commercial domestic ducks in South Korea.
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PMID:Highly pathogenic avian influenza (H5N1) in the commercial domestic ducks of South Korea. 1614 75

Respiratory dysfunction during sepsis is common. However, although lung function can often be adequately supported, death frequently results from cardiovascular collapse. Despite intense investigation, the mechanism underlying the myocardial dysfunction of sepsis remains unclear. Macrophage migration inhibitory factor (MIF), an important cytokine released in sepsis and the acute respiratory distress syndrome, is a known cardiac depressant. We hypothesized that MIF released from the lung results in myocardial dysfunction during sepsis. In murine models of polymicrobial sepsis, we demonstrate a significant increase in the lungs of total and lavagable MIF between 20 and 30 h post induction of sepsis. At 30 h post sepsis, the lungs released MIF into the pulmonary circulation, increasing the plasma concentration by up to 51% in a single pass. Exogenous MIF, instilled into the lungs, increased alveolar keratinocyte-derived chemokine (KC), Macrophage inflammatory protein-2 (MIP2), and tumor necrosis factor alpha (TNFalpha) at 3 h, and plasma KC and MIP2 at 6 h postinstillation. This was associated with an increase in p38 mitogen-activated protein kinase and c-Jun N-terminal kinase phosphorylation. Because changes in mitogen-activated protein kinase activation can lead to myocardial depression, these data suggest that MIF released from the lungs may be responsible, at least in part, for the cardiac dysfunction seen in the late stages of sepsis.
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PMID:Macrophage migration inhibitory factor within the alveolar spaces induces changes in the heart during late experimental sepsis. 1631 87

The general methodology, strengths and weaknesses, and political uses of meta-analysis are examined. As a systematic study of all studies that have been conducted to answer a specific question or hypothesis, meta-analysis is strong in revealing structural flaws and sources of bias in primary research and in posing promising research questions for future study. It cannot exceed, however, the limits of what is reported by primary researchers. Meta-analysis is particularly challenged to quantify the size of a common effect of treatment across reported trials because of (1) the clinical diversity of the trials and (2) the myriad of potential differences among patients with varying characteristics within the trials. Without access to the original data of reported trials, meta-analysis cannot overcome the bias of underpowered trials toward overstatement of the size of main treatment effects, nor the tendency for such trials to falsely conclude there were no statistically significant adverse events. Although severely compromised by ghost-written or honorary-authored reports of primary research, meta-analysis can make use of its methods to focus on the conflicts of interest and likely sources of bias of such research and make known what precautions should be taken by would-be consumers. Examples show how meta-analysis has clarified thinking about the off-label use of selective serotonin reuptake inhibitors for treating child and adolescent depression, use of low-tidal volume respirator assistance for acute lung injury and acute respiratory distress syndrome patients, and the long-term use of COX-2 inhibitors for relieving arthritic pain. Recommendations are made for Congressional action.
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PMID:Meta-analysis: Methods, strengths, weaknesses, and political uses. 1644

Percy Medicine is a nonprescription gastrointestinal suspension containing bismuth subsalicylate as the active ingredient (1050 mg/10-ml dose). A 3-month-old infant with colic developed salicylate toxicity requiring hospitalization in the pediatric intensive care unit (PICU) as a result of continued administration of this medicine. Bismuth subsalicylate has an aspirin equivalency conversion factor of 0.479 (approximately half the strength of aspirin). For 3.5 weeks the infant's parents administered the medicine, which provided the equivalent of aspirin 57-84 mg/kg/day with no reported problems. However, on the day of admission the baby presented with central nervous system depression and respiratory distress. Assessment at a local emergency facility revealed metabolic acidosis; his serum salicylate concentration was 747 mg/L. After acute management, the patient was transferred to our hospital, where he was treated with whole bowel irrigation and alkalinization therapy. Subsequently, the baby required 4 days of management in the PICU and 2 additional days of observation in a general nursing unit before he was discharged home without incident. The parents had chosen Percy Medicine based on the picture of a baby on the front of the package and because of its placement on the shelf next to a drug their family physician had recommended previously. Salicylate-containing products are not routinely recommended for children aged 1 year or younger. The general public may assume that over-the-counter products are safe because they do not require a prescription. Health care professionals must be responsible for educating the public regarding risks associated with over-the-counter products and the need to read and follow label directions.
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PMID:Salicylate toxicity associated with administration of Percy medicine in an infant. 1650 21

The purpose of this study was to compare the efficacy of diazepam and the pro-diazepam avizafone in preventing the severity of soman-induced pathology in guinea pig. Survival, respiration and seizures of experimental animals were investigated with on-line monitoring of respiratory and EEG parameters. Guinea pigs were pretreated with pyridostigmine (0.1mg/kg i.m.) and 30 min later challenged with 1 or 2 LD50 soman. One minute after intoxication they were treated with atropine (3 or 33.8 mg/kg), pralidoxime chloride (32 mg/kg) and either diazepam (2 mg/kg), avizafone (3.5 mg/kg) or saline solution. The highest dose of atropine (33.8 mg/kg) gave a protective effect in groups treated without anticonvulsants by reducing the severity of clinical signs and death within 24 h but also by decreasing seizure occurrence and brain injuries. When injected at the similar molar dose of 7 micromoles/kg, the protection of anticonvulsants against soman neurotoxicity was higher with the atropine/pralidoxime/avizafone combination than with atropine/pralidoxime/diazepam. Indeed, when atropine was used at the lowest dose, avizafone was found to prevent early mortality and seizures occurrence with better efficacy than diazepam. On the other hand, when added to the therapy, the both anticonvulsants did not prevent the moderate EEG depression (reduction of amplitude by 30-52%) observed under 2 LD50 soman. Moreover, the number of animals suffering from respiratory distress (defined as a decrease of minute ventilation of more than 20% from the baseline value) was enhanced when diazepam or avizafone were used in the therapy. This effect was dependent on the atropine dose and the nature of the anticonvulsant. The beneficial effects of the different therapeutics tested were assessed and compared to the previous data obtained with the same therapies against sarin and from the pharmacokinetics properties of the atropine/diazepam mixture.
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PMID:Protection against soman-induced neuropathology and respiratory failure: a comparison of the efficacy of diazepam and avizafone in guinea pig. 1678 1

We present a case of respiratory distress in a morbidly obese woman, which was complicated by a severe tracheal stenosis of the third to sixth cartilage. She had a history of sleep apnea and could only breathe sitting upright. An anesthetic, technique using dexmedetomidine was selected because of its properties of anxiolysis and sedation, with lack of respiratory depression. No intraoperative or postoperative opioids were required. Dexmedetomidine in high doses offers another approach to managing the patient with a compromised airway. Opioids were avoided in this patient, who was at major risk of postoperative respiratory depression and sleep apnea.
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PMID:Tracheal resection in the morbidly obese patient: the role of dexmedetomidine. 1698 Jan 64

An 11-month-old boy with multiple surface anomalies and respiratory distress due to upper airway narrowing developed generalized tonic seizures coinciding with apnea. The ictal electroencephalography showed an abrupt onset of right-sided unilateral rapid activity with increasing amplitude followed by bursts of spike and wave complexes. The seizures were completely controlled with non-intravenous high-dose phenobarbital therapy. The serum level of phenobarbital at seizure control was 8 microg/ml. The serum level of phenobarbital peaked as high as 123 microg/ml; the patient developed neither liver function abnormality nor hypotension which necessitated any pressor agents. Although the patient was intubated, spontaneous respiration was intact after seizure control. Extubation, however, failed twice because of diminished cough reflex. After decrease of the phenobarbital dose and the development of drug tolerance, the patient was successfully weaned from respiratory support. High-dose phenobarbital therapy is effective for refractory epilepsy in patients complicated by respiratory distress. Although it was reported that respiratory depression was not severe with high-dose phenobarbital therapy, respiratory status may worsen in such patients due to the diminished cough reflex. Therefore the careful and prolonged management is essential.
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PMID:[High-dose phenobarbital therapy is effective for the control of intractable tonic seizure with apnea in a case of multiple anomalies syndrome]. 1698 37

Two major epidemiological studies using standardized instruments for diagnosis have revealed that the prevalence of mental disorders in general hospital inpatients range from 41.3% to 46.5%. The most prevalent groups of psychiatric disorders among general hospital inpatients are organic mental illness, depressive disorders, and alcohol dependence or abuse. The prevalence rates of organic brain syndromes, adjustment disorders with depressed mood, and alcohol dependence in general hospital inpatients are above those of the general population. In nearly half of the studied general hospital inpatients receiving a psychiatric diagnosis Consultation-Liaison (C-L) psychiatry interventions were found to be necessary. However, psychiatric consultation rates found in most recently presented studies in Germany and Austria range from 2.66% to 3.30%, and remain low when compared to the reported prevalence figures of psychiatric disorders and the demonstrated necessity for specific therapeutic interventions among general hospital inpatients. There is also evidence stemming from newly presented C-L follow-up studies that the remarkable advances in intensive care treatment, organ transplantation medicine and cardiac surgery with cardiopulmonary bypass within the past decade have an important impact on the general hospital inpatients; psychosocial outcome. One follow-up study of long-term acute respiratory distress syndrome (ARDS) survivors using the Structural Clinical Interview for the DSM-IV (SCID) has shown that 43.5% of these patients met the criteria for a full posttraumatic stress disorder (PTSD), 8.9% of these patients for a subthreshold or partial PTSD (sub-PTSD) at hospital discharge, and 23.9% of them still suffered from full PTSD, 17.8% of them from sub-PTSD. ARDS-Patients with PTSD symptomatology exhibited major impairments in a variety of dimensions of health-related quality of life. Another outcome study examining concurrently psychiatric morbidity and quality of life in intermediate-term survivors of orthotopic liver transplantation (OLT) survivors has documented that 5.4% of these patients had a full PTSD, and 17.3% of them a sub-PTSD at 4 year-follow-up. OLT- related PTSD symptomatology was associated with maximal decrements in health-related quality of life. The duration of intensive care treatment, the number of medical complications, and the occurrence of acute rejection were positively correlated with the risk of PTSD symptoms subsequent to OLT. Finally, one prospective 1-year outcome study has focused on psychiatric morbidity including postoperative delirium in patients who had undergone cardiac surgery employing cardiopulmonary bypass. Postoperative delirium developed in 32.4% of these patients, however, only in 5.9% of them severe delirium was noted. Short-term consequences of cardiac surgery included adjustment disorders with depressed features (32.4%), acute full in-hospital PTSD (17.6%), and in-hospital major depression (17.6%). The diagnostic status of in-hospital PTSD was linked to postoperative delirium. At 12 months, the severity of depression and anxiety disorders including PTSD improved and returned to the preoperative level. However, patients who were found to have major depression or PTSD before discharge, C-L psychiatric consultations were conducted. In conclusion, PTSD symptoms following medical illness and treatment are not rare. If they are untreated, PTSD symptoms such as intrusive recollections, avoidance and hyper-arousal may impair the patients; quality of life more than the primary disease. This seems to be also true for a subthreshold PTSD. To adequately diagnose and treat patients at risk of developing PTSD, close collaboration between physicians of all subspecialties and C-L psychiatrists will be necessary.
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PMID:[Mental disorders in general hospital patients]. 1709 9


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