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)

For the treatment of HBV/HIV-co-infection, study data on interferon-based therapy are very limited and insufficient to draw any specific conclusions. In contrast, data on HBV-polymerase inhibitors (lamivudine, adefovir, tenofovir) are available from controlled trials. Lamivudine is well tolerated and safe, however, development of HBV-resistance is frequent. Adefovir has a nephrotoxic potential and may at least theoretically induce antiretroviral resistance in HBV/HIV-patients treated with adefovir. Tenofovir has gastrointestinal side effects, is associated with hypophospatemia, which has not induced serious osteopenia so far and may have a nephrotoxic potential. For HCV/HIV-co-infection pegylated interferon alpha plus ribavirin is standard of care. Flu-like symptoms, fatigue and depressive mood changes are frequent. In patients with a history of neurotic or minor depression initiation of treatment with antidepressants before the start of interferon-based therapy should be considered. Weight loss may be pronounced in individual cases. A marked decrease in absolute, but not relative CD4 +/- cells is the rule, but no relevant increase in opportunistic infection was observed, and anaemia (<10 g/dl) is reported in up to 30% of patients. Neutropenia (< 1,000 cells/microl) is observed in up to 50% of the patients. Adverse events specific to the HCV/HIV-patient population as compared to HCV-mono-infected patients are the occurrence of hyperlactataemia/lactic acidosis and hepatic decompensation.
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PMID:Treatment of viral hepatitis in HIV-coinfected patients-adverse events and their management. 1635 79

Mitochondrial DNA (mtDNA) disease is an important genetic cause of neurological disability. A variety of different clinical features are observed and one of the most common phenotypes is MELAS (Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis and Stroke-like episodes). The majority of patients with MELAS have the 3243A>G mtDNA mutation. The neuropathology is dominated by multifocal infarct-like lesions in the posterior cortex, thought to underlie the stroke-like episodes seen in patients. To investigate the relationship between mtDNA mutation load, mitochondrial dysfunction and neuropathological features in MELAS, we studied individual neurones from several brain regions of two individuals with the 3243A>G mutation using dual cytochrome c oxidase (COX) and succinate dehydrogenase (SDH) histochemistry, and Polymerase Chain Reaction Restriction Fragment Lenght Polymorphism (PCR-RFLP) analysis. We found a low number of COX-deficient neurones in all brain regions. There appeared to be no correlation between the threshold level for the 3243A>G mutation to cause COX deficiency within single neurones and the degree of pathology in affected brain regions. The most severe COX deficiency associated with the highest proportion of mutated mtDNA was present in the walls of the leptomeningeal and cortical blood vessels in all brain regions. We conclude that vascular mitochondrial dysfunction is important in the pathogenesis of the stroke-like episodes in MELAS patients. As migraine is a commonly encountered feature in MELAS, we propose that coupling of the vascular mitochondrial dysfunction with cortical spreading depression (CSD) might underlie the selective distribution of ischaemic lesions in the posterior cortex in these patients.
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PMID:Molecular neuropathology of MELAS: level of heteroplasmy in individual neurones and evidence of extensive vascular involvement. 1686 82

The central nervous system (CNS) is, after the peripheral nervous system, the second most frequently affected organ in mitochondrial disorders (MCDs). CNS involvement in MCDs is clinically heterogeneous, manifesting as epilepsy, stroke-like episodes, migraine, ataxia, spasticity, extrapyramidal abnormalities, bulbar dysfunction, psychiatric abnormalities, neuropsychological deficits, or hypophysial abnormalities. CNS involvement is found in syndromic and non-syndromic MCDs. Syndromic MCDs with CNS involvement include mitochondrial encephalomyopathy, lactacidosis, stroke-like episodes syndrome, myoclonic epilepsy and ragged red fibers syndrome, mitochondrial neuro-gastrointestinal encephalomyopathy syndrome, neurogenic muscle weakness, ataxia, and retinitis pigmentosa syndrome, mitochondrial depletion syndrome, Kearns-Sayre syndrome, and Leigh syndrome, Leber's hereditary optic neuropathy, Friedreich's ataxia, and multiple systemic lipomatosis. As CNS involvement is often subclinical, the CNS including the spinal cord should be investigated even in the absence of overt clinical CNS manifestations. CNS investigations comprise the history, clinical neurological examination, neuropsychological tests, electroencephalogram, cerebral computed tomography scan, and magnetic resonance imaging. A spinal tap is indicated if there is episodic or permanent impaired consciousness or in case of cognitive decline. More sophisticated methods are required if the CNS is solely affected. Treatment of CNS manifestations in MCDs is symptomatic and focused on epilepsy, headache, lactacidosis, impaired consciousness, confusion, spasticity, extrapyramidal abnormalities, or depression. Valproate, carbamazepine, corticosteroids, acetyl salicylic acid, local and volatile anesthetics should be applied with caution. Avoiding certain drugs is often more beneficial than application of established, apparently indicated drugs.
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PMID:Central nervous system manifestations of mitochondrial disorders. 1694 41

Propofol-induced metabolic acidosis is well recognised in the paediatric literature, but the existence of such a syndrome in adults remains contentious. In most reported cases, metabolic acidosis complicated prolonged administration of propofol in critically ill patients. We present a case of severe non-fatal reversible metabolic acidosis, without ventilatory depression or hypoxia, related to short-term propofol infusion in an adult during and after coronary artery bypass grafting. We suggest that lactic acidosis occurred in a genetically susceptible patient with an abnormality of mitochondrial function. This report discusses an unusual adverse effect of propofol anaesthesia and sedation and highlights the need for further investigation to define propofol toxicity.
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PMID:Short-term low-dose propofol anaesthesia associated with severe metabolic acidosis. 1706 43

A 53-year-old man with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) underwent a gastrectomy. We administered bicarbonated Ringer's solution, which has a physiological concentration of bicarbonate. The level of serum lactate did not increase significantly, and metabolic acidosis did not occur throughout surgery or for 3 h after surgery. Aggressive warming was needed to maintain normothermia, presumably because the mitochondrial respiratory chain, which is responsible for thermogenesis, is impaired in MELAS patients. It is important to maintain normothermia in MELAS patients in order to avoid further mitochondrial metabolic depression.
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PMID:Anesthetic management of a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) during laparotomy. 1728 19

Apical hypertrophic cardiomyopathy (AHC) is associated with neurological abnormalities such as transient ischemic attack, stroke, limb-girdle muscular dystrophy, or eosinophilic myositis in single cases. The association of AHC and metabolic myopathy has not been reported. In an 84-year-old woman with long-standing gait disturbance, dementia, Parkinson syndrome, ptosis, ophthalmoparesis, tetraparesis, polyneuropathy, lactacidosis, polyarthralgia, dorsalgia, and osteoporosis, cardiac examination for long-standing anginal chest pain and palpitations, revealed supraventricular and monomorphic ventricular ectopic beats, hypertrophic signs, ST-depression and negative T waves on electrocardiogram (ECG), diastolic dysfunction with impaired relaxation, and AHC on transthoracic echocardiography. AHC was confirmed by cardiac magnetic resonance imaging, which additionally showed a small left ventricular apical aneurysm with a wall-thickness of only 3 mm. The patient was suspected to additionally have a multisystem disease, most likely due to impaired oxidative metabolism. This case shows that AHC may take a mild course and be associated with a number of extracardiac abnormalities.
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PMID:Apical hypertrophic cardiomyopathy in encephalomyopathy. 1816 25

Fatigue-induced changes in the proprioceptive reflex loop were explored in humans by using the tonic electromyographic (EMG) response to vibration (TVR) and relating it to lactic acidosis (LA) and oxidative stress. TVR was measured in flexor digitorum superficialis before and after sustained or intermittent handgrip at maximal voluntary contraction (MVC). TVR variations were compared with the changes in EMG power spectrum preceding contractile fatigue, the Hoffman reflex (H-reflex), and plasma concentrations of LA and thiobarbituric acid reactive substances (TBARS). After both sustained and intermittent handgrips, TVR amplitude first declined then increased, independently from the changes in EMG power spectrum and H-reflex. TVR depression and facilitation were respectively concomitant with increases in LA and TBARS. The TVR depression was proportional to the increased LA level. The origin of TVR changes after muscle fatigue is questioned because the relationship between TVR depression and LA accumulation might be temporal, not causal, and changes in muscle stiffness were not explored.
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PMID:Fatigue-induced changes in tonic vibration response (TVR) in humans: relationships between electromyographic and biochemical events. 1881 27

Since the initial description almost 25 years ago, the syndrome of mitochondrial encephalopathy, lactic acidosis, and strokelike episodes (MELAS) has been a useful model to study the complex interplay of factors that define mitochondrial disease. This syndrome, most commonly caused by an A-to-G transition mutation at position 3243 of the mitochondrial genome, is typified by characteristic neurological manifestations including seizures, encephalopathy, and strokelike episodes, as well as other frequent secondary manifestations including short stature, cognitive impairment, migraines, depression, cardiomyopathy, cardiac conduction defects, and diabetes mellitus. In this review, we discuss the history, pathogenesis, clinical features, and diagnostic and management strategies of mitochondrial disease in general and of MELAS in particular. We explore features of mitochondrial genetics, including the concepts of heteroplasmy, mitotic segregation, and threshold effect, as a basis for understanding the variability and complicated inheritance patterns seen with this group of diseases. We also describe systemic manifestations of MELAS-associated mutations, including cardiac, renal, endocrine, gastrointestinal, and endothelial abnormalities and pathology, as well as the hypothetical role of derangements to COX enzymatic function in driving the unique pathology and clinical manifestations of MELAS. Although therapeutic options for MELAS and other mitochondrial diseases remain limited, and recent trials have been disappointing, we also consider current and potential therapeutic modalities.
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PMID:Mitochondrial encephalopathy, lactic acidosis, and strokelike episodes: basic concepts, clinical phenotype, and therapeutic management of MELAS syndrome. 1899 Jan 25

Three months previously, a 17-year-old girl had complained of right-hand side hemiparesis, and her brain magnetic resonance imaging (MRI) showed a signal change in the left temporoparietooccipital area. The 3243A>G mutation was found in mitochondrial DNA. She was diagnosed with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and was prescribed dichloroacetic acid to treat lactic acidosis. Her health improved. Two months later, she developed drowsiness and generalized weakness. A New lesion was not found on brain MRI, and electrodiagnostic findings were compatible with acute motor sensory axonal neuropathy. Her negative symptoms, such as depressed mood, loss of interest in activities, psychomotor retardation, and hypersomnia, were aggravated. She was prescribed antidepressants and psychostimulants by a psychiatrist after diagnosis of severe depression episode with catatonic features. One month later, her catatonic condition had improved with medication. Our experience shows that psychiatric diagnostic evaluation of abruptly regressed neurologic and clinical features is important, even in a patient with devastating underlying disease.
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PMID:Depressive episode with catatonic features in a case of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). 1945 Dec 68

There are several problems in anesthetic management for patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS); susceptibility to malignant hyperthermia, metabolic disorders such as lactic acidosis and diabetes, and dysfunction of vital organs such as cardiomyopathy. Here we report an anesthetic management of emergency laparotomy in a 58-year-old woman with MELAS and systemic inflammatory response syndrome (SIRS). Pre-operative examinations revealed lactic acidosis, hyperglycemia, moderate cardiac depression, and slightly decreased renal function. We chose total intravenous anesthesia to avoid risks of malignant hyperthermia. Anesthesia was induced by rapid-sequence fashion and maintained using midazolam, propofol, ketamine, fentanyl and vecuronium. Based on arterial blood gas analyses, we adjusted ventilator settings, restored blood volume using acetated-Ringer's solution and alubumin preparation with transfusion, and administered sodium bicarbonate and catecholamines, to keep adequate oxygen demand/supply balance and improve acid-base balance. We applied a patient warming system to avoid the progression of hypothermia. After the surgery, the patient was transferred to the intensive care unit, and underwent the endotoxin absorption therapy as well as antibiotics therapy for the treatment of SIRS. The post-operative course was almost uneventful. We consider that careful anesthetic management was essential for the uneventful peri-operative course of this patient.
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PMID:[Anesthetic management of emergency total gastrectomy in a patient with mitochondrial encephalomyopathy: a case of gastric perforation accompanied by systemic inflammatory response syndrome]. 2056 Mar 85


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