Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cases are described of 3 female adolescents evaluated at the Cincinnati Adolescent Clinic for delayed or incomplete secondary sexual development due to primary ovarian failure. All 3 patients had normal blood leukocyte and ovarian tissue karyotypes. The clinical, laboratory, and pathological findings are discussed with emphasis on distinguishing chromosome incompetent ovarian failure (CIOF-Turner's syndrome) from chromosome competent ovarian failure (CCOF). The patients included a 15 1/2 year old black female who sought evaluation of obesity and lethargy, a 17 1/2 year old white female with secondary amenorrhea in whom oral provera failed to induce menstrual flow, and a 17 1/2 year old black female with scanty, infrequent menses who achieved a normal amount and duration of menstrual flow with Norinyl 1 + 80. Hypoestrogenization should be suspected in cases of incomplete breast development for age, thin vaginal mucosa with a prepubertal pattern of the vaginal cytology, scant cervical mucus without ferning, and lack of withdrawal bleeding after progesterone administration. If any decrease in ovarian steroid production is clinically suspected in an adolescent with primary or secondary amenorrhea associated with delayed or incomplete puberty, serum gonadotropin levels should be measured. A single elevated follicle stimulating hormone (FSH) level in the menopausal range is diagnostic of primary ovarian failure in an adolescent. If the FSH is low or normal, hypothalamic or pituitary disease would be suspected. A blood leukocyte karyotype is the next diagnostic procedure for patients with primary ovarian failure to distinguish between CCOF and CIOF. If the blood karyotype is XO or a variant without a Y cell line, no further cytogenic workup or visualization of the gonads is needed, but girls with blood karyotype of XX or a mosaic pattern with 1 cell line with a Y chromosome should undergo laparoscopy and gonadal biopsy. A unilateral testis should be removed to avoid malignant changes in later years. Patients with CCOF may have other endocrine dysfunction, particularly autoimmune disease. Other possible diagnoses include resistant ovary syndrome, pure gonadal dysgenesis, premature menopause, or infectious, chemical, or other causes of ovarian failure. The incidence of CIOF is greater than that of CCOF among patients with primary ovarian failure. Optimal treatment requires medical and psychosocial intervention.
 ...
PMID:Chromosomally competent ovarian failure at adolescence. 631 54

Hypothyroidism is commonly thought to cause decreased gastric emptying and secretion, but these may be related to associated autoimmune disease or chronic changes. Therefore, we measured gastric emptying and secretion in 11 healthy controls and in nine patients (19-54 years old; five females and 4 males) rendered athyreotic by surgery and/or 131I for thyroid cancer. Replacement T4 was stopped 47-65 days and subsequent replacement T3 was stopped 33-40 days before the study. All patients were symptomatic with complaints including weight gain, lethargy, and constipation. Deep tendon reflexes had delayed relaxation phase. Serum cholesterol and creatine phosphokinase levels were elevated. Thyroid hormone levels were markedly decreased (means +/- SE; T4: 0.7 +/- 0.3 micrograms/dl; free T4: 0.2 +/- 0.1 ng/dl; T3: 28 +/- 6 ng/dl) and TSH was markedly increased (88 +/- 16 microU/ml). Gastric fractional emptying rate (%/min) and hydrogen ion (H+) output (meq/hr) were determined before and following two sequential stimulations: a 250-ml water load and an intravenous infusion of pentagastrin (6 micrograms/kg/hr). There were no significant differences between controls and athyreotic patients. Our data demonstrated that short-term, profound, thyroid hormone deficiency does not modify gastric emptying or acid output.
 ...
PMID:Gastric secretion and emptying in hypothyroidism. 671 56

Most attempts at developing a model of autoimmune inner ear disease have focused on the immunization of healthy animals with cochlear tissue. We have chosen an alternate route of studying this entity utilizing the MRL-lpr/lpr (Lupus) mouse, an animal known to spontaneously develop multisystemic, organ nonspecific autoimmune disease. We report on the auditory pathology found in animals at early stages of this systemic disease. At the onset of clinical signs of illness (cachexia, weight loss, lethargy) animals were sacrificed and their cochleas and kidney prepared for morphologic analysis. Significant pathology was seen in the MRL/lpr animals involving the basal and middle turns of the cochlea which could not be correlated with the presence or degree of glomerulonephritis. Findings included outer and inner haircell degeneration, strial edema and degeneration, and an acellular infiltrate in the tunnel of Corti. Cochlear pathology was not found in control animals. Thus, at early stages of systemic disease, MRL/lpr mice manifest significant cochlear pathology not seen in control animals. The implications of these results with regard to the pathogenesis of these lesions as well as their clinical relevance are discussed.
 ...
PMID:The MRL-lpr/lpr mouse: a potential model of autoimmune inner ear disease. 847 29

Primary biliary cirrhosis (PBC) is a chronic progressive cholestatic disease where there is progressive, granulomatous destruction of the middle-sized bile ducts. The disease affects mainly middle-aged women. The association with other autoimmune diseases and the widespread disturbance of the humoral and cellular immune systems has led to the inclusion of PBC as an autoimmune disease. However, there are several lines of evidence that suggest that both host and environmental factors are implicated in triggering the disease. Without a clear aetiology, it is difficult to find a logical approach to treatment. Well constructed clinical trials are difficult to run because of the variable and long natural history of the disease; and suitable endpoints are difficult to define and validated surrogate endpoints have not been defined. The only drug licensed for use is the bile acid, ursodeoxycholic acid. This drug is associated with significant biochemical improvement and improvement in the immunological disturbances (including a reduction in the titre of the diagnostic autoantibody, antimitochondrial antibody), but the effect on survival and histological progression is still controversial. There is little effect on symptoms. Nonetheless, its safety and lack of toxicity have meant that it has become the drug of choice and most studies now assess the effect of additional treatments. Many other agents have been studied. There is some evidence, from prospective, controlled studies, for a beneficial effect of azathioprine and ciclosporin (cyclosporine); evidence for a beneficial effect of corticosteroids and of mycophenolate is limited and there is little firm evidence for a beneficial effect of methotrexate, penicillamine, thalidomide or colchicine. Other treatments being evaluated include fibric acid derivatives (fibrates), NSAIDs and leukotriene antagonists. Liver transplantation remains the only option for end-stage disease but recurrence of disease may be found in the graft. Experimental therapies include antiretroviral therapy. Symptomatic treatment is required for pruritus and the mainstays are the bile acid binding agents such as colestyramine. For those who are intolerant of the drug or where it is ineffective, rifampicin and naltrexone may be effective. There is no effective treatment for the associated lethargy.
 ...
PMID:Options for treatment of primary biliary cirrhosis. 1545 26

A Belgian draft horse stallion presented with classical signs of purpura haemorrhagica: oedema of the distal limbs, ventral abdomen and head, ecchymotic haemorrhage of mucous membranes, epistaxis, fever, lethargy, reluctance to move, and anorexia. Serum chemistry revealed a highly elevated gamma-globulin fraction. Streptococcal lymphadenitis (strangles) had been present on a neighbouring farm in the past few months. After an initial positive response to therapy with benzylpenicillin, flunixin and dexamethasone, the horse's condition deteriorated suddenly on day 4 of hospitalization, with signs of severe endotoxaemia and small-intestine obstruction. The horse was euthanized because of its poor prognosis and because of economic considerations. On necropsy, large serosal haemorrhages in the small and large intestine and multiple jejunojejunal intussusceptions were found. Intussusception is a well-known complication in children with Henoch-Schonlein purpura, a human autoimmune disease resembling purpura haemorrhagica in horses. To the author's knowledge, this is the first report to describe intussusception as a complication of purpura haemorrhagica in a horse.
 ...
PMID:Multiple small-intestine intussusceptions: a complication of purpura haemorrhagica in a horse. 2169 93

Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease of the central nervous system (CNS) that typically presents as a monophasic disorder associated with multifocal neurologic symptoms and encephalopathy. ADEM is considered an autoimmune disorder that is triggered by an environmental stimulus in genetically susceptible individuals. The diagnosis of ADEM is based on clinical and radiological features. Most children with ADEM initially present with fever, meningeal signs, and acute encephalopathy. The level of consciousness ranges from lethargy to frank coma. Deep and subcortical white-matter lesions and gray-matter lesions such as thalami and basal ganglia on magnetic resonance imaging (MRI) are associated with ADEM. In a child who presents with signs of encephalitis, bacterial and viral meningitis or encephalitis must be ruled out. Sequential MRI is required to confirm the diagnosis of ADEM, as relapses with the appearance of new lesions on MRI may suggest either multiphasic ADEM or multiple sclerosis (MS). Pediatric MS, defined as onset of MS before the age of 16, is being increasingly recognized. MS is characterized by recurrent episodes of demyelination in the CNS separated in space and time. The McDonald criteria for diagnosis of MS include evidence from MRI and allow the clinician to make a diagnosis of clinically definite MS on the basis of the interval preceding the development of new white matter lesions, even in the absence of new clinical findings. The most important alternative diagnosis to MS is ADEM. At the initial presentation, the 2 disorders cannot be distinguished with certainty. Therefore, prolonged follow-up is needed to establish a diagnosis.
 ...
PMID:Acute disseminated encephalomyelitis in children: differential diagnosis from multiple sclerosis on the basis of clinical course. 2194 17

Seventy-four 9-week old female C57BL/6J mice housed in a conventional facility were manipulated to induce experimental autoimmune encephalomyelitis, among which 26 developed clinical signs including lethargy, absence of defecation, and abdominal distension. By gross necropsy examination, there was distension of the cecum and colon with fecal impaction. By histologic examination, there was severe ulcerative and proliferative typhlocolitis. Fecal ELISA confirmed the presence of toxins A and B of Clostridium difficile. Alteration in immune status of the immunocompetent mice, due to stress caused by experimental manipulation or autoimmune disease, may have led to intestinal dysbiosis, followed by opportunistic infections resulting in C. difficile-associated disease. This report brings to light the occurrence of the disease in immunocompetent laboratory mice during experimental manipulations associated with alteration in immune status, and it discusses potential hazards associated with conventional housing within a hospital-associated research institute.
 ...
PMID:Outbreak of abdominal distension and obstipation in a C57BL/6J experimental autoimmune encephalomyelitis study. 2226 50

A two and half year old female was admitted at the emergency room suffering from gradually worsening headache followed by nausea. The child presented with reduced level of consciousness and bilateral hypoacusis. The patient was lethargic. Ophthalmic examination showed branch retinal artery occlusion (BRAO). This finding was crucial to the diagnosis of Susac's syndrome (SS), a rare autoimmune disease characterized by, endotheliopathy of retina, encephalic tissues and cochlea. Magnetic resonance imaging of the brain also showed typical features. Thorough blood investigations did not reveal any other abnormality. Patient was treated with immunosuppressive to prevent her from developing severe sequelae of this disease. The child showed dramatic improvement in her systemic condition within 48 h of starting the treatment. This is the youngest ever and first case report from India.
...
PMID:Susac's syndrome: first from India and youngest in the world. 2408 34

A humanized TLR7/TLR8 transgenic mouse line was engineered for studies using TLR7/8 ligands as vaccine adjuvants. The mice developed a spontaneous immune-mediated phenotype prior to six months of age characterized by runting, lethargy, blepharitis, and corneal ulceration. Histological examination revealed a marked, multisystemic histiocytic infiltrate that effaced normal architecture. The histological changes were distinct from those previously reported in mouse models of systemic lupus erythematosus. When the mice were crossed with MyD88-/- mice, which prevented toll-like receptor signaling, the inflammatory phenotype resolved. Illness may be caused by constitutive activation of human TLR7 or TLR8 in the bacterial artificial chromosome positive mice as increased TLR7 and TLR8 expression or activation has previously been implicated in autoimmune disease.
...
PMID:Humanized TLR7/8 expression drives proliferative multisystemic histiocytosis in C57BL/6 mice. 2522 18