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

We evaluated spinal and femoral bone mass and density utilizing dual-energy x-ray absorptiometry (DEXA) in rats in which severe hyperparathyroidism was produced by the expression of the gene for human PTH-(1-84) (hPTH). This gene was incorporated into a retroviral vector that was transfected into fibroblasts which were subsequently injected into their peritoneal cavities. Further, we examined the effect of the administration of pamidronate on bone mass and density in the presence of extremely high concentrations of hPTH. Three groups of rats were studied. Groups 1 and 2 receive the hPTH-secreting fibroblasts; group 2 subsequently received pamidronate (2.5 mg/kg IV) 18 and 27 days after receiving the fibroblasts. These animals developed levels of hPTH greater than 1.0 microgram/liter and became hypercalcemia within 20 days. These animals became lethargic and were significantly lower in weight than age-matched controls (group 3, p less than 0.05). After accounting for the animal weight there was a further significant decrease in bone mineral content and density (BMC and BMD) on day 29 attributable to hPTH-mediated bone loss. Treatment with pamidronate resulted in a higher BMC of the lumbar spine than in the untreated animals, with elevated concentrations of hPTH. The BMD was significantly higher at both the lumbar spine and femur in the pamidronate-treated animals (p less than 0.05). The CV of paired measurements of BMD was 2.7% at the spine and 1.5% of a femur, respectively. The BMC of the lumbar spine and femur was closely correlated with the ashed weight of the same bones (r = 0.92 and 0.85, respectively).
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PMID:Pamidronate reduces PTH-mediated bone loss in a gene transfer model of hyperparathyroidism in rats. 179 42

The concept of an androgen deficiency syndrome in women is a relatively old one, although it has gained substantially increased attention in recent years. Androgens are quantitatively the predominant sex steroid in women, circulating in the micro- and nanomolar concentration range, compared with picomolar levels of oestrogen. The most significant biologically active androgen is testosterone, which circulates bound tightly to sex hormone-binding globulin (SHBG) and loosely to albumin. It is generally held that the non-SHBG bound fraction is the bioavailable moiety. Hence interpretable testosterone measurements require data on total concentrations as well as the SHBG level. Testosterone deficiency occurs in a number of situations such as hypopituitarism, primary ovarian and adrenal failure, exogenous corticosteroid use and oral oestrogen therapy (due to the elevation of SHBG and suppression of gonadotrophins). Clinical symptoms of androgen deficiency include lethargy, tiredness and loss of sex drive and interest, and have responded well to androgen replacement, generally without significant side-effects.
Best Pract Res Clin Obstet Gynaecol 2002 Jun
PMID:The role of androgen therapy. 1209 69

Abdominal epilepsy is an uncommon syndrome in which gastrointestinal complaints, most commonly abdominal pain, result from seizure activity. It is characterized by (1) otherwise unexplained, paroxysmal gastrointestinal complaints, (2) symptoms of a central nervous system disturbance, (3) an abnormal electroencephalogram with findings specific for a seizure disorder, and (4) improvement with anticonvulsant medication. We review the history of the syndrome and analyze all 36 cases reported in the English literature from the last 34 years. The most common gastrointestinal symptoms include abdominal pain, nausea and vomiting, while the most common neurological symptoms include lethargy and confusion. After exclusion of more common etiologies for the presenting complaints, workup should proceed with an electroencephalogram. Where the diagnosis is seriously considered, neurological consultation should be considered. Treatment typically begins with anticonvulsant medication, and resolution of symptoms with therapy helps to confirm the diagnosis.
Best Pract Res Clin Gastroenterol 2005 Apr
PMID:Abdominal epilepsy. 1583 92

Mutations in VMD2, encoding bestrophin (best-1), cause Best vitelliform macular dystrophy (BMD), adult-onset vitelliform macular dystrophy (AVMD), and autosomal dominant vitreoretinochoroidopathy (ADVIRC). BMD is distinguished from AVMD by a diminished electrooculogram light peak (LP) in the absence of changes in the flash electroretinogram. Although the LP is thought to be generated by best-1, we find enhanced LP luminance responsiveness with normal amplitude in Vmd2-/- mice and no differences in cellular Cl- currents in comparison to Vmd2+/+ littermates. The putative Ca2+ sensitivity of best-1, and our recent observation that best-1 alters the kinetics of voltage-dependent Ca2+ channels (VDCC), led us to examine the role of VDCCs in the LP. Nimodipine diminished the LP, leading us to survey VDCC beta-subunit mutant mice. Lethargic mice, which harbor a loss of function mutation in the beta4 subunit of VDCCs, exhibited a significant shift in LP luminance response, establishing a role for Ca2+ in LP generation. When stimulated with ATP, which increases [Ca++]I, retinal pigment epithelial cells derived from Vmd2-/- mice exhibited a fivefold greater response than Vmd2+/+ littermates, indicating that best-1 can suppress the rise in [Ca2+]I associated with the LP. We conclude that VDCCs regulated by a beta4 subunit are required to generate the LP and that best-1 antagonizes the LP luminance response potentially via its ability to modulate VDCC function. Furthermore, we suggest that the loss of vision associated with BMD is not caused by the same pathologic process as the diminished LP, but rather is caused by as yet unidentified effects of best-1 on other cellular processes.
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PMID:The light peak of the electroretinogram is dependent on voltage-gated calcium channels and antagonized by bestrophin (best-1). 1663 5

Central adrenal insufficiency (CAI) is a life-threatening condition caused by either pituitary disease (secondary adrenal insufficiency) or impaired hypothalamic function with inadequate CRH production (tertiary adrenal insufficiency). ACTH deficiency may be isolated or, more frequently, occur in conjunction with other pituitary hormone deficiencies and midline defects. Genetic mutations of the TBX19 causing isolated CAI are rare but a number of genes encoding transcription factors involved in hypothalamic-pituitary gland development, as well as other genes including POMC and PC1, are associated with ACTH deficiency. CAI is frequently identified in congenital, malformative, genetic, and epigenetic syndromes as well as in several acquired conditions of different etiologies. The signs and symptoms vary considerably and depend on the age of onset and the number and severity of associated pituitary defects. They may include hypoglycemia, lethargy, apnea, poor feeding, prolonged cholestatic jaundice, jitteriness, seizures, and sepsis in the neonate, or nonspecific signs such as fatigue, hypotension, vomiting and hyponatremia without hyperkalemia in children. The diagnosis of CAI relies on the measurement of morning cortisol concentrations along with dynamic test for cortisol release with different stimulating agents. Early recognition of CAI and its correct management are mandatory in order to avoid both morbidity and mortality in affected neonates, children and adolescents.
Best Pract Res Clin Endocrinol Metab 2018 08
PMID:Central adrenal insufficiency in children and adolescents. 3008 67