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)

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.
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PMID:Chromosomally competent ovarian failure at adolescence. 631 54

This paper outlines methods of therapy utilizing newer combinations of estrogens and progestins. The specific agent and length of treatment depends on the extent of disease, severity of symptoms, presence of infertility and response to pseudopregnancy. Structural formulas for 19 synthetic preparations are shown. Of 36 patients with proven endometriosis in which pseudopregnancy was induced by the use of these newer agents, satisfactory objective in 82%. Pregnancy occurred later in 6 of 10 patients who had previously been infertile and wished to become pregnant. The optimum maintenance dose is 4-6 mg of chlormadinone acetate or ethnodiol diacetate with .2 mg of mestranol and 5-10 mg of megestrol acetate with .2 mg of ethniyl estradiol. Dosage is increased only when break through bleeding occurs. Gain in weight occurred in almost 1/2 of the patients. The decidual reaction was just as great as that produced formerly by large doses of Enovid. In a more recent study 60 patients were treated with Norlestrin, 20 with Lyndiol and 20 with Ovral. Satisfactory objective and subjective remissions were obtained in 89%. Pregnancy has occurred subsequently in 17 to 43 patients who desired pregnancy. All infants have been normal. The optimum maintenance doses seem to be 10-15 mg if Norlestrin, 2.5-5 mg Lyndiol or .5-1 mg of Ovral. The most common side effect was weight gain in 35%. These agents may be used prior to conservative surgery in order to soften areas of fibrotic endometriosis or to pinpoint areas otherwise overlooked. The length of preoperative treatment depends on the extent of disease, 6 weeks being usual. The indication for prolonged pseudopregnancy is recurrent endometriosis following surgery, also proven vaginal endometriosis. Subsequent to conservative surgery, 12 to 24 weeks of therapy are given in order to inhibit ovulation and prevent reactivation of any remaining areas of endometriosis. Tables show commercial combinations and dosage regimens. Nausea, break through bleeding, breast soreness, acne, water retention, isoninia, irritability, lethargy, headaches or development of leiomyomas are side effects to be dealt with by modifying the treatment. Thromboembolic disease has not been a complication in over 500 patients but should be looked for as it has been reported by others. The effect of long-term use of these drugs has been shown to be entirely reversible without subsequent deleterious effects. Severe hepatic disease or previous mammary carcinoma are contraindications. Excessive side effects may necessitate other treatment but the newer drugs reduce this chance. The diagnosis of endometriosis should first be proven.
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PMID:Newer synthetic progestins for the treatment of endometriosis. 1233 29

The prevalence of attention-deficit hyperactivity disorder (ADHD) in the USA is estimated at approximately 4-9% in children and 4% in adults. It is estimated that prescriptions for ADHD medications are written for more than 2.7 million children per year. In 2010, US poison centers reported 17,000 human exposures to ADHD medications, with 80% occurring in children <19 years old and 20% in adults. The drugs used for the treatment of ADHD are diverse but can be roughly separated into two groups: the stimulants such as amphetamine, methylphenidate, and modafinil; and the non-stimulants such as atomoxetine, guanfacine, and clonidine. This review focuses on mechanisms of toxicity after overdose with ADHD medications, clinical effects from overdose, and management. Amphetamine, dextroamphetamine, and methylphenidate act as substrates for the cellular monoamine transporter, especially the dopamine transporter (DAT) and less so the norepinephrine (NET) and serotonin transporter. The mechanism of toxicity is primarily related to excessive extracellular dopamine, norepinephrine, and serotonin. The primary clinical syndrome involves prominent neurological and cardiovascular effects, but secondary complications can involve renal, muscle, pulmonary, and gastrointestinal (GI) effects. In overdose, the patient may present with mydriasis, tremor, agitation, hyperreflexia, combative behavior, confusion, hallucinations, delirium, anxiety, paranoia, movement disorders, and seizures. The management of amphetamine, dextroamphetamine, and methylphenidate overdose is largely supportive, with a focus on interruption of the sympathomimetic syndrome with judicious use of benzodiazepines. In cases where agitation, delirium, and movement disorders are unresponsive to benzodiazepines, second-line therapies include antipsychotics such as ziprasidone or haloperidol, central alpha-adrenoreceptor agonists such as dexmedetomidine, or propofol. Modafinil is not US FDA approved for treatment of ADHD; however, it has been shown to improve ADHD signs and symptoms and has been used as an off-label pharmaceutical for this diagnosis in both adults and children. The mechanism of action of modafinil is complex and not fully understood. It is known to cause an increase in extracellular concentrations of dopamine, norepinephrine, and serotonin in the neocortex. Overdose with modafinil is generally of moderate severity, with reported ingestions of doses up to 8 g. The most common neurological effects include increased anxiety, agitation, headache, dizziness, insomnia, tremors, and dystonia. The management of modafinil overdose is largely supportive, with a focus on sedation, and control of dyskinesias and blood pressure. Atomoxetine is a selective presynaptic norepinephrine transporter inhibitor. The clinical presentation after overdose with atomoxetine has generally been mild. The primary effects have been drowsiness, agitation, hyperactivity, GI upset, tremor, hyperreflexia, tachycardia hypertension, and seizure. The management of atomoxetine overdose is largely supportive, with a focus on sedation, and control of dyskinesias and seizures. Clonidine is a synthetic imidazole derivative with both central and peripheral alpha-adrenergic agonist actions. The primary clinical syndrome involves prominent neurological and cardiovascular effects, with the most commonly reported features of depressed sensorium, bradycardia, and hypotension. While clonidine is an anti-hypertensive medication, a paradoxical hypertension may occur early with overdose. The clinical syndrome after overdose of guanfacine may be mixed depending on central or peripheral alpha-adrenoreceptor effects. Initial clinical effects may be drowsiness, lethargy, dry mouth, and diaphoresis. Cardiovascular effects may depend on time post-ingestion and may present as hypotension or hypertension. The management of guanfacine overdose is largely supportive, with a focus on support of blood pressure. Overdose with ADHD medications can produce major morbidity, with many cases requiring intensive care medicine and prolonged hospital stays. However, fatalities are rare with appropriate care.
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PMID:Overdose of drugs for attention-deficit hyperactivity disorder: clinical presentation, mechanisms of toxicity, and management. 2375 86