Gene/Protein Disease Symptom Drug Enzyme Compound
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Chronic renal failure is almost invariably accompanied by symptomatic anemia. It has been demonstrated that the primary cause of this anemia is inadequate production of erythropoietin by the diseased kidneys. The isolation of erythropoietin, followed by the cloning and expression of the human erythropoietin gene, made possible clinical trials of rHuEPO in uremic patients. rHuEPO produced dramatic increases in the hematocrit in almost all patients treated and also ameliorated many symptoms, such as lethargy, dizziness, and poor appetite, that had long been attributed to the effect of uremic toxins. Adverse effects of treatment with rHuEPO noted in the early clinical trials included hypertension, seizures, arteriovenous fistula or shunt thrombosis, and hyperkalemia. Further study of rHuEPO has shown that many of these side effects may be no more frequent in patients receiving rHuEPO than in other uremic patients not receiving rHuEPO. Reduction of the rHuEPO dosage and subcutaneous administration produce less rapid increases in the hematocrit and may lessen the incidence and severity of these side effects. rHuEPO therapy places great demands on both the body's iron stores and the capacity to rapidly transfer iron from storage sites to the erythroid progenitor cells. Thus, almost all patients treated with rHuEPO become iron deficient and require oral or parenteral iron replacement. Response to rHuEPO in uremic patients is diminished if the anemia is complicated by iron deficiency, inflammatory disorders, aluminum overload, or deficiency of folate or vitamin B12. rHuEPO therapy is safe and effective in the treatment of the anemia of chronic renal failure. The use of rHuEPO leads to enhanced quality of life and eliminates the need for red cell transfusions. In addition to hemodialysis patients, predialysis patients and those on CAPD benefit from and are candidates for rHuEPO therapy.
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PMID:Anemia of renal failure. Use of erythropoietin. 157 66

A 69-year-old female was treated for hyperthyroidism and hypertension. In August 1984, she suddenly began suffering from polyuria and polydipsia. In October, she exhibited fever, headache, vertigo, and poor appetite, probably due to pituitary apoplexy. Her endocrine function was normal, except for partial diabetes insipidus. A contrast-enhanced CT brain scan revealed a pituitary adenoma with a ring-enhanced outer edge and a central low-density area. The MRI scan also indicated cystic adenoma. A CT scan examination repeated 6 months later showed an empty sella with a markedly decreased pituitary adenoma. This case report demonstrates that some empty sella are the final result of pituitary adenoma bleeding or infarction.
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PMID:Pituitary adenoma results in the empty sella syndrome. 258 92

Dietitians are multifunctional and play an important role in humanitarian missions as educators, planners, and consultants. Three dietitians deployed to Thailand in support of the 16th Annual Joint and Combined Exercise, Cobra Gold 1997. The goal of the Medical Civic Assistance Program (MEDCAP) was to promote long-term public health improvements in rural Thai villages. The dietitians counseled 140 patients and taught an additional 5,300 individuals during nutrition classes. The primary nutrition-related clinical diagnoses included malnutrition, anemia, diabetes, hypertension, goiter, and poor appetite. The dietitian who deployed as the medical planner and MEDCAP executive officer facilitated coordination and planning for all phases of the MEDCAP operation. The teams were made up of U.S. and Thai military forces and Thai civilian medical personnel. The mission requirements were established with the Royal Thai Supreme Command, Thai governors, Ministry of Public Health officers, military and medical officers, and veterinarians of the three provinces.
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PMID:U.S. Army dietitians deploy in support of Cobra Gold: a humanitarian mission. 1041 64

Polya partial gastrectomy was performed for peptic ulcer in a previously healthy woman aged 28 years. She complained afterwards of a variety of non-specific symptoms including weakness, tiredness, debility, slowness of walking, poor appetite and constipation. Within ten years her back became bent. She was treated for intercurrent hypertension and epilepsy. Bone fractures on low-impact trauma occurred in her fifties. At 57 years, she was unable to care for herself and had to be admitted to a nursing home. She could still walk slowly with the aid of a stick. For three months at the age of 65 years, she was unable to rise from her chair. Investigations disclosed severe post-gastrectomy bone disease. At no time had she complained of bone pains.
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PMID:Post-gastrectomy bone disease undiagnosed for forty years. 1049 25

Rhodiola rosea is a popular plant in traditional medical systems in Eastern Europe and Asian with a reputation for stimulating the nervous system, decreasing depression, enhancing work performance, eliminating fatigue, and preventing high altitude sickness. Rhodiola rosea has been categorized as an adaptogen by Russian researchers due to its observed ability to increase resistance to a variety of chemical, biological, and physical stressors. Its claimed benefits include antidepressant, anticancer, cardioprotective, and central nervous system enhancement. Research also indicates great utility in asthenic conditions (decline in work performance, sleep difficulties, poor appetite, irritability, hypertension, headaches, and fatigue) developing subsequent to intense physical or intellectual strain. The adaptogenic, cardiopulmonary protective, and central nervous system activities of Rhodiola rosea have been attributed primarily to its ability to influence levels and activity of monoamines and opioid peptides such as beta-endorphins.
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PMID:Rhodiola rosea: a possible plant adaptogen. 1141 73

Atomoxetine is the first nonstimulant drug approved by the United States Food and Drug Administration (FDA) for the treatment of attention-deficit-hyperactivity disorder (ADHD), and the only agent approved by the FDA for the treatment of ADHD in adults. Atomoxetine is a norepinephrine transport inhibitor that acts almost exclusively on the noradrenergic pathway. Its mechanism of action in the control and maintenance of ADHD symptoms is thought to be through the highly specific presynaptic inhibition of norepinephrine. Clinical trials to evaluate the short-term effects of atomoxetine in children and adults have shown that atomoxetine is effective in maintaining control of ADHD. Likewise, long-term trials have determined that atomoxetine is effective in preventing relapse of ADHD symptoms without an increase in adverse effects. A comparative trial of atomoxetine with methylphenidate in school-aged children indicated similar safety and efficacy without the abuse liability associated with some psychostimulants. The most commonly reported adverse effects in children and adolescents are dyspepsia, nausea, vomiting, decreased appetite, and weight loss. The rates of adverse events in the trials were similar for both the once- and twice-daily dosing regimens. The discontinuation rate was 3.5% in patients treated with atomoxetine versus 1.4% for placebo and appeared to be dose dependent, wit a higher percentage of discontinuation at dosages greater than 1.5 mg/kg/day. In clinical trials involving adults, the emergence of clinically significant or intolerable adverse events was low. The most common adverse events in adults were dry mouth, insomnia, nausea, decreased appetite, constipation, urinary retention or difficulties with micturition, erectile disturbance, dysmenorrhea, dizziness, and decreased libido. Sexual dysfunction occurred in approximately 2% of patients treated with atomoxetine. Atomoxetine should be used with caution in patients who have hypertension or any significant cardiovascular disorder. Overall, atomoxetine therapy in patient with ADHD appears to be effective in controlling symptoms and maintaining remission, with the advantages being comparable efficacy with that of methylphenidate, a favorable safety profile, and non-controlled substance status. Additional long-term studies are needed to determine its continued efficacy for those who require lifelong treatment, and comparative trials against other stimulant and nonstimulant agents.
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PMID:Atomoxetine, a novel treatment for attention-deficit-hyperactivity disorder. 1533 51

A 31-year-old woman presented with a one-week history of headache, generalised lethargy, weakness and poor appetite. Clinical examination showed that her blood pressure was 200/120 mmHg. On an earlier occasion, her blood pressure was found to be normal by a general practitioner whom she last visited three months earlier when she had an upper respiratory tract infection. Investigations showed hypokalaemia, suppressed serum renin and aldosterone. Further history was taken and revealed that she had been craving for guava fruits which she ate with flavoured "asam boi" (containing glycyrrhizic acid) at least three spoonfuls twice a day for the past six weeks. The hypertension and hypokalaemia resolved after two weeks of stopping the "asam boi". Her clinical picture was compatible with exogenously-induced hypermineralocortoidism.
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PMID:Exogenously-induced apparent hypermineralocorticoidism associated with ingestion of "asam boi". 1643 60

Duloxetine has demonstrated efficacy for the treatment of major depressive disorder (MDD) at a dose of 60 mg/day (given once daily). Whereas the target dose for the majority of patients is 60 mg/day, higher duloxetine doses (up to 120 mg/day) have been studied using a twice-daily dosing schedule. To further investigate the pharmacological profile of duloxetine within a once-daily dosing regimen at doses above 60 mg, we examined the safety and tolerability of duloxetine during a dose escalation from 60 mg/day to 120 mg/day. This single-arm, non-placebo-controlled study incorporated a 7-week dose escalation phase, in which patients and investigators were blinded as to timing of dose increases, followed by an open-label extension phase of up to 2 years duration. Patients (age >or=18 years) meeting DSM-IV criteria for MDD (n=128) received placebo for 1 week, followed by duloxetine (60 mg/day) titrated after 1 week to 90 mg/day, and after a further week to 120 mg/day. The dose of 120 mg/day was then maintained for 4 weeks. The extension phase comprised an initial 6-week dose stabilization period, during which duloxetine was tapered to the lowest effective dose, followed by continuation therapy at the stabilized dose. We assessed safety using spontaneously reported treatment-emergent adverse events (TEAEs), changes in vital signs, electrocardiograms (ECGs), laboratory analytes, and visual analogue scales (VAS) for gastrointestinal (GI) disturbance. Efficacy measures included the 17-item Hamilton Rating Scale for Depression (HAM-D-17) total score, the Clinical Global Impression of Severity (CGI-S) and Patient Global Impression of Improvement (PGI-I) scales, and VAS assessments of pain severity and interference. The rate of discontinuation due to adverse events during the acute phase of the study was 15.6%. The most frequently reported TEAEs were nausea, headache, dry mouth, dizziness, and decreased appetite. The majority of TEAEs were associated with initial duloxetine dosing; further escalations in dose produced few additional adverse events. VAS measures of GI disturbance worsened significantly compared with baseline values after 1 week of duloxetine treatment. Subsequent assessments of GI disturbance, following dose escalation to 90 mg/day and 120 mg/day, showed either no significant difference or a significant improvement from baseline. Significant improvements (P<.001) were observed in all assessed depression efficacy measures, and in five of six VAS pain outcomes, during acute phase treatment. During 2 years of extension phase therapy, the rate of discontinuation due to adverse events was 11.9%, and the only TEAEs reported by >10% of patients were upper respiratory tract infection (13.1%), headache (10.7%), and insomnia (10.7%). Mean changes from baseline to the end of the extension phase in supine systolic and diastolic blood pressure were 3.8 and 0.5 mm Hg, respectively, and there were no reports of sustained hypertension. Mean increase in heart rate was 5.9 bpm, while patients exhibited a mean weight increase of 3.1 kg over 2 years of treatment. Results from this study suggest that rapid dose escalation of duloxetine (60 mg/day --> 90 mg/day --> 120 mg/day) is safe and tolerable. Despite weekly escalation, the majority of adverse events were mild and transient and occurred in the first week of duloxetine dosing (at 60 mg once daily). Long-term treatment at a stabilized duloxetine dose was associated with a relatively low incidence of TEAEs and treatment discontinuation due to adverse events. Time course profiles of body weight and heart rate showed modest increases during 2 years of treatment [ClinicalTrials.gov number, NC T000 42575].
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PMID:Duloxetine for the treatment of major depressive disorder: safety and tolerability associated with dose escalation. 1684 41

Modafinil is a wake-promoting agent that is pharmacologically different from other stimulants. It has been investigated in healthy volunteers, and in individuals with clinical disorders associated with excessive sleepiness, fatigue, impaired cognition and other symptoms. This review examines the use of modafinil in clinical practice based on the results of randomized, double-blind, placebo-controlled clinical trials available in the English language in the MEDLINE database. In sleep-deprived individuals, modafinil improves mood, fatigue, sleepiness and cognition to a similar extent as caffeine but has a longer duration of action. Evidence for improved cognition in non-sleep-deprived healthy volunteers is controversial.Modafinil improves excessive sleepiness and illness severity in all three disorders for which it has been approved by the US FDA, i.e. narcolepsy, shift-work sleep disorder and obstructive sleep apnoea with residual excessive sleepiness despite optimal use of continuous positive airway pressure (CPAP). However, its effects on safety on the job and on morbidities associated with these disorders have not been ascertained. Continued use of CPAP in obstructive sleep apnoea is essential. Modafinil does not benefit cataplexy.In very small, short-term trials, modafinil improved excessive sleepiness in patients with myotonic dystrophy. It was efficacious in fairly large studies of attention deficit hyperactivity disorder (ADHD) in children and adolescents, and was as efficacious as methylphenidate in a small trial, but has not been approved by the FDA, in part because of its serious dermatological toxicity. In a trial of 21 non-concurrent subjects, with 2-week treatment periods, modafinil was as effective as dexamfetamine in adult ADHD. Modafinil was helpful for depressive symptoms in bipolar disorder in a trial that excluded patients with stimulant-induced mania. A single dose of modafinil may hasten recovery from general anaesthesia after day surgery. A single dose of modafinil improved the ability of emergency room physicians to attend didactic lectures after a night shift, but did not improve their ability to drive home and caused sleep disturbances subsequently.Modafinil had a substantial placebo effect on outcomes such as fatigue, excessive sleepiness and depression in patients with traumatic brain injury, major depressive disorder, schizophrenia, post-polio fatigue and multiple sclerosis; however, it did not provide any benefit greater than placebo.Trials of modafinil for excessive sleepiness in Parkinson's disease, cocaine addiction and cognition in chronic fatigue syndrome provided inconsistent results; all studies had extremely small sample sizes. Modafinil cannot be recommended for these conditions until definitive data become available.Modafinil induces and inhibits several cytochrome P450 isoenzymes and has the potential for interacting with drugs from all classes. The modafinil dose should be reduced in the elderly and in patients with hepatic disease. Caution is needed in patients with severe renal insufficiency because of substantial increases in levels of modafinil acid. Common adverse events with modafinil include insomnia, headache, nausea, nervousness and hypertension. Decreased appetite, weight loss and serious dermatological have been reported with greater frequency in children and adolescents, probably due to the higher doses (based on bodyweight) used. Modafinil may have some abuse/addictive potential although no cases have been reported to date.
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PMID:Approved and investigational uses of modafinil : an evidence-based review. 1872 34

A small amount of Methamphetamine (MA) can produce behavioural changes such as euphoria, increased alertness, paranoia, decreased appetite and increased physical activity. In cardiovascular system, it can produce chest pain and hypertension which can result in cardiovascular collapse. In addition, MA causes accelerated heartbeat, elevated blood pressure. It can also cause irreversible damage to blood vessels in the brain. A number of sympathomimetic amines are capable of causing myocardial damage, but the cardio-toxic action of MA has been of particular interest since standardized dosage consistently produces myocardial lesions. As this drug is a choice of many teenagers and young adults, the damage to their health, as well as their future aspects could be greatly affected, therefore more evidence must be sought to convince them the negative root and show them the optimism of recovery and salvation. To clarify the effect of Methamphetamine (MA) on myocardium, 56 male Wister rats aged four weeks were divided equally into MA, Methamphetamine withdrawal (MW), Placebo (P) and Control (C) group were examined following daily intra-peritoneal administration of MA at a dose of 5 mg/kg body weight for 2, 4, 8 and 12 weeks. Normal saline was similarly injected in P group. Light microscopic changes was seen in the myocardium of MA treated group including eosinophilic degeneration, atrophy, hypertrophy, disarray, edema, cellular infiltration, myolysis, granulation tissue, fibrosis and vacuolization. On the other hand, the withdrawal group showed evidence of gradual recovery of those myocardial changes. Optimism is therefore generated about possibility of returning towards normal by withdrawing of this drug by the addicts.
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PMID:Histopathological studies of cardiac lesions after long term administration of methamphetamine in high dosage--Part II. 1934 31


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