Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Carbon monoxide (CO) has the toxic effects of tissue hypoxia and produces various systemic and neurological complications. The main clinical manifestations of acute CO poisoning consist of symptoms caused by alterations of the cardiovascular system such as initial tachycardia and hypertension, and central nervous system symptoms such as headache, dizziness, paresis, convulsion and unconsciousness. CO poisoning also produces myocardial ischemia, atrial fibrillation, pneumonia, pulmonary edema, erythrocytosis, leucocytosis, hyperglycemia, muscle necrosis, acute renal failure, skin lesion, and changes in perception of the visual and auditory systems. Of considerable clinical interest, severe neurological manifestations may occur days or weeks after acute CO poisoning. Delayed sequelae of CO poisoning are not rare, usually occur in middle or older, and are clinically characterized by symptom triad of mental deterioration, urinary incontinence, and gait disturbance. Occasionally, movement disorders, particularly parkinsonism, are observed. In addition, peripheral neuropathy following CO poisoning usually occurs in young adults.
 ...
PMID:Carbon monoxide poisoning: systemic manifestations and complications. 1141 Jun 84

The majority of human malignancies have aberrancies in the Retinoblastoma (Rb) pathway. Loss in Rb function results from the phosphorylation and inactivation of Rb by the cyclin-dependent kinases (cdks), main regulators of cell cycle progression. Thus, modulators of cdks may have a role in the treatment of human malignancies. Flavopiridol, the first cdk modulator tested in clinical trials, demonstrates interesting preclinical features: cell cycle block, induction of apoptosis, promotion of differentiation, inhibition of angiogenic processes and modulation of transcriptional events. Initial clinical trials with infusional flavopiridol demonstrated activity in some patients with lymphomas and renal, colon gastric carcinomas. Main side effects were diarrhea and hypotension. Phase 2 trials with infusional flavopiridol, other schedules and combination with standard chemotherapies are ongoing. The second cdk modulator tested in clinical trials, UCN-01, is a PKC inhibitor that can also modulate cdk activity. Similar to flavopiridol, UCN-01 blocks cell cycle progression and promotes apoptosis. Moreover, UCN-01 may abrogate checkpoints induced by genotoxic stress due to inhibition of chk1 kinase. The first clinical trial of UCN-01 demonstrated very prolonged half-life (approximately 600 h), due to high binding affinity of UCN-01 to the human alpha-1-acid glycoprotein. Main side effects were headaches, vomiting, hypoxemia and hyperglycemia. Clinical activity was observed in some patients with melanoma and lymphoma. Trials of shorter infusions of UCN-01 or in combination with standard chemotherapeutic agents are ongoing. Although several important basic and clinical questions remain unanswered, development of cdk modulators is a reasonable strategy for cancer therapy.
 ...
PMID:Small molecule modulators of cyclin-dependent kinases for cancer therapy. 1142 45

This prospective randomized study compared the efficacy and toxicity of granisetron and dexamethasone to those of granisetron alone for antiemetic control in patients receiving high-dose chemotherapy with or without total body irradiation (TBI) for stem cell transplantation. Patients were divided randomly into 2 groups. Groups received granisetron twice daily at a dose of 40 microg/kg with or without 4 mg dexamethasone (GS group and G group, respectively), starting 30 minutes before each dose of chemotherapeutic agent or TBI, or 12 hours after the first dose if TBI or a drug was given once a day. Fifty patients were evaluated for the analysis. During the first 24 hours of conditioning, 23 of 25 patients (92.0%) in the GS group achieved complete control of emesis (no emetic episodes over the course of a day), compared with 72.0% in the G group (P = .06). For patients receiving TBI on the first day of conditioning, complete emetic control was achieved in all patients (100.0%) in the GS group, compared with 63.2% in the G group (P = .02). The same degree of emetic control was maintained throughout the conditioning period in 38.8% of the GS group and 29.9% of the G group (P = .10). Adverse reactions were observed more frequently in the GS group (68.0% versus 5.0% in the G group). These reactions included insomnia, headache, flushing, and hyperglycemia. None of the events were serious. We conclude that granisetron with dexamethasone seems superior to granisetron alone for the prevention of emesis resulting from the conditioning regimen; however, the more frequent side effects may limit the wide use of this combination.
 ...
PMID:Granisetron plus dexamethasone versus granisetron alone in the prevention of vomiting induced by conditioning for stem cell transplantation: a prospective randomized study. 1256 5

Erection is a neurovascular event that involves spinal and supra spinal pathways. The final common pathway involves the release of nitric oxide (NO) from both endothelial cells and neurons, which acts as a vasodilator causing penile engorgement and erection. NO is degraded by the enzyme phosphodiesterase (PDE) type 5 in the penis. Erectile dysfunction (ED), defined as the persistent inability to achieve and/or maintain an erection sufficient for satisfactory sexual performance, results when the neurovascular pathway is interrupted by medical conditions or drugs. A 15-item self-administered questionnaire, the International Index of Erectile Function (IIEF), is one of the most useful tools to evaluate erectile function (EF) in clinical trials, although of much less use in routine clinical practice. The MMAS (Massachusetts Male Aging Study) was the first major epidemiological investigation to study the prevalence of ED. The study found that ED was three times more common in patients with diabetes mellitus. The aetiopathogenesis of ED in diabetes is multifactorial, with vascular and neural factors being equally implicated. Hyperglycaemia is believed to give rise to biochemical perturbations that lead to these microvascular changes. In the MMAS, ED in diabetes was strongly correlated with glycaemic control, duration of disease and diabetic complications. The incidence increased with increasing age, duration of diabetes and deteriorating metabolic control, and was higher in individuals with type 2 diabetes than those with type 1.ED in men with diabetes often affects their quality of life and, as patients are often reluctant to come forward with their symptoms, a carefully taken history is one of the most useful approaches in identifying affected individuals. The PDE inhibitors have revolutionised the management of ED and oral drug therapy is currently first-line therapy for the condition. These agents act by potentiating the action of intracavernosal NO, thereby leading to a more sustained erection. Sildenafil was the first PDE5 inhibitor to undergo evaluation and has been studied extensively. More recently two other agents, vardenafil and tadalafil, have been introduced. All the drugs have been shown to be effective across a wide range of aetiologies of ED, including diabetes. The drugs have been shown to improve EF domain scores, penetration and maintenance of erection, resulting in more successful intercourse. Their effects are greater at higher doses. Sildenafil and vardenafil are shorter-acting agents, while tadalafil has a longer half-life allowing the user more flexibility in sexual activity. Common adverse effects include headache, nasal congestion and dyspepsia, all actions related to inhibition of PDE5. The drugs are generally well tolerated and withdrawal from the clinical studies as a result of drug-related adverse effects were rare. The use of PDE5 inhibitors in the presence of oral nitrates is absolutely contraindicated. The clinical studies to date have not evaluated the use of one drug in the case of treatment failure with another agent. Sublingual apomorphine, which stimulates central neurogenic pathways, is a new agent and may be a suitable alternative in those patients in whom PDE5 inhibitors are ineffective or contraindicated. In clinical trials, all IIEF domains except sexual desire were found to have improved after apomorphine. The median times to erection in these studies were 18.9 and 18.8 minutes for the 2 and 3mg doses, respectively. Intraurethral and intracavernosal alprostadil may be a useful alternative when oral drug therapy is ineffective or contraindicated. The management of ED in the diabetic patient may often involve a multidisciplinary approach where psychosexual counselling and specialist urologist advice is required in addition to the skills and expertise of the diabetologist. Finally, the introduction of the new oral agents have completely revolutionised the management of ED and allowed more individuals to come forward for treatment.
 ...
PMID:New treatment options for erectile dysfunction in patients with diabetes mellitus. 1553 69

We report herein the case of a 28-year-old man presenting with hyperglycemic chorea-ballism (HCB) in addition to mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). He was admitted to a local hospital due to weight loss, general fatigue and thirst. The patient had diabetes mellitus, with a blood glucose level of 738 mg/dl and HbA1c of 19.8%. Although insulin therapy improved hyperglycemia, he noticed involuntary movements in the right upper and lower limbs, which subsequently extended to the left side. The patient was thus transferred to our hospital. He displayed short stature (154 cm) and emaciation, and a maternal family history of diabetes mellitus was elicited. He had no history of stroke-like episode, headache, vomiting and seizure. Neurological examination revealed low intelligence (IQ 57), mild sensorineural deafness, and chorea-ballism in the extremities and head without ptosis or eye movement disturbance. Brain computed tomography (CT) demonstrated areas of high density, while T1-weighted magnetic resonance imaging (MRI) revealed extreme hyperintensity and T2-weighted MRI showed hyperintensity in bilateral caudate nuclei, putamina and globi pallidus. HCB was diagnosed. In, CSF, lactate level was increased to 43.9 mg/dl (n, 4-16), pyruvate level was 1.65 mg/dl (n, 0.3-0.9) and total protein concentration was 59 mg/dl. Histological examination of a biopsy sample from the biceps brachii muscle demonstrated ragged-red fibers. An A3243G point mutation in the tRNA(Leu(UUR)) gene was detected, indicating the presence of MELAS. Involuntary movements improved on treatment with haloperidol up to 4.5 mg/day. HCB usually appears in elderly individuals, and cases less than 40-years-old are very rare. The mitochondrial dysfunction in MELAS may accelerate development of HCB.
 ...
PMID:[A case of MELAS presenting juvenile-onset hyperglycemic chorea-ballism]. 1611 32

Accidental or intentional ingestion of carbofuran can produce a life-threatening syndrome that requires prompt diagnosis and treatment. This paper investigates unintentional carbofuran poisoning in farm workers. Thirteen patients were admitted to the emergency department with carbofuran poisoning between January 2002 and August 2004 (2 female, 11 male). The patients had been poisoned while mixing the liquid form of carbofuran with seeds. Their hands were red on admission. Complaints most commonly reported by the patients on admission were nausea, vomiting, headache, weakness, dizziness and blurred vision. The most commonly observed signs were tachycardia, tachypnea, salivation, miosis, elevated blood pressure, and fasciculation. Three patients were agitated and one was lethargic on admission. We reviewed the patients' medical charts retrospectively, as well as the demographic data, intoxication route, clinical and laboratory presentations, and outcomes. We made the diagnosis according to a compatible exposure history and clinical findings. The most commonly observed laboratory finding was hyperglycemia, which was found in 6 patients. Serum pseudocholinesterase level was low in only one patient. All the patients were cured and discharged from the hospital in good physical condition. Rapid onset, mild illness and quick recovery are typical characteristics of acute occupational carbofuran poisoning. We conclude that public health efforts should educate farm workers about the dangers of pesticide application so that its threat can be diminished.
 ...
PMID:Carbofuran poisoning among farm workers. 1635 64

Tacrolimus is a calcineurin inhibitor that has been widely used to prevent allograft rejection after transplantation. We report a case of a living-donor liver transplant recipient experiencing a considerable increase in the trough blood concentration of tacrolimus after concomitant ingestion of grapefruit juice (250 mL) 4 times for 3 days. The trough blood concentrations of tacrolimus were not changed during or immediate after the repeated intake of grapefruit juice. However, almost 1 week after the final ingestion, the blood concentration of tacrolimus markedly increased to as much as 47.4 ng/mL from 4.7 ng/mL before the ingestion, resulting in a profound reduction of calcineurin phosphatase activity in peripheral blood mononuclear cells. Furthermore, headache and nausea, but not nephrotoxicity or hyperglycemia, took place throughout the period of the elevated blood concentrations. Grapefruit juice may have a clinically significant effect on the pharmacokinetics and pharmacodynamics of tacrolimus. It is recommended to avoid the consumption of grapefruit juice in transplant recipients treated with tacrolimus.
 ...
PMID:Delayed effect of grapefruit juice on pharmacokinetics and pharmacodynamics of tacrolimus in a living-donor liver transplant recipient. 1670 31

Arsenic trioxide (ATO) induces remission in 85% of adults with refractory acute promyelocytic leukemia (APL). We conducted a phase 1 trial of ATO in children (median age 13 y, range, 2-19) with refractory leukemia. ATO was administered intravenously over 2 hours, 5 d/wk for 20 doses/cycle. Patients with APL (n=13) received 0.15 mg/kg per day, and patients with other types of leukemia received 0.15 mg/kg per day (n=2) or 0.2 mg/kg per day (n=4). Nineteen of the 24 enrolled patients were fully evaluable for toxicity. At 0.15 mg/kg per day, 2 of 15 patients experienced dose-limiting corrected QT interval (QTc) prolongation, pneumonitis, or neuropathic pain. At 0.2 mg/kg per day, 2 of 4 patients had dose-limiting QTc prolongation or pancreatitis. Non-dose-limiting toxicities included elevated serum transaminases, nausea, vomiting, abdominal pain, constipation, electrolyte imbalance, hyperglycemia, dermatitis, and headache. At 0.15 mg/kg per day, the median (range) plasma arsenic maximum concentration (Cmax) was 0.28 microM (0.11-0.37 microM) and at 0.2 mg/kg per day, Cmax was 0.40 and 0.46 microM; area under the concentration times time curve (AUC0-24) was 2.50 microM-hr (1.28-3.85 microM-hr) and 4.37 microM-hr and 4.69 microM-hr, respectively. Morphologic complete response (CR) was achieved in 85% of patients with APL; no responses were observed in non-APL patients. ATO is well-tolerated in children at the recommended dose of 0.15 mg/kg per day. The response rate in children with relapsed APL is similar to the response rate in adults. This trial was registered as #NCT00020111 at www.ClinicalTrials.gov.
 ...
PMID:Phase 1 trial and pharmacokinetic study of arsenic trioxide in children and adolescents with refractory or relapsed acute leukemia, including acute promyelocytic leukemia or lymphoma. 1795 55

Pheochromocytoma is a rare form of secondary hypertension and may be potentially lethal if left untreated. The classical symptoms are paroxysmal hypertension, headaches, palpitations and sweating. They are caused by sudden catecholamine release. Hyperglycemia is reported in some patients with pheochromocytoma but diabetic ketoacidosis is an extremely rare complication of pheochromocytoma with only four cases reported. We report a case of a young woman with pheochromocytoma manifested as diabetic ketoacidosis.
 ...
PMID:Pheochromocytoma presenting as diabetic ketoacidosis. 1841 69

Pituitary apoplexy indicates pituitary adenoma hemorrhage, which could result in acute pituitary insufficiency and mortality. The typical symptoms are headache, visual disturbance, nausea, vomiting, altered mental status, and panhypopituitarism. However, cortisol-induced hyperglycemia and acute delirium could be an initial presentation of a pituitary adenoma hemorrhage with stormy release of the adrenocorticotrophic hormone. A 28-year-old woman presented with severe vomiting, irritable state, and delusion. She had medical history of irregular menstrual cycles and marked body weight gain after her second childbirth 8 years ago. She was diagnosed of diabetic ketoacidosis 2 days before this visiting at local medical department. On physical examination, Cushing appearance without definite neurological deficit was disclosed. Further blood tests revealed high blood sugar, cortisol, and adrenocorticotrophic hormone levels without evidence of diabetic ketoacidosis. The brain computed tomography and magnetic resonance imaging showed pituitary macroadenoma and pituitary hemorrhage. Cushing disease with pituitary apoplexy was then diagnosed. Conservative management with delayed neurosurgery was applied. The patient became clear with normalized cortisol and blood sugar levels soon after. Follow-up computed tomography scan of the brain revealed no progression of tumor bleeding or mass effect. To our knowledge, pituitary apoplexy associated with cortisol-induced hyperglycemia and acute delirium has never been reported before. This case reminds us of pituitary apoplexy and its rare manifestations.
 ...
PMID:Pituitary apoplexy associated with cortisol-induced hyperglycemia and acute delirium. 1909 Dec 87


<< Previous 1 2 3 4 5 6 Next >>