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)

Pituitary apoplexy has been reported as a rare complication of combined tests and of TRH administration in prolactinomas. A 54-year-old man with a pituitary macroadenoma had a single injection of 100 micrograms GnRH. Twenty minutes later he complained of increasing headache and vomited. These symptoms settled spontaneously and were attributed to the pharmacological effects of GnRH. Five hours later he was found to be blind and disorientated without spontaneous complaint. Emergency CT showed a large adenoma with central necrosis, consistent with pituitary apoplexy. An urgent surgical decompression was carried out and necrotic haemorrhagic debris removed. Baseline bloods revealed non-pulsatile FSH of 40 U/l with LH 0.3 U/l with no hormonal response to GnRH administration, but the sequence of events strongly suggests a causal relationship between this and pituitary apoplexy. To our knowledge this is the first time that GnRH administration has been associated with pituitary apoplexy of a glycoprotein secreting pituitary adenoma.
 ...
PMID:Pituitary apoplexy and sudden blindness following the administration of gonadotrophin releasing hormone. 782 63

The reported decrease of platelet serotonin receptors in patients with migraine could be due to an autoimmune reaction. We therefore, examined sera from 42 migraineurs without aura, 26 migraineurs with aura, and 107 headache-free blood donors for platelet-reactive antibodies using the platelet adhesion immunofluorescence test, the NIH-lymphocytotoxicity test, and the monoclonal antibody-specific immobilization of platelet antigens test. IgG antibodies against non-HLA class I platelet antigens were found in 9.5% of patients with migraine without aura, 7.6% of patients with migraine with aura, and in 7.5% of controls; IgM antibodies were found in 11.9% of patients with migraine without aura, in 30.8% of patients with migraine with aura, and in 13.1% of controls. Most antibodies were directed against glycoprotein complexes II-III (fibrinogen receptor) or Ib-IX (thrombin receptor). Two patients with migraine without aura but no patient with migraine with aura nor any control subject had IgG antibodies of unknown specificity. One patient (2.4%) with migraine without aura and two patients (7.7%) with migraine with aura, as well as 2 controls (1.9%) had IgM antibodies not further specified. The differences in frequency of platelet antibodies of antibodies of known or unknown specificity in patients with migraine without aura and migraine with aura and controls were not statistically significant. Therefore, our data do not support the hypothesis of a pathophysiologically relevant autoimmune reaction against platelet serotonin receptors in th majority of patients with migraine. We can not exclude the occurrence of antibodies against neuron-specific serotonin receptors.
Headache 1998 Jun
PMID:Platelet antibodies in patients with migraine. 966 54

In a dose-ranging study of amprenavir (formerly 141W94), an inhibitor of the protease enzyme of human immunodeficiency virus (HIV) type 1, single-dose and steady-state pharmacokinetic parameters were estimated from plasma samples collected on day 1 and during week 3, respectively. Amprenavir was administered on either a twice-daily (b.i.d.) or three-times-daily dosage schedule to 62 HIV-infected adults, 59 of whom had pharmacokinetic data. Log-log regression analysis (the power model) revealed that the steady-state area under the curve (AUC(ss)) and the maximum, minimum, and average concentrations at steady state (C(max,ss), C(min,ss), and C(avg,ss), respectively) increased in a dose-proportional manner over the 300- to 1,200-mg dose range. Steady-state clearance was dose independent. AUC(ss)/AUC(0-->infinity) decreased linearly with dose and correlated significantly with treatment-associated decreases in alpha(1)-acid glycoprotein. After 3 weeks, the dose of 1,200 mg b.i. d. provided a median amprenavir C(min,ss) (0.280 microg/ml) that was higher than the median in vitro 50% inhibitory concentration for clinical HIV isolates (0.023 microg/ml), even after adjustment for protein binding. The median amprenavir C(min,ss) was also greater than the estimated in vivo trough concentration calculated to yield 90% of the maximum antiviral effect (0.228 microg/ml) over 4 weeks. A pharmacodynamic analysis of the relationship between steady-state pharmacokinetic parameters and safety revealed headache and oral numbness to be the only side effects significantly associated with C(max). The pharmacodynamic relationship defined in this study supports the use of 1,200 mg b.i.d. as the approved dose of amprenavir.
 ...
PMID:Pharmacokinetic and pharmacodynamic study of the human immunodeficiency virus protease inhibitor amprenavir after multiple oral dosing. 1112 Sep 40

The majority of hematopoietic malignancies have aberrancies in the retinoblastoma (Rb) pathway. Loss in Rb function is, in most cases, a result of the phosphorylation and inactivation of Rb by the cyclin-dependent kinases (cdks), main regulators of cell cycle progression. Flavopiridol, the first cdk modulator tested in clinical trials, is a flavonoid that inhibits several cdks with evidence of cell cycle block. Other interesting preclinical features are the 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 non-Hodgkin's lymphoma, renal, prostate, colon and gastric carcinomas. Main side-effects were secretory diarrhea and a pro-inflammatory syndrome associated with hypotension. Phase 2 trials with infusional flavopiridol in CLL and mantle cell lymphoma, other schedules and combination with standard chemotherapies are ongoing. The second cdk modulator tested in clinical trials, UCN-01, is a potent protein kinase C inhibitor that inhibits cdk activity in vitro as well. UCN-01 blocks cell cycle progression and promotes apoptosis in hematopoietic models. Moreover, UCN-01 is able to abrogate checkpoints induced by genotoxic stress due to modulation in chk1 kinase. The first clinical trial of UCN-01 demonstrated very prolonged half-life (approximately 600 h), 100 times longer than the half-life observed in preclinical models. This effect is due to high binding affinity of UCN-01 to the human plasma protein alpha-1-acid glycoprotein. Main side-effects in this trial were headaches, nausea/vomiting, hypoxemia and hyperglycemia. Clinical activity was observed in patients with melanoma, non-Hodgkin's lymphoma and leiomyosarcoma. Of interest, a patient with anaplastic large cell lymphoma refractory to high-dose chemotherapy showed no evidence of disease after 3 years of UCN-01 therapy. Trials of infusional UCN-01 in combination with Ara-C or gemcitabine in patients with acute leukemia and CLL, respectively, have commenced. In conclusion, flavopiridol and UCN-01 are cdk modulators that reach biologically active concentrations effective in modulating CDK in vitro, and show encouraging results in early clinical trials in patients with refractory hematopoietic malignancies. Although important questions remain to be answered, these positive experiences will hopefully increase the therapeutic modalities in hematological malignancies.
 ...
PMID:Development of cyclin-dependent kinase modulators as novel therapeutic approaches for hematological malignancies. 1124 75

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

The safety of the triptans has been established, with more than 8 million patients treating greater than 340 million attacks with sumatriptan alone. All triptans narrow coronary arteries by 10% to 20% at clinical doses and should not be administered to patients with coronary or cerebrovascular disease. Some triptans have the potential for significant drug-drug interactions (sumatriptan, rizatriptan, and zomitriptan and monoamine oxidase inhibitors; rizatriptan and propanolol; zolmitriptan and cimetidine; and eletriptan and CYP3A4 metabolized medications and p-glycoprotein pump inhibitors). Rational use of triptans should be governed by the use of these medications for patients with disability associated with migraine. Patients with greater than 10 days of at least 50% disability during 3 months have benefited from treating with triptans as their first-line treatment for acute attacks. When the decision has been made to treat with a triptan, the patient should be instructed to treat early in the attack, when the pain is at a mild phase. This approach increases the likelihood of achieving a pain-free response, with fewer adverse events and lower likelihood of the headache recurring.
 ...
PMID:Safety and rational use of the triptans. 1148 Feb 67

In May of 2001 a Nigerian woman visiting the United Kingdom presented with fever, headache and difficulty swallowing. Within 24 h she showed a marked deterioration and died shortly afterwards. Autopsy samples from a range of tissues were analysed to confirm a clinical diagnosis of rabies. Phylogenetic analysis of the viral nucleoprotein gene confirmed that this was an infection with a genotype 1 virus (classical rabies) belonging to the Africa 2 group, which is endemic in Northern Africa. Comparison of both the nucleoprotein and glycoprotein coding sequences of this isolate with an imported case of human rabies from 1996, also from Nigeria, showed that the two viruses were 99% homologous.
 ...
PMID:Investigation of a human case of rabies in the United Kingdom. 1242 99

The aim of this study was to determine the prevalence and clinical significance of antiphospholipid antibodies (aPL) in children with migraine. The values of anticardiolipin (aCL) and antibeta2 glycoprotein I (antibeta2GPI) antibodies were assayed by an ELISA method in 52 children with migraine and 22 children with tension-type headache. The control group consisted of 61 apparently healthy children at regular preventive visits. Two monoclonal beta2GPI dependent aCL (HCAL and EY2C9) were used as calibrators. Lupus anticoagulant (LA) was determined by a modified dilute Russell viper venom time test. Persistently positive aPL were observed during the follow-up in 16.3% of children with migraine (9.3% for aCL, 7.0% for antibeta2GPI and 0% for LA) and in 16.7% of children with tension-type headache (11.1% for aCL, 5.6% for antibeta2GPI and 0% for LA). The prevalence of aPL did not differ significantly between patient groups and healthy children. The prevalence of aPL does not appear to be increased in an unselected group of children with migraine, however, the possible role of aPL in individual cases of paediatric migraine can not be excluded.
Cephalalgia 2004 Oct
PMID:Estimation of antiphospholipid antibodies in a prospective longitudinal study of children with migraine. 1537 13

Headache is common in systemic lupus erythematosus with reported prevalence as high as 70%. The aims of this study were: to estimate the prevalence and types of headache in a sample of patients with systemic lupus erythematosus comparing it with rheumatoid arthritis, to determine clinical and serological associations. Eighty-one systemic lupus erythematosus and 29 rheumatoid arthritis consecutive patients seen in our outpatient clinic were interviewed. Headache was evaluated using the diagnostic criteria proposed by the International Headache Society. Additional evaluations were carried out in the 81 systemic lupus erythematosus patients including depression, disease activity, lupus damage, function disability, quality of life, and severity degree using a validated scales. We analysed the following autoantibodies: anti-double stranded DNA, anti-nucleosomes, anti-histones, anti-ribosomal P, anti-cardiolipin antibodies, anti-beta2-glycoprotein-I (GPI), and antinuclear antibodies. Forty-one per cent of systemic lupus erythematosus and 17% of rheumatoid arthritis patients suffered from headache (P = 0.02). No significant difference for any primary headache type between the two groups was found. Frequency of headache types in systemic lupus erythematosus patients was: migraine 24%, tensional-type headache 11%, and mixed headache 5%. In systemic lupus erythematosus patients the risk factors associated with headaches were Raynaud's phenomenon (OR 3.6; 95% CI 1.3-9.5; P = 0.009) and beta2GPI antibody positivity (OR 4.5; 95% CI 1.2-16.2; p = 0.016). We conclude that headache is more common in systemic lupus erythematosus than in rheumatoid arthritis patients and was independently associated with Raynaud's phenomenon and beta2GP-I antibodies.
Cephalalgia 2004 Dec
PMID:Prevalence and factors associated with headache in patients with systemic lupus erythematosus. 1556 14

Basiliximab is a chimeric anti-intcrleukin-2 receptor monoclonal antibody. Basiliximab is a glycoprotein produced by recombinant technology. It is used to prevent white blood cells from acute renal transplantation rejection. It specifically binds to and blocks the alpha chain of interleukin-2 receptors (IL-2R alpha), also known as CD25 antigen, on the surface of activated T-lymphocytes. Due to its monoclonal nature it provides safer and more predictable therapeutic, that is, immunosuppressive response of the polyclonal antibodies. The most common adverse effects in adult patients are constipation, infections, pain, nausea, peripheral oedema, hypertension, anaemia, headache, hyperkalacmia, hypercholesterolemia, increase in serum creatinine, and hypophosphataemia.
 ...
PMID:Basiliximab, mechanism of action and pharmacological properties. 1564 37


<< Previous 1 2 3 4 5 Next >>