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

"New Era for Injectables," a report published in the most recent issue of the Johns Hopkins University School of Hygiene and Public Health's Population Reports, notes that injectable contraceptives are among the most effective family planning methods. Most clinical trials report less than one pregnancy per 100 women during the first year of use, making injectables as effective as Norplant implants, the best copper IUDs, and voluntary sterilization. Injectables also protect women against ectopic pregnancy, help to prevent endometrial and possibly ovarian cancer, and may help women with anemia and sickle-cell disease. The major side effect of injectable use is changes in menstrual bleeding. Some women also experience weight gain, and a few report headaches, dizziness, abdominal discomfort, acne, and moodiness. The most widely-used injectable is the progestin-only DMPA (depot medroxyprogesterone acetate), known under the brand name Depo-Provera and manufactured by the Upjohn Company. Women receive an injection every 3 months. Another progestin-only injectable, NET EN (norethindrone enanthate), is taken every 2 months. Cyclofem and Mesigyna, two new monthly injectables which combine estrogen and progestin, are currently being introduced in a number of countries. Worldwide, 1.5% of all married women of reproductive age who use some form of family planning use injectables. The highest level of use among such women is in Indonesia and Thailand where 15% and 12%, respectively, use injectables. Donor agencies have been responding to increasing numbers of orders for injectables from family planning programs in developing countries, while the UN Population Fund, the largest supplier, shipped 12 million doses of injectables in 1992 and 20 million in 1994. The 1992 US Food and Drug Administration approval of DMPA has made it possible for the US Agency of International Development to respond to requests for it.
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PMID:Millions of couples to have choice of injectable contraceptive. 1234 10

Increased bone marrow angiogenesis and vascular endothelial growth factor (VEGF) levels are adverse prognostic features in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDSs). VEGF is a soluble circulating angiogenic molecule that stimulates signaling via receptor tyrosine kinases (RTKs), including VEGF receptor 2 (VEGFR-2). AML blasts may express VEGFR-2, c-kit, and FLT3. SU5416 is a small molecule RTK inhibitor (RTKI) of VEGFR-2, c-kit, and both wild-type and mutant FLT3. A multicenter phase 2 study of SU5416 was conducted in patients with refractory AML or MDS. For a median of 9 weeks (range, 1-55 weeks), 55 patients (33 AML: 10 [30%] primary refractory, 23 [70%] relapsed; 22 MDS: 15 [68%] relapsed) received 145 mg/m2 SU5416 twice weekly intravenously. Grade 3 or 4 drug-related toxicities included headaches (14%), infusion-related reactions (11%), dyspnea (14%), fatigue (7%), thrombotic episodes (7%), bone pain (5%), and gastrointestinal disturbance (4%). There were 11 patients (20%) who did not complete 4 weeks of therapy (10 progressive disease, 1 adverse event); 3 patients (5%) who achieved partial responses; and 1 (2%) who achieved hematologic improvement. Single agent SU5416 had biologic and modest clinical activity in refractory AML/MDS. Overall median survival was 12 weeks in AML patients (range, 4-41 weeks) and not reached in MDS patients. Most observed toxicities were attributable to drug formulation (polyoxyl 35 castor oil or hyperosmolarity of the SU5416 preparation). Studies of other RTKI and/or other antiangiogenic approaches, with correlative studies to examine biologic effects, may be warranted in patients with AML/MDS.
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PMID:SU5416, a small molecule tyrosine kinase receptor inhibitor, has biologic activity in patients with refractory acute myeloid leukemia or myelodysplastic syndromes. 1264 63

Inflammatory pseudotumors (IPs), mostly benign lesions characterized by fibrotic ground tissue and polyclonal mononuclear infiltrate, may affect all organ systems. IPs originating in the central nervous system (IP-CNS) are very rare, and their distinct histopathologic features are poorly characterized. Three otherwise healthy patients (age 8, 15, and 17 years) presented with focal neurologic symptoms (seizures, n = 2; headaches, n = 1), corresponding to a left temporal, left occipital, and left frontal IP, respectively, extending from meningeal structures into brain tissue. After resection, no recurrence was observed in patient 1 during 5 years of follow-up, whereas patient 2 developed a rapidly progressive local recurrence and a second intracerebral lesion despite antiviral, immunosuppressive, antibiotic, and radiation therapy. In patient 3, who also showed local recurrences, sequential histopathologic investigations revealed transformation to a semimalignant fibrohistiocytic tumor. In this patient, anaplastic lymphoma kinase (ALK) expression was also positive, whereas it was negative in patient 1. A detailed literature analysis confirmed that most IP-CNS arise from dural/meningeal structures (n = 34). Intraparenchymatous (n = 7), mixed intraparenchymatous/meningeal (n = 4), and intraventricular lesions (n = 7) or IP extending per continuitatem from intracerebral to extracerebral sites (n = 5) were rare. The recurrence rate was 40% within 2 years in general. It was increased after incomplete resection and in female patients (multivariate Cox regression model, P < 0.02). Although rare, IP-CNS are important differential diagnoses among tumor-like intracranial lesions. Their potential risk of malignant transformation and high risk of recurrence necessitate close follow-up, especially when resection is incomplete. Prospective multicenter trials are needed to optimize classification and treatment of this rare inflammatory lesion.
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PMID:Inflammatory pseudotumors of the central nervous system: report of 3 cases and a literature review. 1267 60

Peripheral T-cell lymphoma primary to the central nervous system is a rare occurrence. The authors report a case of an 89-year-old woman who presented with a 3-month history of worsening confusion and recent onset of headache, nausea and vomiting, and upper limb tremors. Computed tomography and magnetic resonance imaging examinations demonstrated a 4.5-cm solitary brain mass in the right basal ganglia with compression along the ventricular system. No other lesion was found in the patient. Histologic and immunohistochemical studies of a stereotactic biopsy of the mass showed a T-cell lymphoproliferative lesion positive for CD3, CD8, CD57, and T-cell intracellular antigen 1 and negative for CD4, CD56, CD30, anaplastic lymphoma kinase, and CD20. A monoclonal T-cell receptor-gamma gene rearrangement was detected by polymerase chain reaction analysis of genomic DNA isolated from paraffin-embedded tumor tissue sections. These findings were consistent with peripheral T-cell lymphoma of cytotoxic/suppressor phenotype, resembling the phenotype of T-cell large granular cell leukemia. To the authors' best knowledge, this represents the first reported case of primary brain T-cell lymphoma with a cytotoxic/suppressor immunophenotype. A brief review of the literature of primary brain T-cell lymphoma is also presented.
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PMID:Primary central nervous system cytotoxic/suppressor T-cell lymphoma: report of a unique case and review of the literature. 1271 53

Gastrodia elata (G. elata) is a traditional Chinese herbal medicine for treating headaches, dizziness, tetanus, and epilepsy. In this study, differential methanol (MeOH) extracts of G. elata were found to prevent serum-deprived rat pheochromocytoma (PC12) cell apoptosis by the MTT assay and Hoechst staining. A serine/threonine kinase inhibitor attenuated this protection. G. elata resulted in phosphorylation and dephosphorylation of ERK1/2 and JNK1/2-p38 MAPKs (members of the serine/threonine kinase family), respectively, as revealed by Western blot analysis. An upstream ERK inhibitor attenuated G. elata-induced ERK phosphorylation but not protective effect. Although JNK and p38 inhibitors attenuated their related enzyme activities during serum deprivation, only JNK inhibitor prevented serum-deprived apoptosis. Thus, G. elata prevents serum-deprived apoptosis through activation of the serine/threonine kinase-dependent pathway and suppression of JNK activity.
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PMID:Gastrodia elata prevents rat pheochromocytoma cells from serum-deprived apoptosis: the role of the MAPK family. 1526 68

Gliosarcoma (GSa) is a rare primary central nervous system neoplasm (CNS) characterized by biphasic histological pattern with both glial and sarcomatous components. Our objective is to describe the clinical, morphological and immunohistochemical features of four cases of GSa and to discuss its pathogenetic mechanisms. The male:female ratio was 3:1. The mean age was 39 years, ranging from 19 to 48. Headache was the commonest clinical symptom. All patients underwent craniotomy with microsurgery and total resection of the tumor. Diagnosis was suspected due to microscopic architecture and confirmed by detection of reticulin fibers through histochemical techniques. Immunohistochemical analysis was positive for p53 in both glial and sarcomatous cells in all four cases. EGFR was focally positive in glial cells in one case. Our findings support monoclonal origin of GSa involving the TP53 tumor-suppressor gene. However, alternative pathways cannot be ruled out.
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PMID:Gliosarcoma: report of four cases with immunohistochemical findings. 1533 17

GW572016 is a dual EGFR-ErbB2 inhibitor that has promise as an anticancer agent. Two phase I studies were conducted to determine the safety, tolerability and pharmacokinetics of single and multiple doses given to healthy subjects. The single dose study evaluated two groups of eight subjects in an ascending dose, 4-way cross-over, while the multiple dose study evaluated twenty-seven healthy volunteers in an ascending dose, double-blind, randomized, placebo-controlled, staggered parallel design. No serious adverse events were seen in either study. The most common adverse events for subjects receiving GW572016 were headache, diarrhea, rash, cold symptoms, gastrointestinal symptoms, and elevated LFTs, which were similar between treatment and placebo groups. Absorption of single doses of GW572016 was slightly delayed, with median t(lag) of 15 minutes (range 0-90 minutes) and achieved peak serum concentrations at a median of three hours (range 1.5-6 hours) post-dose. Serum concentrations after multiple doses of GW572016 demonstrated no significant accumulation at the 25 mg dose, and approximately 50% accumulation at the 100 mg and 175 mg doses, achieving steady state in six to seven days. A modest time-dependent increase in serum concentrations also was detected with multiple doses of GW572016. Single and multiple oral doses of GW572016 were well tolerated in healthy subjects, and resulted in dose-related systemic exposure of GW572016.
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PMID:Phase I pharmacokinetic studies evaluating single and multiple doses of oral GW572016, a dual EGFR-ErbB2 inhibitor, in healthy subjects. 1552 79

Although migraine is more common in women than men and often linked to the menstrual cycle, few studies have investigated the biological basis of hormonal influences on the trigeminovascular system. In the present study we investigated the effect of physiological levels (10(-9) m) oestrogen on female rat trigeminal ganglia in vitro. Immunocytochemical analysis demonstrated the presence of oestrogen receptor-alpha in a predominantly cytoplasmic location and in neurites. Microarray analysis demonstrated that oestrogen treatment regulates several genes with potential relevance to menstrual migraine. The genes that were upregulated included synapsin-2, endothelin receptor type B, activity and neurotransmitter-induced early gene 7 (ania-7), phosphoserine aminotransferase, MHC-1b, and ERK-1. Down-regulated genes included IL-R1, bradykinin B2 receptor, N-tropomodulin, CCL20, GABA transporter protein, fetal intestinal lactase-phlorizin hydrolase, carcinoembryonic antigen-related protein, zinc finger protein 36, epsin 1 and cysteine string protein. Protein activity assays demonstrated that exposure of the cultured neurons to oestrogen leads to activation of ERK, which has been linked to inflammatory pain. Immunocytochemistry demonstrated that activated ERK was present in neurons containing peripherin, a marker of nociceptive neurons. Several of the genes in the present study may provide potential targets for understanding the association of oestrogen with migraine and other hormone-related orofacial pain.
Cephalalgia 2006 Jan
PMID:Effects of oestrogen on trigeminal ganglia in culture: implications for hormonal effects on migraine. 1639 64

Outcome of patients with acute myeloid leukemia (AML) who are older than 60 years of age remains unsatisfactory, with low remission rates and poor overall survival. We have previously established the activity of clofarabine plus cytarabine in AML relapse. We have now conducted a phase 2 study of clofarabine plus cytarabine in patients aged 50 years or older with previously untreated AML. Clofarabine was given at 40 mg/m2 as a 1-hour intravenous infusion for 5 days (days 2 to 6) followed 4 hours later by cytarabine at 1 g/m2/d as a 2-hour intravenous infusion for 5 days (days 1 to 5). Of 60 patients, 29 (48%) had secondary AML, 30 (50%) had abnormal karyotypes (monosomy 5 and/or 7 in 15 [25%]), and 11 (21%) showed FLT3 abnormalities. The overall response (OR) rate was 60% (52% CR, 8% CRp). Four patients (7%) died during induction. Adverse events were mainly grade 2 or lower and included diarrhea, nausea, vomiting, mucositis, skin reactions, liver test abnormalities, and infusion-related facial flushing and headaches. Myelosuppression was common. Clofarabine plus cytarabine has activity in adult AML, achieving a good CR rate. However, survival does not appear to be improved compared with other regimens. Modifications of this combination in AML therapy of older patients warrant further evaluation.
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PMID:Clofarabine and cytarabine combination as induction therapy for acute myeloid leukemia (AML) in patients 50 years of age or older. 1640 5

Brucellosis is a significant health problem in countries where control of zoonoses is inadequate. During 1993-98, we analysed sera and cultures from 792 suspected brucellosis patients who presented with histories of fever, chills, night sweating, weakness, malaise and headache to the referral hospital in Yazd. Cases were investigated by tube agglutination test (TAT) and 2-mercaptoethanol test (2-MET) and a questionnaire was completed for each.TAT titre was > or = 1:1 60 for 745 patients (94.1%) and 2-MET was positive for 42 (5.3%). Of 745 confirmed cases, 460 were from 1996-1997. Prevalence was highest in summer (39.5%) and more common males than among females. Prevalence was highest among those aged 10-19 years (27.7%). Most patients had a history of infected cheese, milk and milk product consumption (98%).
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PMID:Selected epidemiological features of human brucellosis in Yazd, Islamic Republic of Iran: 1993-1998. 1645 May 37


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