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)

DepoCyte is a slow-release formulation of cytarabine designed for intrathecal administration. The goal of this multi-centre cohort study was to determine the safety and efficacy of DepoCyte for the intrathecal treatment of neoplastic meningitis due to breast cancer. DepoCyte 50 mg was injected once every 2 weeks for one month of induction therapy; responding patients were treated with an additional 3 months of consolidation therapy. All patients had metastatic breast cancer and a positive CSF cytology or neurologic findings characteristic of neoplastic meningitis. The median number of DepoCyte doses was 3, and 85% of patients completed the planned 1 month induction. Median follow up is currently 19 months. The primary endpoint was response, defined as conversion of the CSF cytology from positive to negative at all sites known to be positive, and the absence of neurologic progression at the time the cytologic conversion was documented. The response rate among the 43 evaluable patients was 28% (CI 95%: 14-41%); the intent-to-treat response rate was 21% (CI 95%: 12-34%). Median time to neurologic progression was 49 days (range 1-515(+)); median survival was 88 days (range 1-515(+)), and 1 year survival is projected to be 19%. The major adverse events were headache and arachnoiditis. When drug-related, these were largely of low grade, transient and reversible. Headache occurred on 11% of cycles; 90% were grade 1 or 2. Arachnoiditis occurred on 19% of cycles; 88% were grade 1 or 2. DepoCyte demonstrated activity in neoplastic meningitis due to breast cancer that is comparable to results reported with conventional intrathecal agents. However, this activity was achieved with one fourth as many intrathecal injections as typically required in conventional therapy. The every 2 week dose schedule is a major advantage for both patients and physicians.
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PMID:Intrathecal treatment of neoplastic meningitis due to breast cancer with a slow-release formulation of cytarabine. 1116 70

Investigators at the Royal Marsden Hospital and University College in London have studied thalidomide (Thalomid) as both low-dose (100 mg orally, every night) and high-dose (600 mg, given as 300 mg twice per day) therapy for patients with a variety of solid tumors. In the phase II low-dose study, responses were disappointing in patients with melanoma, ovarian cancer, and breast cancer. Results for patients with renal-cell carcinoma were more encouraging. A case study of a patient with metastatic renal-cell carcinoma in the lung and lymph nodes in the low-dose thalidomide study illustrates that (1) responses may be very slow; (2) the palliative response is separate from the overall response, occurs much earlier, and is not consistent with an antiangiogenic action; and (3) peripheral neuropathy is a manageable side effect. Besides peripheral neuropathy, patients can experience severe constipation (even on low doses) as well as headache, edema, and skin rash for which treatment recommendations can be made. Anecdotal benefits of thalidomide include enhanced or maintained appetite, improved sleeping, and reduced sweating. The high-dose study has been submitted for publication.
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PMID:Thalidomide in solid tumors: the London experience. 1120 68

The focus of this review is hormone replacement therapy (HRT) with continuous administration of micronised, oral 17beta-estradiol 1 mg/day (herein referred to as continuous estradiol) plus micronised, oral norgestimate 90 microg/day administered for 3 days then withdrawn for 3 days in a 6-day repeating sequence (herein referred to as intermittent norgestimate). According to data from randomised, comparative trials of 1 year's duration, continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day relieves climacteric symptoms (vasomotor symptoms and vulvovaginal atrophy) in postmenopausal women. Continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day appeared as effective as estradiol 1 mg/day alone or continuous estradiol 2 mg/day plus continuous norethisterone acetate 1 mg/day in the treatment of postmenopausal women with vasomotor symptoms. Continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day was as effective as continuous estradiol 1 mg/day in causing the maturation of vaginal epithelial cells. In a randomised, double-blind study, bone mineral density (BMD) increased to a significantly greater extent and the rate of bone turnover was slower in postmenopausal women treated with continuous oral estradiol 1 mg/day plus intermittent norgestimate 90 microg/day than in placebo-treated patients. Two randomised, double-blind studies indicated that the addition of norgestimate 90 microg/day to continuous estradiol 1 mg/day did not attenuate the beneficial effects of estradiol on lipid parameters. Continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day was associated with increases in mean serum high density lipoprotein (HDL)-cholesterol levels and decreases in total cholesterol, low density lipoprotein (LDL)-cholesterol and lipoprotein (a) levels, compared with baseline. There was no statistically significant increase in triglyceride levels. In comparative trials, continuous oral estradiol 1 mg/day plus intermittent oral norgestimate 90 microg/day was well tolerated. Headache, breast pain or discomfort, abdominal pain or discomfort, uterine bleeding, dysmenorrhoea, oedema, nausea and depression were the most commonly reported adverse events. Continuous estradiol 1 mg/day plus intermittent oral norgestimate 90 microg/day was associated with a favourable uterine bleeding profile that improved over time. In a randomised trial, 80% of women were free from bleeding (irrespective of spotting) during month 12 of treatment. Norgestimate 90 microg/day was effective in protecting postmenopausal women against induction of endometrial hyperplasia by continuous estradiol 1 mg/day. In conclusion, data from a limited number of randomised studies indicate that HRT with continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day is effective in relieving climacteric symptoms, increasing BMD and slowing the rate of bone turnover in postmenopausal women. This HRT regimen is well tolerated and is associated with a similar incidence of adverse events to that reported in recipients of continuous estradiol 1 mg/day. The norgestimate component of the regimen provides good endometrial protection and is associated with a favourable bleeding profile. Long-term studies investigating the associated risk of breast cancer and thromboembolic events in recipients of continuous estradiol plus intermittent norgestimate are needed. In the meantime, continuous oral estradiol plus intermittent oral norgestimate can be regarded as an effective new option for HRT in postmenopausal women.
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PMID:Estradiol and norgestimate: a review of their combined use as hormone replacement therapy in postmenopausal women. 1177 26

Cerebral sinus thrombosis (CST) is known to be related to a number of underlying aetiologies including otitis media, trauma, pregnancy, birth control pills, tumours, malnutrition, dehydration, haematologic disorders and malignancy (Fishman, 2000; Raizer and Abbott, 2000). We present the case of a patient with breast cancer receiving the antioestrogen drug tamoxifen who developed CST. A 40-year-old female presented as an emergency with a 10-day history of headache and left sided weakness. On questioning her past medical history included a diagnosis of breast cancer 3 years ago treated by radical mastectomy and tamoxifen 20 mg daily. At the time of admission, neurologic examination revealed a mild left sided hemiparesis and a present Babinksi sign. Non-contrast enhanced tomography was normal. Magnetic resonance imaging (MRI) showed thrombosis in the superior sagittal sinus, right lateral sinus and jugular vein in addition venous infarction in the right temporal lobe was present (Figs 1a and b). Routine haematology and biochemistry was normal. Anticoagulation tests, antithrombin III, protein S and C levels were also found to be normal. She was treated with anticoagulation therapy and her hemiparesis improved within 3 days. Control MRI showed the resorption of the venous infarction and resolution of the thrombosis (Fig. 1c).
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PMID:A case with cerebral thrombosis receiving tamoxifen treatment. 1178 61

Leptomeningeal metastases are a late, devastating complication of systemic cancer that typically occurs in conjunction with other systemic relapse. The most common neurologic symptoms include headache, altered mentation, and difficult walking. Diagnosis is established by neuroimaging and cerebrospinal fluid analysis. The prognosis is poor with a median survival of 6 to 8 weeks; therefore most treatment interventions are palliative. Radiotherapy should be given to sites of bulky or symptomatic tumor. Intrathecal chemotherapy is most effective in patients with lymphoma, leukemia, and breast cancer. Systemic chemotherapy may be more effective in treating bulky leptomeningeal tumor. Ventriculoperitoneal shunting can be extremely useful in patients with obstructive hydrocephalus or increased intracranial pressure.
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PMID:Leptomeningeal Neoplasms. 1182 47

A multicenter, open labeled, randomized early Phase II study for CGS 20267 was conducted at the doses 0.5 mg once daily and 1.0 mg once daily in postmenopausal women with advanced breast cancer. Sixty-four patients were randomly assigned to the doses of either 0.5 mg once daily (n = 33) or 1.0 mg once daily (n = 31). Thirty-one patients were eligible for 0.5 mg group, and 29 for 1.0 mg group. A total of 57 patients (30 in the 0.5 mg group and 27 in the 1.0 mg group) were eligible for the evaluation of efficacy. There were 3 CR, 5 PR, 5 stable disease (SD: NC lasting over 24 weeks), 7 NC and 10 PD in the 0.5 mg group. The objective response rate (ORR) was 26.7%. There were 4 CR, 7 PR, 8 SD, 3 NC and 5 PD in the 1.0 mg group. The ORR was 40.7%. A total of 57 patients (29 in the 0.5 mg group and 28 in the 1.0 mg group) were eligible for safety evaluation. Adverse clinical events related to CGS 20267 in the 0.5 mg group were headache, nausea, cold sweat, sleepiness and muscle ache in the lower extremities (2 patients, incidence rate 6.9%) whereas those in the 1.0 mg group were generalized itching and generalized hot feeling (2 patients, incidence rate 7.1%). All of the adverse events were grade 1 except the generalized itching which was grade 2. CGS 20267-related abnormalities in the laboratory tests for the 0.5 mg group were a decrease in WBC, and increases in GOT, GPT, LDH and gamma-GTP (5 patients, 14.3%) whereas those in the 1.0 mg group were increases in GPT, gamma-GTP, alkaline phosphatase, and total bilirubin (1 patient, 3.6%). The increases in GOT and GPT were grade 2, but others were grade 1. The data show both CGS 20267 0.5 mg once daily and 1.0 mg once daily to be effective and tolerable in the treatment of postmenopausal women with advanced breast cancer.
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PMID:[CGS 20267 (Letrozole), a new aromatase inhibitor: early phase II study for postmenopausal women with advanced breast cancer]. 1197 39

Science and modern medicine accord us many advantages, e.g., contraceptive drugs, but many people still do not use them. Contraceptive drugs include oral contraceptives and injectables. OCs are very effective and are associated with minor side effects (e.g., mood changes, breast tenderness, nausea, and changes in weight, mild headache, and spotting between periods), perhaps explaining why they are one of the most often used contraceptive in essentially every country. Women who smoke; are 35 years old; or either have or have a family history of hypertension, diabetes, cardiovascular disease and use OCs are at higher risk of a cardiovascular episode. On the other hand, OCs protect against ovarian and endometrial cancers. Research does not yet confirm or disprove their effect on breast cancer development. OCs appear not to be linked to breast cancer through age 59. Yet, studies of women 45 years old suggest that OCs increases the breast cancer risk in these women who had their first menses before age 13 and used OCs for a long time before their first pregnancy. OCs may facilitate growth of breast tumors that other causes activated, and therefore, do not likely increase the overall risk. Researchers recognize the death of knowledge about breast cancer development, so they call for more research, including basic molecular, cellular, and biochemical studies. In Nigeria, breast cancer is rare, while deaths due to pregnancy and childbirth are common, indicating that OC use can prevent many female deaths. Prolonged breast feeding; later age at first menses; earlier age at menopause; earlier age at first full-term pregnancy larger families; low fat, high fiber diets; and thinness, all of which are common in developing countries, have a protective effect against breast cancer. Further, women in developing countries begin OC use later than women in developed countries.
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PMID:The myth about contraceptives and breast cancer. 1217 9

Results of a survey of gynecologists and general practitioners in France concerning their opinions of the advantages and drawbacks of oral contraceptives (OCs) and a brief history of the successive improvements in OCs over the past 3 decades are presented. The 300 gynecologists and 600 general practitioners interviewed in all regions of France felt that OCs were an important contraceptive method. Almost all reported they were very concerned about possible longterm effects: 78% with cardiovascular risks, 77% with lipid metabolic effects, 63% with glucose metabolic effects, and 62% with androgenic effects. Fewer than 1/2 were very concerned about shortterm clinical problems such as weight gain, spotting, and dermatological effects which have less serious prognoses. Almost 90% of the physicians considered that too high a dose of estrogen dominance was a very important cause of problems. Over 1/2 of the physicians felt that information furnished them regarding OCs should be more detailed and precise. Enovid, the 1st combined OC commercially available in the US, contained 150 mcg of mestranol and 9.85 mg of norethynodrel. Isolated cases of serious vascular problems began to be reported soon after its introduction. In 1961 a formulation with half the estrogen dose was developed, and in 1964 ethinyl estradiol, a better tolerated synthetic estrogen, replaced mestranol and is still the only estrogen used. New and better tolerated progestins were subsequently synthesized, as were formulations with lower steroid doses. Results of large epidemiological studies demonstrated that estrogens were responsible for venous thromboembolic accidents while progestins were directly correlated with arterial accidents. No increased risk of breast cancer has been found in OC users in the most recent controlled studies. Hepatic or biliary problems are possible because of the hepatic catabolism of the steroids, justifying the contraindication for women who have had hepatic accidents. Headaches are usually but not always harmless. Weight gain is due not to increased adipose mass but to water retention and is often responsible for termination of use. Benefits of OCs include effective fertility control and regular medical surveillance of users, which allows medical problems to be discovered at earlier stages. OCs have favorable effects on dysmenorrhea, spontaneous hyperestrogenism, endometriosis and provide protection against-rheumatoid polyarthritis and osteoporosis. The recent development of biphasic and especially triphasic pills has provided better cycle control at the same time that steroid doses have been reduced. The next innovation in combined OCs will probably be the use of new progestins combining powerful antigonadotropic action with an absence of metabolic effects at contraceptive doses. Gestodene, a derivative of 19 nortestosterone, offers great promise. Its use will decrease the effects of combined OCs on different metabolic factors that influence individual cardiovascular risk.
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PMID:[Oral contraception: evolution of concepts over the last thirty years]. 1228 8

The injectable contraceptive depot-medroxyprogesterone acetate (DMPA) dissolves slowly and is released over 3 months to suppress ovulation. It is more than 99% effective at preventing pregnancy. More than 30 million women in 90 countries have used DMPA and none have died from using it. A World Health Organization [WHO] study showed that DMPA did not significantly increase the risk of breast cancer or other cancers. One study points to a small reduction in bone density with DMPA use, but the reduction did not become larger with long-term use and may even be reversible. The US Food and Drug Administration (FDA) thoroughly reviewed these studies and the experiences of DMPA users. This review resulted in the FDA's approving DMPA as a contraceptive in October, 1992. Almost all DMPA users experience menstrual changes with irregular bleeding and spotting occurring during the 1st few months. After 12 months, at least 50% of DMPA users experience amenorrhea, which some women consider a benefit. Other possible but rare side effects are weight gain, headache, breast tenderness, loss of libido, depression, nervousness, and fatigue. It takes longer for past DMPA users to conceive after stopping DMPA use than users of other contraceptive methods, but by 18 months more than 90% of past DMPA users who wanted to become pregnant conceived. DMPA does not protect users from sexually transmitted diseases (STDs) or HIV/AIDS. They need to use latex condoms to prevent STD/HIV transmission. DMPA users must return to their health care provider every 3 months for another injection. DMPA is a viable contraceptive for women wanting a safe, reliable, long-term, reversible contraceptive. Any woman wanting to use DMPA should discuss it with her provider.
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PMID:Facts about injectable contraception. 1228 37

Barrier methods of contraception and natural family planning may pose unacceptable risks of unintended pregnancy for women with medical conditions in which pregnancy could be dangerous. Although more effective at preventing pregnancy, hormonal methods may affect the course of a chronic disease. The table that comprises this article outlines contraceptive choices and contraindications for women with the following diseases: breast cancer; endometrial, ovarian, and cervical cancer; deep venous thrombosis/pulmonary embolism; hypertension (past, moderate, or severe); diabetes (with and without vascular disease); liver disease; epilepsy; headache; and sickle cell disease.
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PMID:Chronic diseases and contraceptive use. 1229 56


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