Gene/Protein Disease Symptom Drug Enzyme Compound
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FDA has approved medroxyprogesterone acetate as Depo Provera Contraceptive Injection, effective for 3 months in preventing pregnancy in women. In clinical studies, the drug's failure rate was less than 1%. However, physicians must ensure that patients receive injections on schedule to prevent pregnancy. The recommended dose is 150 mg administered every 3 months by deep, intramuscular injection in the gluteal or deltoid muscle. Most women in clinical studies of Depo Provera experienced menstrual irregularities. As use continued, amenorrhea became common, reported by 57% of the women by the end of a year of treatment. Other side effects included weight gain, headache, nervousness, abdominal pain or discomfort, dizziness, and asthenia. Physicians should administer the drug only to women found not to be pregnant, because fetal exposure may lead to low birth weight and other problems. Recent data have demonstrated that longterm use may contribute to osteoporosis, and the drug's manufacturer, the Upjohn Company of Kalamazoo, Michigan, will conduct additional research to study this possible side effect. Contraindications are similar to those for other contraceptives and include undiagnosed vaginal bleeding, known or suspected malignancy of breast, thromboembolic disorders, cerebral vascular disease, and liver dysfunction. Depo Provera was developed in the 1960s and has been approved for contraception in many other countries. When FDA first reviewed data on the drug in the 1970s, animal studies raised questions about its potential to cause breast cancer. Since then, longterm controlled clinical studies in other countries have shown a risk of breast cancer comparable to oral contraceptives, and no increased risk for ovarian, liver, or cervical cancer. The studies also showed that the contraceptive injection reduced the risk of endometrial cancer. FDA approved the drug October 29, 1992.
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PMID:3-month contraceptive injection approved. 1231 15

Depot medroxyprogesterone acetate (DMPA, Depo-Provera) is used for contraception by 8-9 million women in more than 90 countries, including the US, as of January 1993. Pharmacologically active levels of DMPA persist for 3-4 months following injection. A 150 mg dose is used most often for high contraceptive efficacy every 3 months. Norethindrone enanthate (NET-EN, Noristerat) is somewhat less widely used and is not marketed in the US. Injectables act primarily by inhibiting ovulation, lowering the levels of follicle-stimulating hormone and luteinizing hormone. Approximately 50% of women using DMPA for 1 year report amenorrhea whose occurrence is less frequent with NET-EN. Menstrual changes are the most frequent causes of discontinuation of injectables. In cases of heavy bleeding it is appropriate to undergo gynecological examination to rule out unrelated conditions, such as vaginitis, cervicitis, or cervical lesions. The use of conjugated estrogen (12.5-2.5 mg daily) for 10-21 days will minimize bleeding. Some women using injectables experience headache, dizziness, bloating of the abdomen or breast, and mood changes. Long-term use of DMPA or NET-EN can often result in 1-3 kg weight gain. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives was launched in 1979 to examine cancer risks with the use of DMPA in Thailand, Mexico, and Kenya. The relative risk of breast cancer was 1.21, which was statistically not significant. In women diagnosed with breast cancer under age 35, short-term exposure to DMPA was associated with a slightly increased breast cancer risk, which, however, was not associated with duration of use. DMPA dramatically lowers the risk of endometrial cancer for at least eight years following discontinuation of its use. DMPA did not alter the risk of cervical cancer. Fertility returns in 70% of former users within 12 months; it is suitable for postpartum and lactating women, and provides other noncontraceptive benefits.
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PMID:Injectable contraception: the USA perspective. 1234 20

Due to the long-term health risks now associated with hormone replacement therapy, many menopausal women are actively seeking alternative treatments. One such alternative is black cohosh (Actaea racemosa, syn. Cimicifuga racemosa), which has been used in the United States for the treatment of gynecologic complaints for more than 100 years. Review of the published clinical data suggests that black cohosh may be useful for the treatment of menopausal symptoms, such as hot flashes, profuse sweating, insomnia, and anxiety. Results from the most recently published trial, however, indicate that black cohosh is not effective for the treatment of menopausal symptoms in breast cancer survivors being treated with tamoxifen. Because the overall quality of the published clinical trials is low, two new randomized, double-blind, placebo-controlled clinical trials are currently underway in the United States. To date, only one standardized black cohosh extract has been tested clinically; the current recommended dose is 40-80 mg per day. At least 4-12 weeks of treatment may be required before any therapeutic benefits may be apparent. Adverse reactions such as nausea, vomiting, headaches, dizziness, mastalgia, and weight gain have been observed in clinical trials. No drug interactions are reported in the medical literature. The estrogenic effects of black cohosh are controversial, and the more recent data indicate that black cohosh extracts may have an anti-estrogenic activity. Owing to potential effects on sex hormones, however, black cohosh should not be administered to children or during pregnancy and lactation.
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PMID:Black cohosh: an alternative therapy for menopause? 1255 11

A 73-year old woman presented with mild paraparesis and hypesthesia of the legs. Furthermore, she complained dizziness, fainting and dyspnea. There was a history of peripheral artery disease, diabetes mellitus, arterial hypertension and chronic atrial fibrillation. Five years ago she had breast cancer with removal of the left mamma and additional radiation therapy. Cardiac catheterization at that time demonstrated no significant coronary stenoses. A contrast-enhanced CT-scan excluded lumbal spinal metastases. Instead, a subtotal occlusion of the abdominal aorta was noticed, but was initially interpreted as a chronic thrombosis because there were no typical symptoms and only moderate pain. About 24 hours later the patient developed an acute ischemic syndrome of the legs with progressive paraparesis, cold and pale legs in combination with acidosis and hyperventilation. Color-coded duplex ultrasound showed only a small turbulent flow in the ilial arteries, highly suspicious of a complete occlusion of the distal aorta. Angiography revealed an acute total occlusion of the infrarenal aorta without collaterals. During surgical intervention, complete obstruction of the abdominal aorta above the bifurcation was confirmed. Subsequent embolectomy was performed and an embolus consisting of several layers of different age was extracted. After successful surgical intervention with subsequent clinical improvement, the patient's clinical condition deteriorated a few day later. She died on day 9 after surgery from a complete ischemia of the small intestine and the colon ascendens.
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PMID:[Atypical Leriche syndrome]. 1265 74

We report a case of a 44-year-old woman with metastatic brain tumors who suffered peri-tumoral hemorrhage soon after stereotactic radiosurgery (SRS). She had been suffering from breast cancer with multiple systemic metastasis. She started to have headache, nausea, dizziness and speech disturbance 1 month before admission. There was no bleeding tendency in the hematological examination and the patient was normotensive. Neurological examination disclosed headache and slightly aphasia. Magnetic resonance imaging showed a large round mass lesion in the left temporal lobe. It was a well-demarcated, highly enhanced mass, 45 mm in diameter. SRS was performed on four lesions in a single session (Main mass: maximum dose was 30 Gy in the center and 20 Gy in the margin of the tumor. Others: maximum 25 Gy margin 20 Gy). After radiosurgery, she had severe headache, nausea and vomiting and showed progression of aphasia. CT scan revealed a peritumoral hemorrhage. Conservative therapy was undertaken and the patient's symptoms improved. After 7 days, she was discharged, able to walk. The patient died of extensive distant metastasis 5 months after SRS. Acute transient swelling following conventional radiotherapy is a well-documented phenomenon. However, the present case indicates that such an occurrence is also possible in SRS. We have hypothesized that acute reactions such as brain swelling occur due to breakdown of the fragile vessels of the tumor or surrounding tissue.
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PMID:[Peritumoral hemorrhage immediately after radiosurgery for metastatic brain tumor]. 1296 95

Presented here is the case of a paraneoplastic cerebral degeneration (PCD) in a female patient with breast cancer and the indication of anti-Yo antibodies in the cerebrospinal fluid (CSF) and serum. The patient's primary indications were dizziness and a severe gait ataxia. The indication of anti-Yo antibodies led to the conclusion of the existence of a paraneoplastic cerebral degeneration. The antibodies in question are anti-Purkinje-cell autoantibodies acting against the antigens common to tumor and Purkinje cells which occur in association with a certain percentage of breast or ovarian cancers. The diagnosis of the primary tumor, that is clinically undetectable with conventional imaging processes, is performed with the aid of positron emission tomography (PET) to detect the presence of axillary lymph node metastases. The micro-invasive mammary carcinoma was able to be localized with the aid of MR mammography and, after MR mammography marking, was removed. The patient subsequently received adjuvant treatment with epirubicine and cyclophosphamide. This treatment failed to influence the paraneoplastic neurological symptoms.
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PMID:Paraneoplastic neurological syndrome: patient with anti-Yo antibody and breast cancer: a case report. 1460 24

Paraneoplastic neurologic syndromes are disorders of the nervous system function caused by cancer but not due to metastatic disease, vascular or metabolic deficits, infections, nutritive deficiency, nor side effects of antineoplastic drugs or irradiation. Immunologic factors probably play the crucial role in the pathogenesis of paraneoplastic neurologic syndromes, but nonimmunologic mechanisms that include metabolic abnormalities and competition for substrate are also involved. Paraneoplastic cerebellar degeneration most commonly occurs in the setting of gynecologic cancers, but it accompanies the small-cell lung cancer too. Other tumors are infrequently associated with cerebellar degeneration. Several paraneoplastic antibodies have been identified in patients with paraneoplastic cerebellar degeneration. Their association with particular cancers may help identify an occult lesion. Anti-Yo antibodies are directed against Purkinje cell antigens and occur in patients with cerebellar degeneration who have breast cancer or gynecologic tumors. A target antigen of anti-Yo antibody is CDR2 protein that is normally expressed only in the brain and testis. Patients with paraneoplastic cerebellar degeneration present with dizziness, nausea and vomiting followed by gait instability, diplopia, gait and appendicular ataxia, dysarthria and dysphagia. Therapeutic options include tumor excision, chemotherapy and/or irradiation, and adjuvant therapy with glucocorticoids, immunoglobulins and plasmapheresis. The role of plasmapheresis in the treatment of paraneoplastic cerebellar degeneration is still uncertain. Reports of its efficacy are anecdotal. We present patient with paraneoplastic cerebellar degeneration with positive anti-Yo antibodies and tumor of the ovaries whose neurologic status significantly improved after four daily plasmaphereses, which was accompanied by a fourfold decrease in the anti-Yo antibodies titer. Further investigations are needed to define a protocol for plasmapheresis in the treatment of patients with paraneoplastic syndromes.
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PMID:[Importance of plasmapheresis in the treatment of paraneoplastic cerebellar degeneration]. 1512 96

The objectives of this study were to evaluate quality of life (QOL) and identify its associated factors in climacteric women with a history of breast cancer. A cross-sectional study was performed including 75 breast cancer survivors age 45-65 years who had undergone complete oncologic treatment and nonusers of hormone therapy or tamoxifen in the last 6 months. Sociodemographic and clinical characteristics in addition to the prevalence of climacteric symptoms were evaluated. QOL was evaluated by the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) questionnaire, including eight components that can be condensed into two summaries: a physical component summary (physical functioning, role-physical, body pain, general health) and a mental component summary (vitality, social functioning, role-emotional, and mental health). Generalized linear models were used to analyze the data, allowing the identification of factors affecting QOL, adjusting for confounding variables. The mean age of the participants was 53.1+/-5.9 years. Breast cancer survivors reported good QOL. The most prevalent symptoms were nervousness (69%) and hot flashes (56%). Factors associated with poorer QOL were dizziness, postmenopausal status, and breast-conserving therapy (physical component), as well as insomnia and being married (mental component). In conclusion, participants demonstrated good QOL. We identified factors that may influence QOL in women with breast cancer, highlighting being married, climacteric symptoms, postmenopausal status, and breast-conserving therapy. Given the impact of these factors, health professionals and patients must discuss choices for alleviating climacteric symptoms and explanations for the potential repercussions of breast cancer treatment.
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PMID:Quality of life in Brazilian breast cancer survivors age 45-65 years: associated factors. 1776 Jun 86

4-Hydroxyandrost-4-ene-3,17-dione (formestane) is a selective aromatase inhibitor. It is indicated for postmenopausal patients with advanced breast cancer. The aim of the present study was to investigate the effect of 4-hydroxyandrost-4-ene-3,17-dione on the bile secretion and metabolism of 4-(14)C-cholesterol to bile acid. The experiments were carried out in the ovariectomized and sham-operated female Wistar rats. Formestane (20 mg/kg, i.m., daily) was administered to animals for 2 weeks. Twenty four hours after the last drug administration, rats were anesthetized with ethyl urethane. 4-(14)C-cholesterol (740 kBq/kg, s.a. 2.28 GBq/mmol) was infused for 1 min by catheter inserted into the jugular vein. Bile samples were assayed for total 14C radioactivity 14C-bile acids were determined in bile (after thin-layer chromatographic separation) by the use of isotopic technique with liquid scintillator. Previous studies showed that systemic adverse effects occurred in about 12% of patients following intramuscular drug administration. Many of them such as hot flushes, vaginal spotting and emotional lability were related to the mechanism of action of formestane i.e. estrogen suppression. Lethargy, rash, nausea, dizziness, indigestion, ataxia, cramps and facial swelling have also been reported. The results of the present study have shown that formestane administered to the female ovariectomized rats decreased the bile secretion and diminished conversion of 4-(14)C-cholesterol to trihydroxy bile acids. The decreased synthesis of trihydroxy bile acids and increased concentrations of cholesterol and litocholic acid in bile may be associated with increased risk of gallstone formation.
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PMID:Effect of 4-hydroxyandrost-4-ene-3,17-dione (formestane) on the bile secretion and metabolism of 4-(14)C-cholesterol to bile acids. 1638 15

The purpose of this study was to explore the effect of Chan-Chuang qigong on symptoms distress and psychological distress of breast cancer patients who underwent chemotherapy. A quasi-experimental design was adopted. Subjects were recruited from breast cancer outpatients receiving chemotherapy at an 1800-bed medical center in Taipei, Taiwan. Of these subjects, 35 were assigned to the control group and 32 to the experimental group in which Chan-Chuang qigong was administered. Assignment was not random. The instruments included a 21-item symptom distress scale and psychological distress with the symptom checklist-90-revised. Data of the symptoms and psychological distress were collected on the day before chemotherapy as baseline values, and also collected on days 8, 15 and 22 of chemotherapy. The results showed that the overall severity of symptom distress in the experimental group was significantly lower than the control group on day 22 (p < 0.05). The symptoms with significant improvement included pain, numbness, heartburn and dizziness (p < 0.05). With regard to psychological distress, the difference of overall severity between the two groups was not statistically significant (p > 0.05). However, the items of "unwillingness to live" (p < 0.05) and "hopelessness about the future" (p < 0.05) were significantly improved in the experimental group. In conclusion, Chan-Chuang qigong had the effect of attenuating the symptom distress and probably some part of the psychological distress of chemotherapy patients.
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PMID:Effects of chan-chuang qigong on improving symptom and psychological distress in chemotherapy patients. 1643 37


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