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The US Food and Drug Administration (FDA) has not approved any injectable contraceptives, but, in December 1990, it approved Norplant, an implantable contraceptive. Family planning providers insert 6 capsules, each with 36 mg levonorgestrel, in a fan shape under the dermis of the upper arm. Norplant protects against pregnancy for at least 5 years . Fecundity returns within 2 weeks after capsules' removal. The steady low levels of levonorgestrel keep down both luteinizing hormone and follicle stimulating hormone levels. It suppresses ovulation and thickens the cervical mucus. Contraindications of Norplant are active thromboembolism, undiagnosed genital bleeding, acute liver disease, liver tumors, and breast cancer. Phenytoin and other drugs which speed up liver metabolism reduce Norplant's efficacy. The leading side effect of Norplant is irregular bleeding patterns. Some less common side effects include headaches, nervousness, dizziness, and acne. First year continuation rates range from 76 to 99% and 25 to 78% for 5 years of use. More than 85% of Norplant users are satisfied. Both continuation and satisfaction are associated with patient counseling. Research and development of biodegradable and other nonbiodegradable implants is ongoing. The most common injectable contraceptive in the world is Depo-Provera. 150 mg of Depo-Provera every 3 months suppresses ovulation, deteriorates the endometrium, thickens cervical mucus, and reduces motility of the tubes, thereby providing adequate protection against pregnancy. Some research shows Depo-Provera use significantly increases the low-density lipoprotein to high-density lipoprotein ratio, thereby increasing the risk for atherogenesis. Effectiveness rates match those of Norplant. Norethindrone enanthate was the first injectable contraceptive. Even though 40 countries approve it, the US does not. Animal studies of injectable microspheres or microcapsules with either progestogen or progestogen and estrogen are in progress.
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PMID:Injectable and implantable contraceptives. 138 11

A patient who had bilateral distal anterior cerebral artery aneurysms and a right middle cerebral artery aneurysm in association with polycystic kidney and liver disease is reported. A 57-year-old woman was referred to our center with headache and disturbance of consciousness. On admission, her level of consciousness as evaluated by the Japan Coma Scale was 10. CT revealed subarachnoid hemorrhage, especially in the interhemispheric fissures. Right carotid angiography demonstrated bilateral distal anterior cerebral artery aneurysms and a right middle cerebral artery aneurysm. All three aneurysms were clipped in a one-stage procedure. The patient was discharged without any neurological deficits two weeks after the operation. Bilateral distal anterior cerebral artery aneurysms are extremely rare. This is the first report of such aneurysms and a right middle cerebral artery aneurysm in association with polycystic kidney and liver disease. The etiology of these aneurysms is discussed.
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PMID:[Bilateral distal anterior cerebral artery aneurysms associated with polycystic kidney and liver disease; a case report]. 150 18

User compliance is not a problem for the recently approved subdermal, longterm contraceptive delivery system, Norplant. It delivers 50-80 mcg of levonorgestrel/day during the 1st year and 30-35 mcg for years 2-5. The levonorgestrel is encased in 6 36 mm x 2.4 mm capsules which are placed in the upper arm in 5-10 minutes using local anesthesia. Since the implants systemically release levonorgestrel, the shock to the liver experienced in oral contraceptive (OC) users does not occur. Levonorgestrel prevents pregnancy by decreasing luteinizing hormone and follicle stimulating hormone which prevents ovulation, reducing the rate of ovum transfer in the tube, making the endometrium incompatible for implantation, and making the cervical mucus too thick and scanty for sperms to migrate if ovulation does occur. 1-year pregnancy rates for Norplant users are much lower than for women who use other contraceptives (0.6/100 users vs. 2.3/100 for OC users and 2.4/100 for IUD users). The ectopic pregnancy rate is also low (1.47/1000 Norplant users). The 1-year continuation rate is 80% compared with 50% for OC users. Fertility returns within 3 months for 50% of users and within 1 year for 80%. Because Norplant does not adversely affect lipid metabolism there is no increase in the risk of atherogenesis. Menstrual irregularities are the leading side effect of Norplant. The irregular cycles tend to occur during the 1st 3-6 months after insertion. Other side effects include headaches, acne, breast discharge, weight gain, and transient ovarian cysts. Contraindications are abnormal uterine bleeding, possible pregnancy, active liver disease, and women taking phenytoin. The cost for the initial exam and insertion of the Norplant capsules is $500 at Planned parenthood of the Rocky Mountains in Colorado (mean=$8.30/month vs. $13/month for 5 years of taking OCs). Due to the possibility of exploitation of women and involuntary infertility, nurse practitioners must thoroughly explain the system to each patient and answer all questions so the patient can give informed consent.
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PMID:New concepts in contraception: Norplant subdermal implant. 156 6

Enoximone, a new phosphodiesterase-inhibitor with positive inotropic and vasodilating activities is available for intravenous use in patients with severe heart failure. A review of the current knowledge regarding the adverse effects of this substance reveals that they are characterized by cardiovascular, central nervous, and gastrointestinal side effects. Adverse effects occurred in 20% of patients and were mostly due to the pharmacological properties of enoximone. Cardiovascular side effects (10%) were the most frequent; ventricular and supraventricular arrhythmias were most common. Two to three percent of the patients experienced hypotension due to the vasodilator activity of enoximone. Headache, insomnia, and anxiety were the most frequent adverse effects on the central nervous system. Three percent of the patients treated experienced vomiting, nausea, abdominal pain, and diarrhea. An increase of liver enzymes and serum glucose could be observed, mostly in patients with previous liver disease or diabetes. Pharmacokinetic drug interactions are not known; possible pharmacodynamic interactions result from the pharmacological properties of the drugs. Intravenous therapy with enoximone causes a few serious side effects that can only be controlled by careful observation of the patients treated.
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PMID:[Tolerance of enoximone in patients with heart failure]. 183 4

Twenty-four patients with reversible airflow obstruction under suboptimal control on conventional therapy entered a double-blind placebo-controlled trial of additional oral sustained release aminophylline. Assessment was by diary cards, twice daily PEFR, and weekly FEV1. Nineteen patients completed the trial satisfactorily. Eleven were improved subjectively by addition of aminophylline. The mean PEFR for all 19 patients rose from 232 1 min-1 SEM +/- 5, to 247 1 min-1 SEM +/- 4 (p less than 0.0001); nine individuals showed a statistically significant improvement in mean PEFR and 10 showed an improvement of greater than 200 ml in their FEV1. Improvement in PEFR on aminophylline was not at the expense of benefit from inhaled salbutamol. Unwanted effects of nausea, headache, and abdominal discomfort were recorded by 12 of the 24 patients entering the trial. Seventeen of the 19 patients completing the trial had plasma theophylline levels in the accepted therapeutic range of 10-20 mg 1(-1). The drug doses required to achieve these levels varied from 8.6-30.8 mg kg-1 24 hr-1 in the patients with no clinical or biochemical evidence of liver disease. Oral aminophylline can improve control of airflow obstruction in patients with moderately severe disease who are already receiving multiple medication, but side-effects often limit its use. The wide dose range required to achieve therapeutic plasma levels indicates that measurements of plasma theophylline are necessary for adequate interpretation of trials of theophylline compounds.
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PMID:Sustained release oral aminophylline in patients with airflow obstruction. 702 36

There is little absolute data in the form of prospective studies in patients with specific illnesses who are on oral contraceptives (OCs). Consequently, the clinician must depend on well-founded empiric decisions in prescribing the pill for these patients. The basis for the decision should be a firm understanding of the pathophysiology and laboratory effects of OCs. This needs to be juxtaposed with an understanding of the efficacy and effects of the estrogen and progestational components of the birth control pill and their interactions with maintenance medications. Available evidence is reviewed for the following medical disorders: central nervous system disorders (depression, Wilson's disease, headaches, epilepsy, multiple sclerosis, and the eye); immunologic and connective tissue diseases; diseases of the endocrine system, the gastrointestinal system, the genitourinary system, the memopoietic system; and skin disorders. 7% of women on OCs have increased or newly reported depression. Whether these are primarily psychogenic or metabolically derived is yet to be definitively determined. Wilson's disease can be exacerbated by OCs because of increased plasma ceruloplasmin and increased absorption of copper from the gastrointestinal tract. Headaches can be either a vague or a specific symptom, such as migraines, but 1/3 of these patients will become worse on OCs. There is good evidence that the headaches are caused by falling estrogen levels. There is no good evidence that epilepsy, in general, becomes worse on OCs. OCs have relatively no effect on the longterm prognosis in multiple sclerosis. Increased corneal sensitivity has been observed with OC use, and this has usually presented an intolerance to the use of contact lenses. This is primarily the result of increased edema of the cornea and changing of its contour. By inference, OCs cause some basic universal changes in the immunologic system. OCs have been reported as a cause of a rare form of rheumatoid arthritis, but the Royal College reports a decrease in incidence of cell-mediated immunologic disease, specifically rheumatoid arthritis in its more familiar form. There is no evidence that OCs markedly influence thyroid disease, but they do markedly alter thyroid function testing. OCs do not produce a chronic addisonian state nor do they inhibit the ability of the adrenal-pituitary axis to respond to stress. OCs can be used in thyroid disease but with some caution in hypothyroid states. They should not be used in patients with Cushing's syndrome and are not recommended in patients with adenomas. In general, estrogen works as an irritant to the gastric mucosa, but there is no increase in peptic ulcer diseases associated with OC use, and the incidence of duodenal ulcer disease is decreased. The most striking liver disease seen with OCs is cholelithiasis. The incidence is increased 2-fold. OCs should not be prescribed for patients with chronic renal disease because of the vascular effects as well as the reported increased risk of urinary tract infection. The Royal College report has shown a decreased incidence of iron deficiency anemia in patients on OCs. Various skin changes have been reported in women using OCs. The most common of these is chloasma. In all the diseases studied thus far, the use of OCs has not precipitated a catastrophic change.
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PMID:The use of birth control pills in women with medical disorders. 702 14

A case of acute hypervitaminosis A complicating viral hepatitis is reported. Twenty days after presenting with hepatitis B, a 42-yr-old vegetarian developed acute hypervitaminosis A in the absence of recent, massive exposure to the vitamin. Findings included headache, confusion, skin desquamation, and hypercalcemia. Prior to developing hepatitis, he had ingested supplemental vitamin A without recognized ill effect. Liver and serum vitamin A without recognized ill effect. Liver and serum vitamin A levels were both elevated; the liver biopsy showed abundant, lipid-filled Ito cells and perisinusoidal fibrosis. This case demonstrates that patients with excessive hepatic stores of vitamin A may develop hypervitaminosis A during acute, intercurrent liver disease. Levels of retinol binding protein are reduced in hepatitis. This phenomenon may account for the findings in this case, since vitamin A is more toxic when not specifically bound to retinol binding protein. The size of the population at risk for this complication of hepatitis in unknown, but presumably it is growing with the widespread use of supplemental vitamin A.
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PMID:Hypervitaminosis A unmasked by acute viral hepatitis. 719 70

The patient referred for liver transplantation typically has complications from a progressive, irreversible liver injury. Less traditional complications of end-stage liver disease, such as bone disease and some hepatobiliary malignancies, may also prompt referral. However, there are contraindications to liver transplantation, such as metastatic malignancy and persistent substance abuse. Each patient should be referred as early as possible. The evaluation process includes a complete physical examination and social and psychologic evaluations. If transplantation is agreed upon, the patient is listed by clinical status and enters a waiting period for a donor liver. Following transplantation, the patient is maintained on a regimen of immunosuppressive drugs to prevent allograft rejection. Each patient is also maintained on prophylactic medications, to decrease the risk of opportunistic infection. Many of the postoperative problems in liver transplantation are a result of immunosuppression, either as side effects of the medications used to prevent and control rejection or from the intensity of the resulting immunosuppression. These problems include headaches, systemic hypertension, acute and chronic allograft rejection, renal dysfunction, opportunistic infection with cytomegalovirus or Pneumocystis carinii, disease recurrence, and neoplasia. Routine, long-term care includes systematic clinical follow-up and repetitive blood tests. Communication among the transplant center, the patient, and the referring physician are essential to a successful outcome over the long term.
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PMID:Primary care management of the liver transplant patient. 810 82

The US Food and Drug Administration approved the contraceptive implant system, Norplant, in February 1990. It has been used in other countries for more than 15 years before the US approved it. The 6 subdermally placed capsules in the upper inner arm release 50-80 mcg levonorgestrel/day into the bloodstream, resulting in a 99.8% efficacy rate. Patient education and counseling, especially about changes in the bleeding pattern and Norplant's inability to protect against sexually transmitted diseases, are important to maintain client satisfaction and continued use of Norplant. Side effects, from most to least common, are changes in menstrual bleeding, constant bleeding, missed periods, weight gain/increased appetite, headache, oily skin or acne, weight loss/nausea, breast tenderness, nervousness or loss of appetite, and hair loss. It is rare when complications are so severe that they require removal of the implants. Contraindications to Norplant include active liver disease, active thromboembolic disease, breast cancer, pregnancy, and undiagnosed dysfunctional uterine bleeding. Antiepileptic medications, barbiturates, treatment for tuberculosis, and Butazolidin/phenylbutazone reduce Norplant's efficacy. A trained person should insert Norplant within the first 5-7 days of the menstrual cycle when it is evident there is no pregnancy. Some reports recommend that, after childbirth, it should be inserted 6 weeks postpartum to avoid hemorrhage. Yet, nurse-midwives at the Center for Addiction and Pregnancy at the Francis Scott Key Medical Center in Baltimore, Maryland, insert Norplant 24-48 hours postpartum in non-breast-feeding mothers with no increase in hemorrhage. Norplant must be removed no longer than 5 years after insertion. Certified nurse-midwives wanting to incorporate Norplant into their practices should follow the Guidelines for the Incorporation of New Procedures into Nurse-Midwifery Practice and have available a consulting physician who is familiar with and skilled in inserting Norplant. The manufacturer conducts training sessions for health professionals.
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PMID:Subdermal contraceptive implants in nurse-midwifery practice. 848 13

Alpers' syndrome is a progressive neurodegenerative disorder with liver disease that usually presents in the first few years of life. Only rarely have patients presented later in life with delayed onset of Alpers' syndrome. Herein we present a case of a 17-year-old male with a progressive 8-month course of severe headaches, multiple stroke-like episodes with visual deficits, and seizures that concluded with acute hemorrhagic pancreatitis. Neuropathological findings were characteristic for Alpers' syndrome: neurodegeneration and astrogliosis of the occipital cortices including the striate cortices, similar but less advanced changes in the parietal cortices, right Ammons horn sclerosis, degeneration of the posterior columns, and mild cerebellar Purkinje cell loss. Examination of the liver revealed extensive centrilobular hepatocyte necrosis. Skeletal muscle did not contain ragged red fibers, nor were there mitochondrial DNA point mutations characteristic for mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS).
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PMID:Alpers' syndrome presenting with seizures and multiple stroke-like episodes in a 17-year-old male. 860 37


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