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A young female with a cholangiocarcinoma in the past: is pregnancy allowed?

BACKGROUND: A 28-year-old woman developed a cholangiocarcinoma after using oral contraceptives for eight years. The common bile duct and the gallbladder were removed and four hepaticojejunostomies were performed. RESULTS: Seven years after surgery no evidence of disease recurrence is detectable and the patient wants advice regarding her wish for pregnancy. CONCLUSION: The possible role of oestrogens in the development of cholangiocarcinoma makes it difficult to give an adequate advice. As in patients with breast cancer in the past, it seems reasonable to admit pregnancy in our patient, because of a disease-free interval of longer than five years.

Adult↗

Doxapram treatment for apnea in preterm infants.

BACKGROUND: Recurrent apnea is common in preterm infants, particularly at very early gestational ages. These episodes of loss of effective breathing can lead to hypoxemia and bradycardia which may be severe enough to require resuscitation including use of positive pressure ventilation. Doxapram has been used to stimulate breathing and so prevent apnea and its consequences. OBJECTIVES: In preterm infants with recurrent apnea, does treatment with doxapram lead to a clinically important reduction in apnea and use of Intermittent positive airways pressure (IPPV), without clinically important side effects? SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal trials, the Cochrane Collaboration Clinical Trials Register, MEDLINE (using text words 'doxapram', 'apnea or apnoea' and Mesh term 'infant, premature') previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, mainly in the English language. Also an expert informant's search in the Japanese language was made by Prof. Y. Ogawa in 1996. SELECTION CRITERIA: All trials utilising random or quasi-random patient allocation, in which doxapram was used for the treatment of apnea in preterm infants were included. DATA COLLECTION AND ANALYSIS: Each author evaluated the papers for quality and inclusion criteria. Independent data extraction was carried out. MAIN RESULTS: Only one trial, which randomized 11 infants to intravenous doxapram and 10 infants to placebo, was found. There were fewer treatment failures after 48 hours in the group of preterm infants treated with doxapram (4/11) compared with the group treated with placebo (8/10). The wide confidence intervals made this result non-significant [RR 0.45 (0.20, 1.05)]. Only one infant, who was from the placebo group, was given IPPV. Of the seven responders by 48 hours in the group of 11 who received doxapram, five failed to respond between 48 hours and seven days after commencement of therapy. This gives a late failure rate of 9/11, similar to the short term failure rate in the placebo group of 8/10. It is not possible to evaluate the late responses of all those in the placebo group since they crossed over to a treatment arm. REVIEWER'S CONCLUSIONS: Although intravenous doxapram might reduce apnea within the first 48 hours of treatment, there are insufficient data to evaluate the precision of this result or to assess potential adverse effects. No longterm outcomes have been measured. Further studies are needed to determine the role of this treatment in clinical practice.

Apnea↗

Azathioprine in patients with juvenile chronic arthritis: a longterm followup study.

OBJECTIVE: To evaluate drug survival, efficacy, side effects, and longterm toxicity of azathioprine treatment in patients with juvenile chronic arthritis (JCA). METHODS: In an uncontrolled, prospective study we evaluated 129 consecutive patients with JCA refractory to therapy in whom azathioprine treatment was begun during 1980-1989. In the first 29 patients, a 2 year trial was planned, while for the remaining 100 patients the protocol was to continue until remission or dropout. The median treatment period was 13 months (range 3 days-8.5 yrs). Patients were assessed every 2 months for 2 years for efficacy, side effects, growth and need for glucocorticoids, and outcome evaluated in late 1996. RESULTS: Remission without drugs was attained in 19 patients (15%); in addition, temporary remission in patients continuing treatment was attained in 18 cases (14%). Treatment was discontinued due to side effects in 18 cases (14%); in two-thirds of these cases side effects occurred during the first 2 months. Of the total number of patients, 49 (38%) completed 2 years of treatment, with significant improvement in both clinical and laboratory indices of disease activity. Treatment had no noticeable effect on iridocyclitis. One patient died of cytomegalovirus infection during azathioprine treatment. CONCLUSION: Azathioprine is a useful drug in severe JCA, with a sustained effect and acceptable side effects. Even in cases of incomplete remission, its glucocorticoid sparing effect was noteworthy.

Adolescent↗

Effect of a nonsteroidal antiinflammatory drug on synovial fluid in osteoarthritis.

OBJECTIVE: The use of nonsteroidal antiinflammatory drug (NSAID) therapy in osteoarthritis (OA) is controversial because of suggestions that pure analgesics can be as effective as NSAID for pain relief. In addition, there is incomplete information whether antiinflammatory effects have any longterm benefit in OA. NSAID have been known to affect synovial fluid (SF) prostaglandins in rheumatoid arthritis. We describe the first examination of the effect of an NSAID, etodolac, on SF prostaglandins, cytokines, and cells in OA. METHODS: Joint fluids were studied before and 2 weeks after initiation of therapy with etodolac 400 mg tid. Leukocyte counts, prostaglandin, interleukin 6, and tumor necrosis factor were measured. RESULTS: Pretreatment features of SF did not predict clinical response. We found no change in the relatively low leukocyte counts. However, SF prostaglandin levels and interleukin 6 levels were significantly decreased and tumor necrosis factor alpha levels were increased after therapy with NSAID. CONCLUSION: This NSAID had potentially important local effects that could be either beneficial or deleterious. Further studies on effects of this and other NSAID on a broader variety of SF and synovial cytokines may help predict longterm effects of NSAID on progression of OA.

Anti-Inflammatory Agents, Non-Steroidal↗

Preterm outcomes research: a critical component of neonatal intensive care.

While early preterm outcome studies described the lives of preterm survivors to justify the efforts required to save them, subsequent studies demonstrated their increased incidence of cerebral palsy, mental retardation, sensory impairments, minor neuromotor dysfunction, language delays, visual-perceptual disorders, learning disability and behavior problems compared to fullterm controls. Because infants born at the lower limit of viability require the most resources and have the highest incidence of neurodevelopmental disability, there is concern that resources have gone primarily to neonatal intensive care and are not available for meeting the followup, health, educational and emotional needs of these fragile infants and their families. Despite many methodological concerns, preterm outcome studies have provided insight into risk factors for and causes of CNS injury in preterm infants. Nevertheless, it remains difficult to predict neurodevelopmental outcome for individual preterm infants. Perinatal and neonatal risk factors are inadequate proxies for neurodevelopmental disability. Recent randomized controlled trials with one to five year neurodevelopmental followup have provided valuable information about perinatal and neonatal treatments. Recognizing adverse longterm neurodevelopmental effects of pharmacological doses of postnatal steroids is a sobering reminder of the need for longterm neurodevelopmental followup in all neonatal randomized controlled trials. Ongoing longterm preterm neurodevelopmental studies, analysis of changes in outcomes over time and among centers, and evaluation of the longterm safety, efficacy and effectiveness of many perinatal and neonatal management strategies and proposed neuroprotective agents are all necessary for further medical and technological advances in neonatal intensive care.

Hospitalization↗

Clinical and metabolic considerations of long-term oral contraceptive use.

Newer lower dose formulations are associated with an improved cardiovascular disease risk marker profile, which supports their use for longer periods and among older women. Epidemiologic studies of the newer formulations are limited. Without clinical information, an evaluation of the effects of more recent formulations on metabolic risk markers for cardiovascular disease is useful. In a large cross-sectional study, a reduction in the progestin dose and use of alternative progestins substantially reduced the proportion of oral contraceptive users with values associated with an increased risk of cardiovascular disease. No progression in metabolic changes was found by analyzing the effect of the duration of oral contraceptive use. The user's age interacted positively with the oral contraceptive--induced increase in serum triglyceride levels, but there was no interaction of age with the oral contraceptive's effect on oral glucose tolerance, glucose and insulin responses, low-density lipoprotein cholesterol, or high-density lipoprotein subfraction 2 cholesterol levels.

Age Factors↗

Metabolic effects of depot-medroxyprogesterone acetate in long-term users: a cross-sectional study.

Oral glucose tolerance test and determination of insulin, cholesterol, triglycerides, total bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase and cortisol in blood were performed on 57 Thai women who had used depot-medroxyprogesterone acetate (DMPA) for 5 years or more and 24 healthy non-DMPA users. Plasma insulin, alkaline phosphatase and morning cortisol levels were significantly higher in the DMPA users than in the non-users. There were no significant differences for other laboratory tests. The findings suggest some effects of DMPA on carbohydrate metabolism and liver function in long-term users.

Adult↗

A synergistic effect of oestradiol and prolactin influencing the incidence of 3-methylcholanthrene induced cerivical carcinomas in mice.

Castrated NMRI mice were laparotomized and a thread impregnated with beeswax-methylcholanthrene was inserted into the uterine cervix. Beginning on the day of operation and for a further 5 days the animals were injected with oestradiol, prolactin, oestradiol-prolactin, oestradiol-prolactin-progesterone, or the solvents for the hormones only. One group of animals were injected with oestradiol-prolactin for 6 days and later with progesterone every third day until death. The animals were killed one or 4 weeks after the operation. Among the one-week animals the number of cervices presenting epithelial downgrowths ("buds") into the stroma was higher after treatment with a combination of oestradiol and prolactin than after treatment with each hormone separately or among the controls. Four weeks after operation, the incidence of squamous cervical carcinomas was seen to be significantly higher among animals injected with both oestradiol and prolactin than in controls or in those injected with oestradiol or prolactin alone. Progesterone had no definite effect on the oestradiol-prolactin induced incidence. The mechanism behind the synergistic effect of prolactin and oestradiol is discussed.

Animals↗

[Longterm study of the effectiveness of different dental care programs in school children].

The caries prevalence was examined in children from the first to the tenth grade in Rostock and Krakow between 1974 and 1988. In Krakow, a town with a preventive orientated dental care program, a significance caries reduction was found. Therefore there is an increase of health and an improvement of oral situation for the children on the way to the goals of WHO for oral health by the year 2000.

Adolescent↗

Longterm neuroendocrine and metabolic effects of physical training in intermittent claudication.

Twenty-five elderly patients with peripheral vascular disease and intermittent claudication were prospectively followed during a six-month session of physical training. Neuroendocrine and metabolic patterns as well as effects on walking performance were assessed during the training period. At the initial evaluation there was an inverse association between walking distance and serum cortisol and blood glucose levels. The walking distance increased during the training period. A positive effect on glucose homeostatis was seen with decreased basal fructosamine levels after training. During physical exercise a decrease in insulin and an increase in growth hormone was seen. Changes in growth hormone were, in contrast to insulin, more related to the pain level perceived than to the work load imposed. Apart from the marked effects on physical performance the results of the study suggest an improvement of hormonal and metabolic balance after physical training. This regularly applied exercise program improved the health status of rather old people.

Aged↗