Hepatic adenoma associated with oral contraceptive use: an unusual clinical presentation

A young woman who had taken contraceptive steroids for many years had the acute onset of abdominal pain because of central necrosis and hemorrhage into a hepatic adenoma. She had multiple lesions confined to one lobe of the liver. Persistent pyrexia and leukocytosis were also prominent clinical findings. She has had no evidence of recurrence of this problem during the seven years following right hepatic lobectomy. A review of the anabolic and contraceptive steroid-associated hepatic neoplasms is presented with comments directed toward the recognition of the critical clinical sequelae that can befall the patient with hepatic adenoma. Although all the patients in the steroid-treated group have tumors with benign and striking histologic similarity, microscopic evidence of malignant invasion of surrounding tissue is occassionally noted.     

Value of breast imaging in women with painful breasts: observational follow up study

OBJECTIVES: To determine the value of breast imaging in patients with localised or diffuse pain in the breast in whom physical examination shows no abnormalities. DESIGN: Observational follow up study. SETTING: Radiology department of a teaching hospital in the Netherlands. SUBJECTS: Altogether 987 women referred for radiological breast imaging because of pain alone and a control group of 987 asymptomatic women referred for a screening mammogram. MAIN OUTCOME MEASURES: Correlation of the radiological findings with clinical and pathological findings over two years of follow up. RESULTS: Radiological examination of the painful breast(s) showed the following: normal findings in 854 (86.5%) women, benign abnormalities in 85 (8.6%; mainly small cysts or mastopathy), abnormalities that were probably benign in 36 (3.6%), suspicious findings in 8 (0.8%), and malignancy in 4 (0.4%). Biopsy of the painful area was performed in 10 of the 939 women with normal findings or benign abnormalities, in two of 36 women with radiological abnormalities that were probably benign, and in all women with suspicious or malignant findings. Only the four lesions that had been classified radiologically as malignant were found to be malignant at surgery. The prevalence of breast cancer was similar in symptomatic and control women. CONCLUSIONS: Breast imaging in women who present with pain alone is of value only in providing reassurance--no abnormalities are usually found in the painful area, radiological abnormalities classified as benign do not generally have any clinical consequences, and the prevalence of cancer is low in these women. Biopsy of the painful area should be performed only where radiological findings are suspicious.     

Design, objectives, and lessons from a pilot 25 year follow up re-survey of survivors in the Whitehall study of London Civil Servants

Deposition of immune complexes (IC) is an important step in the pathogenesis of lupus nephritis. Impairment of IC-clearance contributes to the accumulation of IC. It may be partly attributed to decreased complement containing immune complex (ICC) binding by erythrocytic complement receptor 1 (ECR1). Stimulating erythropoiesis with recombinant human erythropoietin (rHuEPO) may enhance the IC-clearance as increasing ECR1 expression and/or functional activity. Ten anemic patients with lupus nephritis were treated with 50 IU rHuEPO (Eprex) per kg body weight three times a week during a five week period. ICC-binding capacity of ECR1 was determined with 125I-labelled, C3ib containing BSA-anti-BSA complexes. In addition to effective correction of anemia, indicated by increased red blood cell count (RBC), hemoglobin concentration and reticulocyte ratio, rHuEPO significantly improved decreased ECR1 functional (ICC-binding) activity in patients with lupus nephritis. This improvement correlated with the increase in reticulocyte ratio. Although patients were kept on their previous therapy during Eprex administration, their clinical condition also improved. That was shown by a decrease in Westergreen ratio, serum creatinine concentration and anti-dsDNA level and also by an increase in creatinine clearance. Results suggest a beneficial immune modulatory effect of rHuEPO in lupus nephritis.     

The development and reliability of the Royal College of General Practitioners' questionnaire for measuring senior house officers' satisfaction with their hospital training

BACKGROUND: The training provided for senior house officers (SHOs) has been the subject of debate, and variable satisfaction with training has been reported. The reliability of the instruments used for measuring satisfaction has not been adequately addressed. AIM: To develop a reliable questionnaire to measure SHO satisfaction with hospital training. METHOD: A 42-item questionnaire with eight scales was developed using criteria from the joint hospital visiting guidelines of the Royal College of General Practitioners. The questionnaire was sent to SHOs in Anglia before monitoring visits from the royal colleges, the postgraduate dean and the Joint Committee on Postgraduate Training for General Practice. RESULTS: Response rates varied from 37.0% to 100%, with an overall response rate of 58.8%. The internal reliability of the whole questionnaire was 0.82. Levels of internal reliability for the individual scales were satisfactory, Cronbach's alpha coefficient being 0.75 or more in all but two of the scales. Test-retest reliability using Pearson's product moment correlation coefficient was greater than 0.82 for six of the scales. There were significant differences in total satisfaction between SHOs reporting on posts accredited by the different royal colleges and also between SHOs training for general practice and those training to be specialists. CONCLUSION: A reliable questionnaire has been developed to measure SHO satisfaction with hospital training that is acceptable to doctors and feasible to administer. National acceptance of a single questionnaire for monitoring SHO posts would enable standards to be monitored regularly at a time of considerable change in hospital training.     

Mortality associated with HIV-1 infection over five years in a rural Ugandan population: cohort study

OBJECTIVE: To assess the impact of HIV-1 infection on mortality over five years in a rural Ugandan population. DESIGN: Longitudinal cohort study followed up annually by a house to house census and medical survey. SETTING: Rural population in south west Uganda. SUBJECTS: About 10,000 people from 15 villages who were enrolled in 1989-90 or later. MAIN OUTCOME MEASURES: Number of deaths from all causes, death rates, mortality fraction attributable to HIV-1 infection. RESULTS: Of 9777 people resident in the study area in 1989-90, 8833 (90%) had an unambiguous result on testing for HIV-1 antibody; throughout the period of follow up adult seroprevalence was about 8%. During 35,083 person years of follow up, 459 deaths occurred, 273 in seronegative subjects and 186 in seropositive subjects, corresponding to standardised death rates of 8.1 and 129.3 per 1000 person years. Standardised death rates for adults were 10.4 (95% confidence interval 9.0 to 11.8) and 114.0 (93.2 to 134.8) per 1000 person years respectively. The mortality fraction attributable to HIV-1 infection was 41% for adults and was in excess of 70% for men aged 25-44 and women aged 20-44 years. Median survival from time of enrollment was less than three years in subjects aged 55 years or more who were infected with HIV-1. Life expectancy from birth in the total population resident at any time was estimated to be 42.5 years (41.4 years in men; 43.5 years in women), which compares with 58.3 years (56.5 years in men; 60.5 years in women) in people known to be seronegative. CONCLUSIONS: These data confirm that in a rural African population HIV-1 infection is associated with high death rates and a substantial reduction in life expectancy.     

Refractive outcome in eyes with retinopathy of prematurity treated with cryotherapy or diode laser: 3 year follow up

AIMS: To compare the refractive error 1 to 3 years after cryotherapy or diode laser treatment for threshold retinopathy of prematurity. METHODS: Twenty six infants treated with diode laser and 17 infants treated with cryotherapy underwent cycloplegic refraction during follow up. RESULTS: After 3 years of follow up, 94.1% of patients had myopia (right eye if bilateral) following cryotherapy and 45.5% of patients had myopia following diode laser treatment. The difference between the two proportions was 48.7% (95% confidence interval 17.8 to 80.1, p = 0.004). In the cryotherapy group 55% of patients were highly myopic (> -6.00 dioptres) while in the laser group there were no high myopes. CONCLUSIONS: In the diode laser group there were significantly fewer myopes than in the cryotherapy group up to 3 years after the procedure. There was no trend towards increasing myopia in the laser treated group and the refraction in these eyes stabilised after 1 year. In the cryotherapy group there was a significant increase in the degree of myopia between year 1 and year 3 of follow up (p = 0.02). Diode laser treatment is thought to be as effective as cryotherapy, and has the added benefit of reducing myopia, in the treatment of ROP.     

Popularity of less frequent follow up for breast cancer in randomised study: initial findings from the hotline study

OBJECTIVE: To compare the experiences of patients with breast cancer who were conventionally monitored with those in whom routine follow up was restricted to the time of mammography. DESIGN: Randomisation to conventional schedule of clinic visits or to visits only after mammography. Both cohorts received identical mammography and were invited to telephone for immediate appointments if they detected symptoms. SETTING: Combined breast clinic, Chelsea and Westminster Hospital. SUBJECTS: 211 eligible outpatients with a history of breast cancer. MAIN OUTCOME MEASURES: Acceptability of randomisation, interim use of telephone and general practitioner, satisfaction with allocation to follow up. RESULTS: Of 211 eligible patients, 196 (93%) opted for randomisation in the study. Of these, 55 were under 50 years, 78 were diagnosed fewer than five years before, 90 had stage T2-4 tumours, and 71 had involved axillary nodes. Patients who did not participate were more likely to be under 50 years, to be two to five years after diagnosis, and to have had aggressive primary disease. Twice as many patients in both groups expressed a preference for reducing rather than increasing follow up. No increased use of local practitioner services or telephone triage was apparent in the cohort randomised to less frequent follow up by specialists. CONCLUSIONS: Reducing the frequency of routine follow up has so far proved popular among patients with breast cancer at standard risk in this cohort. A multicentre study is needed to determine the effectiveness and cost-effectiveness of routine follow up with respect to disease outcomes.     

Surgical outcome and cost-minimisation-analyses of laparoscopic and open hernia repair: a randomised prospective trial with one year follow up

OBJECTIVE: To compare outcome and costs between laparoscopic and open hernia repair. DESIGN: Prospective randomised study. SETTING: One university and two district hospitals in Sweden. SUBJECTS: 200 men aged 25-75 years. MAIN OUTCOME MEASURES: Operating time, hospital stay, complications, and time to recovery. A cost-minimisation-analysis was used in which the total costs were calculated for a defined period of time for each option. RESULT: The one year follow-up rate was 98%. Mean (SD) operation times in the laparoscopic and open groups were 72 (30) and 62 (25) minutes, respectively (p = 0.009). Hospital stay and complication rates did not differ between the groups. Among employees the mean (SD) periods off work in the laparoscopic and open groups were 10 (8) and 23 (21) days, respectively (p = 0.0001). The mean direct costs of the laparoscopic operation were increased by SEK 4037 (US$ 483) but the savings in indirect costs resulting from earlier return to work were SEK 11392 (US$ 1364). CONCLUSIONS: Laparoscopic hernia repair gave the employed patients faster recovery and return to work, and was the most cost-effective strategy provided that both direct and indirect costs were included.     

A study of the interactive effects of oral contraceptive use and dietary fat intake on blood pressure, cardiovascular reactivity and glucose tolerance in normotensive women

A morphometrical evaluation was made of the seasonal changes affecting the numbers of lymphocytes in the thymus, spleen and pronephros of wild brown trout, Salmo trutta, while the size of the thymus and the three thymic zones were also determined. Results reveal statistically significant changes throughout the year in the number of lymphocytes in the lymphoid organs studied. The spleen and pronephros have similar annual patterns of lymphocyte distribution with high numbers in two seasons, spring and autumn, and two periods of lymphoid involution in winter and summer. The highest numbers of thymocytes occur in trout caught in May and August, and the lowest in winter. In addition to normal lymphocytes, degenerated lymphoid cells that show pale cytoplasm devoid of cell organelles, also occurred in all the lymphoid organs. A negative correlation exists between the numbers of normal lymphocytes and that of degenerated lymphoid cells. The thymic size, as well as that of the subcapsular, inner and outer thymic zones, undergo very significant changes over the year. We discuss the relevance of cell proliferation, cell migration and in situ cell death for the circannual variations observed in the cell content of trout lymphoid organs, together with the possible causes.     

Reduced fetal growth rate and increased risk of death from ischaemic heart disease: cohort study of 15 000 Swedish men and women born 1915-29

OBJECTIVE: To establish whether fetal growth rate (as distinct from size at birth) is associated with mortality from ischaemic heart disease. DESIGN: Cohort study based on uniquely detailed obstetric records with 97% follow up over the entire life course and linkage to census data in adult life. SUBJECTS: All 14 611 babies delivered at the Uppsala Academic Hospital, Sweden, during 1915-29 followed up to end of 1995. MAIN OUTCOME MEASURES: Mortality from ischaemic heart disease and other causes. RESULTS: Cardiovascular disease showed an inverse association with birth weight for both men and women, although this was significant only for men. In men a 1000 g increase in birth weight was associated with a proportional reduction in the rate of ischaemic heart disease of 0.77 (95% confidence interval 0.67 to 0.90). Adjustment for socioeconomic circumstances at birth and in adult life led to slight attenuation of this effect. Relative to the lowest fourth of birth weight for gestational age, mortality from ischaemic heart disease in men in the second, third, and fourth fourths was 0.81 (0.66 to 0.98), 0.63 (0.50 to 0.78), and 0.67 (0.54 to 0.82), respectively. The inclusion of birth weight per se and birth weight for gestational age in the same model strengthened the association with birth weight for gestational age but removed the association with birth weight. CONCLUSION: This study provides by far the most persuasive evidence of a real association between size at birth and mortality from ischaemic heart disease in men, which cannot be explained by methodological artefact or socioeconomic confounding. It strongly suggests that it is variation in fetal growth rate rather than size at birth that is aetiologically important.     

Prognostic value of prostate-specific antigen for women with breast cancer: a large United States cohort study

Prostate-specific antigen (PSA) is a valuable tumor marker used for diagnosis and management of prostate cancer. Recently, PSA has been found in various female tissues and body fluids. Female breasts, both normal and abnormal, including cancerous tissues, can produce PSA, and this production is regulated by androgens and progestins. Preliminary data suggested that patients with breast tumors positive for PSA may have better prognosis compared to those with PSA-negative breast tumors. This study examines the prognostic value of PSA in a large cohort study of United States patients. Using a PSA assay that has a lower detection limit of 0.001 ng/ml, we measured PSA in tumor cytosolic extracts of 953 women with primary breast cancer. Other information available for this study included age, follow-up time, survival outcome, tumor size, nodal status, steroid hormone receptor levels, DNA analysis by flow cytometry, and postoperative treatment. The median follow-up time was 73 months. During the follow-up, 200 patients relapsed and 188 died. PSA presence was found to be significantly associated with smaller tumors, tumors with low S-phase fraction, diploid tumors, younger patient age, and tumors with lower cellularity. Survival analysis indicated that the relative risks (RRs) for relapse and death were both significantly lower [RR = 0.67 (P = 0.01) for relapse; RR = 0.72 (P = 0.05) for death] in PSA-positive patients (levels higher than the 30th percentile of PSA values) than in PSA-negative patients. The reduced risks for relapse and death remained statistically significant after other clinical and pathological variables were adjusted in the multivariate analysis [RR = 0.68 (P = 0.02) for relapse; RR = 0.65 (P = 0.02) for death]. Our results suggest that the measurement of PSA in breast tumor extracts provides additional information on the prognosis of patients with primary breast cancer.     

Ursodeoxycholic acid in the treatment of primary biliary cirrhosis: a short-term, randomized, double-blind controlled, cross-over study with long-term follow up

In order to evaluate the efficacy of ursodeoxycholic acid (UDCA) in the treatment of Chinese patients with primary biliary cirrhosis, a short-term, randomized, double-blind controlled, cross-over study was done with long-term follow up. In the first part of the study, 12 patients were randomly chosen to receive either UDCA 600 mg/day for 3 months followed by a placebo for 3 months or a placebo for 3 months followed by UDCA for 3 months. The clinical symptoms of pruritus improved when the patients were receiving UDCA but became worse when receiving a placebo. Mean serum levels of alkaline phosphatase (ALPase), gamma-glutamyl transferase (gamma-GT), total bilirubin, cholesterol, alanine aminotransferase (ALT) and aspartate aminotransferase all decreased below the baseline values when receiving UDCA treatment and all increased above the baseline values when receiving the placebo. The difference was statistically significant. In the second part of the study, 19 patients received long-term UDCA treatment (mean 20 months). The clinical symptoms of pruritus improved in 90% of the pruritic patients. Serum levels of ALPase, gamma-GT and ALT fell significantly from the pretreatment values, 6, 12 and from the mean 20 months after UDCA treatment. Serum levels of total bilirubin fell significantly 6 and 12 months after UDCA treatment but did not reach statistical significance at the last follow up. No patient lost antimitochondrial antibody and elevated immunoglobulin levels did not improve significantly, but the Mayo clinical risk score improved significantly after long-term UDCA treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Recurrence risks in offspring of adults with major heart defects: results from first cohort of British collaborative study

BACKGROUND: Congenital heart defects are generally assumed to have a multifactorial aetiology. We have tested this hypothesis by studying adults with heart defects and their families. METHODS: We identified 1094 patients who survived surgery for major cardiac defects before 1970. We chose individuals with disturbance of situs or segmental connection, with atrioventricular septal defect or with tetralogy of Fallot. After exclusion and non-participation, 727 individuals were traced. Each was visited by an investigator and completed a detailed questionnaire. If possible, all "normal" offspring were examined by a paediatric cardiologist. FINDINGS: The 727 individuals had 393 live offspring. There were 71 miscarriages and five terminated pregnancies. Overall, we found recurrent heart defects in 16 liveborn offspring--a recurrence risk of 4.1%. This result differed significantly from sibling risk (2.1%; p=0.021). More congenital heart defects occurred in the offspring of affected women than in those of affected men (p=0.047); when all malformations (cardiac and non-cardiac) in the offspring were taken into account the excess was more significant (p=0.032). We found an excess of miscarriages in the offspring of affected women (p=0.001). In tetralogy of Fallot, heart defects occurred in seven (3.1%) of 223 offspring, 12 (2.2%) of 539 siblings, five (0.3%) of 1575 second-degree relatives, and eight (0.3%) of 2728 third-degree relatives. INTERPRETATION: Our findings do not support a polygenic basis for all heart defects. Atrioventricular septal defect seems to be a single-gene defect and tetralogy of Fallot a polygenic disorder with a small number of interacting genes. Our data suggest that isolated transposition of the great arteries is a sporadic defect.     

Epidemiology of infection with Epstein-Barr virus types 1 and 2: lessons from the study of a T-cell-immunocompromised hemophilic cohort

In apparent contrast to earlier work on Epstein-Barr virus (EBV) carriage in the general Caucasian population, in vitro virus isolations from human immunodeficiency virus (HIV)-positive male homosexual cohorts have shown frequent examples of multiple EBV infection and an overall prevalence of type 2 EBV strains exceeding 30%. Here we ask to what extent these findings might hold true in another T-cell-immunocompromised cohort, HIV-positive hemophilic patients. Resident EBV strains were rescued within lymphoblastoid cell lines derived from the blood and throat washings of 39 such individuals, using the same in vitro protocols of virus isolation as for the homosexual cohort. A mean of 19 independent cell lines was made per patient, and in each case the resident virus was characterized by PCR-based viral genomic analysis and by immunoblotting to reveal the viral "EBNAprint." By these criteria a significant proportion (14 of 39) of the hemophilic cohort carried more than one EBV strain, suggesting that T-cell impairment does indeed sensitize virus carriers to reinfection with new strains of exogenously transmitted virus. However, the overall incidence of type 2 EBV infection was 10%, which is close to that observed in the earlier work with healthy carriers and substantially lower than that seen in HIV-positive homosexuals. We infer that type 2 EBV is relatively rare in the general Caucasian population but has become endemic in the homosexual community.     

Psychosocial factors associated with the stages of change for condom use among women at risk for HIV and STDs: implications for intervention development

This study examined the prevalence of consistent condom use among inner-city women at risk for HIV, measured the distribution of these women across the stages of change for condom use, determined psychosocial factors associated with the stages, and suggested intervention strategies based on the results. The 5-city sample of women aged 15-34 years consisted predominantly of African Americans. Only 18% reported consistent condom use with main partners and 45% with other partners. Logistic regressions compared women in each stage of change with those in higher stages for each partner type. Results indicated that women who practice or intend to practice consistent condom use were more likely to talk with others about condoms, acknowledge the advantages of condoms, have higher self-efficacy for condom use, and indicate that people important to them favored condom use. Intervention approaches are suggested for women in different stages of change for condom use.     

Induction chemotherapy is associated with an increase in the incidence of locoregional recurrence in patients with carcinoma of the oral cavity: results from a single institution

BACKGROUND: This study was conducted to determine long term survival rates and the pattern of failure in patients with carcinoma of the oral cavity treated with induction chemotherapy or preoperative radiotherapy followed by surgery. METHODS: A retrospective analysis was performed of 141 eligible patients with Stage II-IV International Union Against Cancer (UICC) staging system squamous cell carcinoma of the oral cavity at the study department between 1985 and 1994. These patients received one of three treatments: surgery with or without peplomycin chemotherapy (Group A; n = 49); preoperative radiotherapy with or without concomitant peplomycin chemotherapy followed by surgery (Group B; n = 59); and induction chemotherapy followed by surgery (Group C; n = 33). Induction chemotherapy was comprised of two cycles of cisplatin, vincristine, peplomycin, with or without mitomycin C. RESULTS: When all 141 patients were analyzed, there was no significant difference in overall survival or disease free survival. However, a statistically significant increase in the incidence of neck recurrence in Group C was observed compared with Group A (P = 0.002). Within 79 patients with N0 disease, a statistically significant disadvantage was detected for Group C in terms of disease free survival compared with Group A (P = 0.038). In patients with Stage II disease (50 patients), there was a significant difference in disease free survival, with Group C inferior to both Group A (P = 0.04) and Group B (P = 0.066). CONCLUSIONS: Induction chemotherapy was associated with a significant increase in regional failure for patients with carcinoma of the oral cavity with N0 disease and those with Stage II disease.     

The recovery of silver from photographic film: A study of the leaching reaction with cyanide solution for industrial use

A process for the recovery of silver present in photographic and X-ray films is described. It is based on leaching by sodium cyanide solution which is accelerated in the presence of hydrogen peroxide. The process can be used industrially. The control of the use of CN⁻ allows us to repeatedly use the initial solution, the silver content of which increases after each application. The subsequent recovery of the silver is achieved by electrolysis. The process gives a product of good quality and offers a very high yield.     

Maternal use of antiepileptic drugs and the risk of major congenital malformations: a joint European prospective study of human teratogenesis associated with maternal epilepsy

PURPOSE: To quantify the risks of intrauterine antiepileptic drug (AED) exposure in monotherapy and polytherapy. METHODS: Data from five prospective European studies totaling 1,379 children were pooled and reanalyzed. Data were available for 1,221 children exposed to AED during pregnancy and for 158 children of unexposed control pregnancies. RESULTS: Overall, when comparing a subgroup of 192 children exposed to AED with 158 children of matched nonepileptic controls, there was an increased risk of major congenital malformations (MCA) in children exposed to AED during gestation [relative risk (RR) 2.3; 95% confidence interval (CI): 1.2-4.7]. A significant increase in risk was found for children exposed to valproate (VPA) (RR 4.9; 95% CI: 1.6-15.0) or carbamazepine (CBZ) (RR 4.9; 95% CI: 1.3-18.0) in monotherapy. When comparing different AED regimens during all 1,221 pregnancies, risks of MCA were significantly increased for the combination of phenobarbital (PB) and ethosuximide (RR 9.8; 95% CI: 1.4-67.3) and the combination of phenytoin, PB, CBZ, and VPA (RR 11.0; 95% CI: 2.1-57.6). Offspring of mothers using > 1,000 mg VPA/day were at a significantly increased risk of MCA, especially neural tube defects, compared to offspring exposed < or =600 mg VPA/day (RR 6.8; 95% CI: 1.4-32.7). No difference in risk of MCA was found between the offspring exposed to 601-1,000 mg/day and < or =600 mg/day. CONCLUSIONS: This reanalysis shows that VPA is consistently associated with an increased risk of MCA in babies born to mothers with epilepsy. Significant associations were also observed with CBZ. Larger prospective population-based studies are needed to evaluate the risks of many other less frequently prescribed treatment regimens, including newly marketed AEDs.