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PubMed1983

Follow-up of patients with prolactinomas after discontinuation of long-term therapy with bromocriptine.

The effects of bromocriptine discontinuation after a 2 year course of therapy on prolactin (Prl) serum levels and the radiological size of the sella turcica were investigated in 16 women with amenorrhoea-galactorrhoea due to prolactinoma. During therapy, all but 2 patients had normalized serum Prl levels, and 4 women with macroprolactinomas exhibited a reduction in the size of the tumour as documented by CT-scanning and tomography of the sellae. After bromocriptine withdrawal and follow-up during 2 additional years, Prl levels remained normal in 6 patients, 2 of them with microprolactinomas and 4 with macroprolactinoma. The remaining 10 women developed hyperprolactinaemia associated with amenorrhoea and galactorrhoea within 3 months after discontinuation of therapy. No tumour expansion was observed in any case during the 4 year observation period. In the present study bromocriptine treatment seemed to result in permanent cure in 6 out of 16 cases of prolactinomas; nevertheless it is difficult to justify an indefinite medical treatment since the natural history of prolactinoma remains unknown. We presently feel that bromocriptine is more appropriate than neurosurgical transsphenoidal exploration for the primary treatment of prolactinomas. Further investigation is needed before a more definitive conclusion regarding the management of prolactinomas can be reached.

Adult↗
PubMed1997

[Acute disseminated encephalomyelitis and meningococcal A and C vaccine: case report].

A 25-year-old women developed acute disseminated post-vaccinal encephalomyelitis (ADEM) following vaccination with A plus C meningococcal vaccine (Pasteur-Merieux). Fast disappearance of symptoms and gradual resolution of MRI demyelinating lesions occurred after steroid treatment with high doses of intravenous methylprednisolone. To our knowledge, ADEM has not been previously described in association with meningococcal vaccine. Although most cases of ADEM occur following viral infections and vaccination, the syndrome has previously been related to leptospirosis and Mycoplasma pneumoniae infections. This suggests that it may also be related to exposure to polysaccharide-protein vaccines such as the Group A plus Group C meningococcal vaccine.

Adult↗
PubMed2000

Dynamic MR imaging of the pelvic floor in asymptomatic subjects.

OBJECTIVE: Dynamic MR imaging may be used as an alternative to dynamic cystoproctography for the evaluation of pelvic floor prolapse and configuration. MR criteria for normality are derived from proctographic studies because no large MR study of asymptomatic individuals has been performed. Our study aimed to define the normal range of dynamic pelvic MR appearances in a large group of asymptomatic individuals. SUBJECTS AND METHODS: Fifty healthy adult volunteers (25 men and 25 women; age range, 20-66 years; mean age, 34 years) were prospectively recruited and examined using dynamic MR imaging. All subjects were interviewed and established as healthy using a validated questionnaire. Axial, coronal, and sagittal MR imaging was performed at rest and during maximum pelvic strain using a static 1.0-T unit and a fast-field-echo sequence, providing 10 slices in 31 sec. Standardized measurements of pelvic configuration were taken, and rest and strain imaging were compared to determine the range of normal appearances. RESULTS: Three women developed a cystocele during maximum pelvic strain, two of whom also showed grade 1 uterocervical prolapse, which was also seen in another woman. Three men showed posterior pelvic floor descent in excess of 3 cm during straining. No rectocele, enterocele, rectal prolapse, or perineal hernia was seen in any subject. CONCLUSION: The normal range of pelvic organ descent in asymptomatic subjects seen on dynamic MR imaging included cystocele, uterocervical prolapse, and excessive anorectal junction descent. Although we encountered pelvic prolapse in seven volunteers, it was infrequent and low grade, suggesting that criteria for abnormality derived from proctography are generally applicable to MR imaging.

Adult↗
PubMed2003

Gestational diabetes induces placental genes for chronic stress and inflammatory pathways.

A physiological state of insulin resistance is required to preferentially direct maternal nutrients toward the feto-placental unit, allowing adequate growth of the fetus. When women develop gestational diabetes mellitus (GDM), insulin resistance is more severe and disrupts the intrauterine milieu, resulting in accelerated fetal development with increased risk of macrosomia. As a natural interface between mother and fetus, the placenta is the obligatory target of such environmental changes. However, the molecular basis for the imbalance that leads to fetal, neonatal, and adult metabolic compromises is not well understood. We report that GDM elicits major changes in the expression profile of placental genes with a prominent increase in markers and mediators of inflammation. Within the 435 transcripts reproducibly modified, genes for stress-activated and inflammatory responses represented the largest functional cluster (18.5% of regulated genes). Upregulation of interleukins, leptin, and tumor necrosis factor-alpha receptors and their downstream molecular adaptors indicated an activation of pathways recruiting stress-activated protein/c-Jun NH(2)-terminal kinases. Transcriptional activation of extracellular matrix components and angiogenic activators pointed to a major structural reorganization of the placenta. Thus, placental transcriptome emerges as a primary target of the altered environment of diabetic pregnancy. The genes identified provide the basis to elucidate links between inflammatory pathways and GDM-associated insulin resistance.

Adult↗
PubMed1991

Diabetes Intervention Study. Multi-intervention trial in newly diagnosed NIDDM.

OBJECTIVE: In a randomized 5-yr multi-intervention trial, we tested the efficacy of intensified health education (IHE) in improving metabolic control and reducing the level of coronary risk factors and incidence of ischemic heart disease (IHD). RESEARCH DESIGN AND METHODS: Within the intervention group, the benefit of clofibric acid was evaluated in a double-blind study. One thousand one hundred thirty-nine newly diagnosed middle-aged (30- to 55-yr-old) patients with non-insulin-dependent diabetes mellitus (NIDDM) entered the study. They were classified as diet controlled after a 6-wk screening phase with conventional dietary treatment. During the follow-up, the control group (n = 378) was cared for at different diabetes outpatient clinics with a standardized surveillance. The intervention group (n = 761) had a structured IHE that included dietary advice, antismoking and antialcohol education, and ways to enhance physical activity. RESULTS: Randomly, 379 of the IHE patients received 1.6 g clofibric acid/day, and the others received placebo. IHE resulted in improved glucose control (adjusted fasting blood glucose) levels after 5 yr (control subjects 9.27 mM, IHE group 8.71 mM, and IHE plus clofibric acid group 8.60 mM, P less than 0.01). The better glycemic control was achieved with fewer antidiabetic drugs. After 5 yr, antidiabetic drugs were prescribed to 47% of the control subjects, 28% of the IHE group, and 34% of the IHE plus clofibric acid group (cutoff limit for drug application was postprandial blood glucose of greater than or equal to 13.87 mM). The ratio of polyunsaturated to saturated fatty acids (0.26 vs. 0.40, P less than 0.01) and physical activity (174 vs. 327 scores, P less than 0.01) were increased, and blood pressure, tobacco, and alcohol consumption were significantly reduced by IHE. However, IHE had no effect on calorie intake, percentage of fat in the diet (45%), and body weight. The most important finding was the significant increase of blood cholesterol in all three groups (+0.47, +0.36, and +0.34 mM, respectively). Clofibric acid only prevented the increase of triglyceride levels (+0.56, +0.24, and +0.05 mM, respectively). The incidence rate per 1000 for myocardial infarction was 30.3 for control subjects, 53.6 for the IHE group, and 55.6 for the IHE plus clofibric acid group. The corresponding rates for IHD incidence were 90.9, 97.8, and 98.8, respectively. Men suffered more frequently from myocardial infarction, whereas women developed ECG criteria for IHD more frequently. Among the 35 cases of death, besides cardiovascular diseases, liver cirrhosis and neoplasia were the predominant causes. The death rate per 1000 in control subjects was 46.2, 30.6 in the IHE group, and 27 among patients with IHE plus clofibric acid. CONCLUSIONS: IHE was of substantial benefit for the control of glycemia, significantly diminished the need for antidiabetic drugs, and reduced a cluster of risk factors but had no effect on the control of blood lipids. This could be one major reason for the failure of IHE, effective lowering of blood pressure, and clofibric acid to prevent cardiovascular complications. Clofibric acid was only effective in reducing triglycerides.

Adult↗
PubMed1995

Incidence and determinants of elevated urinary albumin excretion in Pima Indians with NIDDM.

OBJECTIVE: To examine the incidence and determinants of elevated urinary albumin excretion in Pima Indians with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: The incidence of elevated urinary albumin excretion (> or = 30 mg albumin/g creatinine) and its relationship with baseline characteristics was determined in 456 Pima Indians > or = 15 years old with NIDDM who were followed for up to 11.6 years (median 4.7 years). RESULTS: Of these 456 subjects, 192 (42%; 58 men, 134 women) developed elevated urinary albumin excretion, 172 of whom (90%) were within the microalbuminuric range (30-299 mg/g). The incidence of elevated urinary albumin excretion was related to retinopathy, type, of diabetes treatment, longer duration of diabetes, lower body mass index, and higher values of mean arterial pressure, HbA1, and fasting and 2-h postload plasma glucose concentration at the baseline examination, but not to sex. A relationship with cholesterol was found in durations of diabetes of > or = 10 years. The cumulative incidence of elevated albumin excretion was 17% after 5 years of NIDDM. CONCLUSIONS: The incidence of elevated urinary albumin excretion in Pima Indians with NIDDM is at least as high as that reported previously in insulin-dependent diabetes mellitus, and its major determinants are the same as those shown previously to predict the development of more advanced renal disease in this population.

Adolescent↗
PubMed1997

Longitudinal study of carbohydrate metabolism in healthy obese pregnant women.

OBJECTIVE: To longitudinally characterize changes in insulin sensitivity in obese women during and after pregnancy. RESEARCH DESIGN AND METHODS: Six glucose-tolerant obese women underwent a 4-h euglycemic-hyperinsulinemic (500-600 pmol/l) clamping during the second (22.5 +/- 2 weeks [mean +/- SD]) and third trimester (36.8 +/- 0.9) of pregnancy and again 15.6 +/- 1.4 weeks after delivery. Rates of total body glucose turnover (with [6.6-2H2]glucose) and oxidation (with indirect calorimetry) were measured. RESULTS: There were no significant changes with respect to the action of insulin on rates of glucose disappearance (GRd), carbohydrate oxidation, or endogenous glucose production (EGP), comparing the second trimester of pregnancy with the nonpregnant (postpartum) state. The third trimester, however, was characterized 1) by reductions in insulin-stimulated GRd (-28%, P < 0.05, compared with the second trimester and -40%, P < 0.05, compared with postpartum); 2) by even larger reductions in insulin-stimulated carbohydrate oxidation (-46%, P < 0.05, compared with the second trimester and -54%, P < 0.02, compared with postpartum); and 3) by reduction of insulin suppression of EGP (-39% compared with -79% at the second trimester and -77% postpartum, P < 0.01). CONCLUSIONS: Glucose-tolerant obese women developed peripheral was well as hepatic insulin resistance during the third trimester of pregnancy. These alterations were reversed after delivery and appeared to be adaptive mechanisms to cope with the increased demand for glucose of the growing fetus.

Adaptation, Physiological↗
PubMed1986

Eclampsia in Sweden, 1976-1980.

Among 480,969 births in Sweden during the period 1976 to 1980, 74 parturients with eclampsia were identified. The clinical characteristics of women developing eclampsia before 37 completed weeks of gestation differed markedly from those with eclampsia at term. In the pre-term group, subjective symptoms nearly always preceded the eclamptic attack, the newborns were generally small-for-gestational-age, the perinatal mortality was high, and the mothers more frequently had complications related to eclampsia. The only maternal death occurred in this group. In the term group the first convulsion often came unexpectedly without typical premonitory signs. The infants were with few exceptions within the average for gestational age. The general outcome for mothers and their babies was favorable and the length of hospital stay was on average 3 days longer than that of the overall obstetric population. Eclampsia cases in Sweden represent a small subfraction of parturients with hypertensive disorders of pregnancy. The incidence (29/100,000) in our material is, to our knowledge, the lowest yet reported. Despite the very regular attendance at the antenatal clinic, weekly from 36 weeks onwards, fewer than half of the patients had hypertension diagnosed 4 days or more prior to the eclamptic convulsion. A shortening of the intervals between the antenatal visits therefore does not seem warranted.

Adolescent↗
PubMed1989

Efficacy of gonadotropin-releasing hormone agonist (buserelin) in the treatment of endometriosis.

In a multicenter study, the efficacy of and tolerance of 6 months' intranasal gonadotropin-releasing hormone agonist (buserelin) treatment (300 micrograms x 3/day) on laparoscopically verified endometriosis was evaluated in 25 patients. At second-look laparoscopy at the end of medication, the mean endometriosis score had fallen by 82.2%. All endometriosis-associated symptoms and physical findings decreased or almost disappeared during buserelin administration. After discontinuing therapy, they showed a tendency to reappear, but nevertheless they were milder after one year of follow-up, than before treatment. Seven (54%) of the 13 women wishing pregnancy actually conceived. Vaginal irregular spotting bleedings during the first 2 months occurred in 7 patients. No patient withdrew from the trial because of side effects, although almost all women developed symptoms of estrogen deficiency (serum estradiol concentrations fell to menopausal levels).

Administration, Intranasal↗
PubMed1981

Histologic follow-up of alpha-methyldopa-induced liver injury.

Alpha-methyldopa-induced liver injury was studied in six patients by clinical, biochemical, histologic, and morphometric methods. The patients, all women, developed hepatic injury after long-term therapy lasting 2 to 8 years. Withdrawal of the drug resulted in improvement of the symptoms. Hepatitis with fibrosis and moderate to severe fatty accumulation was seen in most of the liver biopsies at onset of symptoms. Follow-up ranged from 7 to 24.5 months, at the end of which the liver function test results were in the normal range. A second liver biopsy showed significant decrease in fatty infiltration. Three patients showed a decrease in lipid content from moderate to mild or normal and two other patients from severe to moderate. A 73-year-old patient had chronic aggressive hepatitis with massive necrosis of the parenchyma after 8 years of therapy, and follow-up biopsy 12 months later showed cirrhosis. In this study alpha-methyldopa withdrawal resulted in a reduction of lipid and fibrous trabeculae content, possibly caused by alpha-methyldopa-induced derangement of liver function.

Aged↗
PubMed1993

Imported relapsing fever in European tourists.

Two 'imported' cases of relapsing fever after a trip through Senegal are described. Two women developed a tick-borne relapsing fever after having slept outdoors on a terrace in Zinguichor, Senegal. The first patient was rapidly cured after a course of doxycycline. The second patient initially received erythromycin, but despite this treatment she developed neurological symptoms and Borrelia persisted in the thick-smear examination. After treatment with doxycycline she developed a Jarish-Herxheimer reaction. Treatment with doxycycline was continued and finally all symptoms disappeared within 36 hours after starting this treatment. A diagnosis of relapsing fever should be considered in all patients returning from the tropics with recurrent fever, especially if no malaria parasites are found.

Adult↗
PubMed1978

Clinical and histological kidney involvement in human kala-azar.

A 19-year-old women developed prolonged fever, weight loss, hepatosplenomegaly, anemia, leukopenia, and hyperglobulinemia. Appropriate tests indicated that she had visceral leishmaniasis (kala-azar). Urinalysis demonstrated significant proteinuria and microhematuria with the presence of red cell casts. A kidney biopsy was performed. Light microscopy showed a slight mesangial thickening and segmental mesangial proliferation. Immunofluorescence demonstrated deposits of immunoglobulins A and M, complement, and fibrinogen. Electron microscopy showed subendothelial and intramembranous deposits. After treatment with N-methylglucamine antimonate the proteinuria and microhematuria disappeared and the patient recovered uneventfully.

Adult↗
PubMed2003

Serum insulin-like growth factor I and risk for heart failure in elderly individuals without a previous myocardial infarction: the Framingham Heart Study.

BACKGROUND: Several experimental investigations have emphasized the favorable effects of insulin-like growth factor I (IGF-I) on left ventricular remodeling, partly through its antiapoptotic effects. Cross-sectional clinical studies have reported that low serum IGF-I levels in patients with heart failure correlate with cachexia and severity of ventricular dysfunction. It is unclear whether low serum IGF-I is a risk factor for heart failure. OBJECTIVE: To prospectively study the association between serum IGF-I level and the incidence of congestive heart failure. DESIGN: Community-based, prospective cohort study. SETTING: Framingham, Massachusetts. PARTICIPANTS: 717 elderly individuals (mean age, 78.4 years; 67% women) who did not have myocardial infarction and congestive heart failure at baseline. MEASUREMENT: Incidence of a first episode of congestive heart failure on follow-up. RESULTS: During follow-up (mean, 5.2 years), 56 participants (35 women) developed congestive heart failure. In multivariable Cox regression models adjusting for established risk factors at baseline, there was a 27% decrease in risk for heart failure for every 1 standard deviation increment in log IGF-I. Individuals with serum IGF-I level at or above the median value (140 microg/L) had half the risk for heart failure (hazard ratio, 0.49 [95% CI, 0.26 to 0.92]) of those with serum IGF-I levels below the median. These comparisons were maintained in analyses adjusting for the occurrence of a myocardial infarction on follow-up. CONCLUSIONS: In our prospective, community-based investigation, serum IGF-I level was inversely related to the risk for congestive heart failure in elderly people without a previous myocardial infarction. Additional investigations are warranted to confirm these findings.

Aged↗
PubMed1975

Cyclic premenstrual unconjugated hyperbilirubinemia. Report of two cases.

Two young women developed unconjugated hyperbilirubinemia that fluctuated with the menstrual cycle. They were otherwise healthy, and there was no evidence of hematologic or chronic liver disease. Serum unconjugated bilirubin rose concomitant with the rise of basal temperature during the premenstrual period, and it declined immediately after the end of menses. Administration of progesterone during the postmenstrual period elevated unconjugated bilirubin. A close relation of hyperbilirubinemia to female hormones was suggested. The condition may be called "constitutional unconjugated hyperbilirubinemia with a menstrual cycle.

Adult↗
PubMed1998

Use of transvaginal ultrasonography to monitor the effects of tamoxifen on uterine leiomyoma size and ovarian cyst formation.

To evaluate the effects of tamoxifen on leiomyomas and ovarian cysts in postmenopausal breast cancer patients, uterine and leiomyoma volumes were monitored sonographically in 17 postmenopausal women receiving postoperative tamoxifen for breast cancer; patients were examined twice with a mean of 1.18 +/- 0.17 years between examinations. The mean increase in leiomyoma volume was 1.26 +/- 0.73 cm3. The mean myoma volume was significantly larger at follow-up evaluation than at initial ultrasonography (5.75 +/- 1.09 cm3 versus 4.36 +/- 0.817 cm3, respectively; Wilcoxon signed rank test, P = 0.0218). Six women developed new leiomyomas. Of the 21 leiomyomas initially detected, 13 increased, six decreased, and two were unchanged in volume. The mean increase in uterine volume was 17.45 +/- 8.49 cm3. Three patients had simple ovarian cysts at initial ultrasonographic examination, two of which remained unchanged in size, and the third resolved. Two patients had newly developed simple ovarian cysts. The increase in uterine and leiomyoma volumes with the development of new leiomyomas and the persistence or development of ovarian cysts in some patients support the existence of agonistic tamoxifen effects. Serial measurements of uterine and leiomyoma volumes and surveillance for ovarian cysts is recommended for tamoxifen users.

Aged↗
PubMed1998

Pregnancy management and outcomes in women with thalassaemia major.

The health background, management and outcomes of 25 pregnancies in 18 women with transfusion dependent beta thalassaemia are described with particular consideration of appropriate preconceptual guidance for such women. This is an observation study of women attending three collaborating London hospitals. Nine of the pregnancies required induction of ovulation. Two pregnancies were complicated by diabetes and three by hepatitis C. One patient was hepatitis B positive. Two pregnancies were in women with cardiac problems, one of whom died of cardiac failure nine months after delivery of a live child. Two of the pregnancies miscarried and three were terminated, with the others resulting in 21 live children (including one set of twins). 14 of the pregnancies were delivered by caesarean section. After pregnancy five women developed secondary amenorrhoea, two developed cardiac problems and two developed diabetes.

Abortion, Spontaneous↗
PubMed1998

Precancer of the human cervix.

The tumour biology of cervical precancer is unusual. A large variety of individually distinct forms crudely divided into slight, moderate, severe dysplasia and carcinoma in situ exist. Virtually all contain genital human papillomavirus (HPV) either as infectious virions or as episomal or integrated DNA. HPV, which occurs as hundreds of types, subtypes and variants, has a high prevalence in all human populations. Most males are symptomless reservoirs, whereas a proportion of infected women develop condyloma, precancer and subsequently, in a minority, invasive cancer. HPV has unequivocal features of a sexually transmitted infectious agent. Risk of precancer is statistically related to infection with genital HPV, but differences in risk between populations with high and low prevalence of HPV are larger than expected from a direct correlation. Findings fit with HPV as a major risk factor, but other factors must also be operative. These may include shifts in number of target cells, depending on regeneration and infection by various micro-organisms, hormones, smoking and immunity. Final proof of necessity of HPV infection for precancer can probably be delivered only after its elimination by successful vaccination. Genital condyloma, which is not precancerous, is caused by HPV low risk types, typically 6 or 11, in analogy with papilloma formation in skin and mucosa in a large variety of species. This benign lesion is the hallmark of mammalian HPV pathology and a source of interindividual spread of virus. Slight dysplasia is heterogeneous. Many lesions seem to be polyclonal, self limited cell proliferative responses to infection with low grade HPV. A small proportion are associated with either simultaneous presence or subsequent development of higher grades of dysplasia, in situ or invasive cancer. Evidence exists for two mechanisms: clonal selection of cells with increasingly undifferentiated phenotypes, and independent development of different morphological types of precancer. The relative importance of the two is unknown. High risk HPV, typically 16 or 18, is preferentially associated with high grade dysplasia and in situ cancer, either because it increases risk of clonal progression to these forms or induces them de novo. Severe dysplasia, in situ and invasive cancer always present as monoclonal lesions. Genetic links indicate that these pathologies arise by clonal selection from less advanced precursors. The number of potential target cells for precancer confined to a narrow transformation zone is small. Risk of precancer and malignant transformation per target cell is therefore probably far higher than in any other human tissue subject to cancer. Spontaneous mutation rate and physicochemical carcinogens seem insufficient for the creation of a malignant phenotype in cells of the transformation zone. Currently HPV is the only strong candidate for such a feat. Any or all of the following mechanisms may play a role: overexpression of viral E6 and E7 genes, often triggered by disruption of control elements upon integration of viral DNA into the cellular genome, activity of specific (E6?) configurations in certain HPV variants, inactivation of TP53 with decreased capacity for DNA repair and enhanced likelihood of accumulation of "transforming" mutations and viral integration at sites controlling function of cellular oncogenes and/or suppressor genes. Target cells within the transformation zone have the capacity for bidirectional (squamous and/or glandular) differentiation. HPV types seem to drive cells preferentially in different directions after infection/transformation. Low risk types are almost always associated with squamous differentiation, HPV 16 usually also with squamous differentiation and HPV 18 with adenosquamous or adenomatous differentiation. (ABSTRACT TRUNCATED)

Carcinoma in Situ↗