Temporal trends in the prescription of vitamin K antagonists in patients with atrial fibrillation.

OBJECTIVES: Anticoagulation therapy is recommended in patients with atrial fibrillation (AF) and risk factors for stroke. We studied the temporal trends in the prescription of vitamin K antagonists (VKA) in patients with a first hospital diagnosis of AF in Denmark, 1995-2002. DESIGN: The Danish National Hospital Registry was used to identify subjects with a first hospital diagnosis of AF and the Danish Register of Medical Products Statistics to determine the proportion of these patients who claimed a prescription of VKA within 3 months from discharge. RESULTS: Amongst 68 546 patients aged 50-99 years with a diagnosis of AF who survived 3 months following discharge, 24 991 (36%) patients claimed a prescription of VKA within 3 months. In both men and women a gradual increase in the use of VKA with time was observed, the relative increase being largest amongst the 80- to 99-year olds. In all age groups, the prescription of VKA was lower in women than in men, including patients with a prior or concurrent stroke. CONCLUSIONS: From 1995 to 2002 the proportion of AF patients receiving VKA therapy increased significantly but the use of VKA therapy amongst women was lagging behind that of men. Even in patients with AF and prior stroke, the use of VKA seems to be less than optimal.

Reduced lung function and risk of atrial fibrillation in the Copenhagen City Heart Study.

Chronic obstructive pulmonary disease has been associated with a high frequency of arrhythmias. Few studies have analysed the role of reduced lung function in predicting atrial fibrillation (AF). The aim of the present study was to investigate the relationship between forced expiratory volume in one second (FEV1) and risk of first episode of AF in a prospective study. Data from 13,430 males and females without previous myocardial infarction, who participated in the Copenhagen City Heart Study, were analysed. New AF was assessed at re-examination after 5 yrs and by hospital admission for AF during a period of 13 yrs. Multivariate analyses were used with adjustment for cardiopulmonary risk factors. There were 62 new cases of AF at 5-yr follow-up (0.58%) and 290 cases (2.20%) diagnosed at hospitalisations. Risk of new AF at re-examination was 1.8-times higher for FEV1 between 60-80% of predicted compared with FEV1 > or = 80% after adjustment for sex, age, smoking, blood pressure, diabetes and body mass index. The risk of AF hospitalisation was 1.3-times higher for FEV1 between 60-80% and 1.8-times higher for FEV1 < 60% compared with FEV1 > or = 80%, when additional adjustment was made for education, treatment with diuretics and chest pain at activity. The authors conclude that reduced lung function is an independent predictor for incident atrial fibrillation.

[Emergency echocardiography in Denmark]. / Ekkokardiografi uden for dagtid i Danmark.

In spring 1997, all medical departments in Denmark and the Faroe Islands, not including cardiological centers, were asked to reply to a questionnaire concerning their ability to perform echocardiography at hours different from normal daytime. The response rate was 94.5%. In 21 (30.4%) of 69 departments none of the senior doctors on duty were able to perform echocardiography. In only eight (11.6%) of the departments were more than 50% of the senior doctors on duty able to perform echocardiography (M-mode/2D). Echocardiography is the most informative investigation for patients with suspected acute heart failure or with acute dyspnoea of unknown cause. In these cases acutely performed echocardiography will often be of critical diagnostic value and thereby deciding for correct and rapid therapy. This investigation shows that only a very small fraction of the medical departments in Denmark are able to perform acute echocardiography on a 24-hour basis.

Subcutaneous estradiol pellets for endometrial preparation in donor oocyte recipients with a poor endometrial response.

PURPOSE: The purpose of this study was to evaluate the clinical effectiveness of subcutaneous estradiol pellets in donor oocyte recipients with an inadequate endometrial response. METHODS: The subjects were 13 women with ovarian failure and a maximal endometrial thickness < 10 mm on standard estrogen regimens, as demonstrated during mock and/or prior oocyte donation cycles. They underwent pellet implantation (100-250 mg of estradiol) 6-13 weeks before oocyte donation. RESULTS: maximal (mean +/- SD) endometrial thickness was 8.7 +/- 1.5 mm on standard regimens, in contrast to 11.7 +/- 1.8 mm on pellets, while estradiol levels were 674 +/- 844 and 815 +/- 706 pg/ml, respectively. The estradiol:estrone ratio on pellets was > 1. There was 1 pregnancy with early loss during 10 cycles on other estrogen regimens and 12 pregnancies during 19 cycles on pellets. The pregnancy and implantation rates were, respectively, 63 and 27% on pellets and 41 and 14% on standard regimens in historical controls. CONCLUSIONS: We conclude that estradiol pellets after a single administration provide constant estradiol levels extending into the first trimester of pregnancy, a physiologic estradiol:estrone ratio, and a better endometrial response than standard estrogen regimens. Implantation and pregnancy rates are higher. This approach may be especially suitable for recipients with a poor endometrial response.

Total fat replacement of the pancreas: case report and review of the literature.

One case of total fatty replacement of the pancreas is presented. This benign, uncommon entity is detected with US, CT and MR and is associated with atypical abdominal complaints and/or steatorrhea and/or mass effect of the pancreas on the duodenal loop.

Temperature dependency of skin susceptibility to water and detergents.

Exposure to water and detergents is an important factor for development of irritant contact dermatitis. The aim of the present study was to investigate the effect of temperature on the damaging effects of water and detergents on the skin. Twenty healthy volunteers participated in the study. Ten participants had right and left forearms immersed into a detergent (soap) solution for 2 days twice daily for 10 min. Another 10 participants had both forearms immersed into sterile water. Right and left forearms were randomized to immersion into 20 degrees C and 40 degrees C solutions, respectively. Reactions were evaluated clinically, and by measurement of transepidermal water loss, electrical capacitance and erythema. Immersions into 40 degrees C sodium lauryl sulphate solution caused significantly increased transepidermal water loss as compared to immersion into 20 degrees C sodium lauryl sulphate solution. Electrical capacitance and erythema were not significantly influenced by temperature. Immersion into water caused no significant changes in any observed parameter. Water temperature influences the irritant capacity of a detergent. Change of temperature may be a simple but important means for prevention of irritant contact dermatitis.

Efficiency of discography followed by chemonucleolysis in the treatment of sciatica.

One hundred and twenty-eight patients underwent discography in our department over a period of 3 years. Eighty-four of them were treated by chemonucleolysis. All the patients were punctured by a postero-lateral approach of the intervertebral disc under fluoroscopy. Although several contraindications to chemonucleolysis are known, in our study, only one case of spondylodiscitis was noted. Overall success rate was 72.6%. Twenty-three patients (27.4%) experienced similar or increased pain after treatment.

The effect of endometriosis, its stage and activity, and of autoantibodies on in vitro fertilization and embryo transfer success rates.

OBJECTIVES: To analyze IVF cycle parameters, including pregnancy rates (PR), in women with and without endometriosis and to evaluate the effect of the stage and activity of endometriosis and of autoantibodies. DESIGN: A retrospective analysis of 237 consecutive IVF cycles (193 patients), 119 in women with and 118 without endometriosis. The endometriosis group was further subdivided according to the stage and activity of the disease and autoantibody positivity. SETTING: Hospital-based and freestanding IVF programs with the same IVF team. PATIENTS: One hundred ninety-three women of reproductive age undergoing IVF; 84 had prior diagnosis of endometriosis, and 109 had other indications for IVF. Within the endometriosis group, 40 did and 44 did not have evidence of active disease. Autoantibodies were measured in 50 patients. INTERVENTIONS: The IVF protocol was standard with GnRH agonist administered from the midluteal phase of the preceding cycle. Variables included the method of ET and the use of corticosteroids. MAIN OUTCOME MEASURES: Number of follicles produced, number of eggs retrieved, fertilization rates, number of embryos transferred, and PR per transfer. RESULTS: There was no difference between groups in the response to stimulation, number of oocytes retrieved, number fertilized, and number cleaved. The overall PR was 27% per transfer; it was similar in women with and without endometriosis (29% and 25%, respectively). There was also no difference in PR according to the stage or activity of the disease. However, PR in autoantibody-positive and -negative patients were significantly different (22.9% and 45.7%, respectively). Among autoantibody-positive patients treated with corticosteroids, 8 of 10 conceived. CONCLUSIONS: This study confirms previous reports that IVF success rates are comparable in women with and without endometriosis regardless of the activity and stage of the disease. However, our study also indicates that autoantibodies may affect adversely implantation of embryos and that this effect can be overcome by administration of corticosteroids.

Portal vein thrombosis after acute pancreatitis: diagnostic confirmation with computed tomography during arterial portography.

Portal vein thrombosis is a rare complication of pancreatic inflammatory disease. Usually, the radiologic diagnosis is made either by ultrasonography, contrast-enhanced CT or angiography. Moreover, MRI seems a very promising method. CT during arterial portography (CTAP) focused on portal system proved to have a place in the evaluation of portal vein thrombosis in a particular case.

Culture of amebocytes in a nutrient mist bioreactor.

We report the first use of nutrient mist bioreactor (NMB) technology to culture animal cells. The nutrient mist approximated the amebocyte stem tissue's natural environment, which is a thin layer of fluid in the gill leaflets of the horseshoe crab Limulus polyphemus. NMB culture was tried in an attempt to increase production of amebocytes, which are the source of the Limulus Amebocyte Lysate (LAL), the basis for a sensitive and commercially valuable endotoxin assay. Amebocyte growth in the nutrient mist bioreactor is comparable to growth in liquid medium. However, the current design of the bioreactor presents problems for primary cultures such as ours where a pyrogen-free environment is necessary and fungal decontamination is difficult.

Ovarian stimulation protocol for in vitro fertilization with gonadotropin-releasing hormone agonist widens the implantation window.

Pregnancy rates vary considerably with the type of ovarian stimulation used for in vitro fertilization and embryo transfer (IVF-ET). The window of implantation may represent one of the rate-limiting steps in IVF success. We therefore investigated estimated implantation times of 10 consecutive IVF singleton pregnancies, achieved using pituitary suppression with gonadotropin-releasing hormone agonist (GnRH-a) before and during ovarian stimulation with human menopausal gonadotropins (hMG), and compared those with 9 consecutive IVF pregnancies achieved by hMG stimulation only. Estimated implantation times were calculated by regression analysis of serial human chorionic gonadotropin (hCG) measurements between days 7 and 16 after ET. The GnRH-a/hMG pregnancies implanted between days 7 and 11, whereas hMG pregnancies implanted between days 7 and 9 after ET. The hCG regression curve for the GnRH-a/hMG pregnancies revealed a delay of 1.5 days in estimated implantation time compared with the hMG only group. There were no significant differences in pretransfer in vitro embryos development between the two groups. Thus, the delay in hCG rise probably reflects a delay in embryo implantation. We therefore conclude that a GnRH-a/hMG stimulation protocol appears to widen the implantation window in comparison with a hMG only protocol. This observation may at least in part explain the improved IVF pregnancy success with GnRH-a/hMG stimulation protocols.

Reproductive failure because of autoantibodies: unexplained infertility and pregnancy wastage.

Abnormal polyclonal B cell activation has been demonstrated in patients with endometriosis. To determine whether the noted B cell abnormalities were primarily a feature of the disease endometriosis or its manifestations of infertility and pregnancy wastage, we investigated antibody profiles in 26 female patients with unexplained infertility (group A) and 24 patients with unexplained pregnancy wastage (group B) but without documented endometriosis. Group A and B patients exhibited an unusual incidence of gammopathies (10 of 26 patients in group A and 11 of 24 in group B), with a majority representing immunoglobulin M gammopathies. Mean immunoglobulin M values were significantly elevated in both groups (p less than 0.03 and p less than 0.05, respectively, Student t test), whereas immunoglobulin G was significantly increased only among group B patients (p less than 0.05, Student t test). Lupus anticoagulant by tissue thromboblastin inhibition test was abnormally elevated in 2 of 26 group A and 2 of 24 group B patients. Activated partial thromboplastin time values were abnormal in only 3 of 26 group A and 2 of 24 group B women. Immunoglobulin G, immunoglobulin M, and immunoglobulin A autoantibodies to two phospholipid antigens, five histones, and four polynucleotide autoantibodies were detected in 23 of 26 (88%) group A patients and 17 of 24 (70.8%) group B patients. We conclude that some patients with unexplained infertility and pregnancy wastage suffer from polyclonal B cell activation. It is therefore tempting to speculate that autoantibody abnormalities may be causally related to infertility and pregnancy loss.

The thromboelastogram and circulating lupus anticoagulant.

Abnormal lupus anticoagulant (LA) levels, as measured with the activated partial tissue thromboplastin and tissue thromboplastin inhibition tests, are associated with a predisposition toward thromboembolic phenomena. Thromboelastogram (TEG) measurements have been proposed as a standardized assay to predict such a predisposition. We therefore correlated LA and TEG assessments in 46 women who were either apparently healthy controls or who had abnormal LA levels with such conditions as endometriosis and repeated pregnancy wastage. The coefficient of correlation (Rho) was .3282 (P = .025). Seven patients with an abnormal LA demonstrated a normal TEG, and eight with a normal LA exhibited an abnormal TEG. Only nine had concomitant LA and TEG abnormalities. We conclude that LA and TEG apparently are not interchangeable as predictors of a hypercoagulable state. While this study did not address which of the two assays has a better predictive value for thromboembolic phenomena, it suggested that each can identify a different patient population.

Improved penetration of spermatozoa into uterine fluids of women with abnormal postcoital tests.

Cervical mucus-uterine fluid cross-penetration of husbands' and control sperm was assessed in 13 couples with poor or negative postcoital tests. Cervical mucus scoring and tray agglutination test identified six women with sperm-agglutinating antibodies and seven women with cervical dysmucorrhea. All males were normozoospermic, with penetration into control cervical mucus and control uterine fluids. Control sperm penetrated into cervical mucus and uterine fluids of three and five of the women with sperm-agglutinating antibodies and cervical dysmucorrhea, respectively. Penetration of husbands' spermatozoa into uterine fluids of patients with sperm-agglutinating antibodies was lower than that of control semen (P less than .05). Control and husbands' sperm penetration into uterine fluids of women with cervical dysmucorrhea were identical. In both groups, husbands' and control sperm penetrated uterine fluids more frequently than cervical mucus (75 versus 12%; P less than .001). On a six-month follow-up and midcycle intrauterine inseminations, six patients (46%) conceived. We conclude that uterine fluids of patients with sperm-agglutinating antibodies and cervical dysmucorrhea may provide a better milieu for spermatozoa than cervical mucus. This observation suggests a rationale for intrauterine inseminations to achieve pregnancy.

Preliminary experience with transcervical balloon tuboplasty.

We developed a new technique, transcervical balloon tuboplasty, an adaptation of established balloon angioplasty techniques that facilitates recanalization of proximally occluded oviducts. Sixteen patients with obstruction of the proximal portion of one or two fallopian tubes (based on at least two hysterosalpingograms and one laparoscopic examination) were selected for the procedure. Four patients (25%) were found to have patent oviducts on intraoperative third tubal patency evaluation and were therefore excluded from study. Of the remaining 12 patients, tubal patency was achieved in at least one fallopian tube in 7 patients (58%), as demonstrated by hysterosalpingogram immediately after the transcervical balloon tuboplasty procedure. On follow-up 2 months to 1 year afterward, two pregnancies and one delivery occurred. We conclude that transcervical balloon tuboplasty appears to represent a useful and safe technique to achieve patency in selected cases of tubal interstitial obstruction. Reocclusion rates, long-term complication rates, and pregnancy rates after transcervical balloon tuboplasty remain to be established before the procedure should be considered a recommended alternative for either surgical tuboplasty or in vitro fertilization.

Spontaneous recanalization of cornual tubal occlusion following a pregnancy achieved by in vitro fertilization.

A patient with bilateral tubal occlusion conceived by IVF and delivered a healthy infant vaginally. Four months postpartum, the patient again conceived spontaneously and carried to term. Recanalization of one fallopian tube was demonstrated on HSG performed after delivery of the second infant. Mechanical stretching and pregnancy-induced hormonal changes may explain spontaneous recanalization of obstructed fallopian tubes.

Autoantibodies and common idiotypes in men and women with sperm antibodies.

Antisperm antibodies have been implicated as a causative factor of infertility and pregnancy wastage. Since concomitant autoimmune phenomena were reported in men with antisperm antibodies, we investigated known antisperm antibody-positive sera from 25 women, 27 men, and the respective seminal plasma samples. The investigated autoimmune panel included a search for antinuclear antibodies, autoantibodies (in IgG, IgM and IgA isotypes) to seven phospholipids (cardiolipin, phosphatidylserine, phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidic acid), to four histone subfractions (H1, H2A, H3, H4), and to four polynucleotides [ssDNA, dsDNA, poly(I), and poly(dT)], total immunoglobulin levels, and sperm antibody titers. The sera were also evaluated for the presence of a common anti-deoxyribonucleic acid antibody, and anticardiolipin antibody idiotypes. Levels of sperm antibody titers were significantly lower in women than in men. Both men and women with antisperm antibodies demonstrated elevated total IgG levels compared with those of normal control subjects. Only women showed elevated levels of total IgM. Sera from 24% of women and 11% of men with antisperm antibodies demonstrated antinuclear antibody titers greater than 1:40. The most striking autoantibody abnormalities were found among antiphospholipid antibodies. Sera from women with antisperm antibodies demonstrated higher autoantibody production than was found in their male counterparts. A significant correlation was found between antisperm antibodies and IgM anticardiolipin and IgA anti-phosphatidylinositol in women and between sperm antibodies and IgA phosphatidylserine antibodies in men. The presence of anticardiolipin and anti-deoxyribonucleic acid antibody idiotypes was significantly more frequent in women than in men. By means of discriminant analysis and variables selected by this mathematical model, the identification of 24 of 25 women and 26 of 27 men with antisperm antibodies was correctly predicted. These results suggest that women and men respond differently to sperm antigens. The apparent cross-reactivity between sperm antibodies and other autoantibodies, usually associated with autoimmune disease, suggests that a polyclonal B cell activation, similar to that seen in autoimmune diseases, occurs in patients with sperm antibodies.