Search

With the advent of classification criteria for psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), patients with axial manifestations associated with psoriasis, initially described in the l950s as a specific entity termed psoriatic spondylitis (PS), are now categorized within PsA, ankylosing spondylitis (AS), and axSpA. Thus, different terms are used to describe axial disease in patients with PsA including PS, axial psoriatic arthritis (axPsA), and psoriatic spondyloarthritis. Patients with PS may present with inflammatory and/or mechanical back pain, but also may display axial disease on imaging despite not complaining of back pain. Cervical spondylitis has been reported in 35% to 75% of patients with PsA. Axial disease is silent in 20% and 25% of patients with axial PsA and PsA, respectively. The majority of axPsA patients have peripheral arthritis alongside the axial involvement, whereas only 2% to 5% of PsA patients have solely axial arthritis with no peripheral arthritis.A debate is currently underway as to whether inflammatory axial disease and psoriasis represent axSpA with psoriasis or a subset of PsA named axPsA. Studies have recognized that axial disease in PsA patients seems to be different demographically, genetically, clinically, and radiographically when compared with AS with or without psoriasis. This narrative review summarizes current knowledge regarding axial involvement of PsA in terms of history, terminology, classification, epidemiology, clinical presentation, imaging, diagnosis, and treatment, with the aim of providing advice for management of PS in clinical evidence-based practice. Data-driven studies are needed to develop clear, nonoverlapping classification criteria for spinal involvement in PsA.

Background and purpose We have previously shown that patients with multiple sclerosis receiving immunomodulatory treatment have reduced seroprotection rates after influenza immunization. The aim of this study was to further investigate the influence of immunomodulatory therapies on the antibody response and seroprotection rates in patients immunized with seasonal influenza vaccine in 2012/2013 compared with healthy controls. Methods Ninety patients receiving fingolimod, glatiramer acetate, interferon beta-1a/1b, natalizumab or no therapy were compared with 62 healthy controls. All subjects received the inactivated split virus vaccine in 2012 and serum samples were collected pre-vaccination and 3, 6 and 12 months post-vaccination. The vaccine responses were evaluated by the hemagglutination inhibition assay and adjusted for age and gender. Results No significant differences in rates of protection against H1N1 for interferon beta-1a/1b and glatiramer acetate were observed as compared with controls at 3, 6 and 12 months. Fingolimod provided reduced protection at all time points post-vaccination, whereas natalizumab displayed reduced protection at 3 and 6 months. Patients without immunomodulation did not display protection rates that were significantly different from the controls at 3 and 12 months. Conclusion These findings suggest that patients with multiple sclerosis receiving fingolimod or natalizumab should be considered for a second dose of the vaccine in cases of insufficient protection. Our results further indicate that new immunomodulatory treatment regimens should be systematically evaluated for their influence on influenza-specific vaccine responses.

The clinical relevance of antibodies that bind to glutamic acid decarboxylase 65 (GAD65) is controversial regarding diagnostic utility in screening for neurological disease or cancer. We did a retrospective study of 3152 GAD65 antibody-positive patients to examine whether analysis of the antibody levels could predict neurological disease or cancer. Serum GAD65 antibody levels were not associated with any of the following groups: neurological disease, neurological disease and diabetes, diabetes only, no neurological diagnosis and no diabetes mellitus, or cancer. Analysis of serum GAD65 antibody levels had no prognostic value in neurological disease or cancer. GAD65 antibodies should therefore be measured in selective cases of autoimmune neurological diseases.

The Danish Adult Diabetes Database (DADD) annually reports a quality indicator for lipid-lowering treatment of type 2 diabetes mellitus (T2DM) patients. This retrospective cohort study aims to A) investigate the reasons for inadequate or lacking lipid-lowering treatment and to B) assess the validity of the DADD indicator as a measure of quality of care.A) A pop-up questionnaire enquiring about reasons for lack of treatment was added to the clinicians' data entry tool in the Central Denmark Region. B) The DADD indicator was compared on a per-clinic basis with the achieved median low-density lipoprotein (LDL) cholesterol level and with an internationally widely used indicator of lipid-lowering treatment quality.A) A total of 3,491 patients were registered from 1 January 2013 to 28 February 2015. For 170 (62%) of 309 patients with an LDL level2.5 mmol/l who were not receiving lipid-lowering treatment, there was no "good" explanation for lacking treatment. Among 518 patients with an LDL level2.5 mmol/l despite lipid-lowering treatment, 259 (50%) did not receive high-intensity treatment. B) The DADD quality indicator was neither associated with the international quality indicator nor with the median per-clinic LDL level for T2DM patients.A) We found substantial potential for improvement of lipid management among T2DM patients in Denmark by initiating and/or intensifying lipid-lowering treatment. B) The current DADD indicator is not a valid measure of lipid-lowering quality of care.supported by the Rosa and Asta Jensen Foundation.not relevant.

Background: The immunogenicity of influenza vaccines in MS patients undergoing immunomodulatory treatment is not well studied. Objectives: This explorative study investigated the influence of immunomodulatory treatment on MS patients receiving pandemic H1N1 (swine flu) vaccination in 2009 and seasonal influenza vaccination in 2010. Methods: We investigated the immune response to pandemic H1N1 vaccination among 113 MS patients and 216 controls during the pandemic of 2009. We also investigated the serological response to seasonal influenza vaccination (2010 – 2011 season) among 49 vaccinated and 62 non-vaccinated MS patients, versus 73 controls. We evaluated these vaccine responses by haemagglutination inhibition assay. Results: MS patients receiving immunomodulatory treatment had reduced protection (27.4%), compared to controls (43.5%) ( p = 0.006), after pandemic H1N1 vaccination (2009). The rates of protection were not influenced by interferon beta treatment (44.4% protected), but were reduced among patients receiving glatiramer acetate (21.6%), natalizumab (23.5%), and mitoxantrone (0.0%). A similar pattern emerged after MS patients received a seasonal influenza vaccination in 2010. Conclusions: These findings suggest that MS patients receiving immunomodulatory therapies other than interferon beta should be considered for a vaccine response analysis and perhaps be offered a second dose of the vaccine, in cases of insufficient protection.

The objective of this study was to investigate any association between anterior open bite and periodontal health of the front teeth during mixed dentition. We investigated the periodontal and gingival status of the teeth with dysfunctional and/ or subfunctional loading in the open-bite area in 9- to 12-year-old children. We examined 36 subjects with anterior open bite between the ages of 9 and 12 years who had presented for the first time at the Department of Orthodontics, University of Tubingen. A control group of 36 children of the same age with a physiologic incisor relationship – vertical overbite and sagittal overjet were between 1 and 3 mm – were compared. In addition to overjet, the Silness-Loe plaque index, the modified Loe-Silness gingival index, pocket depth and attachment loss were measured and documented at each of the four surfaces (mesial, distal, oral and vestibular) of the upper and lower incisors. The subjects with anterior open bite exhibited significantly more plaque in the malocclusion area than children with a physiologic incisor relationship; the differences were statistically highly significant. The subjects with anterior open bite demonstrated slightly higher degrees of inflammation and a slight increase in periodontal pocket depths than the control group. Periodontal attachment loss was diagnosed in very few areas in both study groups, while attachment loss was slightly more frequent in those with anterior open bite. We observed a higher risk for caries in the malocclusion area in the late mixed dentition phase, as the subjects with anterior open bite presented significantly more plaque accumulation in the incisor area. However, no pathological periodontal anomalies have been detected so far.

Suppression of osteoblastic function plays an important pathogenic role for the development of glucocorticosteroid-induced osteoporosis. Serum osteocalcin (OC) is a sensitive marker of bone formation. The diurnal rhythm in serum OC can be changed by administration of single doses of either 1,25-(OH)2D3 or prednisone. However, the two steroids have opposing effects: 1,25-(OH)2D3 increases and prednisone decreases serum OC. The aim of the present study was to examine whether 1,25-(OH)2D3 can oppose the acute suppressive effect of prednisone on serum OC in normal subjects. We compared the effect of a combined dose of 2 micrograms 1,25-(OH)2D3 and 10 mg prednisone on the diurnal rhythm of serum OC with the effect of 2 micrograms 1,25-(OH)2D3 + placebo in a crossover study. Seven normal subjects aged 23-36 years were investigated twice at an interval of 1 week. Blood samples were collected every 60 minutes from 1900 until 1100 h the following day. Study drugs were given at 2000 h. The data from the present investigation were compared with data obtained from a similar study with placebo and prednisone in the same subjects. After administration of 1,25-(OH)2D3 serum OC followed the placebo curve during the first 8 h, but in contrast to the placebo curve it then continued to increase and remained elevated throughout the observation period (p less than 0.05). Prednisone inhibited and reversed the nocturnal rise in serum OC levels (p less than 0.01). The course of serum OC after administration of 1,25-(OH)2D3 + prednisone almost paralleled the course after placebo. We conclude that 1,25-(OH)2D3 and prednisone have opposing effects on serum OC.

The effects of recombinant human growth hormone (rhGH) on biochemical markers of bone turnover and bone mineral content (BMC) were investigated in 20 normal male volunteers (aged 22-31 years) randomized to treatment for 7 days with either rhGH (0.1 IU/kg subcutaneously twice a day) or placebo. Serum somatomedin C rose during treatment (p less than 0.001) but was not significantly different from baseline at day 14. The fasting urinary hydroxyproline/creatinine (p less than 0.001) and calcium/creatinine ratios (p less than 0.01) increased during treatment and remained elevated for 4 and 2 weeks, respectively. Serum bone gamma-carboxyglutamic acid-containing protein (BGP) increased during treatment (p less than 0.001) and remained elevated for 6 months (p less than 0.02). Serum bone alkaline phosphatase (B-AP), after an initial fall in the treatment period (p less than 0.001), increased slightly in the following months (p less than 0.01). In the rhGH group BMC was significantly higher than the prestudy value at day 14 (p less than 0.05) but was unaltered at the end of study. The simultaneous increase in markers of bone resorption and formation during rhGH treatment followed by a decline in resorption parameters within a few weeks and the prolonged effect on BGP and B-AP demonstrate that rhGH treatment stimulates osteoblasts and activates bone remodeling.

Biochemical markers of bone resorption and bone formation were measured in 14 patients with autosomal dominant osteopetrosis, and compared with age- and sex-matched controls. There were eight patients with the radiological type I characterized by diffuse, symmetrical osteosclerosis with pronounced sclerosis of the skull and enlarged thickness of the cranial vault, and six patients with type II characterized by diffuse, symmetrical osteosclerosis, "Rugger-Jersey spine" and "endobones" (bone within a bone) in the pelvis. Serum levels of alkaline phosphatase and osteocalcin in types I and II did not differ from controls indicating normal bone formation. However, a significantly decreased fasting renal excretion of phosphate and hydroxyproline in both types compared with normal controls, suggests a reduced bone resorption. Serum levels of parathyroid hormone (PTH), albumin-corrected calcium, phosphate, and acid phosphatase were normal in type I. In type II serum levels of albumin-corrected calcium and PTH were significantly increased (p less than 0.05 and p less than 0.01). The level of acid phosphatase was markedly increased in this type (p less than 0.01). These findings suggest differences between the two types in calcium homeostasis and bone metabolism, and thus corroborate the evidence that the two radiological types reflect two different disorders of bone resorption.

To provide tools for predicting the course of AV conduction disturbances after ethanol-induced septal ablation (PTSMA) for hypertrophic obstructive cardiomyopathy (HOCM).Based on a scoring system developed 1996-1998 and including parameters from baseline ECG, heart rate profile, severity of outflow obstruction (LVOTO), peri-interventional enzyme kinetics, and peri-interventional conduction problems, the risk of permanent AV block following PTSMA was assessed in 155 consecutive HOCM patients (pts.; mean age: 53+/-13 years) between 1999 and 2004. During PTSMA with 2.1+/-0.5 ml of ethanol, transient complete AV block occurred in 71 pts. (46%). Pts. were grouped into a low, intermediate, and high risk group for permanent conduction damage, and treated accordingly (early discharge from monitoring, prolonged monitoring, early DDD-PM implantation). Permanent pacing was necessary in 11 cases (7%), 0/116 of these (0%) in the low, 4/31 (13%) in the intermediate, and 7/8 (87%) in the high-risk group. While a new right bundle branch block was the most frequent ECG finding after PTSMA, a left bundle branch block at baseline was associated with 4 of the 11 DDD-PM implantations (p0.0001). In-hospital mortality was 0%, short-term (3-months) follow up was complete. During follow-up, AV conduction recovered in 4 pts. (46%) with a DDD-PM. New onset AV blocks did not occur. Significant improvement of symptoms was reported by 141 pts. (91%).Catheter-based septal ablation is an effective non-surgical technique for reducing symptoms and outflow gradients in HOCM. The proposed scoring system appears to reliably discriminate pts. with a high risk for permanent PM dependency from those with stable AV conduction after PTSMA. Pts. with left bundle branch block at baseline should undergo DDD-PM implantation prior to ablation.

Aims: To analyze the impact of intra-procedural echocardiographic imaging on the interventional strategy in ethanol-induced septal ablation (PTSMA) for symptomatic hypertrophic obstructive cardiomyopathy (HOCM), based on a single-center experience of 7 years. Methods and results: PTSMA was intended for refractory symptoms in 337 patients (pts.) with HOCM (mean age: 54±15 years), with 312 procedures completed by injection of 2.8±1.2 ml ethanol. In 25 pts. (8%) the intervention was aborted without ethanol injection, mostly because of echocardiographic findings ( n = 18/6%). An echocardiography-driven target vessel change was necessary in 33 pts. (11%). In the 312 pts. who received ethanol, permanent pacing was necessary in 22 cases (7%). In-hospital mortality was 1.3% (4 pts.). After 3 months, mean NYHA functional class was reduced from 2.9±0.5 to 1.5±0.6 ( p

The authors describe the case of a 76-year-old woman who presented with acute inferior myocardial infarction 8 years after prosthetic aortic valve replacement. Echocardiography and cardiac catheterization revealed a false aneurysm of the ascending aorta with fistulous communication to the right ventricle. The right coronary artery originated from the false aneurysm with no antegrade perfusion.

This study was designed to explore the role of human papillomavirus (HPV) in esophageal squamous cell carcinoma (ESCC). Fifty-five patients receiving diagnostic upper gastrointestinal endoscopy at Zomba Central Hospital or Queen Elizabeth Hospital in Blantyre (Malawi) in 2010, were included in our study. Formalin-fixed paraffin-embedded biopsies were collected for histopathological diagnosis. HPV DNA was detected using multiplex Quantitative PCR (qPCR) and in situ hybridization (ISH). p16INK4a staining served as a surrogate marker for HPV oncogene activity. Cell proliferation was determined by Ki-67 staining. Human immunodeficiency virus (HIV) status was evaluated by serology. Data on the consumption of alcohol and tobacco, and history of tuberculosis (TBC), oral thrush, and Herpes zoster, were obtained by questionnaire. Forty patients displayed ESCC, three displayed dysplastic epithelium, and 12 displayed normal epithelium. HPV16 was detected in six ESCC specimens and in one dysplastic lesion. Among HPV-positive patients, viral load varied from 0.001 to 2.5 copies per tumor cell. HPV DNA presence could not be confirmed by ISH. p16INK4a positivity correlated with the presence of HPV DNA (p = 0.03). Of particular note is that the Ki-67 proliferation index, in areas with diffuse nuclear or cytoplasmatic p16INK4a staining ≥50%, was significantly higher in HPV-positive tumors compared to the corresponding p16INK4a stained areas of HPV-negative tumors (p = 0.004). HPV infection in ESCC was not associated with the consumption of tobacco or alcohol, but there were significantly more patients drinking locally brewed alcohol among HPV-positive tumor patients compared to non-tumor patients (p = 0.02) and compared to HPV-negative tumor patients (p = 0.047). There was no association between HIV infection, history of TBC, Herpes zoster, oral thrush, or HPV infection, in ESCC patients. Our indirect evidence for viral oncogene activity is restricted to single tumor cell areas, indicative of the role of HPV16 in the development of ESCC. The inhomogeneous presence of the virus within the tumor is reminiscent of the “hit and run” mechanism discussed for β-HPV types, such as HPV38.

We present the case of a 41-year-old woman who was admitted to our centre with progressive symptoms of congestive heart failure (NYHA class III) 5 years after a radical nephrectomy for renal cell carcinoma. Magnetic resonance imaging demonstrated a 5 x 3 cm homogeneous intracardial mass causing right ventricular outflow tract obstruction, not accessible to surgical resection. Serial echo-guided, percutaneous coil embolization of the cardial metastasis was performed with Contour SE Microparticles (150-250 or 300-500 microm) after identification of the target region of the metastasis by contrast injection (Levovist) through the balloon catheter into the coronary artery under transoesophageal echocardiographic control prior to induction of the necrosis, corresponding to the technique which has been described for septal ablation in hypertrophic obstructive cardiomyopathy. Follow-up after serial embolization showed a good haemodynamic and a marked clinical response (dyspnoea NYHA I-II) which lasted during the 19 month of survival after the index procedure.

Highly active antiretroviral therapy can effectively decrease the levels of human immunodeficiency virus type 1 (HIV-1) virions in peripheral plasma and seminal fluid of infected men. Whether the genital tract of HIV-1-infected men who are receiving highly active antiretroviral therapy and who have no detectable virus in the peripheral plasma harbors replication-competent virus is not known.We collected peripheral-blood and semen samples from seven men with HIV-1 infections who were receiving highly active antiretroviral therapy and who had no detectable viral RNA (fewer than 50 copies per milliliter) in plasma and analyzed the samples for cell-associated proviral DNA using a quantitative polymerase-chain-reaction assay. Replication-competent viruses were evaluated by cell-coculture assays. Proviral DNA and replication-competent virus obtained from peripheral-blood and seminal cells were also analyzed by sequencing relevant viral genes.Despite the long-term suppression of HIV-1 RNA in the plasma of the seven men, proviral DNA was detected in seminal cells in four. Replication-competent viruses were recovered from peripheral-blood cells in three men and from the seminal cells in two of these three men. The viruses recovered from the seminal cells had no genotypic mutations suggestive of resistance to antiretroviral drugs and were macrophage-tropic, a feature that is characteristic of HIV-1 strains that are capable of being sexually transmitted.In HIV-1-infected men who are receiving highly active antiretroviral therapy and who have no detectable levels of viral RNA in plasma the virus may be present in seminal cells and therefore may be capable of being transmitted sexually.

Objectives. We report the acute results and midterm clinical course after percutaneous transluminal septal myocardial ablation (PTSMA) in symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM).Background. In the treatment of HOCM, surgical myectomy and DDD pacemaker therapy are considered the standard procedural extensions to drug therapy with negatively inotropic drugs. As an alternative nonsurgical procedure for reducing the left ventricular outflow tract (LVOT) gradient, PTSMA by alcohol-induced septal branch occlusion was introduced. However, clinical follow-up has not been sufficiently described.Methods. In 25 patients (13 women, 12 men; mean [±SD] age 54.7 ± 15.0 years) who were symptomatic despite sufficient drug therapy, 1.4 ± 0.6 septal branches were occluded with an injection of 4.1 ± 2.6 ml of alcohol (96%) to ablate the hypertrophied interventricular septum. After 3-months, follow-up results of LVOT gradients and clinical course were determined.Results. The invasively determined LVOT gradients could be reduced in 22 patients (88%), with a mean reduction from 61.8 ± 29.8 mm Hg (range 4 to 152) to 19.4 ± 20.8 mm Hg (range 0 to 74) at rest (p < 0.0001) and from 141.4 ± 45.3 mm Hg (range 76 to 240) to 61.1 ± 40.1 mm Hg (range 0 to 135) after extrasystole. All patients had angina pectoris for 24 h. The maximal creatine kinase increase was 780 ± 436 U/liter (range 305 to 1,810) after 11.1 ± 6.0 h (range 4 to 24). Thirteen patients (52%) developed a trifascicular block for 5 min to 8 days requiring temporary (n = 8 [32%]) or permanent (DDD) pacemaker implantation (n = 5 [20%]). An 86-year old woman died 8 days after successful intervention of uncontrollable ventricular fibrillation in conjunction with beta-sympathomimetics in chronically obstructive pulmonary disease. The remaining patients were discharged after 11.3 ± 5.4 days (range 5 to 24), after an uncomplicated hospital course. Clinical and echocardiographic follow-up was achieved in all 24 surviving patients after 3 months. No cardiac complications occurred. Twenty-one patients (88%) showed clinical improvement, with a New York Heart Association functional class of 1.4 ± 1.1. A further reduction in LVOT gradient was shown in 14 patients (58%).Conclusions. PTSMA of HOCM is a promising nonsurgical technique for septal myocardial reduction, with a consecutive reduction in LVOT gradient. Possible complications are trifascicular blocks, requiring permanent pacemaker implantation, and tachycardiac rhythm disturbances. Clinical long-term observations of larger patient series and a comparison with conventional forms of therapy are necessary to determine the conclusive therapeutic significance.

Voltage-gated potassium channels (VGKC) are essential for the cellular action potential. Antibodies against the VGKC-complex are associated with a wide spectrum of diseases involving both the peripheral and central nervous system, including neuromyotonia, Morvan disease, limbic encephalitis, faciobrachial dystonic seizures and cerebellar ataxia.1 Leucine-rich, glioma-inactivated 1 antigen (LGI1) and contactin-associated protein-2 (Caspr2) have been found to be part of the VGKC-complex and targets for auto-antibodies.2 ,3 However, for the majority of the VGKC-complex antibodies, the specific antibody targets remain unknown. Moreover, apart from a recent study,4 little information exists on the relevance of VGKC-complex antibody level and neurological diseases, or the subgroups of VGKC antibodies and the presence of other encephalitic or paraneoplastic antibodies. We decided therefore to characterise our patients according to these parameters. The study was approved by the regional committee for medical and health research ethics in Western-Norway. We identified 36 patients tested positive for VGKC-complex antibodies (tested by radioimmunoprecipitation in Oxford, >100 pM) at Haukeland University Hospital, Bergen, Norway, between 2001 and 2012. The sera were sent by neurologists who decided the indications for the test. The highest VGKC-complex antibody level was chosen for each patient (table 1). Two patients were of foreign origin and excluded …

To investigate the possible use of oral phosphate as an activator of bone remodeling in coherence treatment of osteoporosis, 82 postmenopausal females, aged 50-75 years, were randomized to treatment with oral phosphate (750, 1500, or 2550 mg/day) or placebo for 7 days and followed for 4 months thereafter. All patients had sustained at least one previous fracture of the distal forearm and had a bone mineral content of the contralateral forearm or bone mineral density of the lumbar spine lower than normal mean for age. Urinary phosphate/creatinine ratio increased in a dose-dependent fashion during treatment (P less than 0.001), whereas no significant changes were seen in serum phosphate or serum calcium. Serum parathyroid hormone (PTH) rose significantly (P less than 0.05) during treatment to a maximum of 36 and 33% in the groups receiving 1500 and 2250 mg/day, respectively, whereas serum 1,25-dihydroxycholecalciferol remained unchanged. In the group receiving 1500 mg/day, mean serum osteocalcin was increased in the period from day 1 to day 28 (P less than 0.05), but no significant changes were observed in urinary hydroxyproline/creatinine ratio, or serum bone alkaline phosphatase. We conclude that a short course of oral phosphate treatment increases serum PTH considerably. Furthermore, 1500 mg/day but not 2250 mg/day increases serum osteocalcin. No clear biochemical evidence, however, of increased activation of bone remodeling could be demonstrated in either group.

Background— Percutaneous closure of atrial septal defects is well established in children and adults and has been found to improve symptoms and positively influence right-heart remodeling. The aim of this study was to evaluate the efficacy and long-term outcome in adult patients older than 60 years. Methods and Results— The study population comprised 96 patients in the age group of 60 to 84 years. Percutaneous closure was performed effectively in all patients. Functional capacity according to New York Heart Association functional class and peak oxygen uptake (VO 2 max) in the cardiopulmonary exercise testing improved significantly after atrial septal defects closure, especially in patients with a pulmonary-to-systemic flow ratio >2. Echocardiographic measurements of the right ventricular end-diastolic diameter showed a significant decrease. No device-associated complications were observed, but in 16 patients, paroxysmal atrial fibrillation occurred after device implantation. Conclusions— Percutaneous atrial septal defects closure can be performed safely and with minimal risk even in elderly patients. They profit in terms of symptom reduction, improvement of exercise capacity, and right-heart remodeling.

Interventional closure of atrial septal defects (ASD) has become a standard procedure in pediatric and adult patients. We report immediate and mid-term results in different adult age groups. A retrospective analysis of 332 patients undergoing percutaneous ASD closure between 1998 and 2008 was performed. Beside echocardiographic and hemodynamic measurements, the NYHA functional class was assessed before and after ASD closure. The peak oxygen uptake (VO2peak) was available in a subgroup of 154 patients. The different age groups did not differ significantly in shunt volume or defect diameter, but a significant increase could be detected in mean pulmonary arterial pressure, mean left atrial pressure and pulmonary vascular resistance (PVR9 with increasing age). Right ventricular enlargement was present in all age groups, but the degree of enlargement increased with age. Transcatheter ASD closure was successful in 99.4%, major adverse events occurred in four patients (1.2%). At 3 months from closure, 123 patients reported an improvement, 7 of worsening and 163 of no change in their functional capacity. A significant increase in VO2peak could be registered in all subgroups after ASD closure. When classified by shunt volume no change could be detected in VO2peak in the patients with a Q p:Q s 2 had a highly significant VO2peak increase. Patients benefit from interventional closure of hemodynamically significant ASD regardless of their age. However, the defect should be repaired as early as possible to prevent hemodynamic complications, such as the development of pulmonary hypertension and cardiac arrhythmias.

To investigate bone collagen metabolism during vitamin D treatment, 15 healthy males (aged 28-45 years, median 34) were treated orally with calcitriol, 2 μg daily for 7 days and followed for a total of 2 weeks. The serum concentration of calcitriol rose markedly (median difference and 95% confidence limits: 49% (5-82), ps=0.71, p

We examined the role of sleep, growth hormone (GH), and parathyroid hormone [PTH(1-84)] as regulators of the diurnal rhythm of the osteoblastic bone marker, serum osteocalcin (OC). Nine normal subjects were followed with hourly blood sampling during one 24-hour period with normal sleep pattern, and one 24-hour period with absolute sleep deprivation. We found that the rhythm in serum OC did not exhibit significant changes (P greater than 0.50). Serum OC (mean +/- SE) was 30.9 +/- 2.5 micrograms/liter during sleep (2330-0730 hours) versus 29.9 +/- 4.9 micrograms/liter during sleep deprivation (not significantly different). The serum GH rhythm was significantly different on the two occasions (P less than 0.01). A maximum GH peak (mean +/- SE) of 10.3 +/- 2.4 micrograms/liter occurred at 0136 hours +/- 6 minutes during sleep compared with a maximal peak of 7.6 +/- 1.2 micrograms/liter (P less than 0.01) at 0245 hours +/- 20 minutes (P less than 0.01) during sleep deprivation. During sleep (2330-0730 hours), mean serum GH was 3.61 +/- 0.60 micrograms/liter compared with 2.39 +/- 0.40 micrograms/liter during sleep deprivation (P less than 0.005). Small insignificant changes occurred in serum PTH (1-84) and serum ionized calcium during the two occasions. We conclude that sleep and GH are not acute controlling factors of the diurnal rhythm in serum OC and the role of serum PTH(1-84) remains unsettled.

Serum osteocalcin varies in a diurnal rhythm, with peak values during the night and minimum levels before noon, but the factors controlling this rhythm are unknown. In this study, we evaluated the temporal relations between the osteocalcin rhythm and variations in serum concentrations of cortisol, intact parathyroid hormone (PTH(1-84)), and ionized calcium (Ca2+) in 15 normal volunteers, aged 22-46 years. Serum cortisol varied in a typical way preceding inverse changes in serum osteocalcin by about 4 h (r=0.78, p2+ varied in an almost bi-phasic pattern (p2+ correlated inversely with PTH (1-84) (r=0.53, p2+ at concurrent time points (r=0.59, p2+ 3-5 h after ingestion (p2+ is uncertain.

Serum osteocalcin and bone alkaline phosphatase (BAP) were measured in samples drawn at 8 a.m. in 7 patients with GH deficiency treated with recombinant human growth hormone (rhGH) (2 IU/day subcutaneously at 8 p.m.), and 7 normal controls. Patients treated with 2 IU/day had lower BAP than controls (P less than 0.05). Further, increasing doses of rhGH were given subcutaneously to each of the 7 patients for 3 consecutive 14-day periods (2, 4, and 6 IU/day at 8 p.m.) followed by 14 days off treatment. At the end of each period, the patient was hospitalized for frequent blood sampling from 8 p.m. to 11 a.m. the following day. A dose-dependent increase in area under the curve (AUC) was seen for osteocalcin (P less than 0.05), whereas the increase in AUC for BAP just failed to reach significance (P less than 0.10). The nocturnal pattern of serum osteocalcin in patients on 4 and 6 IU/day were statistically indistinguishable from those in controls. During treatment with 2 IU/day and the off-treatment period, the pattern was significantly different from controls (P less than 0.05). In conclusion, rhGH has a dose-dependent effect on basal osteoblastic activity and the nocturnal pattern of osteocalcin. Serum osteocalcin increases within hours following rhGH administration. However, 2 IU/day is inadequate to maintain normal levels and nocturnal variation in markers of osteoblastic activity.

Intracervical application of prostaglandin E2 (PGE2) in a viscous gel was compared with conventional wax-based PGE2 vagitories (pessaries) for ripening of the cervix prior to induction of labor. A total of 226 healthy pregnant women at term were randomly allocated to receive intracervical gel with an effective dose of 0.5 mg (n = 116) or vagitories containing 2.5 mg PGE2 (n = 110). All women had a modified cervical score of less than or equal to 4. The numbers of cases contributed by each of the three centers were similar. There was no significant difference in parity, gestational length, maternal characteristics, indications for induction or preinduction cervical scores between the treatment groups. The rate of spontaneous birth was 71% in the gel group, compared with 69% in the vagitory group. Successful treatment was defined as active labor within 24 h or a change in cervical dilatation allowing artificial rupture of the membranes with subsequent progressive labor. The success rate was not significantly different in the gel group (82%) compared with the vagitory group (80%). There were no differences in the frequency of fetal distress, outcome of labor, assisted delivery rates or maternal side effects. The cervical scores were not different at 12 and 24 h after application. Intracervical gel and intravaginal application of PGE2 were similar in their efficacy and safety for ripening of the cervix and inducing labor at term.

Hypercholesterolemia impairs endothelial function and subsequently decreases coronary vasodilatatory capacity. We examined the quantitative effects of one single LDL apheresis on vasodilatatory capacity. Using N-13 ammonia as a tracer for dynamic quantitative positron emission tomography (PET), mean myocardial perfusion measurements were carried out before and 20 h later after LDL apheresis, both under resting conditions and after pharmacological vasodilatation with dipyridamole. LDL apheresis was carried out using the heparin induced extracorporeal LDL precipitation (H.E.L.P.) procedure. We examined 47 patients (12 women and 35 men), with angiographically-proven coronary artery disease. All of them suffered from hypercholesterolemia. Of the patients, 35 received a chronic weekly H.E.L.P. procedure (group A), while H.E.L.P. procedure treatment was started for the first time in 12 patients, who were subsequently enrolled in a chronic apheresis program (group B). H.E.L.P. apheresis was combined with cholesterol lowering drugs in all patients. Both groups underwent positron emission tomography twice (prior to LDL apheresis and 20 h later). In group A, LDL cholesterol levels decreased from 175 +/- 50 mg/dL to 60 +/- 21 mg/dL immediately after H.E.L.P. (77 +/- 25 mg/dL before the second PET). Corresponding values for fibrinogen levels were 287 +/- 75 mg/dL to 102 +/- 29 mg/dL (155 +/- 52 mg/dL), minimal coronary resistance dropped from 0.56 +/- 0.20 to 0.44 +/- 0.17 mm Hg x 100 g x min/mL (P < 0.0001). Plasma viscosity decreased by 7.8%. In group B, LDL cholesterol decreased from 187 +/- 45 mg/dL to 75 +/- 27 mg/dL (85 +/- 29 mg/dL) and fibrinogen from 348 +/- 65 mg/dL to 126 +/- 38 mg/dL (168 +/- 45 mg/dL). Minimal coronary resistance was reduced from 0.61 +/- 0.23 to 0.53 +/- 0.19 mm Hg x 100 g x min/mL (P < 0.01). Plasma viscosity was observed to decrease by 7.6%. The strong LDL drop in patients under chronic H.E.L.P. treatment has a significant impact on coronary vasodilatatory capacity within 20 h leading to an improved overall cardiac perfusion. Nearly the same effect can be seen in patients after their first H.E.L.P. treatment.

Patients with restenosis after open or closed surgical commissurotomy (SC) often demonstrate more severe valve degeneration than patients without prior surgery. This may affect the result of balloon mitral valvotomy (BMV) in this patient group.The immediate- and long-term results (maximum 106 months; mean 26 months) of BMV with the Inoue balloon in patients with prior SC were compared with findings in patients without prior surgery. Between February 1989 and July 2001, a total of 1,156 BMV interventions was performed, of which 127 were conducted in patients (106 women, 21 men; mean age 56 +/- 12 years) with prior SC.After BMV, the mitral valve area (MVA) increased from 1.0 +/- 0.2 cm2 to 1.6 +/- 0.4 cm2 after SC compared with 1.0 +/- 0.3 cm2 to 1.8 +/- 0.4 cm2 without SC. After three months, the average MVA was 1.7 +/- 0.3 cm2 in both patient groups. The mean NYHA class improved from 2.8 to 2.0 (after SC) versus 2.7 to 1.8 (no SC) three months after BMV. The main complications were cardiac tamponade in three patients (2.4 %), and more than moderate mitral regurgitation (grade 2+) in six (4.7 %) compared to 5.8% in no-SC patients.In view of the satisfactory clinical and hemodynamic results, BMV with the Inoue balloon can be considered the treatment of choice for mitral valve restenosis after SC in selected patients.

109 (76%) 667 (80%) 128 (88%) 904 (80%) Rheumatic fever history 49 (34%) 320 (38%) 46 (32%) 415 (37%) Atrial fibrillation 23 (16%) 443 (53%) 101 (69%) 567 (50%) Previous surgical commissurotomy 13 (9%) 103 (12%) 11 (8%) 127 (11%) MR grades I-II 51 (35%) 349 (42%) 60 (41%) 460 (41%) Previous cerebral and/or peripheral embolism 12 (8%) 159 (14%) 48 (33%) 219 (20%)

To study the association between smoking and thyroid disease (Graves' disease [E05.0], nodular toxic goiter [E05.2], and autoimmune hypothyroidism [E03.9]) in a low-iodine intake area a case-control study was undertaken. A self-administered questionnaire was issued to 864 consecutive patients with hyperthyroidism and 628 patients with autoimmune hypothyroidism treated at five university or regional endocrinologic clinics in Denmark between January 1, 1990 and December 31, 1998. Each respondent was compared to an age- (+/- 5 years) and gender-matched normal control person randomly drawn from the background population. A total of 621 patients with hyperthyroidism (72%) and 411 patients with autoimmune hypothyroidism (66%) responded. Of these, 617 (542 females) and 408 (364 females) could be analyzed, respectively. There was an increased risk of both Graves' disease (odds ratio [OR] = 2.5, 95% confidence interval [CI]: 1.8-3.5), toxic nodular goiter (OR = 1.7, 95% CI: 1.1-2.5), and autoimmune hypothyroidism (OR = 1.5, 95% CI: 1.1-2.1) with ever smoking compared to never smoking in women, but not in men. With the high proportion of ever-smokers among women (56%), the attributable risk of smoking in women was 45% in Graves' disease, 28% in toxic nodular goiter, and 23% in autoimmune hypothyroidism. Ever use of oral contraceptives was associated with a slightly lower risk of Graves' disease in women, but not of toxic nodular goiter or autoimmune hypothyroidism. In conclusion, smoking is a powerful risk factor for thyroid disease, especially in populations with a high smoking frequency. Oral contraceptive use is associated with a slightly lower frequency of Graves' disease.

To investigate the potential use of growth hormone (GH) in Activate-Depress-Free-Repeat treatment of postmenopausal osteoporosis, we measured changes in serum levels of biochemical markers of bone turnover, insulin-like growth factor-I (IGF-I), calciotropic hormones, and bone mineral density in 40 postmenopausal women with osteopenia (ages 52-73 years) in response to 7 days of treatment with either placebo or GH (0.05, 0.10, or 0.20 IU/kg/day) administered subcutaneously in the evening. GH treatment increased serum osteocalcin (p < 0.01) and C-terminal type-I procollagen propeptide (p < 0.01) and also serum levels of type-I collagen telopeptide (p < 0.001), fasting urinary hydroxyproline/creatinine (p < 0.05), pyridinoline/creatinine (p < 0.05), and deoxypyridinoline/creatinine (p < 0.01) in a dose-dependent fashion. Even the lowest dose of GH tested induced a significant increase in these parameters; however, the effects were transient lasting only 1-2 weeks. In the highest dose group, however, a somewhat prolonged effect (30 days) on serum osteocalcin was observed. Furthermore, GH increased serum levels of IGF-I, insulin, and tri-iodothyronin. No effect on serum 1,25-dihydroxyvitamin D3 or parathyroid hormone could be demonstrated. Adverse effects were mainly related to fluid retention. They were clearly dose-dependent and rapidly reversible. In conclusion, short-term GH treatment stimulates bone formation and bone resorption in postmenopausal women with osteopenia.

Three low-dose oral contraceptives Trinordiol, Gynatrol, and Marvelon, containing ethinylestradiol (EE) in combination with triphasic levonorgestrel (LNg), monophasic levonorgestrel, and monophasic desogestrel (DGS), respectively, were given to 65 healthy women, n = 21-22 in each group. Blood levels of antithrombin III (AT III), alpha 2-macroglobulin (alpha 2M) alpha 1-antitrypsin (alpha 1at), complement factors (factor B, C3, C4), pregnancy zone protein (PZP), corticosteroid binding globulin (CBG), sex hormone binding globulin (SHBG) and albumin were measured before treatment and during the first and third treatment cycles. AT III levels decreased and alpha 1at levels increased in all three groups during treatment. alpha 2M increased during cycle 3 in the Trinordiol and Gynatrol groups. CBG, PZP and SHBG levels increased in all 3 groups, the CBG and PZP increase being higher in the Marvelon group than in the Gynatrol group. Increases in SHBG levels were found in the order MarvelonTrinordiolGynatrol. Plasma levels of complement factors B, C3 and C4 remained unchanged. It is concluded that the increase in alpha 1at partly compensates for the fall in AT III, that the rise in PZP presumably enhances fibrinolysis, and that LNg has higher anti-estrogenicity and androgenicity than DSG.Clinicians administered 3 types of oral contraceptives (OCs) to 65 healthy 15-31 year old women attending the Public Family Planning Clinic in Odense, Denmark, to determine the effect of the 3 OCs on enzyme inhibitors, complement factors, and steroid dependent proteins. The OCs were a low-dose monophasic containing ethinyl estradiol (EE) and desogestrel (Marvelon), another low dose monophasic containing EE and levonorgestrel (Gynatrol), and a triphasic containing EE and levonorgestrel (Trinordiol). 21-22 women were assigned to each group. Pretreatment values of the biochemical parameters were not significantly different between the 3 groups. In each group, mean plasma antithrombin III (AT III) levels fell (p .04-.002) and alpha1-antitrypsin (alpha1-at) levels increased (p .0001). Mean plasma levels of alpha2-macroglobulin rose sharply during cycle 3 in the Trinordiol and Gynatrol groups (p .04 and .002, respectively). In all 3 groups, mean serum levels of corticosteroid binding globulin (CBG), pregnancy zone protein (PZP), and sex hormone binding globulin (SHBG) increased significantly (p .03-.0001). The CBG and PZP levels were higher in the women using Marvelon than in those using Gynatrol. The increase in SHBG levels were only significant in the Trinordiol and Marvelon groups, however (p .0001). Mean plasma levels of complement factors B, C3, and C4 and of albumin did not change. Based on these results, the researchers concluded that the increase in alpha1-at only partially offsets the decrease in AT III, that the increase in PZP may intensify fibrinolysis, and that levonorgestrel has greater antiestrogenicity and androgenicity than desogestrel.

A single dose of 2.5 mg prednisone leads to a significant transient decrease in serum osteocalcin, which is only demonstrated by frequent serum sampling. The aim of the present study was to evaluate whether a single dose of inhaled beclomethasone dipropionate causes transient changes in serum osteocalcin, indicating a systemic effect on bone cells. In a double-blind, placebo controlled, cross-over design we evaluated the effects of single doses of 250 micrograms and 1000 micrograms beclomethasone on the circadian rhythm in serum osteocalcin. Fifteen normal subjects aged 23-38 years were studied twice with an interval of one week with hourly blood sampling from 16.30 until 17.00 the following day; 1000 micrograms beclomethasone, but not 250 micrograms, suppressed serum cortisol by 14.4 +/- 6.7% (p = 0.03). Neither of the beclomethasone doses significantly altered the time pattern of serum osteocalcin. We conclude that a single inhaled dose of beclomethasone in the therapeutical range does not acutely influence osteoblastic activity as judged from serial measurements of serum osteocalcin.

We measured changes in serum insulin-like growth factor-1 (IGF-1), calcitriol, parathyroid hormone (PTH), thyroid hormones, insulin, and plasma glucagon in response to seven days of treatment with a pharmacological dosage of recombinant human growth hormone (r-hGH) (0.1 IU/kg sc twice daily) or placebo in 20 normal male volunteers to evaluate whether the effect of r-hGH on biochemical bone markers could be attributed to changes in these hormones. Serum IGF-1 (p3. The increase in these hormones may be co-responsible for some of the observed effects of r-hGH on bone turnover and calcium homeostasis.

Osteocalcin (OC) in serum varies in a remarkably constant circadian rhythm with zenith at night and nadir in the morning. The factors controlling this rhythm are unknown, but several studies indicate that serum cortisol could be of major importance. We tested this hypothesis in a double-blind, placebo-controlled, cross-over study comprising 10 normal male volunteers (aged 23-31 yr) by measuring the response in serum OC and cortisol rhythms to a single dose of metyrapone (30 mg/kg body weight) administered at midnight. During placebo, serum cortisol consistently peaked early in the morning before 0730 h. Ingestion of metyrapone at 2400 h significantly postponed and flattened this peak (P less than 0.01). On both occasions, serum OC increased towards peak levels around 0300 h (P less than 0.01) with no overall differences in the OC profiles. However, when the serum OC time series were synchronized according to the individual cortisol nadirs, we found a significant (P less than 0.01) decrease in serum OC on the placebo day approximately 4 h after the cortisol nadir, whereas no significant changes (P greater than 0.50) were seen on the metyrapone day. Moreover, the mean serum OC level tended to be higher (P less than 0.10 in the interval 0-12 h, and P = 0.06 in the interval 4-8 h) on the metyrapone day compared with the placebo day. On the placebo day, the mean level of serum cortisol during the interval 0-4 h correlated inversely with the mean level of serum OC in the interval 4-8 h (r = 0.77, P less than 0.05). This relation was not found on the metyrapone day. In conclusion, administration of metyrapone, which reduced and postponed the early morning cortisol peak, abolished the normal morning decrease in serum OC. This strongly supports that changes in endogenous serum cortisol are of major importance for the circadian rhythm in serum OC.

Forty postmenopausal women with a former Colles' fracture were enrolled in a 1-year study to determine the dose-effect relationship of nasal salmon calcitonin (SCT) on bone mass. They were randomized to receive either placebo, 50, 100, or 200 IU per day of SCT given as a nasal spray. The rate of change in the bone mineral content of the lumbar spine was 0.7, 0.2, 1.1, and 2.0 gHA per year, respectively, and the rate of change in the bone mineral content in the forearm was -0.4, -0.1, 0.0, and -0.1 AU per year, respectively. The rate of change in the bone mineral content of the lumbar spine in patients receiving 200 IU of SCT per day differed significantly from zero (P less than 0.01). Except for one patient, who experienced intolerable nausea, no systemic side effects were observed. Seven patients withdrew, two patients from nasal intolerance to the spray. These preliminary data suggest that SCT given by the nasal route has a positive and dose-dependent effect on spinal bone mass, but affects forearm bone mass only minimally.

Serum levels of osteocalcin (S-OC) and lectin-precipitable alkaline phosphatase activity (S-LAP) are sensitive markers of osteoblastic activity. Diurnal variation has been found for S-OC but has not been reported for S-LAP. We measured S-LAP and serum total alkaline phosphatase (S-TAP) in samples drawn every 60 min during a 24-h study period in nine normal subjects and correlated the findings with the diurnal variation in S-OC. A significant (p less than 0.05) diurnal variation in S-LAP characterized by peaks at 1430 hours and 2330 hours and nadir at 0630 hours was found. Peak levels were 30% higher than nadir level (p less than 0.05). S-TAP also varied significantly (p less than 0.05) with nadir at 0630 hours, showing a difference of 23% between peak and nadir levels (p less than 0.05). Significant cross-correlation was found between S-OC and S-LAP and S-TAP when these lagged 4 h after S-OC: r = 0.51 (p less than 0.02) and r = 0.65 (p less than 0.003), respectively. In other words, changes in S-LAP and S-TAP preceded changes in S-OC by 4 h. There were no significant cross-correlations between the non-lectin-precipitable fraction of AP and S-OC. In conclusion, S-LAP varies in a diurnal rhythm closely related with the diurnal rhythm of S-OC. The almost similar patterns in the diurnal serum levels of these two osteoblastic products strongly suggest that osteoblastic activity fluctuates rhythmically during the day in humans.

Serum levels of osteocalcin [OC; bone Gla protein (BGP)] and bone alkaline phosphatase (B-AP) are both correlated to osteoblastic activity, which may be regulated by several hormones, including estrogen, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], and PTH. Estrogen shows reproducible variations during the menstrual cycle, while available data on variations in serum 1,25-(OH)2D3 and serum immunoreactive PTH show midcyclic increases or no changes. In the present study we evaluated osteoblastic activity by measuring serum OC and B-AP during the menstrual cycle in eight healthy women, aged 20-47 yr. The cycles were synchronized by LH peaks, and follicular and luteal periods were normalized by lengths. Repeated measures analysis of variance showed that serum OC varied significantly (P less than 0.05), with highest levels during the luteal period. Although the same pattern was seen for serum B-AP, the variation just failed to reach significance (P less than 0.10), but the mean level was significantly higher during the luteal than during the follicular period (P less than 0.05). Gonadotropins and ovarian sex hormones showed significant variations. There were no significant changes in serum vitamin D-binding protein, serum total and free 1,25-(OH)2D3 index, or serum immunoreactive PTH-(1-84), but serum levels of somatomedin-C showed a significant variation, with the highest level during the luteal period (P less than 0.05). Blood levels and urinary excretion of minerals exhibited no significant variations. Cross-correlation studies between OC and estradiol showed the highest correlation coefficient, when OC was lagged about 7 days after estradiol (r = 0.69; P less than 0.05). Moreover, a high correlation was found between OC and somatomedin-C when matched at concurrent time points (r = 0.76; P less than 0.01). No significant correlations were found between the other calcium-regulating hormones and OC when matched at concurrent time points. In conclusion, we found a significant effect of the menstrual cycle on the serum levels of two osteoblastic bone markers, OC and B-AP. The changes indicated that osteoblastic activity is higher during the luteal period. However, whether the changes are caused by direct or indirect effects of the fluctuations in calciotropic hormones is still unresolved.

Animal and cell culture studies indicate glucocorticoid regulation of 1,25-dihydroxyvitamin D3 receptors and interference with cellular effects of vitamin D. These investigations prompted us to examine the effects of prednisone on the nuclear uptake of 1,25-dihydroxyvitamin D3 in freshly isolated human monocytes. Eighteen normal subjects were studied in a randomized, double-blind, placebo-controlled study. Analysis of receptor kinetics revealed that the maximal nuclear uptake (Bmax) of (3H)-1,25-dihydroxyvitamin D3 in monocytes decreased 40% (P less than .001) after prednisone treatment. In the group treated with prednisone (40 mg/d for 5 days) s-1,25-dihydroxyvitamin D increased 46% (P less than .01). S-25-Hydroxyvitamin D, S-phosphat, S-calcium, and S-iPTH remained unchanged. Osteoblastic production of the matrix protein, bone gla protein (BGP) is stimulated by 1,25-dihydroxyvitamin D3. However, despite increased serum levels of 1,25-dihydroxyvitamin D3, the prednisone-treated group revealed a 75% reduction in s-BGP. The present data indicate that corticosteroids decrease the nuclear uptake of 1,25-dihydroxyvitamin D3 in human monocytes. Further investigations are necessary, however, to elucidate the biologic mechanism for this observation and whether the mechanism is operative in other human tissues including bone.

Serum osteocalcin (OC), which is a sensitive marker of bone formation, is reduced during chronic glucocorticoid treatment in accordance with the finding of reduced bone formation, and even short term glucocorticoid treatment reduces serum OC. In a double blind placebo-controlled study, we measured the effects of 2.5 and 10 mg prednisone, orally, on the circadian variation of serum OC in 15 normal subjects (8 women and 7 men), aged 22-46 yr. All subjects were studied twice at an interval of 1 week. Blood samples were collected every 60 min from 1630 until 1700 h the following day. Prednisone or placebo was given at 2000 h. Serum OC was measured by an in-house RIA. After placebo administration serum OC increased from 2230 h to a peak value around 0230 h, followed by a gradual decline to a nadir around 1500 h. Both doses of prednisone inhibited and even reversed the nocturnal rise in serum OC levels; the inhibition occurred within 3-4 h. There was no significant difference in the time from prednisone ingestion to maximal decrease (7.2 h vs. 9.8 h) or in the maximal decrease (52% vs. 54%). However, the duration of the inhibition was significantly shorter after 2.5 mg than after 10 mg prednisone (approximately 6 h vs. 12 h; (p less than 0.01). We conclude that serum OC is sensitive to small doses of prednisone, and that serial serum OC measurements may be a sensitive marker of the effect of exogenous glucocorticoids on osteoblastic activity in vivo.

The efficacy of a two-dose perioperative course of rectally administered metronidazole and/or suction drainage of the vaginal vault in preventing febrile and infectious morbidity was evaluated in a randomized study of 198 patients undergoing abdominal hysterectomy. When compared with the control values, the incidence of febrile morbidity was significantly reduced (from 49% to 10%, 24.5%, and 10% respectively) in the groups treated with metronidazole, T-tube suction drainage, and a combination of the two prophylactic measures. The incidence of infectious morbidity was significantly reduced by using prophylactic metronidazole alone or in combination with suction drainage, but the reduction was most significant in the group treated with metronidazole alone. In the group managed with suction drainage alone, no reduction in infectious morbidity was found. The rate of postoperative urinary tract infection was significantly lower in the group treated with metronidazole alone as compared with the control group. No side effects of metronidazole were encountered.

Circulating human chorionic gonadotrophin (hCG), Schwangerschaftsprotein 1 (SP-1) and pregnancy-associated plasma protein A (PAPP-A) were examined in 10 women with ectopic gestation in relation to distribution and intensity of staining for these molecules using immunohistochemical techniques applied to matched trophoblastic and decidualized endometrial tissues. All 10 women revealed strong staining for hCG and SP-1 in the syncytiotrophoblast, which was apparently unrelated to maternal levels of hCG and SP-1, levels being less than the 10th centile of the normal range in 9/10 and 7/10 women, respectively. By contrast maternal PAPP-A levels seemed to correlate with the intensity and the distribution of staining for PAPP-A. Circulating PAPP-A was undetectable (less than 5 mIU/l) in 4 patients, and below the 10th centile in the remaining 6. Using immunohistochemical techniques hCG, SP-1 and PAPP-A could not be demonstrated in any of the decidualized endometrial tissues studied.

Cylindrical horizontal iliac crest trabecular bone biopsies were obtained from 9 patients with autosomal dominant osteopetrosis type I and 18 normal controls of comparable age/ sex match. Maximum compressive stress, maximum stiffness, energy absorption capacity and maximum strain were calculated from load-deformation curves after a compression test. Ash density of the bone samples was measured after incineration. The maximum compressive stress was significantly increased in the patient group (12.6 ± 2.6 (SE) MPa vs. 3.3 ± 0.4 MPa, p < 0.01), as was the ash density (0.61 ± 0.05 g/cm3 versus 0.27 ± 0.02 g/cm3, p < 0.01). After correction for ash density (normalized maximum stress) the strength of the trabecular bone samples was still significantly increased in the patients (19.7 ± 6.4 MPa × cm3/g versus 12.0 ± 1.2 MPa × cm3/g, p < 0.01). The maximum stiffness and energy absorption capacity were higher in the patients (p < 0.01), with a corresponding lower maximum strain value (p < 0.05). The maximum compressive stress correlated closely to the maximum stiffness and energy absorption capacity in both patients and controls, whereas no correlation to maximum strain was found. The maximum compressive stress thus seems to be representative for the two other biomechanical parameters. No significant correlations between age and maximum compressive stress (R = 0.38), ash density (R = 0.08), or normalized maximum stress (R = 0.45) were observed in type I osteopetrosis, whereas significant age-dependent decreases in maximum compressive stress (R = −0.65, p < 0.02) and in ash density (R = −0.57, p < 0.02) were observed in normal individuals. A significant correlation between ash density and maximum compressive stress was observed in the patient group (R = 0.90, p < 0.01). In conclusion, trabecular bone strength is increased in type I osteopetrosis, and does not decrease with age, as in normal individuals. The findings reflect an increase in absolute trabecular bone volume caused by defective bone resorption.

Summary The localization of human placental lactogen (hPL), pregnancy-specific beta-1 glycoprotein (Schwangerschaftsprotein 1, SP 1 ) and pregnancy-associated protein A (PAPP-A) was examined in intrauterine and tubal ectopic gestation ( n =5) by the immunoperoxidase technique. The distribution of hPL and SP 1 was identical in placental tissues obtained from intra- and extrauterine pregnancies, being uniformly seen throughout the syncytiotrophoblast. hPL and SP 1 were not demonstrated in uterine decidual tissue from ectopic pregnancies. During early (week 8) intrauterine pregnancy, PAPP-A was not restricted to the mature syncytiotrophoblast, being observed also in some trophoblast-like cells adjacent to islands of syncytiotrophoblast. In contrast, in ectopic gestation, PAPP-A was observed in these cells at six weeks' gestation only. We were unable to detect PAPP-A in trophoblastic tissue of chorionic villi and uterine decidual tissue from ectopic gestation.

Six cases of aortic insufficiency were found among 203 patients with ventricular septal defect cathe-terized during a 10-year period. The clinical, haemo-dynamic and angiographic findings are presented and compared with data previously reported in the literature. It is often possible to make a presumptive clinical diagnosis on the basis of auscultatory findings, symptoms of aortic insufficiency, increased pulmonary markings on chest X-rays and electrocardiographic and roentgeno-logic evidence of left ventricular strain. For a final diagnosis and elucidation of the anatomical details both right-sided heart catheterization and aortography are necessary.The clinical picture is variable, with a tendency to poor prognosis in those patients with marked aortic insufficiency.Using extracorporal circulation, closure of the ventricular septal defect and plastic repair of the aortic cusp were performed in 5 patients. One patient died postoperatively, improvement was seen in 3 and no change in condition was noticed i...

152 women admitted for legal abortion in the second trimester of pregnancy were included in an open, randomized, controlled six-centre study. 75 patients received gemeprost 1 mg vaginal pessaries at 3 hours intervals up to a maximum of 5 mg and 66 patients were treated with a single 40 mg intra-amniotic dose of PGF2 alpha. The 24-hour success rate was 81% (n = 61/75) in the gemeprost and 64% (n = 42/66) in the PGF2 alpha group (p less than 0.02). The mean abortion times were 14.3 and 14.8 hours in the gemeprost and the PGF2 alpha groups, respectively. The mean time to onset of pain was shorter and more patients experienced blood loss over 100 ml during the induction in the PGF2 alpha group than in the gemeprost group (p less than 0.02). Apart from that, the nature and severity of side effects were comparable between the two groups. Besides significantly better efficacy, the non-invasive gemeprost treatment was found to be easier and safer as compared to the PGF2 alpha treatment.

Seven out of 54 women with ectopic gestation had uncommon features such as extra-tubal implantation or multiple intratubal pregnancy. Depressed levels (less than 10th centile) or apparent absence of circulating human chorionic gonadotrophin (hCG) and pregnancy-associated plasma protein A (PAPP-A) were seen respectively in 5 and 7 of 7 women studied. Normal levels of hCG were seen in two women, one with an abdominal and one with an angular pregnancy. These data suggest that the synthesis of placental proteins in ectopic pregnancies is independent of the site of implantation and the number of embryos. Measurements of maternal levels of the 2 placental proteins seem to be applicable as auxiliary diagnostic tests for ectopic pregnancy, regardless of the site of implantation.

The concentration of human placental lactogen (hPL), pregnancy specific beta-1 glycoprotein (SP-1) and pregnancy-associated plasma protein A (PAPP-A) were analysed in consecutive serum samples from a patient who gave birth to a child with Cornelia de Lange syndrome. HPL and SP-1 were present in normal concentrations from week 20 to week 35 of gestation whereas PAPP-A could not be detected in any of the samples examined. Immunohisto-chemical examination of two placentae from Cornelia de Lange syndrome revealed normal localization of hPL and SP-1 but the absence of PAPP-A from the syncytiotrophoblast. The significance of association between Cornelia de Lange syndrome and compromised synthesis of PAPP-A is discussed.

Serum levels of total alkaline phosphatase activity (S-T-AP), wheat germ lectin-precipitated alkaline phosphatase activity (S-L-AP), and bone Gla-protein immunoreactivity (S-BGP) were measured in 26 patients (23 females and 3 males) aged 35-73 years (mean 59 years) with primary hyperparathyroidism (n = 7), hyperthyroidism (n = 9), and hypothyroidism (n = 10) in whom the bone mineralization rate (m) was determined by 47Ca-kinetics (continuously expanding calcium pool model). A weak positive correlation (r = 0.42, P less than 0.05) was found between S-T-AP and m, which in the range from 0-18 mmol Ca/day could be estimated with a standard error of 4.6 mmol/day. A closer correlation (r = 0.65, P less than 0.001) was found between S-L-AP and m which was estimated with an error of 3.9 mmol Ca/day. The AP activity in the supernatant showed no significant correlation to m (r = 0.11, P greater than 0.50). The highest correlation coefficient (r = 0.81, P less than 0.001) was found between S-BGP and m which could be predicted with an error of 3.4 mmol Ca/day. S-BGP showed a closer correlation to S-L-AP (r = 0.71, P less than 0.001) than to S-T-AP (r = 0.58, P less than 0.01). We concluded that S-L-AP predicts bone mineralization at organ level better than S-T-AP in selected metabolic bone disorders and that the supernatant activity shows no relation to bone turnover.(ABSTRACT TRUNCATED AT 250 WORDS)