A novel case of neonatal severe hyperparathyroidism successfully treated with a type II calcimimetic drug.

We report a boy with hypercalcemia due to neonatal severe hyperparathyroidism (NSHPT) caused by a compound heterozygous mutation in the calcium sensing receptor (CaSR) managed successfully on a type II calcimimetic drug. The hypercalcemia was temporarily treated by hyperhydration, bisphosphonate and calcium depleted milk. At 29 days of age cinacalcet was introduced. The starting dose was 0.5 mg/kg/day and was subsequently titrated to the point of efficacy (5.2 mg/kg/day) when a persuasive reduction in parathyroid hormone and calcium concentrations was observed. We propose a trial of type II calcimimetics in newborns with NSHPT irrespective of the genetic mutation and advocate that residual functionality of the CaSR predict the drug efficacy.

Low risk of venous thromboembolism following early pregnancy loss in pregnancies conceived by IVF.

STUDY QUESTION: What is the risk of venous thromboembolism (VTE) in the 12 weeks following early pregnancy loss in pregnancies conceived by IVF? SUMMARY ANSWER: The VTE risk is low in the 12 weeks following early pregnancy loss in pregnancies conceived by IVF. WHAT IS KNOWN ALREADY: There is an excess VTE risk during first trimester in complete IVF pregnancies leading to delivery. It is unknown whether this excess VTE risk also is present in IVF pregnancies terminated by early pregnancy loss (implantation failure, missed abortion, or spontaneous or induced abortion before 10 completed gestational weeks). STUDY DESIGN, SIZE, DURATION: A nationwide registry-based cohort study including all Danish IVF pregnancies registered in the Danish IVF Register between 1995 and 2005. Women who underwent frozen embryo replacement or oocyte donation were not included. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included all 24 931 IVF treatments leading to pregnancy among 19 260 women. We identified 16 701 complete IVF pregnancies, 7567 IVF pregnancies with early pregnancy loss, and 663 IVF pregnancies terminated by late abortion (≥gestational weeks 10). We followed women for 12 weeks after termination of pregnancy and calculated the absolute risk of VTE during follow-up with 95% CI. As a relative risk estimate, we calculated the risk ratio for VTE following IVF pregnancies with early loss compared to the VTE risk following complete IVF pregnancies. MAIN RESULTS AND THE ROLE OF CHANCE: During the 12 weeks of follow-up, only one case of VTE occurred in the group of early pregnancy loss, none in the late abortion group, and 13 VTE cases occurred in complete IVF pregnancies. The VTE risk per 10 000 pregnancies was 1.3 [0.03-7.4] for IVF pregnancies with early loss and 7.8 [4.1-13.3] for complete pregnancies; the corresponding risk ratio was 0.17 [0.02-1.3]. Thus, we found a low absolute VTE risk in the 12 weeks following early pregnancy loss in IVF pregnancies. The relative VTE risk was low in comparison to the VTE risk in early gestation reported for complete IVF pregnancies and for Danish background pregnancies. LIMITATIONS, REASONS FOR CAUTION: Despite the use of complete nationwide data, only a few VTE events were available for the statistical analyses thereby limiting the precision of our estimates. We included both inpatient and outpatient VTE hospital diagnoses, but we cannot rule out the occurrence of VTE cases not diagnosed at hospital and hence not registered in the National Patient Registry. No information was available on the use of prophylactic low molecular weight heparin: access to such might have helped to explain our findings, but would not have changed our conclusions. WIDER IMPLICATIONS OF THE FINDINGS: The results of the present study do not indicate a need for prophylactic anticoagulant therapy in women suffering early IVF pregnancy loss without other risk factors. STUDY FUNDING/COMPETING INTEREST(S): No external funding was obtained for this study. There are no conflicts of interest to declare.

Blood Chimerism in Dizygotic Monochorionic Twins During 5 Years Observation.

Dizygotic monochorionic twin pregnancies can result in blood chimerism due to in utero twin-to-twin exchange of stem cells. In this case, we examined the proportion of allogeneic red blood cells by flow cytometry and the proportion of allogeneic nucleated cells by digital polymerase chain reaction at 7 months and again at 5 years. We found an increase in the proportion of allogeneic cells from 63% to 89% in one twin, and a similar increase in autologous cells in the other twin from 57% to 84%. A paradigm for stem cell therapy could be modeled on this case: induction of tolerance and chimerism by antenatal transfusion of donor stem cells. The procedure would hold the promise of transplantation and tolerance induction without myeloablative conditioning for inheritable benign hematological diseases such as sickle cell disease and thalassemia.

Inflammatory bowel disease and venous thromboembolism during pregnancy and the postpartum period.

Essentials Risk of pregnancy-related venous thromboembolism may be increased in inflammatory bowel disease. We performed a study on inflammatory bowel disease and pregnancy-related venous thromboembolism. Inflammatory bowel disease is a risk factor for pregnancy-related venous thromboembolism. Proper disease control before conception is pivotal to avoid venous thromboembolism. SUMMARY: Background The incidence of inflammatory bowel disease (IBD) increases, and thus is more common, in pregnant women. IBD is a risk factor for venous thromboembolism (VTE) but it is not clear whether IBD predisposes women to an excess risk of VTE during pregnancy and the postpartum period. Methods This was a nationwide population-based cohort study of all deliveries during 1980-2013 in Denmark, using data from two nationwide health registries: the Danish National Patient Registry and the Medical Birth Registry. We computed incidence rates (IRs) per 1000 person-years, and crude and adjusted relative risks (RRs) with 95% confidence intervals (CIs) for VTE during pregnancy and the first 12 postpartum weeks in women with and without IBD. Results We included 1 046 754 women with 1 978 701 deliveries. We identified 3465 VTE events during pregnancy and 1302 VTE events postpartum. The IR for VTE during pregnancy was 4.20 (95% CI, 2.83-5.58) in IBD patients and 2.41 (95% CI, 2.33-2.50) in women without IBD, corresponding to an RR of 1.72 (95% CI, 1.22-2.43). Adjustment for maternal age and smoking (pregnancies during 1991-2013) yielded an adjusted RR of 1.67 (95% CI, 1.15-2.41). IBD flare was associated with an RR of 2.64 (95% CI, 1.69-4.14) for VTE during pregnancy. The IR for postpartum VTE was 7.03 (95% CI, 3.87-10.20) among IBD patients and 2.88 (95% CI, 2.72-3.04) in women without IBD, corresponding to an adjusted RR of 2.10 (95% CI, 1.33-3.30). Conclusions IBD is a risk factor for VTE during pregnancy and postpartum.

Preconception venous thromboembolism and placenta-mediated pregnancy complications.

BACKGROUND: Placenta-mediated complications are leading causes of maternal and fetal morbidity and mortality. We hypothesized that a preconception history of venous thromboembolism (VTE) is associated with increased risk of placenta-mediated pregnancy complications. METHODS: A nationwide population-based cohort study of all singleton pregnancies leading to delivery from 1997 to 2012 (n = 964 967). We obtained data on placenta-mediated pregnancy complications from the Danish Medical Birth Registry and data on VTE before pregnancy from the Danish National Patient Registry. We computed absolute risks, crude and adjusted risk differences (RDs) using a binomial regression model, and crude and adjusted risk ratios (RRs) from a modified Poisson regression model. RESULTS: Overall, 1419 women had a preconception history of VTE, while 578 112 did not. Preeclampsia occurred in 4.2% of pregnancies in the VTE group and in 2.7% of pregnancies in a comparison cohort (adjusted RD = 1.3%, 95% confidence interval (CI) 0.6-2.0%; adjusted RR = 1.5, 95% CI 1.3-1.8). Stillbirth occurred in 0.7% of pregnancies in the VTE group and in 0.4% of pregnancies in the comparison cohort (adjusted RD = 0.3%, 95% CI 0.02-0.6%; adjusted RR = 1.8, 95% CI 1.1-3.0). Placental abruption occurred in 0.8% of pregnancies in the VTE group and in 0.5% of pregnancies in the comparison cohort (adjusted RD = 0.3%, 95% CI - 0.05-0.6%; adjusted RR = 1.6, 95% CI 1.1-2.4). Small-for-gestational-age infants accounted for 10.9% of live births in the VTE group and 9.8% of live births in the comparison cohort (adjusted RD = 0.6%, 95% CI - 0.5-1.7%; adjusted RR = 1.1, 95% CI 0.9-1.3). CONCLUSION: Women with a history of VTE were at increased risk of placenta-mediated complications.

Increased venous thrombosis incidence in pregnancies after in vitro fertilization.

STUDY QUESTION: Is venous thrombosis risk increased in pregnancies after in vitro fertilization? SUMMARY ANSWER: The venous thrombosis incidence was significantly increased in pregnancies after in vitro fertilization; especially in the first trimester and in the first 6 weeks post-partum. WHAT IS KNOWN ALREADY: In vitro fertilization without pregnancy is not associated with increased venous thrombosis incidence. STUDY DESIGN, SIZE, DURATION: This national register-based cohort study covered the period from 1995 to 2005. PARTICIPANTS/MATERIALS, SETTING, METHODS: All Danish pregnancies conceived by in vitro fertilization (n = 18 787) were included. Venous thrombosis incidence rates in pregnancies after in vitro fertilization were compared with venous thrombosis incidence rates in reference pregnancies, by calculating incidence rate ratios. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 48 cases were identified. In pregnancies after in vitro fertilization, the overall venous thrombosis incidence rate was 28.6 per 10 000 pregnancy-years (95% confidence interval (CI) 20.6-39.6) in comparison to 10.7 per 10 000 woman-years in reference pregnancies. Post-partum, the venous thrombosis incidence rate was 27.9 per 10 000 woman-years (95% CI 15.8-49.1) after in vitro fertilization in comparison to 17.5 per 10 000 woman-years in reference pregnancies. The overall venous thrombosis incidence rate ratio during in vitro fertilization (IVF) pregnancies compared with reference pregnancies was 3.0 (95% CI 2.1-4.3). The venous thrombosis incidence rate ratios during pregnancy were 2.8 (95% CI 1.9-4.1) in singleton IVF pregnancies and 4.4 (95% CI 2.4-8.3) in multiple IVF pregnancies, compared with reference pregnancies. The venous thrombosis incidence rate ratio post-partum was 1.2 (95% CI 0.6-2.8) for singleton IVF pregnancies and 3.9 (95% CI 1.7-8.8) for multiple IVF pregnancies compared with reference pregnancies. The post-partum venous thrombosis risk was higher in multiple IVF pregnancies compared with singleton IVF pregnancies. Maternal age, smoking and parity did not significantly affect the venous thrombosis risk. Ovarian hyperstimulation syndrome and polycystic ovarian syndrome did increase the risk of venous thrombosis during pregnancy. Caesarean section also increased the post-partum venous thromboembolism risk, but the increase was not significant. LIMITATIONS, REASONS FOR CAUTION: Other known confounders in our reference population could have contributed to the results. Access to such data may have helped to explain the observations, but would not have changed the conclusion that IVF pregnancies have an increased risk of venous thrombosis compared with other pregnancies. WIDER IMPLICATIONS OF THE FINDINGS: Our study adds new insights by demonstrating an excess venous thrombosis incidence post-partum after in vitro fertilization. The high venous thrombosis incidence in first trimester after in vitro fertilization supports previous studies. Our findings are generalizable to other Western Countries. STUDY FUNDING/COMPETING INTERESTS: Expenses for the acquirement of data were covered by a grant from The Secretary of Doctors further education, Central Denmark Region. None of the authors have any competing interests to declare. TRIAL REGISTRATIONS NUMBER: Not applicable.

No evidence that assisted reproduction increases the risk of thrombosis: a Danish national cohort study.

BACKGROUND: Case reports have reported venous and arterial thromboses in women undergoing assisted reproduction. No large systematic studies on the risk of thrombosis have been published. The objective of our study was to investigate whether the risk of thrombosis is increased in women undergoing assisted reproduction. METHODS: A national register-based cohort study was conducted on all women undergoing IVF or ICSI treatment in Denmark from 1994 to 2005. Data were obtained from the National Patient Registry and the IVF Registry. Women with prior malignant or cardiovascular disease were excluded. Thrombosis occurring within the first 6 and 12 months after assisted reproduction was considered potentially related to the treatment. Thromboses during pregnancy as well as the pregnancy-related diagnoses were excluded from the statistical analysis. The incidence rates of venous and arterial thromboses were compared with previously published estimates of the risk of thrombosis among young Danish women. RESULTS: We analyzed 30 884 Danish women undergoing 75 141 treatments from 1994 to 2005. The mean age of the women at first treatment was 32.3 years. The delivery rate per cycle was 22%. The incidence rate ratio, with 95% confidence interval (CI), of venous thrombosis within 6 months was 0.95 (CI: 0.38-1.95). The incidence rate ratio of arterial thrombosis within 6 months was 0.36 (CI: 0.04-1.30). CONCLUSIONS: Our study showed no evidence that assisted reproduction increases the risk of thrombosis.

Concomitant, specific determination of growth hormone and pegvisomant in human serum.

Growth hormone (GH) and the GH receptor blocker, pegvisomant are usually circulating in high concentration in pegvisomant treated acromegalic patients. This and the close similarity between the peptides make determination of either difficult. In the present methodological study, endogenous GH in serum is initially isolated and determined in a slightly modified commercial immunometric assay, whereafter the now GH free medium allows measurement of pegvisomant. Inter-individual steady state levels of serum pegvisomant vary remarkably in both acromegalic patients and healthy controls, while the intra-individual variations are negligible.

Coarse media filtration--an alternative to settling in wastewater treatment.

In this paper coarse media filtration has been analysed as an alternative to the traditional settling in primary, secondary and tertiary treatment of wastewater. Various filter media configurations were evaluated for enhanced primary filtration. It was found that a dual media configuration based on Kaldnes biofilm media (1 and K2modified) were most suitable when taking both separation efficiency as well as filter run time into consideration. SS removal efficiencies of around 75% were achieved in the dual Kaldnes primary filter at around 20 m/h without any chemical addition and around 85% at low dosage (1-2 mg/l) of a high MW cationic polymer FO4440SH. In the latter case COD was removed by around 70%. Further experiments were carried out on a multi-media Kaldnes-Filtralite-Sand (KFS) filter for enhanced primary treatment as well as for secondary filtration directly downstream of a high-rate moving bed biofilm reactor, resulting in an extremely compact secondary treatment process. The secondary KFS-filter gave SS-removal efficiencies around 90% (effluent SS < 15 mg/l) and filter run times of around 24 hrs at filtration rates of 10 m/h (sludge loading rates of around 1 kg/m2h) when a small dose (2 mg/l) of polymer was used. It is also demonstrated that the primary filter may also be utilised as a pre-denitrification reactor. A denitrification rate of 1.5 kg NO3-N(equiv.)/m3d was achieved when the filter was operated at a filtration rate of 5 m/h.

[Carriers of cystic fibrosis are more susceptible to asthma. The Osterbro study]. / Baerere af cystisk fibrose har øget risiko for asthma. Osterbroundersøgelsen.

We tested the hypothesis that individuals heterozygous for the common cystic fibrosis delta F508 mutation are at risk of obstructive pulmonary disease. We studied a cross-sectional sample from the general population of Copenhagen, aged 20 years and older. We performed spirometry to measure FEV1 and FVC, and genotyped blood samples from 9141 individuals. We identified 250 carriers of the delta F508 mutation (2.7%; 95% CI: 2.5%-3.1%). Nine precent of carriers reported having asthma compared with 6% of non-carriers (chi 2: p = 0.04). Furthermore, among individuals with airway obstruction, the percentage of predicted FEV1 and FVC were significantly lower in participants heterozygous for delta F508 than in non-carriers (49% vs. 58%, p = 0.004 and 70% vs. 82%, p < 0.001, respectively). Cystic fibrosis delta F508 heterozygosity may be over-represented among people with asthma and seems to be associated with decreased pulmonary function in people with airway obstruction who also have asthma.

Pasteurella multocida septicaemia in fallow deer (Dama dama).

Thirteen of 100 fallow deer, aged between 6 months and 10 years, died over a 5 week period. The deaths occurred in 2 outbreaks 3 weeks apart. Both outbreaks were preceded by at least 3 days of cold wet and windy weather, and were associated with water-logged pastures. Affected animals were usually found dead, with a frothy blood-stained nasal discharge. In the 8 deer necropsied, gross lesions included widespread subserosal petechial haemorrhages, severe pulmonary congestion and oedema with froth-filled airways, and fibrinous pneumonia and pleurisy in 4 deer. Two deer, also, had extensive subcutaneous petechial and ecchymotic haemorrhages and oedema of skeletal musculature. Histologically, the most significant lesions were present in the lungs. Moderate to severe pulmonary congestion and oedema, with fibrinous exudation into alveoli and septal oedema, were present in all deer. In some deer these changes were accompanied by a diffuse infiltration with polymorphonuclear leucocytes. Pasteurella multocida was isolated from a range of tissues from 7 of 8 deer examined. The remaining animal had been treated with antibiotics 8 hours before death. The isolates had identical polyacrylamide gel electrophoresis patterns and were of the same antigenic type-Carter group A, Heddleston type 3,4.

[Decrease in cardiac mortality and changes of risk factor levels. The Osterbro study]. / Fald i hjertedødelighed og aendring af risikofaktorniveauet. Osterbro-undersøgelsen.

From 1974 to 1984, decreases in the mortality of ischaemic heart disease of 11% for men 30 to 69 years of age and 16% for women in the same age-group were observed. From the Copenhagen City Heart Study, a population study of 20,000 men and women, a significant decrease in per cent of smokers, a significant decrease in P-cholesterol, a significant increase in per cent of joggers, but no change in systolic blood pressure were demonstrated, between 1976-1978 and 1981-1983. The decrease in mortality of ischaemic heart disease, may be due to reduction in risk-factor levels, and to advanced medical and surgical treatment.

Linkage analysis of the human insulin receptor gene and maturity onset diabetes of the young.

The cloning of the insulin receptor cDNA has permitted the definition of restriction fragment length polymorphisms at that locus. These polymorphisms were used to study the role of the insulin receptor in four pedigrees with maturity onset diabetes of the young through linkage analyses. When each pedigree was individually analysed, no linkage was demonstrated in the two larger pedigrees, implying that an insulin receptor defect was not responsible for the predisposition to diabetes in these pedigrees. One of these pedigrees was known to be hypoinsulinaemic, while insulin levels were unavailable in the second pedigree. In the two smaller pedigrees, however, a single haplotype cosegregated with diabetes. One of these pedigrees is known to be hyperinsulinaemic. The small size of the pedigrees which demonstrated cosegregation precluded statistical proof of linkage. Nonetheless, the presence of an uncommon insertional polymorphism which cosegregated with diabetes in both pedigrees was improbable and suggested that this insertion could be responsible for diabetes in these families. This study thus may be additional evidence for heterogeneity in maturity onset diabetes of the young. For the two larger pedigrees, the insulin gene and HLA region have already been eliminated as genetic markers. This study provides data which eliminate a third candidate gene in these two pedigrees.

Insulin-gene flanking sequences, diabetes mellitus and atherosclerosis: a review.

A highly polymorphic locus flanking the human insulin gene contains two major size classes of DNA restriction fragments, which segregate in families as stable genetic elements. The L-allele, i.e. fragments with an average size of about 600 base-pairs seems to be a weak genetic marker for Type 1 (insulin-dependent) diabetes mellitus, whereas the U-allele, i.e. fragments of an average size of about 2500 base-pairs hitherto has been associated with Type 2 (non-insulin-dependent) diabetes mellitus and diabetic hypertriglyceridaemia. The most recent reports on this subject do not confirm an association between the U-allele and Type 2 diabetes. Our own studies indicate that the U-allele is a fairly strong marker for the development of atherosclerosis (relative risk for U-carriers 3.36). The putative functions of the polymorphic region in atherogenesis and the relation of this region to other genetic markers for atherosclerosis are not known.