Evaluation of treatment with human chorionic gonadotropin at transfer of in vitro produced beef embryos on reproductive outcomes in lactating multiparous Jersey cows after a synchronized ovulation.

Our objective was to evaluate the effect of treatment with human chorionic gonadotropin (hCG) at the time of transfer of in vitro produced (IVP) beef embryos on pregnancy outcomes in lactating multiparous Jersey cows. Grade 1, Stage 7 (expanded blastocyst), IVP beef embryos were produced from black Angus-based dams using 3 proven high fertility Angus sires and were frozen for direct transfer. In a preliminary experiment, lactating multiparous Jersey cows were randomized to a 2x2 factorial arrangement of treatments to test the main effect of recipient synchronization protocol (Double-Ovsynch; DO; n = 169 vs. a synchronized estrus; ED; n = 180) and were randomly assigned within recipient protocol to serve as untreated controls (DO-CON, n = 78; ED-CON, n = 44) or to receive i.m. treatment with 2,500 IU of hCG (DO-hCG, n = 79; ED-hCG, n = 46) at the time of embryo transfer (ET). The recipient utilization rate was greater for DO (93%) than for ED (50%) cows, and there was an interaction between recipient synchronization protocol and hCG treatment in which DO-hCG cows had more pregnancies per embryo transfer (P/ET) at 26, 33, and 61 d than DO-CON, ED-hCG, and ED-CON cows. Based on a partial budget analysis, the cost per pregnancy for DO cows was $135.35 less than for ED cows. In Experiment 2, lactating multiparous Jersey cows were submitted to a Double-Ovsynch protocol (DO, n = 386) and were randomly assigned to serve as untreated controls (CON, n = 192) or were treated with 2,500 IU hCG (hCG, n = 194) at ET. Progesterone concentrations and total luteal volume 7 d after ET were greater for hCG than for CON cows. In contrast to the preliminary experiment, treatment with hCG did not affect P/ET at 26, 33, or 61 d, and treatment with hCG did not affect pregnancy loss from 26 to 61 d. In conclusion, treatment with 2,500 IU of hCG at ET increased P4 concentrations and total luteal volume 7 d after ET but did not increase pregnancy outcomes or decrease pregnancy loss in lactating multiparous Jersey cows receiving frozen/thawed IVP beef embryos.

Magnetic circular dichroism spectra from resonant and damped coupled cluster response theory.

A computational expression for the Faraday A term of magnetic circular dichroism (MCD) is derived within coupled cluster response theory and alternative computational expressions for the B term are discussed. Moreover, an approach to compute the (temperature-independent) MCD ellipticity in the context of coupled cluster damped response is presented, and its equivalence with the stick-spectrum approach in the limit of infinite lifetimes is demonstrated. The damped response approach has advantages for molecular systems or spectral ranges with a high density of states. Illustrative results are reported at the coupled cluster singles and doubles level and compared to time-dependent density functional theory results.

[Doppler Sonography during Pregnancy - DEGUM Quality Standards and Clinical Applications]. / Dopplersonografie in der Schwangerschaft ­ Qualitätsanforderungen der DEGUM und klinischer Einsatz (Teil 1).

Doppler sonography is widely established in prenatal medicine and obstetrics and is commonly used in screening for aneuploidy and preeclampsia during the first trimester. More importantly, during the 2nd and 3 rd trimester, it is used in the assessment of fetal health as well as the surveillance of underlying fetal conditions such as IUGR and anemia. Correct use of the method is vital for correct data interpretation and the inferred clinical decision process. Therefore, we aim to provide all users of doppler sonography with a guide for meeting the required quality standards. These quality standards will further be the basis of DEGUM-certified training courses. In the first part, we will introduce the technical principles of the method and potential error sources, vascular disciplines to which the method can be applied, analysis of the spectral curves, patient safety and the needed requirements for successful certification.

Consensus conference statement on fluorescence-guided surgery (FGS) ESSO course on fluorescence-guided surgery.

BACKGROUND: Fluorescence-guided surgery (FGS) has emerged as an innovative technique with promising applications in various surgical specialties. However, clinical implementation is hampered by limited availability of evidence-based reference work supporting the translation towards standard-of-care use in surgical practice. Therefore, we developed a consensus statement on current applications of FGS. METHODS: During an international FGS course, participants anonymously voted on 36 statements. Consensus was defined as agreement ≥70% with participation grade of ≥80%. All participants of the questionnaire were stratified for user and handling experience within five domains of applicability (lymphatics & lymph node imaging; tissue perfusion; biliary anatomy and urinary tracts; tumor imaging in colorectal, HPB, and endocrine surgery, and quantification and (tumor-) targeted imaging). Results were pooled to determine consensus for each statement within the respective sections based on the degree of agreement. RESULTS: In total 43/52 (81%) course participants were eligible as voting members for consensus, comprising the expert panel (n = 12) and trained users (n = 31). Consensus was achieved in 17 out of 36 (45%) statements with highest level of agreement for application of FGS in tissue perfusion and biliary/urinary tract visualization (71% and 67%, respectively) and lowest within the tumor imaging section (0%). CONCLUSIONS: FGS is currently established for tissue perfusion and vital structure imaging. Lymphatics & lymph node imaging in breast cancer and melanoma are evolving, and tumor tissue imaging holds promise in early-phase trials. Quantification and (tumor-)targeted imaging are advancing toward clinical validation. Additional research is needed for tumor imaging due to a lack of consensus.

Specific collaborative group intervention for patients with medically unexplained symptoms in general practice: a cluster randomized controlled trial.

BACKGROUND: Patients with medically unexplained symptoms (MUS) are frequent in primary care and substantially impaired in their quality of life (QoL). Specific training of general practitioners (GPs) alone did not demonstrate sustained improvement at later follow-up in current reviews. We evaluated a collaborative group intervention. METHODS: We conducted a cluster randomized controlled trial. Thirty-five GPs recruited 304 MUS patients (intervention group: 170; control group: 134). All GPs were trained in diagnosis and management of MUS (control condition). Eighteen randomly selected intervention GPs participated in training for a specific collaborative group intervention. They conducted 10 weekly group sessions and 2 booster meetings in their practices, together with a psychosomatic specialist. Six and 12 months after baseline, QoL was assessed with the Short-Form 36. The primary outcome was the physical composite score (PCS), and the secondary outcome was the mental composite score (MCS). RESULTS: At 12 months, intention-to-treat analyses showed a significant between-group effect for the MCS (p = 0.023) but not for the PCS (p = 0.674). This effect was preceded by a significant reduction of somatic symptom severity (15-item somatic symptom severity scale of the Patient Health Questionnaire, PHQ-15) at 6 months (p = 0.008) that lacked significance at 12 months (p = 0.078). As additional between-group effects at 12 months, per-protocol analyses showed less health anxiety (Whiteley-7; p = 0.038) and less psychosocial distress (PHQ; p = 0.024); GP visits were significantly (p = 0.042) reduced in the intervention group. CONCLUSIONS: Compared to pure GP training, collaborative group intervention achieved a progressive, clinically meaningful improvement in mental but not physical QoL. It could bridge gaps between general practice and mental health care.

Retinocytoma Undergoing Retinoblastoma Transformation in an Adult Patient.

We report a 46-year-old male patient with retinocytoma who presented at the age of 31 asymptomatically. An intraocular retinal mass was incidentally found in his right eye, when he underwent ophthalmological assessment for refractive surgery. This tumor consisted of a calcified sessile basis partially covered by a pedunculated salmon-pink growth. Initially, the tumor was diagnosed as a retinocytoma with clinical suspicion of malignant transformation into retinoblastoma and treated by four sessions of laser photocoagulation. Six and a half years later, the tumor relapsed, and he was treated with a Ruthenium plaque. Following brachytherapy, he had two episodes of right-sided vitreous hemorrhage that spontaneously cleared up, and the remaining finding in the vitreous cavity was interpreted as asteroid hyalosis. He underwent vitrectomy about five years following brachytherapy. The analysis of the vitreous material revealed the presence of inactive vitreous seeds composed of small round blue cells, compatible with a type 2 regression.

Individualized correction for maternal weight in calculating the risk of chromosomal abnormalities with first-trimester screening data.

AIM: In the algorithm developed by the Fetal Medicine Foundation (FMF) Germany designed to evaluate the findings of routine first-trimester screening, the false-positive rate (FPR) was determined for the entire study group without stratification by maternal weight. Based on the data received from the continuous audit we were able to identify an increase in the FPR for the weight-related subgroups of patients, particularly for patients with extremely high body weights. The aim of this study was to demonstrate that the variability of the FPR can be reduced through adjusting the concentrations of free ß-HCG and PAPP-A measured in the maternal serum by means of a nonlinear regression function modeling the dependence of these values on maternal weight. MATERIAL AND METHODS: The database used to establish a version of the algorithm enabling control of the FPR over the whole range of maternal weight consisted of n = 123 546 pregnancies resulting in the birth of a child without chromosomal anomalies. The group with positive outcomes covered n = 500 cases of trisomy 21 and n = 159 trisomies 13 or 18. The dependency of the serum parameters free ß-HCG and PAPP-A on maternal weight was analyzed in the sample of negative outcomes by means of nonlinear regression. The fitted regression curve was of exponential form with negative slope. Using this model, all individual measurements were corrected through multiplication with a factor obtained as the ratio of the concentration level predicted by the model to belong to the average maternal body weight of 68.2 kg, over the ordinate of that point on the regression curve which belongs to the weight actually measured. Subsequently, the totality of all values of free ß-HCG and PAPP-A corrected for deviation from average weight were used as input data for carrying out the construction of diagnostic discrimination rules described in our recent paper for a database to which no corrections for over- or under-weight had been applied. This entailed in particular the construction of new reference bands for the corrected biochemical values as the basis for calculating the degree of extremeness (DOE) measures to replace the more traditional MOMs. In the final and most crucial step, stratified FPRs were computed and compared over a set of intervals partitioning the whole range of maternal weight into 18 classes. RESULTS: For the posterior risks of both trisomy 21 and 13 / 18 computed from the weight-corrected database, the use of a cutoff value of 1:150 turned out to be an appropriate choice. For T 21, the overall FPR obtained through comparing the individual risks with this cutoff was found to be 3.51 %. The corresponding proportion of ascertained cases of trisomy 21 detected by means of the new algorithm was 86.2 %. For the trisomy 13 / 18 group, the analogous results were a FPR of 2.07 % and a detection rate (DTR) of 83.0 %, respectively. A comparison between the FPRs obtained for the 18 intervals into which the range of maternal weight had been partitioned, showed the deviation of the strata-specific from the overall FPR to be fairly small: for T 21, the FPR ranged from 2.72 to 4.86 %, and the maximum was found in the group of 87.5 - 95.0 kg. For women with a weight of more than 120 kg, the FPR was only slightly above the FPR for the total sample (3.69 as compared to 3.51 %). Similar results were obtained for the discrimination rule constructed for diagnosing T 13 / 18: here, the minimum FPR (1.17 %) was found for patients weighing more than 120 kg, whereas the maximum (2.66 %) occurred in the interval 75.0 - 77.5 kg. CONCLUSION: In this study we demonstrated that the new algorithm developed by the FMF Germany to estimate risks for fetal trisomies 21 and 13 / 18 combines very good misclassification rates with a far-reaching stability of the false-positive rate against even extreme deviations from the average maternal weight.

Potential errors with rapid analysis techniques: partial duplication 21q resulting from a paternal paracentric insertion uncovered in chorionic villus sampling by fluorescence in situ hybridization.

We report on partial duplication 21q resulting from a paternal insertion identified during prenatal diagnosis. While performing interphase fluorescence in situ hybridization (I-FISH), we were able to identify 3 signals of the LSI 21 Spectrum Orange probe with chorionic villus sampling. Using standard cytogenetic analysis, I-FISH and GTG banding, structural aberrations in 21q in the parents and in the fetus could not be reliably determined. Applying metaphase fluorescence in situ hybridization (M-FISH), we identified a recombinant chromosome 21 carrying an interstitial duplication of the Down syndrome critical region inherited from the father. Both data from our analysis and published literature recommend the use of rapid testing methods such as I-FISH and standard cytogenetic analysis in prenatal diagnosis. It became obvious that I-FISH would not detect such a particular aberration. Thus, karyotyping, I-FISH and M-FISH should be performed in all Down syndrome cases.

Relation between circulating angiotensin II type 1 receptor agonistic autoantibodies and soluble fms-like tyrosine kinase 1 in the pathogenesis of preeclampsia.

CONTEXT: Placental and circulatory soluble fms-like tyrosine kinase 1 (sFlt1) has proven to be elevated in pregnant women with preeclampsia, a disease characterized by hypertension, proteinuria, and endothelial dysfunction. Recent studies also demonstrated an autoantibody against the angiotensin II type 1 (AT1) receptor (AT1-AA) in that disease. OBJECTIVE: Both factors are discussed as key players in the etiology of preeclampsia. However, it has not yet been clarified whether these two circulating factors correlate and whether synergy determines the severity of pathology. DESIGN: AT1-AA was retrospectively determined by a bioassay and sFlt1 by an ELISA. PATIENTS: Serum from second-trimester pregnancies with normal or abnormal uterine perfusion and in women at term with or without pregnancy pathology was analyzed. RESULTS: Most of the preeclamptic patients were characterized by high sFlt1 levels and the presence of AT1-AA, although the agonistic effects of the antibody did not correlate with the sFlt1 concentrations (P = 0.85). Although AT1-AA was also detected in second-trimester pregnancies evidencing abnormal uterine perfusion without later pathology, sFlt1 was not significantly elevated in these pregnancies, compared with those with normal uterine perfusion. However, whereas women with abnormal perfusion and later pregnancy pathology did not differ in AT1-AA, compared with those with normal outcome, sFlt1 was significantly increased. Again, the two factors did not correlate (P = 0.15). CONCLUSIONS: We conclude that AT1-AA bioactivity and sFlt1 concentrations do not correlate, are not mutually dependent, and are thus probably involved in distinct pathogenetic mechanisms. Both factors in combination may not be causative for the early impaired trophoblast invasion and pathological uterine perfusion.

Proteinuria in hypertensive pregnancy diseases is associated with a longer persistence of hypertension postpartum.

As there is growing evidence that hypertensive pregnancy disorders are associated with a risk of cardiovascular diseases later, the resolution of hypertension postpartum (PP) is of high clinical significance. However, there is little knowledge about the factors that influence this normalization. The objectives of our study were (a) to investigate whether or not there are differences in the resolution of hypertension between the distinct types of hypertensive pregnancy disorders and (b) to analyse what clinical parameters may determine the resolution pattern PP. In this retrospective study, 52 patients with preeclampsia (PE), seven with HELLP syndrome (haemolysis, elevated liver enzymes, low platelets), 10 with chronic hypertension (CH) and 21 with pregnancy-induced hypertension (PIH) were recruited. The course of the clinical parameters until day 7 PP was documented. Patients with proteinuria (PE/HELLP) showed the highest blood pressure values PP, while patients with PIH and CH showed no blood pressure changes up to day 7 PP. In patients with proteinuric diseases, there was a significantly higher percentage of cases with persisting hypertension at day 3 PP (71% vs 48% PIH/CH group, P<0.05), and even at day 7 PP this percentage remained significantly higher (31% vs 19% PIH/CH group). Our study shows that patients with proteinuric pregnancy disorders have a delayed PP of hypertension. A high percentage of these women are discharged from hospital with persisting hypertension and proteinuria. These observations demand a more specific and long-term PP care for these women.

Hidden Markov models based on symbolic dynamics for statistical modeling of cardiovascular control in hypertensive pregnancy disorders.

Discrete hidden Markov models (HMMs) were applied to classify pregnancy disorders. The observation sequence was generated by transforming RR and systolic blood pressure time series using symbolic dynamics. Time series were recorded from 15 women with pregnancy-induced hypertension, 34 with preeclampsia and 41 controls beyond 30th gestational week. HMMs with five to ten hidden states were found to be sufficient to characterize different blood pressure variability, whereas significant classification in RR-based HMMs was found using fifteen hidden states. Pregnancy disorders preeclampsia and pregnancy induced hypertension revealed different patho-physiological autonomous regulation supposing different etiology of both disorders.

Dual natriuretic peptide response to volume load in the fetal circulation.

OBJECTIVE: To measure atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in control fetuses and fetuses with Rhesus isoimmunisation before and after intravascular transfusion. The current study was designed to investigate the response of ANP and BNP to cardiac short-term and long-term volume load in the human fetus. METHODS: Fetal blood samples were collected from 18 human fetuses (nine controls, nine anemic fetuses with Rhesus isoimmunisation before and after intravascular transfusion). Fetal ANP and BNP concentrations were measured and compared to maternal plasma levels. RESULTS: Both ANP and BNP were significantly higher in fetal blood compared to the mothers. Fetuses with Rhesus isoimmunisation, characterized by long-term cardiac overload, showed significantly elevated ANP but not BNP concentration compared to the fetal controls (ANP: 80.8+/-16.6 vs. 31.6+/-7.7 pg/ml, P<0.05). However, short-term volume load due to intravascular transfusion leads to a significant increase in the fetal BNP- but not ANP-plasma level (BNP: 112.9+/-14.1 vs. 64.8+/-6.6 pg/ml, P<0.05). CONCLUSION: ANP and BNP respond differently to cardiac short- and long-term volume load in the fetal circulation. Therefore, the data suggest that in the fetus, similar to adults, ANP and BNP constitute a dual natriuretic peptide system responsive to changes in cardiac filling pressure.

PRL as a novel potent cofactor for platelet aggregation.

Pregnancy (including puerperium) is a period of hypercoagulability and seems to be an independent major risk factor for venous thromboembolism (VTE). However, the basis of the increased risk of VTE in pregnancy and around delivery is unknown. We hypothesized that changes in PRL, which is a prominently increased hormone during pregnancy and lactation, might be involved in the activation of platelets. To investigate platelet functional abnormalities in pregnancy, we assessed the ADP-stimulated and nonstimulated P-selectin expression of platelets in 42 consecutive pregnant women, 22 normo- and hyperprolactinemic patients with pituitary tumors, and controls. In addition, the aggregation of platelets by human PRL in vitro was studied. We found a significant correlation between PRL values and ADP stimulation of platelets in pregnant women (r = 0.56; P < 0.0001) and patients with pituitary tumors (r = 0.57; P = 0.006). Hyperprolactinemic pregnant women or hyperprolactinemic patients with pituitary tumors revealed significantly higher ADP stimulation of platelets (P < 0.0001) than healthy controls or normoprolactinemic patients with pituitary tumors. These results were reconciled by increased in vitro stimulation and aggregation of platelets using human PRL. Our novel findings demonstrate that hyperprolactinemia causes increased platelet aggregation via ADP stimulation both in vitro and in vivo. Moreover, our data indicate that PRL may be a physiological cofactor of the delicate coagulation balance during pregnancy and puerperium that might explain the increased risk of VTE in pregnant women around delivery. Further studies of the interaction between PRL and platelets will clarify the clinical relevance of hyperprolactinemia as a potential risk factor for VTE.

Bilateral versus unilateral electroconvulsive therapy: efficacy in melancholia.

The authors compared the therapeutic efficacy of bilateral and unilateral electroconvulsive therapy (ECT) in 51 patients with endogenous depression who were randomly assigned to bilateral (N = 24) or unilateral (N = 27) ECT. Seizures were monitored by oscilloscope. After 6 treatments blind assessment on a modified Hamilton depression scale showed an 81.1% improvement in the bilateral group compared with a 55.5% improvement in the unilateral group. Additional treatments were prescribed ad libitum by a hospital psychiatrist who was unaware of each patient's electrode placement. The unilateral group received more total treatments and were more frequently switched to bilateral ECT. These results were independent of age, severity of illness, or sedative drug administration.

Factors affecting amnesia, seizure duration, and efficacy in ECT.

Twenty-nine patients given unilateral ECT were tested for memory with each treatment. Forgetting of nonverbal material correlated positively with seizure duration and with anesthetic dose. Seizure duration did not correlate with forgetting of verbal material or with changes in Hamilton depression ratings. Seizure duration was inversely related to succinylcholine and methohexital doses. These findings suggest that muscle relaxant and anesthetic doses can be adjusted to lessen the amnestic effects of ECT. There are, however, insufficient data on the relationship between seizure length and ECT efficacy to specify a minimum duration for seizures, individually or cumulatively.

Comparison of schizophrenic patients with formal thought disorder and neurologically impaired patients with aphasia.

This study compares the speech and language of 14 schizophrenic patients having a formal thought disorder with 13 neurologically impaired patients with aphasia. Transcribed interviews with these patients were blindly assessed by five specialists for classification as schizophrenic or aphasic. Three of the five specialists performed better than chance but only one achieved high discriminating ability. Interrater reliability was poor. Five of 14 language abnormalities assessed differentiated the diagnostic groups. These findings suggest that schizophrenic patients share many language abnormalities with aphasic patients but do not exhibit a classic aphasic syndrome.

Thirty-four hour dexamethasone suppression test in depression.

The utility of extending the dexamethasone suppression test past its usual 24 hr period to include a cortisol determination at 34 hr was investigated in 18 depressed patients. Conventional suppressors and non-suppressors differed significantly on their 34 hr cortisol values. However, this difference was small. Furthermore, 34 hr values generally returned close to baseline values, so that the 34 hr DST cannot now be recommended in the assessment of depressed patients without further study.

Ventricular arrhythmias induced by doxepin and amitriptyline: case report.

A case is described of ventricular arrhythmias associated with doxepin and amitriptyline treatment in a patient with preexisting heart disease. A significant correlation was found between the occurrence of premature ventricular depolarizations and serum levels of both antidepressants.

Compulsive buying: descriptive characteristics and psychiatric comorbidity.

BACKGROUND: Compulsive buying is infrequently described in the psychiatric literature despite suggestions that it may be prevalent. The authors investigated the demographics and phenomenology of this syndrome and assessed psychiatric comorbidity via interviews of both compulsive buyers and normal buyers. METHOD: Twenty-four compulsive buyers were compared with 24 age- and sex-matched normal buyers using (1) a semistructured interview for compulsive buying and impulse control disorders, (2) a modified version of the Structured Clinical Interview for DSM-III-R, and (3) scales measuring compulsiveness, depression, and anxiety. RESULTS: The typical compulsive buyer was a 36-year-old female who had developed compulsive buying at age 17 1/2 and whose buying had resulted in adverse psychosocial consequences. Purchases were usually of clothes, shoes, jewelry, or makeup, which frequently went unused. Compared with normal buyers, compulsive buyers had a higher lifetime prevalence of anxiety disorders, substance use disorders, and eating disorders and were more depressed, anxious, and compulsive. Among compulsive buyers, 16 (66.7%) described buying that resembled obsessive compulsive disorder, whereas 23 (95.8%) described buying that resembled an impulse control disorder. CONCLUSION: Compulsive buying is a definable clinical syndrome that can result in significant psychosocial impairment and which displays features of both obsessive compulsive disorder and the impulse control disorders.