The use of a decremental dose regimen in patients treated with a chronic low-dose step-up protocol for WHO Group II anovulation: a prospective randomized multicentre study

BACKGROUND: In women with chronic anovulation, the choice of the FSH starting dose and the modality of subsequent dose adjustments are critical in controlling the risk of overstimulation. The aim of this prospective randomized study was to assess the efficacy and safety of a decremental FSH dose regimen applied once the leading follicle was 10-13 mm in diameter in women treated for WHO Group II anovulation according to a chronic low-dose (CLD; 75 IU FSH for 14 days with 37.5 IU increment) step-up protocol. METHODS: Two hundred and nine subfertile women were treated with recombinant human FSH (r-hFSH) (Gonal-f) for ovulation induction according to a CLD step-up regimen. When the leading follicle reached a diameter of 10-13 mm, 158 participants were randomized by means of a computer-generated list to receive either the same FSH dose required to achieve the threshold for follicular development (CLD regimen) or half of this FSH dose [sequential (SQ) regimen]. HCG was administered only if not more than three follicles >or=16 mm in diameter were present and/or serum estradiol (E(2)) values were <1200 pg/ml. The primary outcome measure was the number of follicles >or=16 mm in size at the time of hCG administration. RESULTS: Clinical characteristics and ovarian parameters at the time of randomization were similar in the two groups. Both CLD and SQ protocols achieved similar follicular growth as regards the total number of follicles and medium-sized or mature follicles (>/=16 mm: 1.5 +/- 0.9 versus 1.4 +/- 0.7, respectively). Furthermore, serum E(2) levels were equivalent in the two groups at the time of hCG administration (441 +/- 360 versus 425 +/- 480 pg/ml for CLD and SQ protocols, respectively). The rate of mono-follicular development was identical as well as the percentage of patients who ovulated and achieved pregnancy. CONCLUSIONS: The results show that the CLD step-up regimen for FSH administration is efficacious and safe for promoting mono-follicular ovulation in women with WHO Group II anovulation. This study confirms that maintaining the same FSH starting dose for 14 days before increasing the dose in step-up regimen is critical to adequately control the risk of over-response. Strict application of CLD regimen should be recommended in women with WHO Group II anovulation.

Ultrasonographic-guided ilioinguinal/iliohypogastric nerve block in pediatric anesthesia: what is the optimal volume?

Recently, our study group demonstrated the usefulness of ultrasonographic guidance in ilioinguinal/iliohypogastric nerve blocks in children. As a consequence, we designed a follow-up study to evaluate the optimal volume of local anesthetic for this regional anesthetic technique. Using a modified step-up-step-down approach, with 10 children in each study group, a starting dose of 0.2 mL/kg of 0.25% levobupivacaine was administered to perform an ilioinguinal/iliohypogastric nerve block under ultrasonographic guidance. After each group of 10 patients, the results were analyzed, and if all blocks were successful, the volume of local anesthetic was decreased by 50%, and a further 10 patients were enrolled into the study. Failure to achieve a 100% success rate within a group subjected patients to an automatic increase of half the previous volume reduction to be used in the subsequent group. Using 0.2 and 0.1 mL/kg of 0.25% levobupivacaine, the success rate was 100%. With a volume of 0.05 mL/kg of 0.25% levobupivacaine, 4 of 10 children received additional analgesia because of an inadequate block. Therefore, according to the protocol, the amount was increased to 0.075 mL/kg of 0.25% levobupivacaine, where the success rate was again 100%. We conclude that ultrasonographic guidance for ilioinguinal/iliohypogastric nerve blocks in children allowed a reduction of the volume of local anesthetic to 0.075 mL/kg.

Myocardial bridging: depiction rate and morphology at CT coronary angiography--comparison with conventional coronary angiography

PURPOSE: To prospectively assess the depiction rate and morphologic features of myocardial bridging (MB) of coronary arteries with 64-section computed tomographic (CT) coronary angiography in comparison to conventional coronary angiography. MATERIALS AND METHODS: Patients were simultaneously enrolled in a prospective study comparing CT and conventional coronary angiography, for which ethics committee approval and informed consent were obtained. One hundred patients (38 women, 62 men; mean age, 63.8 years +/- 11.6 [standard deviation]) underwent 64-section CT and conventional coronary angiography. Fifty additional patients (19 women, 31 men; mean age, 59.2 years +/- 13.2) who underwent CT only were also included. CT images were analyzed for the direct signs length, depth, and degree of systolic compression, while conventional angiograms were analyzed for the indirect signs step down-step up phenomenon, milking effect, and systolic compression of the tunneled segment. Statistical analysis was performed with Pearson correlation analysis, the Wilcoxon two-sample test, and Fisher exact tests. RESULTS: MB was detected with CT in 26 (26%) of 100 patients and with conventional angiography in 12 patients (12%). Mean tunneled segment length and depth at CT (n = 150) were 24.3 mm +/- 10.0 and 2.6 mm +/- 0.8, respectively. Systolic compression in the 12 patients was 31.3% +/- 11.0 at CT and 28.2% +/- 10.5 at conventional angiography (r = 0.72, P < .001). With CT, a significant correlation was not found between systolic compression and length (r = 0.16, P = .25, n = 150) but was found with depth (r = 0.65, P < .01, n = 150) of the tunneled segment. In 14 patients in whom MB was found at CT but not at conventional angiography, length, depth, and systolic compression were significantly lower than in patients in whom both modalities depicted the anomaly (P < .001, P < .01, and P < .001, respectively). CONCLUSION: The depiction rate of MB is greater with 64-section CT coronary angiography than with conventional coronary angiography. The degree of systolic compression of MB significantly correlates with tunneled segment depth but not length.

Prevalence and Risk Factors for Therapy Escalation in Ulcerative Colitis in the Swiss IBD Cohort Study.

BACKGROUND Physicians traditionally treat ulcerative colitis (UC) using a step-up approach. Given the paucity of data, we aimed to assess the cumulative probability of UC-related need for step-up therapy and to identify escalation-associated risk factors. METHODS Patients with UC enrolled into the Swiss IBD Cohort Study were analyzed. The following steps from the bottom to the top of the therapeutic pyramid were examined: (1) 5-aminosalicylic acid and/or rectal corticosteroids, (2) systemic corticosteroids, (3) immunomodulators (IM) (azathioprine, 6-mercaptopurine, methotrexate), (4) TNF antagonists, (5) calcineurin inhibitors, and (6) colectomy. RESULTS Data on 996 patients with UC with a median disease duration of 9 years were examined. The point estimates of cumulative use of different treatments at years 1, 5, 10, and 20 after UC diagnosis were 91%, 96%, 96%, and 97%, respectively, for 5-ASA and/or rectal corticosteroids, 63%, 69%, 72%, and 79%, respectively, for systemic corticosteroids, 43%, 57%, 59%, and 64%, respectively, for IM, 15%, 28%, and 35% (up to year 10 only), respectively, for TNF antagonists, 5%, 9%, 11%, and 12%, respectively, for calcineurin inhibitors, 1%, 5%, 9%, and 18%, respectively, for colectomy. The presence of extraintestinal manifestations and extended disease location (at least left-sided colitis) were identified as risk factors for step-up in therapy with systemic corticosteroids, IM, TNF antagonists, calcineurin inhibitors, and surgery. Cigarette smoking at diagnosis was protective against surgery. CONCLUSIONS The presence of extraintestinal manifestations, left-sided colitis, and extensive colitis/pancolitis at the time of diagnosis were associated with use of systemic corticosteroids, IM, TNF antagonists, calcineurin inhibitors, and colectomy during the disease course.

Gadolinium diethylenetriaminepentaacetate enhancement kinetics in the menisci of asymptomatic subjects: a first step towards a dedicated dGEMRIC (delayed gadolinium-enhanced MRI of cartilage)-like protocol for biochemical imaging of the menisci

It was our aim to investigate the gadolinium diethylenetriaminepentaacetate (Gd-DTPA(2-) ) enhancement kinetics in the menisci of the knee joint over a prolonged period of time. Six asymptomatic volunteers (four men and two women; mean age, 25 ± 2.4 years) were enrolled. Sagittal, T(1) -weighted, spin-echo MR sequences of the right knee joint were obtained at 3 T. Imaging was performed before (baseline), 1 h after and in half-hour intervals up to 9 h after the intravenous administration of 0.2 mmol/kg of Gd-DTPA(2-) . To measure the rates of contrast enhancement relative to the baseline, regions of interest that covered the anterior and posterior horns of the medial and lateral meniscus were defined on each of two adjacent sections, and enhancement curves were constructed. An enhancement peak between 2.5 and 4.5 h after Gd-DTPA(2-) administration was observed, and analysis of variance also revealed no significant difference (p=0.94), in terms of enhancement, within this time interval. Pair-wise, post hoc testing also revealed no significant differences between 2.5 and 3, 3 and 3.5, 3.5 and 4, and 4 and 4.5 h post Gd-DTPA(2-) application. Our preliminary data therefore suggest that the time window suitable for a dGEMRIC (delayed gadolinium-enhanced MRI of cartilage)-like T(1) mapping of the menisci is relatively short, and lies between 2.5 and 4.5 h after Gd-DTPA(2-) injection.

Classification of acute and delayed contrast media-induced reactions: proposal of a three-step system

Physicians and scientists use a broad spectrum of terms to classify contrast media (CM)-induced adverse reactions. In particular, the designation of hypersensitivity reactions is quite varied. Consequently, comparisons of different papers dealing with this subject are difficult or even impossible. Moreover, general descriptions may lead to problems in understanding reactions in patients with a history of adverse CM-reactions, and in efficiently managing these patients. Therefore, the goal of this paper is to suggest an easy system to clearly classify these reactions. The proposed three-step systems (3SS) is built up as follows: step 1 exactly describes the clinical features, including their severity; step 2 categorizes the time point of the onset (immediate or nonimmediate); and step 3 generally classifies the reaction (hypersensitivity or nonhypersensitivity reaction). The 3SS may facilitate better understanding of the clinical manifestations of adverse CM reactions and may support the prevention of these reactions on the basis of personalized medicine approaches.

Surgical Manual of Implant Dentistry: Step-by-Step Procedures

The purpose of this practical manual is to describe and illustrate each step of the basic surgical procedures involved in the placement of implants in qualified patients. To that end, each procedure is briefly but lucidly described; carefully illustrated in a series of drawings of the techniques and instrumentation used; and reinforced through clinical photographs, including radiographic and postoperative follow-up views. In addition to the basic implant surgical principles, evidence-based indications and procedures for guided bone regeneration in apical fenestration and crestal dehiscence defects, and for simultaneous sinus floor elevation via the lateral window and osteotome techniques are featured.

Two-step postmortem angiography with a modified heart-lung machine: preliminary results

OBJECTIVE: The purpose of this study was to adapt and improve a minimally invasive two-step postmortem angiographic technique for use on human cadavers. Detailed mapping of the entire vascular system is almost impossible with conventional autopsy tools. The technique described should be valuable in the diagnosis of vascular abnormalities. MATERIALS AND METHODS: Postmortem perfusion with an oily liquid is established with a circulation machine. An oily contrast agent is introduced as a bolus injection, and radiographic imaging is performed. In this pilot study, the upper or lower extremities of four human cadavers were perfused. In two cases, the vascular system of a lower extremity was visualized with anterograde perfusion of the arteries. In the other two cases, in which the suspected cause of death was drug intoxication, the veins of an upper extremity were visualized with retrograde perfusion of the venous system. RESULTS: In each case, the vascular system was visualized up to the level of the small supplying and draining vessels. In three of the four cases, vascular abnormalities were found. In one instance, a venous injection mark engendered by the self-administration of drugs was rendered visible by exudation of the contrast agent. In the other two cases, occlusion of the arteries and veins was apparent. CONCLUSION: The method described is readily applicable to human cadavers. After establishment of postmortem perfusion with paraffin oil and injection of the oily contrast agent, the vascular system can be investigated in detail and vascular abnormalities rendered visible.

IVIg dose increase in multifocal motor neuropathy: a prospective six month follow-up

In this prospective, non-randomized 6-month observational study we evaluated the efficacy of intravenous immunoglobulin (IVIg) dose increase in patients with multifocal motor neuropathy (MMN). Diagnosis according to AAEM criteria, repetitive IVIg treatment for at least one year, persistent paresis and conduction block, stable symptoms and findings for at least six months were inclusion criteria. Nine patients (7 men) were identified and approved to standardized increase of IVIg dose. Patients were monitored using clinical scores and electrophysiological studies. Dose was increased from a baseline of 0.5 g/kg per month [mean, range: 0.1-1.1], given at variable intervals [4-12 weeks] to 1.2 g/kg per month given over 3 consecutive days planned for 6 cycles. If the patients' motor function did not improve after two cycles they entered step two: Dose was increased to 2 g/kg per month given over 5 consecutive days. The increased dose was maintained for 6 months. Assessments were performed by the same investigator, not involved in the patient's management, at baseline, after 2 and after 6 months. Following dose increase, motor function significantly improved in 6 patients (p = 0.014), 2 patients entered step two, 1 patient withdrew due to absent efficacy. Higher doses of IVIg caused more side effects, however, transient and rarely severe (p = 0.014). IVIg dose increase may improve motor functions in patients with stable MMN on long-term IVIg therapy independent of baseline dose. Improvement of motor function was associated with shorter disease duration (p = 0.008), but not with degree of muscle atrophy (p = 0.483). The treatment strategy to try to find the lowest effective dose and the longest tolerated interval might lead to underdosing in the long-term in many patients.

Marital split-up and widowhood in old age: Differential impact on psychological and social well-being

Marital split-up and spousal loss are among the most stressful critical life events. Numerous studies have documented their detrimental effects on well-being, yet the large individual differences in psychological adaptation are still not well understood. Whereas in old age bereavement is normative and can be anticipated, divorce is an “off-time” transition for this age group. In contrast to bereavement which has been amply studied, research on later life divorce is still missing despite the increasing relevance of the topic due to the significant increase of divorces in older age. Based on a modified and extended view of Amato’s divorce-stress-adjustment model (2000), the aim of this contribution is to explore the differential impact of marital split-up and widowhood in older age on psychological (life satisfaction) and social well-being (social loneliness), and the adaptation to these critical life events. Our analyses are based on data gathered in a questionnaire study, which is part of the Swiss National Centre of Competence in Research LIVES. In a first step we compared three groups of individuals aged 60 to 75 years: a sample of 251 persons with a marital split-up (127 women; 123 men), a sample of 270 widowed persons (170 women; 100 men), and a group of 221 continuously married people (110 women; 111 men), which served as control group. In a second step, we investigated the role of socio-demographic variables, intrapersonal and interpersonal resources and variables of the context of loss as predictors for the psychological adaptation to a marital break-up and loss in old age. First results by ANCOVA indicate significant differences with regard to life satisfaction among the three groups, with divorced persons with the lowest scores, followed by the bereaved ones, and the married controls with the highest. Regarding social loneliness, divorced individuals report higher social loneliness than the bereaved group and the married controls (no significant difference between widowed and the married). In both loss groups, financial and intrapersonal resources, as well as the emotional valence of the loss are the most important predictors for the psychological and social adaptation. However, happiness in the past relationship is an important resource regarding the indicators for adaptation for the widowers, but not for individuals with a marital dissolution.

SMARTnet: First Experience of Setting Up a Telescope System to Survey the Geostationary Ring

Space debris in geostationary orbits may be detected with optical telescopes when the objects are illuminated by the Sun. The advantage compared to Radar can be found in the illumination: radar illuminates the objects and thus the detection sensitivity depletest proportional to the fourth power of the d istance. The German Space Operation Center, GSOC, together with the Astronomical Institute of the University of Bern, AIUB, are setting up a telescope system called SMARTnet to demonstrate the capability of performing geostationary surveillance. Such a telescope system will consist of two telescopes on one mount: a smaller telescope with an aperture of 20cm will serve for fast survey while the larger one, a telescope with an aperture of 50cm, will be used for follow-up observations. The telescopes will be operated by GSOC from Oberpfaffenhofen by the internal monitoring and control system called SMARTnetMAC. The observation plan will be generated by MARTnetPlanning seven days in advance by applying an optimized planning scheduler, taking into account fault time like cloudy nights, priority of objects etc. From each picture taken, stars will be identified and everything not being a star is treated as a possible object. If the same object can be identified on multiple pictures within a short time span, the trace is called a tracklet. In the next step, several tracklets will be correlated to identify individual objects, ephemeris data for these objects are generated and catalogued . This will allow for services like collision avoidance to ensure safe operations for GSOC’s satellites. The complete data processing chain is handled by BACARDI, the backbone catalogue of relational debris information and is presented as a poster.

Step by step: correcting our mental image of the mušlālu

The mušlālu, which is usually understood to be a step- or ramped gate, has so far rarely been discussed in much detail, even though the texts mentioning it have been known for a long time. This is no doubt because the evidence on which to base both philological and archaeological investigations appears sparse and scattered. Up to now, scholars have tended to focus on specific mušlālu-structures. Consequently, there are as many discussions as there are mušlālu-structures. This article attempts to get a sense of the broader picture by bringing together the philological and archaeological data hitherto available with the aim of discussing the mušlālu as term and structure, clarifying the semantics and reassessing the architectural identifications. We hope to demonstrate that it is actually possible to take the evidence one step further and correct the mušlālu image that prevails.