Search

A 31-year-old female asthmatic patient received an infusion of metamizole and tramadol for chronic pain at a GP surgery. After a few minutes, the patient developed breaing difficulties and died in spite of resuscitation measures. The general practitioner was suspected of medical malpractice. Medico-legal investigations confirmed the assumption that death was caused by anaphylacitic shock. In spite of temporary intubation into the oesophagus no evidence of medical malpractice was found, however.

This study examines the influence of patients' immigration background and residence permit status on physicians' willingness to treat patients in due time. A factorial survey was conducted among 352 general practitioners with a background in internal medicine in a German-speaking region in Switzerland. Participants expressed their self-rating (SR) as well as the expected colleague-rating (CR) to provide immediate treatment to 12 fictive vignette patients. The effects of the vignette variables were analysed using random-effects models. The results show that SR as well as CR was not only influenced by the medical condition or the physicians' time pressure, but also by social factors such as the ethnicity and migration history, the residence permit status, and the economic condition of the patients. Our findings can be useful for the development of adequate, practically relevant teaching and training materials with the ultimate aim to reduce unjustified discrimination or social rationing in health care., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

11beta-hydroxysteroid-dehydrogenase type 2 (11β-HSD2) is a high affinity dehydrogenase which rapidly inactivates physiologically-active glucocorticoids to protect key tissues. 11β-HSD2 expression has been described in peripheral cells of the innate and the adaptive immune system as well as in murine thymus. In absence of knowledge of 11β-HSD2 expression in human thymus, the study aimed to localize 11β-HSD2 in human thymic tissue. Thymic tissue was taken of six healthy, non-immunologically impaired male infants below 12months of age with congenital heart defects who had to undergo correction surgery. 11β-HSD2 protein expression was analyzed by immunohistochemistry and Western blot. Kidney tissue, peripheral blood mononuclear cells (PBMCs) and human umbilical vein endothelial cells (HUVEC) were taken as positive controls. Significant expression of 11β-HSD2 protein was found at single cell level in thymus parenchyma, at perivascular sites of capillaries and small vessels penetrating the thymus lobuli and within Hassall's bodies. The present study demonstrates that 11β-HSD2 is expressed in human thymus with predominant perivascular expression and also within Hassall's bodies. To our knowledge, this is the first report confirming 11β-HSD2 expression at the protein level in human thymic tissue underlining a potential role of this enzyme in regulating glucocorticoid function at the thymic level., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Despite initial responsiveness to both chemotherapy and radiotherapy, small cell lung cancer (SCLC) commonly relapses within months. Although neuroendocrine characteristics may be difficult to demonstrate in individual cases, a relevant expression of somatostatin receptors (SSTR) on the cell surface has been described. We aimed to evaluate the prognostic value of SSTR-expression in advanced SCLC. We further examined pre-requisites for successful peptide receptor radionuclide therapy (PRRT). 21 patients with extensive stage SCLC were enrolled. All patients underwent positron emission tomography/computed tomography (PET/CT) with 68Ga-DOTATATE to select patients for SSTR-directed therapy. PET scans were visually and semi-quantitatively assessed and compared to SSTR2a and SSTR5 expression in biopsy samples. Peak standardized uptake values (SUVpeak) of tumors as well as tumor-to-liver ratios were correlated to progression-free (PFS) and overall survival (OS). In 4/21 patients all SCLC lesions were PET-positive. 6/21 subjects were rated "intermediate" with the majority of lesions positive, the remaining 11/21 patients were PET-negative. PET-positivity correlated well with histologic SSTR2a, but not with SSTR5 expression. Neither PET-positivity nor SUVpeak were predictors of PFS or OS. In 4 patients with intensive SSTR2a-receptor expression, PRRT was performed with one partial response and one stable disease, respectively. SSTR-expression as detected by 68Ga-DOTATATE-PET and/or histology is not predictive of PFS or OS in patients with advanced SCLC. However, in patients exhibiting sufficient tracer uptake, PRRT might be a treatment option given its low toxicity and the absence of effective alternatives.

Background: There is much evidence that T cells are strongly involved in the pathogenesis of localized and systemic forms of scleroderma (SSc). A dysbalance between FoxP3+ regulatory CD4+ T cells (Tregs) and inflammatory T-helper (Th) 17 cells has been suggested., Methods: The study aimed (1) to investigate the phenotypical and functional characteristics of Th17 and Tregs in SSc patients depending on disease manifestation (limited vs. diffuse cutaneous SSc, dcSSc) and activity, and (2) the transcriptional level and methylation status of Th17- and Treg-specific transcription factors., Results: There was a concurrent accumulation of circulating peripheral IL-17-producing CCR6+ Th cells and FoxP3+ Tregs in patients with dcSSc. At the transcriptional level, Th17- and Treg-associated transcription factors were elevated in SSc. A strong association with high circulating Th17 and Tregs was seen with early, active, and severe disease presentation. However, a diminished suppressive function on autologous lymphocytes was found in SSc-derived Tregs. Significant relative hypermethylation was seen at the gene level for RORC1 and RORC2 in SSc, particularly in patients with high inflammatory activity., Conclusions: Besides the high transcriptional activity of T cells, attributed to Treg or Th17 phenotype, in active SSc disease, Tregs may be insufficient to produce high amounts of IL-10 or to control proliferative activity of effector T cells in SSc. Our results suggest a high plasticity of Tregs strongly associated with the Th17 phenotype. Future directions may focus on enhancing Treg functions and stabilization of the Treg phenotype., (© 2016 S. Karger AG, Basel.)

How health care providers are paid affects how medicine is practiced. It is thus important to assess provider payment models not only from the economic perspective but also from the ethical perspective. China recently started to reform the provider payment model in the health care system from fee-for-service to case-based payment. This paper aims to examine this transition from an ethical perspective. We collected empirical studies on the impact of case-based payment in the Chinese health care system and applied a systematic ethical matrix that integrates clinical ethics and public health ethics to analyze the empirical findings. We identified eleven prominent ethical issues related to case-based payment. Some ethical problems of case-based payment in China are comparable to ethical problems of managed care and diagnosis related groups in high-income countries. However, in this paper we discuss in greater detail four specific ethical issues in the Chinese context: professionalism, the patient-physician relationship, access to care and patient autonomy. Based on the analysis, we cautiously infer that case-based payment is currently more ethically acceptable than fee-for-service in the context of China, mainly because it seems to lower financial barriers to access care. Nonetheless, it will be difficult to justify the implementation of case-based payment if no additional measures are taken to monitor and minimize its existing negative ethical implications., (© 2014 John Wiley & Sons Ltd.)

Hymen reconstruction surgery (HR), while ethically controversial, is now available in many countries. Little clinical evidence and hardly any surgical standards support the intervention. Nearly as scarce is social science research exploring women's motivations for the intervention, and health care professionals' justifications for its provision. In order to better understand decision-making processes, we conducted semi-structured interviews in metropolitan Tunis, in 2009, with six women seeking the procedure, four friends who supported such women, four physicians who perform the operation, and one midwife. Health care professionals and patient companions expressed moral ambivalence about HR: although they could comprehend the individual situation of the women, they expressed concern that availability of the procedure might further entrench the patriarchal norms that compel the motivation for seeking HR in the first place. Some women seeking HR shared this concern, but felt it was not outweighed by their personal aims, which were to marry and become mothers, or to overcome past violent sexual experiences. The women felt HR to be uniquely helpful in achieving these aims; all made pragmatic decisions about their bodies in a social environment dominated by patriarchal norms. The link between HR and pervasive gender injustice, including the credible threat of serious social and physical harm to women perceived to have failed to uphold the norm of virginity before marriage, raises questions about health care professionals' responsibility while facing requests for HR. Meaningful regulatory guidance must acknowledge that these genuine harms are at stake; it must do so, however, without resorting to moral double standards. We recommend a reframing of HR as a temporary resource for some women making pragmatic choices in a context of structural gender injustice. We reconfirm the importance of factual sexual and reproductive education, most importantly to counter distorted beliefs that conflate an "intact hymen" with virginity., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Most of the lymphoproliferative diseases involving the salivary glands represent indolent non-Hodgkin B-cell lymphoma (marginal zone lymphoma) related to chronic autoimmune sialadenitis (Sjögren disease). Other types of non-Hodgkin lymphomas involve the salivary glands less frequently. On rare occasions, classical Hodgkin lymphoma (CHL) and nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) present initially as a primary salivary gland mass. We analyzed a series of CHL (n=3) and NLPHL (n=6) presenting initially as parotid gland tumors concerning their pattern (parenchymal vs. intraparotid lymph node) and the presence of salivary inclusions and epithelial proliferations within the lymphoma infiltrate. The pattern of infiltration was determined on hematoxylin and eosin-stained slides assisted by immunostaining for pancytokeratin to highlight lobular salivary gland parenchyma. Patients included 6 male and 3 female individuals with a mean age of 62 years (range, 36 to 88 y). Lymphoma was localized within intraparotid lymph nodes in 8 cases and was limited to salivary parenchyma in 1 case. Parenchymal involvement in nodal-based cases was scored as absent (3) or minimal (5). Salivary inclusions (acini and ductules) within affected lymph nodes were noted in 6 cases (4/5 NLPHLs and 2/3 CHLs). In 3/6 NLPHL cases, salivary inclusions showed variable proliferative changes ranging from prominent lymphoepithelial lesions to cystic and oncocytic (Warthin-like) epithelial changes. Scanty small lymphoepithelial lesions were seen in 1 of the 3 CHL cases. One NLPHL in the intraparotid lymph node was accompanied by prominent lymphoepithelial sialadenitis in the absence of clinical signs of Sjögren disease. This study highlights that a majority of parotid gland Hodgkin lymphomas arise within intraparotid lymph nodes. Frequent entrapment and proliferation of salivary ducts and acini within the lymphoma infiltrate might mimic a variety of benign lymphoepithelial mass-forming lesions (nonsebaceous lymphadenoma, Warthin tumor, and autoimmune sialadenitis). Pancytokeratin stain is helpful for reliable assessment of the background architecture.

Endogenous NO and hydrogen sulfide form HNO, which causes CGRP release via TRPA1 channel activation in sensory nerves. In the present study, stimulation of intact trigeminal afferent neuron preparations with NO donors, Na2S or both was analyzed by measuring CGRP release as an index of mass activation. Combined stimulation was able to activate all parts of the trigeminal system and acted synergistic compared to stimulation with both substances alone. To investigate the contribution of both substances, we varied their ratio and tracked intracellular calcium in isolated neurons. Our results demonstrate that hydrogen sulfide is the rate-limiting factor for HNO formation. CGRP has a key role in migraine pathophysiology and HNO formation at all sites of the trigeminal system should be considered for this novel means of activation., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Previous SNP array analyses have revealed genomic alterations of the Notch pathway as being the most frequent abnormality in adrenocortical tumors (ACTs). The aim of the present study was to evaluate the expression of components of Notch signaling in ACTs and to correlate them with clinical outcome. The mRNA expression of JAG1, NOTCH1, and selected target genes of NOTCH1 (HES1, HES5, and HEY2) was evaluated in 80 fresh frozen samples (28 normal adrenal glands (NAGs), 24 adenomas (ACAs), and 28 carcinomas (ACCs)) by quantitative RT-PCR. Immunohistochemistry was performed in 221 tissues on paraffin slides (16 NAGs, 27 ACAs, and 178 ACCs) for JAG1, activated NOTCH1 (aNOTCH1), and HEY2. An independent ACC validation cohort (n=77) was then also investigated. HEY2 mRNA expression was higher in ACCs than it was in ACAs (P<0.05). The protein expression of all of the factors was high (H-score 2-3) in a larger proportion of ACCs as compared to ACAs and NAGs (JAG1 in 27, 15, and 10%; aNOTCH1 in 13, 8, and 0%; HEY2 in 66, 61, and 33% respectively, all P<0.001). High JAG1 expression was associated with earlier tumor stages and lower numbers of metastases in ACCs (both P=0.08) and favorably impacted overall and progression-free survival (PFS) (131 vs 30 months, hazard ratio (HR) 0.45, and 37 vs 9 months, HR 0.51, both P<0.005). This impact on overall survival (OS) was confirmed in the validation cohort. No such association was observed for aNOTCH1 or HEY2. In conclusion, different components of the Notch1 signaling pathway are overexpressed in ACCs, which suggests a role for the pathway in malignant transformation. However, JAG1 is overexpressed in a subgroup of ACCs with a better clinical outcome., (© 2015 Society for Endocrinology.)

Background: Solitary metastases to the pancreas are rare. Therefore the value of resection in curative intention remains unclear. In the literature there are several promising reports about resection of solitary metastasis to the pancreas mainly of renal origin., Case Presentation: Here we report for the first time on the surgical therapy of a 1.5 cm solitary pancreatic metastasis of an adrenocortical carcinoma. The metastasis occurred almost 6 years after resection of the primary tumor. A partial pancreatoduodenectomy was performed and postoperatively adjuvant mitotane treatment was initiated. During the follow-up of 3 years after surgery no evidence of tumor recurrence occurred., Conclusion: Resection of pancreatic tumors should be considered, even if the mass is suspicious for metastatic disease including recurrence of adrenocortical cancer.

Background: Dutch children's diets, like the diets of many children in Europe and the US are not balanced, do not contain enough vegetables and have been associated with a high prevalence of childhood obesity. Promoting children's vegetable intake is challenging., Objective: We investigated the relative effectiveness of repeated exposure and flavour-flavour learning in increasing vegetable intake and acceptance in preschoolers., Methods: During an intervention period of 7 weeks, 39 toddlers (aged 1.5 to 4 years) consumed red beet and parsnip crisps at day-care centres in Wageningen, the Netherlands. Half of the group received red beet crisps with a dip of tomato ketchup (Conditioned [C]) and parsnip with a neutral white sauce (Unconditioned, [UC]), whereas for the other half the order was reversed (red beet [UC], parsnip [C]). Preference and ad libitum consumption of vegetable crisps were measured once before and three times after the intervention over the course of a 6-month follow-up period to assess longer-term effects., Results: Intake increased significantly after the intervention for both vegetables (on average with 8 g; an increase of approximately 300%), and this effect was persistent even 6 months afterwards. The increase was irrespective of crisps being offered with C or UC dip sauce., Conclusions: These results suggest a robust and persistent effect of repeated exposure but no effect of flavour-flavour learning. Offering pure vegetable tastes repeatedly is sufficient to increase intake., (© 2014 The Authors. Pediatric Obesity © 2014 World Obesity.)

Background: Recurrence of adrenocortical carcinoma (ACC) even after complete (R0) resection occurs frequently., Objective: The aim of this study was to identify markers with prognostic value for patients in this clinical setting., Design, Setting, and Participants: From the German ACC registry, 319 patients with the European Network for the Study of Adrenal Tumors stage I-III were identified. As an independent validation cohort, 250 patients from three European countries were included., Outcome Measurements and Statistical Analysis: Clinical, histological, and immunohistochemical markers were correlated with recurrence-free (RFS) and overall survival (OS)., Results: Although univariable analysis within the German cohort suggested several factors with potential prognostic power, upon multivariable adjustment only a few including age, tumor size, venous tumor thrombus (VTT), and the proliferation marker Ki67 retained significance. Among these, Ki67 provided the single best prognostic value for RFS (hazard ratio [HR] for recurrence, 1.042 per 1% increase; P < .0001) and OS (HR for death, 1.051; P < .0001) which was confirmed in the validation cohort. Accordingly, clinical outcome differed significantly between patients with Ki67 <10%, 10-19%, and ≥20% (for the German cohort: median RFS, 53.2 vs 31.6 vs 9.4 mo; median OS, 180.5 vs 113.5 vs 42.0 mo). Using the combined cohort prognostic scores including tumor size, VTT, and Ki67 were established. Although these scores discriminated slightly better between subgroups, there was no clinically meaningful advantage in comparison with Ki67 alone., Conclusion: This largest study on prognostic markers in localized ACC identified Ki67 as the single most important factor predicting recurrence in patients following R0 resection. Thus, evaluation of Ki67 indices should be introduced as standard grading in all pathology reports of patients with ACC.

Purpose: The aim of this study was to prospectively evaluate the feasibility and potential advantages of freehand single-photon emission computed tomography (fhSPECT) compared with conventional intraoperative localization techniques for sentinel lymph node biopsy (SLNB) in oral cancer., Methods: Between November 2012 and February 2014, 23 consecutive patients with clinical T1/T2 oral squamous cell carcinoma and a cN0 neck were recruited. All patients underwent SLNB followed by elective neck dissection (END). All patients received preoperative lymphoscintigraphy. To detect the SLNs intraoperatively, fhSPECT with a combination of conventional acoustic SLN localization and 3-D visual navigation was used., Results: All but one of the SLNs detected by preoperative imaging were successfully mapped intraoperatively by fhSPECT (detection rate 98%), including those in six patients with a tumour in the floor of the mouth. A histopathology analysis revealed positive SLNs in 22% of patients. No further metastases were found in LNs resected during END. SLNB correctly predicted the final LN stage in all patients (accuracy 100%). Additional radioactive LNs, which were not present on preoperative lymphoscintigraphy, were observed in three patients., Conclusion: FhSPECT is a feasible technology that allows the accurate identification of SLNs in oral cancer. FhSPECT overcomes the shine-through phenomenon, one of the most important limitations of SLNB, thereby confirming the importance of SLNB in patients with cN0 oral cancer.

Background: In oral squamous cell carcinoma (OSCC), cervical lymph node status is the most important prognostic factor. Compared to elective neck dissection, reduced morbidity and better quality of life was demonstrated for sentinel lymph node biopsy, which is controversial because of the reduced detection rate of sentinel lymph nodes in close proximity to the injection site (also known as the shine-through phenomenon)., Methods: We report the case of a 44-year-old woman with a biopsy-proven early OSCC of the anterior floor of the mouth, who received SLNB guided with freehand single-photon emission CT (fhSPECT), a system for the 3D visualization of radioactivity in the body., Results: One level III sentinel lymph node and 1 level I sentinel lymph node, in close proximity to the injection site, were detected and dissected. The level I sentinel lymph node contained a metastasis., Conclusion: Using fhSPECT, the issue outlined was overcome, and the precise histopathological lymph node status (pN1; 1 of 49) was determined., (© 2014 Wiley Periodicals, Inc.)

Background: Adrenocortical tumors comprise frequent adenomas (ACA) and rare carcinomas (ACC). Human cytochrome P450 2W1 (CYP2W1) is highly expressed in some cancers holding the potential to activate certain drugs into tumor cytotoxins., Objective: To investigate the CYP2W1 expression in adrenal samples and its relationship with clinical outcome in ACC., Material and Methods: CYP2W1 expression was investigated by qRT-PCR in 13 normal adrenal glands, 32 ACA, 25 ACC, and 9 different non-adrenal normal tissue samples and by immunohistochemistry in 352 specimens (23 normal adrenal glands, 33 ACA, 239 ACC, 67 non-adrenal normal or neoplastic samples)., Results: CYP2W1 mRNA expression was absent/low in normal non-adrenal tissues, but high in normal and neoplastic adrenal glands (all P<0.01 vs non-adrenal normal tissues). Accordingly, CYP2W1 immunoreactivity was absent/low (H-score 0-1) in 72% of non-adrenal normal tissues, but high (H-score 2-3) in 44% of non-adrenal cancers, in 65% of normal adrenal glands, in 62% of ACAs and in 50% of ACCs (all P<0.001 vs non-adrenal normal tissues), being significantly increased in steroid-secreting compared to non-secreting tumors. In ACC patients treated with mitotane only, high CYP2W1 immunoreactivity adjusted for ENSAT stage was associated with longer overall survival and time to progression (P<0.05 and P<0.01, respectively), and with a better response to therapy both as palliative (response/stable disease in 42% vs 6%, P<0.01) or adjuvant option (absence of disease recurrence in 69% vs 45%, P<0.01)., Conclusion: CYP2W1 is highly expressed in both normal and neoplastic adrenal glands making it a promising tool for targeted therapy in ACC. Furthermore, CYP2W1 may represent a new predictive marker for the response to mitotane treatment.

Background: We describe a patient with a high-titer warm immunoglobulin (Ig)A autoantibody resulting in death due to hemagglutination rather than to hemolysis., Case Report: A 47-year-old male patient presented with an intriguing pronounced vascular erythema of the skin. A livedo reticularis associated with cold agglutinin of high thermal amplitude was suspected. The patient's condition unexpectedly and abruptly deteriorated resulting in death 3 days after admission., Study Design and Methods: Conventional serologic procedures and immunochemical methods were used., Results: Serologic and immunochemical examinations revealed a warm IgA autoantibody of high titer with anti-Band 3 specificity. Although the patient presented with severe anemia, only mild signs of hemolysis were observed, with no evidence of complement activation. The autopsy revealed an enormous accumulation of agglutinated red blood cells in liver and spleen and a B-cell lymphoma and cerebral edema. Thus, the patient's death was largely caused by hypoxia related to hemagglutination rather than to hemolysis and/or anemia per se., Conclusion: Strongly hemagglutinating antibodies may not only cause immune hemolysis but also hypoxia due to intravascular hemagglutination., (© 2014 AABB.)

Background: Kaposi sarcoma (KS) is a malignant disease most commonly diagnosed in the setting of a human immunodeficiency virus (HIV) infection and in patients receiving immunosuppressive treatment. Pulmonary KS has never been reported in association with endogenous Cushing's syndrome (CS)., Case Presentation: A 60-year-old woman presented with symptoms and signs of CS. Adrenal CS was confirmed by standard biochemical evaluation. Imaging revealed a right adrenal lesion (diameter 3.5 cm) and multiple pulmonary nodules, suggesting a cortisol-secreting adrenal carcinoma with pulmonary metastases. The patient underwent right adrenalectomy with a pathohistological diagnosis of an adrenal adenoma. Subsequent thoracoscopic wedge resection of one lung lesion revealed pulmonary KS with positive immunostaining for human herpes virus 8 (HHV-8). HIV-serology was negative. Hydrocortisone replacement was initiated for secondary adrenal insufficiency after surgery. Post-operative follow up imaging showed complete remission of all KS-related pulmonary nodules solely after resolution of hypercortisolism., Conclusion: KS may occur in the setting of endogenous CS and may go into remission after cure of hypercortisolism without further specific treatment.

Here we report on a 51-year-old man with the primary diagnosis of cholangiocarcinoma. Workup with CT and contrast-enhanced ultrasound revealed an additional lesion in the spleen, raising the concern for metastasis. Combined FDG PET/CT revealed a different metabolic pattern, making a metastasis unlikely. Histopathology of the splenic lesion confirmed sclerosing angiomatoid nodular transformation, a rare benign lesion of the spleen.

Swiss hospitals were required to implement a prospective payment system for reimbursement using a diagnosis-related groups (DRGs) classification system by the beginning of 2012. Reforms to a health care system should be assessed for their impact, including their impact on ethically relevant factors. Over a number of years and in a number of countries, questions have been raised in the literature about the ethical implications of the implementation of DRGs. However, despite this, researchers have not attempted to identify the major ethical issues associated with DRGs systematically. To address this gap in the literature, we have developed a matrix for identifying the ethical implications of the implementation of DRGs. It was developed using a literature review, and empirical studies on DRGs, as well as a review and analysis of existing ethics frameworks. The matrix consists of the ethically relevant parameters of health care systems on which DRGs are likely to have an impact; the ethical values underlying these parameters; and examples of specific research questions associated with DRGs to illustrate how the matrix can be applied. While the matrix has been developed in light of the Swiss health care reform, it could be used as a basis for identifying the ethical implications of DRG-based systems worldwide and for highlighting the ethical implications of other kinds of provider payment systems (PPS)., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Suicide is generally viewed as an unexpected cause of death. However, some suicides might be expected to a certain extent, which needs to be further studied. The relationships between expecting suicide, feeling understanding for the suicide, and later grief experiences were explored. In total, 142 bereaved participants completed the Grief Experience Questionnaire and additional measurements on expectance and understanding. Results supported the prediction of a link between expecting suicide and understanding the suicide. Higher expectance and understanding were related to less searching for explanation and preoccupation with the suicide. There was no direct association with other grief experiences. We conclude that more attention should be brought to the relation between expecting the suicide of a loved one and later grief responses in research and in clinical practice., (© 2012 The American Association of Suicidology.)

The "reconstruction of the hymen"consists in a surgical suture of the seam of a hymen that has been fissured due to vaginal intercourse or other causes. This intervention aims at triggering bleeding on the occasion of the next intercourse, a phenomenon often required as proof of virginity within certain traditions. Valid data regarding this ethically and medically controversial and predominantly tabooissue is scarce. In an effort to further explore this practice, we have collected information about hymenorrhaphy from the databases of two anonymous, medical, online counselling services provided by the University Hospital Zürich, and explicitly for teenagers by the Children's Hospital Zürich. We found a sample of 22 questions from women seeking advice, and the results vividly illustrate the psycho-social dilemma these women face, prompting us to suggest that further ethical discussion, collection of empirical data and broad public education on issues related to sexuality are necessary.

Cyclic-diguanylate (c-di-GMP) is a widespread bacterial signal molecule that plays a major role in the modulation of cellular surface components, such as exopolysaccharides and fimbriae, and in the establishment of a sessile life style. Here, we report that intracellular c-di-GMP levels influence cupA-encoded fimbriae expression in Pseudomonas aeruginosa. In an autoaggregative P. aeruginosa small colony variant (SCV) CupA fimbriae and the intracellular c-di-GMP concentration were found to be enhanced as compared with the clonal wild-type. The SCV morphology and the expression of CupA fimbriae were dependent on a functional PA1120 and morA gene both encoding a GGDEF domain. Overexpression of the GGDEF domain protein PA1120 complemented the PA1120 and the morA mutant with respect to CupA fimbriae expression. In agreement with these findings, overexpression of the EAL domain containing phenotypic variance regulator (PvrR) in the SCV resulted in a decreased intracellular level of c-di-GMP, a reduced cupA fimbriae expression and a switch to wild-type colony morphology.

The efficacy and safety of the analgesic drug ketorolac tromethamine in the treatment of moderate to very severe postoperative pain was assessed in five dose-ranging studies with single-dose, double-blind, randomized, parallel-group designs. The drug was administered orally (2.5-200 mg, 352 patients in three trials) and intramuscularly (5-90 mg, 395 patients in two trials), and compared with placebo and reference drugs. Patients subjectively evaluated pain intensity and relief using verbal categoric and visual analog scales; efficacy values included pain intensity difference (PID), summed PID, and total pain relief. Oral ketorolac 10, 12.5, 100, and 200 mg were each statistically significantly superior to placebo in all efficacy measurements, and 10 mg was equivalent to intramuscular morphine 10 mg. Intramuscular ketorolac 90 mg was superior to and 10 and 30 mg were similar to intramuscular morphine 12 mg, and all of these ketorolac doses were superior to intramuscular morphine 6 mg. Intramuscular ketorolac 10 and 30 mg were superior to intramuscular meperidine 50 and 100 mg. Ketorolac was well tolerated, with rates of adverse events generally lower than those of the opiate comparators. Ketorolac doses of 2.5 and 5 mg were less effective than higher doses; 10 mg or more resulted in faster onset of action and greater peak efficacy; 90 mg or more gave more prolonged analgesic effects.

This study compared the efficacy and safety of ketorolac tromethamine and morphine sulfate in alleviating moderate or severe pain immediately after major surgery. One hundred twenty-two patients were randomly assigned to receive single intravenous injections of ketorolac 10 mg, ketorolac 30 mg, morphine 2 mg, or morphine 4 mg; patients could receive a second dose 15 minutes thereafter, upon request, and most received both available doses. Analgesic efficacy was measured by interviewing patients and assessing pain intensity and pain relief for 6 hours after the first medication administration. The two drugs showed a similar onset of action, peaking 1 hour after administration. When placed in order of descending efficacy, the mean scores for most efficacy measures fell into the following sequence: ketorolac 30 mg, ketorolac 10 mg, morphine 4 mg, and morphine 2 mg. There were no statistically significant differences among the two ketorolac doses and the high dose of morphine, but all three of these treatments were significantly superior to the low morphine dose. One patient who took morphine 4 mg withdrew because of drowsiness; other common adverse events reported included nausea, vomiting, somnolence, and dyspepsia. There were no statistically significant differences in the frequency of adverse events among the treatment groups. Intravenous ketorolac is effective for the treatment of postoperative pain.