Obstetric gel shortens second stage of labor and prevents perineal trauma in nulliparous women: a randomized controlled trial on labor facilitation

OBJECTIVE: To determine whether the obstetric gel shortens the second stage of labor and exerts a protective effect on the perineum. METHOD: A total of 251 nulliparous women with singleton low-risk pregnancies in vertex position at term were recruited. A total of 228 eligible women were randomly assigned to Group A, without obstetric gel use, or to Group B, obstetric gel use, i.e., intermittent application into the birth canal during vaginal examinations, starting at the early first stage of labor (prior to 4 cm dilation) and ending with delivery. RESULTS: A total of 183 cases were analyzed. For vaginal deliveries without interventions, such as C-section, vaginal operative procedure or Kristeller maneuver, obstetric gel use significantly shortened the second stage of labor by 26 min (30%) (P=0.026), and significantly reduced perineal tears (P=0.024). First stage of labor and total labor duration were also shortened, but not significantly. Results did not show a significant change in secondary outcome parameters, such as intervention rates or maternal and newborn outcomes. No side effects were observed with obstetric gel use. CONCLUSION: Systematic vaginal application of obstetric gel showed a significant reduction in the second stage of labor and a significant increase in perineal integrity. Future studies should further investigate the effect on intervention rates and maternal and neonatal outcome parameters.     

Hypercalcemia in Pregnancy Due to CYP24A1 Mutations: Case Report and Review of the Literature

Pathogenic mutations of CYP24A1 lead to an impaired catabolism of vitamin D metabolites and should be considered in the differential diagnosis of hypercalcemia with low parathyroid hormone concentrations. Diagnosis is based on a reduced 24,25-dihydroxyvitamin D to 25-hydroxyvitamin D ratio and confirmed by genetic analyses. Pregnancy is associated with an upregulation of the active vitamin D hormone calcitriol and may thus particularly trigger hypercalcemia in affected patients. We present a case report and a narrative review of pregnant women with CYP24A1 mutations (13 women with 29 pregnancies) outlining the laboratory and clinical characteristics during pregnancy and postpartum and the applied treatment approaches. In general, pregnancy triggered hypercalcemia in the affected women and obstetric complications were frequently reported. Conclusions on drugs to treat hypercalcemia during pregnancy are extremely limited and do not show clear evidence of efficacy. Strictly avoiding vitamin D supplementation seems to be effective in preventing or reducing the degree of hypercalcemia. Our case of a 24-year-old woman who presented with hypercalcemia in the 24th gestational week delivered a healthy baby and hypercalcemia resolved while breastfeeding. Pathogenic mutations of CYP24A1 mutations are rare but should be considered in the context of vitamin D supplementation during pregnancy.     

Analysis of genes encoding laminin β2 and related proteins in patients with Galloway–Mowat syndrome

Galloway-Mowat syndrome (GMS) is a rare autosomal recessive disorder characterized by early onset nephrotic syndrome and microcephaly with various anomalies of the central nervous system. GMS likely represents a heterogeneous group of disorders with hitherto unknown genetic etiology. The clinical phenotype to some extent overlaps that of Pierson syndrome (PS), which comprises congenital nephrotic syndrome and distinct ocular abnormalities but which may also include neurodevelopmental deficits and microcephaly. PS is caused by mutations of LAMB2, the gene encoding laminin beta2. We hypothesized that GMS might be allelic to PS or be caused by defects in proteins that interact with laminin beta2. In a cohort of 18 patients with GMS or a GMS-like phenotype we therefore analyzed the genes encoding laminin beta2 (LAMB2), laminin alpha5 (LAMA5), alpha3-integrin (ITGA3), beta1-integrin (ITGB1) and alpha-actinin-4 (ACTN4), but we failed to find causative mutations in these genes. We inferred that LAMA5, ITGA3, ITGB1, and ACTN4 are not directly involved in the pathogenesis of GMS. We excluded LAMB2 as a candidate gene for GMS. Further studies are required, including linkage analysis in families with GMS to identify genes underlying this disease.     

Mid-Adulthood Risk Factor Profiles for CKD

Early identification of CKD risk factors may allow risk factor modification and prevention of CKD progression. We investigated the hypothesis that risk factors are present ≥30 years before the diagnosis of CKD in a case-control study using data from the Framingham Offspring Study. Patients with incident CKD (eGFR≤60 ml/min per 1.73 m²) at examination cycles 6, 7, and 8 were age- and sex-matched 1:2 to patients without CKD at baseline (examination 5). CKD risk factors were measured at each examination cycle. Logistic regression models, adjusted for age, sex, and time period, were constructed to compare risk factor profiles at each time point between cases and controls. During follow-up, 441 new cases of CKD were identified and matched to 882 controls (mean age 69.2 years, 52.4% women). Those who ultimately developed CKD were more likely to have hypertension (odds ratio [OR], 1.76; 95% confidence interval [CI], 1.23 to 2.51), obesity (OR, 1.71; 95% CI, 1.14 to 2.59), and higher triglyceride levels (OR, 1.43; 95% CI, 1.12 to 1.83) 30 years before CKD diagnosis, and were more likely to have hypertension (OR, 1.38; 95% CI, 1.07 to 1.79), higher triglyceride levels (OR, 1.35; 95% CI, 1.11 to 1.64), lower HDL_c (OR, 0.89; 95% CI, 0.81 to 0.97), and diabetes (OR, 2.90; 95% CI, 1.59 to 5.29) 20 years before CKD diagnosis. These findings demonstrate that risk factors for CKD are identifiable ≥30 years before diagnosis and suggest the importance of early risk factor identification in patients at risk for CKD.     

Histomorphologic examination of skeletal muscle preparations does not differentiate between malignant hyperthermia-susceptible and -normal patients

BACKGROUND: It has been suggested that malignant hyperthermia (MH) can be diagnosed by specific myopathologic alterations. The purpose of this study was to investigate whether there are characteristic myopathologic changes in skeletal muscles of MH-susceptible (MHS) compared with MH-normal (MHN) patients. METHODS: Four hundred forty patients with clinical suspicion of MH were classified as MHN, MH equivocal (MHE), or MHS by the in vitro contracture test with halothane and caffeine. In addition, a small muscle sample excised from each patient was analyzed by histologic, histochemical, immunohistochemical, and computer-aided morphometric methods. RESULTS: MHN was diagnosed in 243 patients, MHE was diagnosed in 65, and MHS was diagnosed in 132. No myopathologic abnormalities were found in 53.5% of the MHN, 53.9% of the MHE, and 56.1% of the MHS patients. Thirty-five percent of all patients showed one, 9.8% showed two, and only 0.9% showed three different pathologic findings within skeletal muscle preparations. The frequency of pathologic findings did not differ between the MHN and the MHS patients; only fiber type I predominance was observed more often in MHN. MHE patients could not be assigned to a diagnostic group by detection of myopathologic alterations. In six clinically unaffected patients, a former unrecognized myopathy, such as central core disease, was diagnosed. This disease is characterized by a specific alteration (cores). CONCLUSIONS: Histologic differences between MHS and MHN statuses could not be demonstrated in this study. Histopathologic examinations can neither improve the diagnosis of MH nor contribute to a better definition of the MH status. However, histopathologic examinations might be useful to detect formerly unrecognized specific myopathies.     

Acute-phase-proteins and parameters of humoral immunity in patients with advanced Hodgkin's disease

Summary Serum concentrations of acute-phase-proteins C-reactive protein (CRP), ₁-antitrypsin (AAT), ₁-acid glycoprotein (AGP) as well as levels of immunoglobulins G, A and M and of complement components C3 and C4 were evaluated in 15 patients with advanced (stages III and IV) Hodgkin's disease. Of these patients 9 suffered from B symptoms including pruritus, night sweats and fever. While all patients had highly increased concentrations of CRP and AAT and 11 patients also had elevated levels of AGP in their sera, these concentrations were significantly (P<0.001) reducible by the administration of chemotherapy. Patients with B symptoms also had significantly higher concentrations of CRP (P<0.02), AAT (P<0.05) and AGP (P<0.05) in their sera than patients without. Plasmapheresis which was performed in 3 patients did not achieve a long-lasting reduction of serum concentrations of any acute-phase-protein tested. Complement components C3 and C4 exhibited a similar behaviour as acute-phase-proteins in that they were elevated in patients with B symptoms and reducible by the administration of chemotherapy (P<0.001 and P<0.02, respectively). We conclude that serum concentrations of CRP, AAT and AGP can serve as useful markers for the assessment of tumour activity in patients with advanced Hodgkin's disease. Whereas the concentrations of immunoglobulins G and A in patients were comparable to normal controls, IgM was significantly (P<0.05) reduced in patients who had received chemotherapy, but not in those who were newly diagnosed and hat not received any treatment. Thus, chemotherapy lowered serum concentrations of IgM without influencing levels of IgG and IgA.Supported in part by the Anton Dreher Memorial Donation for Medical Research     

Severe Cerebral Venous and Sinus Thrombosis: Clinical Course,Imaging Correlates,and Prognosis

Background

Severe cerebral venous-sinus thrombosis (CVT) is a rare disease, and its clinical course, imaging correlates, as well as long-term prognosis have not yet been investigated systematically.

Methods

Multicenter retrospective study. Inclusion criteria were CVT, Glasgow coma scale ≤9, and treatment in the intensive care unit. Primary outcome was death or dependency, assessed by a modified Rankin Score (mRS) >2 at last follow-up.

Results

114 patients were included. At last follow-up (median 2.5 years), 38 patients (33.3 %) showed no or minor residual symptoms (mRS = 0 or 1), 12 (10.5 %) had a mild (mRS = 2), 13 (11.4 %) a moderate (mRS = 3), 12 (10.5 %) a severe disability (mRS = 4 or 5), and 39 (34.2 %) had died. In bivariate analysis, predictors of poor outcome were any signs of mass effect on imaging, clinical deterioration after admission, and age. In contrast, clinical symptoms on admission and parenchymal lesions per se, such as edema, infarction, or hemorrhage were not predictive. Multivariate predictors of poor outcome were an increase in National Institutes of Health Stroke Scale ≥3 after admission [odds ratio (OR) 6.7], bilateral motor signs in the further course (OR 9.2), and midline shift (OR 5.1).

Conclusion

The outcome of severe CVT is almost equally divided between severe impairment or death and survival with no or only mild handicap. Specifically, space-occupying mass effect and associated neurologic deterioration seem to determine a poor outcome. Therefore, early detection and treatment of mass effect should be the focus of critical care.

     

Diagnostic impact of 18F-FDG PET–CT evaluating solid pancreatic lesions versus endosonography, endoscopic retrograde cholangio-pancreatography with intraductal ultrasonography and abdominal ultrasound

Purpose  This prospective single-centre phase II trial assessed the diagnostic impact of ¹⁸F-FDG PET–CT in the evaluation of solid pancreatic lesions (∅ ≥10 mm) compared to endosonography (EUS), endoscopic retrograde cholangio-pancreatography (ERCP) with intraductal ultrasound (IDUS), abdominal ultrasound (US) and histopathological reference. Methods  Forty-six patients (32 men/14 women, ∅ 61.7 years) with suspected pancreatic neoplasms underwent PET–CT with contrast-enhanced biphasic multi-detector CT of the upper abdomen followed by a diagnostic work-up with EUS, ERCP with IDUS and US within 3 weeks. PET–CT data sets were analysed by two expert readers in a consensus reading. Histology from surgery, biopsy/fine-needle aspiration and/or clinical follow-up ≥12 months served as standard of reference. Results  Twenty-seven pancreatic malignancies were histopathologically proven; 19 patients had benign diseases: 36/46 lesions (78%) were detected in the head of the pancreas, 7/46 and 3/46 in the body and tail region, respectively. Sensitivity and specificity of PET–CT were 89% and 74%, respectively; positive predictive value (PPV) and negative predictive value (NPV) were 83% and 82%, respectively. Sensitivity (81–89%), specificity (74–88%), PPV (83–90%) and NPV (77–82%) achieved by EUS, ERCP and US were not significantly different. PET analysis revealed significantly higher maximum mean standardised uptake values (SUV_max 6.5 ± 4.6) in patients with pancreatic malignancy (benign lesions: SUV_max 4.2 ± 1.5; p < 0.05). PET–CT revealed cervical lymphonodal metastasis from occult bronchogenic carcinoma and a tubular colon adenoma with intermediate dysplasia on polypectomy, respectively. Conclusions   ¹⁸F-FDG PET–CT achieves a comparably high diagnostic impact evaluating small solid pancreatic lesions versus conventional reference imaging modalities. Additional clinical diagnoses are derived from concomitant whole-body PET–CT imaging. Verena Schick and Christiane Franzius contributed equally to this work.     

Complement 5a receptor inhibition improves renal allograft survival

Complement activation plays a key role in mediating apoptosis, inflammation, and transplant rejection. In this study, the role of the complement 5a receptor (C5aR) was examined in human renal allografts and in an allogenic mouse model of renal transplant rejection. In human kidney transplants with acute rejection, C5aR expression was increased in renal tissue and in cells infiltrating the tubulointerstitium. Similar findings were observed in mice. When recipient mice were treated once daily with a C5aR antagonist before transplantation, long-term renal allograft survival was markedly improved compared with vehicle-treatment (75 versus 0%), and apoptosis was reduced. Furthermore, treatment with a C5aR antagonist significantly attenuated monocyte/macrophage infiltration, perhaps a result of reduced levels of monocyte chemoattractant protein 1 and the intercellular adhesion molecule 1. In vitro, C5aR antagonism inhibited intercellular adhesion molecule 1 upregulation in primary mouse aortic endothelial cells and reduced adhesion of peripheral blood mononuclear cells. Furthermore, C5aR blockade markedly reduced alloreactive T cell priming. These results demonstrate that C5aR plays an important role in mediating acute kidney allograft rejection, suggesting that pharmaceutical targeting of C5aR may have potential in transplantation medicine.