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In this retrospective study on 1628 consecutive cycles performed during a period of 4 years, development in vitro is compared of embryos obtained after either conventional in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). At 39-42 h after insemination or injection, embryos obtained after ICSI were significantly (P < 0.01) further developed (mean cell number 3.48 +/- 0.03) as compared with those obtained after IVF (3.22 +/- 0.03), whereas after 63-66 h of in-vitro development this difference was no longer present (mean cell number 6.11 +/- 0.15 versus 6.09 +/- 0.13 respectively). Culture of surplus embryos obtained after IVF resulted in a significantly higher (P < 0.001) mean incidence of blastocyst formation per cycle as compared with the ICSI group (31.8 +/- 1.9 versus 23.0 +/- 1.4 respectively). Blastocysts from both groups consisted of comparable numbers of cells. Blastocyst formation was also significantly higher when embryos were cultured in groups (31.2 +/- 1.8) compared to single culture (23.1 +/- 1.5; P < 0.01), in human tubal fluid (HTF) medium (29.2 +/- 1.7) compared with IVF-50(TM) medium (24.2 +/- 1.6; P < 0.01), and when they were cultured under 5% O(2) (30.3 +/- 1.5) compared with 20% O(2) (21.7 +/- 1.7; P < 0.01). In all culture conditions used, the mean incidence of blastocyst formation per cycle showed comparable differences in favour of the IVF group as compared with the ICSI group. [ABSTRACT FROM AUTHOR]

A Dutch family (family A) with inherited antithrombin-III deficiency and an increased incidence of venous thrombosis was investigated. Antithrombin-III levels were measured by means of a coagulation assay in plasma and by single radial immunodiffusion in plasma and serum. Three groups could be distinguished: group I comprised the relations-in-law of family A, group II the members of family A with a plasma antithrombin-III level higher than 90% of normal, when determined by the immunoassay, and group III the members of family A with an antithrombin-III level of less than 60%. To group III belonged all eight adults with an abnormal tendency to thrombosis, and furthermore nine children, all having a parent with abnormally low antithrombin-III levels. Mean plasma and serum antithrombin-III levels were significantly decreased in group III. However, the results of the coagulation assay showed some overlap between groups II and III. In addition, the immunoassay appeared to be much less laborious than the coagulation assay. Therefore, the former assay is recommended in any search for similar families. The results of our family investigation confirm the findings of Egeberg (1965) that inherited antithrombin-III deficiency, giving rise to plasma levels between 50 and 60% of normal, causes thrombophilia and that the pattern of inheritance is autosomal dominant. [ABSTRACT FROM PUBLISHER]

BACKGROUND: Infected necrotizing pancreatitis is a potentially lethal disease that is treated with the use of a step-up approach, with catheter drainage often delayed until the infected necrosis is encapsulated. Whether outcomes could be improved by earlier catheter drainage is unknown. METHODS: We conducted a multicenter, randomized superiority trial involving patients with infected necrotizing pancreatitis, in which we compared immediate drainage within 24 hours after randomization once infected necrosis was diagnosed with drainage that was postponed until the stage of walled-off necrosis was reached. The primary end point was the score on the Comprehensive Complication Index, which incorporates all complications over the course of 6 months of follow-up. RESULTS: A total of 104 patients were randomly assigned to immediate drainage (55 patients) or postponed drainage (49 patients). The mean score on the Comprehensive Complication Index (scores range from 0 to 100, with higher scores indicating more severe complications) was 57 in the immediate-drainage group and 58 in the postponed-drainage group (mean difference, -1; 95% confidence interval [CI], -12 to 10; P=0.90). Mortality was 13% in the immediate-drainage group and 10% in the postponed-drainage group (relative risk, 1.25; 95% CI, 0.42 to 3.68). The mean number of interventions (catheter drainage and necrosectomy) was 4.4 in the immediate-drainage group and 2.6 in the postponed-drainage group (mean difference, 1.8; 95% CI, 0.6 to 3.0). In the postponed-drainage group, 19 patients (39%) were treated conservatively with antibiotics and did not require drainage; 17 of these patients survived. The incidence of adverse events was similar in the two groups. CONCLUSIONS: This trial did not show the superiority of immediate drainage over postponed drainage with regard to complications in patients with infected necrotizing pancreatitis. Patients randomly assigned to the postponed-drainage strategy received fewer invasive interventions. [ABSTRACT FROM AUTHOR]

The article reports on a trial comparing early nasoenteric tube feeding (ENTF) in acute pancreatic patients at 72 hours after emergency department presentation in 2014. Topics discussed include the 30% primary end point in the early group and 27% in the on-demand group, and the absence of significant differences in major infection rates between the two groups. The article states that ENTF showed no superiority over an oral diet in reducing infection or death rate in patients.

Objectives: Distinction between inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) based on clinical symptoms is often difficult. In this study we assessed the performance of the fully-automated calprotectin immunoassay from DiaSorin in IBD diagnosis and follow-up and compared it to the EliA calprotectin 2 immunoassay., Design: and Methods: The calprotectin immunoassay from DiaSorin run on the LIAISONXL was analytically and clinically validated and compared to the EliA calprotectin 2 immunoassay from Thermo Fisher Scientific run on the ImmunoCAP250. Five patient groups were measured (n ​= ​303): IBD: ulcerative colitis (UC) and Crohn's disease (CD); non-IBD: IBS, other gastrointestinal diseases and controls (healthy patients with no gastrointestinal disease)., Results: The calprotectin immunoassay of DiaSorin showed good analytical performance with frozen samples. The presence of blood in the stool can interfere with the measurement of calprotectin. Patients suffering from IBD (UC or CD) showed significant higher concentrations of fecal calprotectin compared to controls (UC:710 ​± ​921 ​mg/kg; CD:967 ​± ​1243 ​mg/kg; controls:11±8 ​mg/kg) using DiaSorin's immunoassay. The remaining non-IBD groups showed no significant difference compared to controls. Follow-up patients (n ​= ​9) showed a significant decrease in fecal calprotectin after treatment. At 50 ​mg/kg cut-off value, the negative predictive value for DiaSorin's immunoassay was 96% and the positive predictive value 83% (sensitivity of 95% and specificity of 86%)., Conclusions: The lack of standardization contributes to the numerical differences between the two methods, but the qualitative conclusions do not differ. DiaSorin's calprotectin immunoassay can be used both to distinguish between IBD and non-IBD patients as well as for follow-up of IBD patients., Competing Interests: None., (© 2020 The Authors.)

Background: Neuroimaging studies have demonstrated gray matter (GM) volume abnormalities in substance users. While the majority of substance users are polysubstance users, very little is known about the relation between GM volume abnormalities and polysubstance use., Methods: In this study we assessed the relation between GM volume, and the use of alcohol, tobacco, cocaine and cannabis as well as the total number of substances used, in a sample of 169 males: 15 non-substance users, 89 moderate drinkers, 27 moderate drinkers who also smoke tobacco, 13 moderate drinkers who also smoke tobacco and use cocaine, 10 heavy drinkers who smoke tobacco and use cocaine and 15 heavy drinkers who smoke tobacco, cannabis and use cocaine., Results: Regression analyses showed that there was a negative relation between the number of substances used and volume of the dorsal medial prefrontal cortex (mPFC) and the ventral mPFC. Without controlling for the use of other substances, the volume of the dorsal mPFC was negatively associated with the use of alcohol, tobacco, and cocaine. After controlling for the use of other substances, a negative relation was found between tobacco and cocaine and volume of the thalami and ventrolateral PFC, respectively., Conclusion: These findings indicate that mPFC alterations may not be substance-specific, but rather related to the number of substances used, whereas, thalamic and ventrolateral PFC pathology is specifically associated with tobacco and cocaine use, respectively. These findings are important, as the differential alterations in GM volume may underlie different cognitive deficits associated with substance use disorders., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The objective of this study was to evaluate the clinical potential of the Forced Oscillation Technique (FOT) in the detection of the early alterations in respiratory mechanics of Rheumatoid Arthritis (RA) patients. A total of 36 individuals were analyzed, 18 healthy and 18 with RA. The clinical usefulness of the parameters was evaluated investigating sensibility (Se), specificity (Sp) and the area under the receiver operating characteristic curve (AUC). In the RA group, all the 3 studied parameters obtained high accuracy for clinical use (AUC>0.9), while in spirometric parameters, no parameter obtained appropriate accuracy for clinical use (AUC < 0.7). In conclusion, the parameters obtained by FOT presented adequate Se and Sp, indicating that this technique can be helpful in the evaluation of the early respiratory mechanical alterations in patients with RA.

Silicosis is a typical occupational respiratory disease characterized by irreversible alterations throughout the alveolar and interstitial structure. The objectives of this study were (1) investigate the potential of the Forced Oscillation Technique (FOT) in the analysis of the patients with silicosis, and (2) evaluate the ability of FOT to identify early alterations in the respiratory mechanics of these patients. Sixty-one volunteers were analyzed: 20 healthy subjects and 41 with silicosis; these, were divided into 4 groups according to spirometric results: normal spirometric exam (n = 11); mild obstruction (n = 20); moderate and severe obstruction (n = 10.). A significant (p〈0.0001) increase in total resistance (R0) and mean resistance (Rm) were observed, as well as a decrease in the dynamic compliance (p〈0.0003) and mean reactance (p〈0.000004). R0 and Rm obtained adequate accuracy for clinical use (>80%). FOT parameters adequately described the pathophysiological changes associated with silicosis and presented adequate accuracy for clinical use, indicating that this technique can be helpful in the evaluation respiratory mechanics in this disease.

Objective: To study the effect of treating recurrent Clostridium difficile-associated diarrhoea (CDAD) with a suspension of donor faeces., Design: Uncontrolled interventional study., Method: Patients that, despite adequate antibiotic therapy, had developed at least 2 recurrences ofCDAD, including at least one recurrence that had been treated with a vancomycin tapering regimen, were included in the study. Relatives or volunteers served as faeces donor. All donors were previously examined for the presence of HIV, hepatitis B- and C-virus, and acute infection with cytomegalovirus or Epstein-Barr virus. The donor faeces were examined for the presence of C. difficile, Yersinia, Campylobacter, Shigella, Salmonella, and parasites. Before the infusion of donor faeces, the patients were treated for 4 days with vancomycin 500 mg q.i.d., followed by colon lavage. The suspension of 150 g of donor faeces dissolved in 300-400 ml of NaCl was infused into the jejunum via a duodenal catheter or into the caecum via colonoscopy., Results: 7 CDAD patients were included and treated, including 2 with the hypervirulent C. difficile-strain PCR ribotype 027, toxinotype III. In 5 patients, the defaecation frequency returned to normal almost immediately after treatment and the cultures and toxin tests for C. difficile were repeatedly negative. In the remaining 2 patients, the treatment was successful after a repeated infusion of faeces from a different donor., Conclusion: Treatment with donor faeces seems promising for patients who develop repeated recurrences despite adequate therapy and could be valuable in the future during (local) epidemics of the PCR ribotype 027 strain. A randomised nationwide study (FECAL trial) has been started in order to determine the efficacy of this treatment.

The seasonal variability of the intracellular free amino acid (FAA) concentration was studied in 5 Macoma balthica populations and 7 Mytilus spp. populations along their European distribution. Because of the well known physiological role of FAA as organic osmolytes for salinity induced cell volume regulation in marine osmoconformers, FAA variations were compared in bivalve populations that were exposed to high vs. low intraannual salinity fluctuations. In general, seasonal FAA variations were more pronounced in M. balthica than in Mytilus spp. In both bivalve taxa from different locations in the Baltic Sea, highest FAA concentrations were found in autumn and winter and low FAA concentrations were measured in summer. Seasonal patterns were less pronounced in both taxa at locations with constant salinity conditions. In contrast to Baltic Sea populations, Atlantic and Mediterranean bivalves showed high FAA concentrations in summer and low values in winter, regardless of seasonal salinity fluctuations. Significant seasonal FAA variations at locations with constant salinity conditions showed that salinity appeared not to be the main factor in determining FAA concentrations. The seasonal patterns of the main FAA pool components, i.e. alanine, glycine and taurine, are discussed in the context of seasonal variations in environmental factors (salinity, temperature) and physiological state (glycogen content, reproductive stage).

A case of broncholithiasis associated with massive silicosis is reported, showing a rare aspect of parenchymal lesions generating broncholiths as well as the presence of recurrent lithoptysis, with subsequent regression of radiological lesions. Aetiological, clinical, physiopathological, and radiological aspects of the disease are discussed, demonstrating the importance of the use of computed tomography in diagnosis. The mineralogical analysis of expectorated fragments is also shown.

Brunner's gland adenoma is a rare benign tumour of the duodenum. Less than 150 cases have been reported in English literature. We report a 73-year-old woman presenting with upper gastrointestinal obstructive symptoms and melena. Duodenoscopy revealed a large pedunculated tumour in the bulbus duodeni. Endoscopic snare polypectomy was successfully performed. Histological examination revealed a Brunner's gland adenoma. The literature on Brunner's gland adenoma is reviewed.

The effects of aqueous extracts and hydro-alcoholic extract (HAE), and of a dichloromethane fraction (MG1) obtained from the HAE of Mikania glomerata leaves on isolated respiratory and vascular smooth muscle have been investigated. Aqueousextracts and HAE induced a significant inhibition on the histamine contractions on the isolated guinea-pig trachea. HAE extract induced a concentration-dependent relaxation on guinea-pig trachea pre-contracted with histamine (IC50 0.34 (0.29-0.39) mg mL(-1)), acetylcholine (IC50 0.72 (0.67-0.77) mg mL(-1)) or K+ (IC50 1.41 (1.18-1.64) mg mL(-1)) and on isolated human bronchi precontracted with K+ (IC50 0.34 (0.26-0.42) mg mL(-1)). The dichloromethane fraction induced a concentration dependent relaxation in guinea-pig trachea precontracted with K+ (IC50 0.017 (0.012-0.022) mg mL(-1)). The dichloromethane fraction had also a small vasodilator effect on the isolated mesenteric vascular bed and on the isolated rat aorta, and a significant reduction of the oedema induced by subplantar injections of Bothropsjararaca venom in mice. When tested on plasmid DNA, MG1 did not damage the DNA. Chromatographic analysis showed the presence of 11.4% w/w coumarin in MG1. The results supported the indication of M. glomerata products for the treatment of respiratory diseases where bronchoconstriction is present.

Photodynamic therapy (PDT) can exert local damage by direct tumor cytotoxicity, by disruption of the microvasculature or by a combination of these effects. Although systemic effects after PDT of small tissue areas (< 1% total body surface area) are unlikely, treatment of larger areas may result in an accumulated effect leading to toxicity. Several investigators have described animal death after high dose PDT to tumors on the hind limb of animals and hypothesized that a toxic shock syndrome caused by vasoactive agents released after PDT is responsible. Because one of the most vulnerable organs to toxic shock injury is the lung, we studied the systemic effects of local PDT to this organ by intravital microscopy using a pulmonary window chamber. The PDT treatment conditions (25 mg/kg Photofrin, 24 h, 150 J/cm2 630 nm, maximum area 6.28 cm2) were chosen that produce systemic toxicity and lethality in rats. Adhesion of leukocytes in the lung was monitored in vivo using anti-CD-13-labeled microspheres. The progression of pulmonary edema was assessed by monitoring the leakage of rhodamine-labeled albumin and by wet-to-dry lung weight ratios. Although an increased leukocyte adherence was observed and a significant number of animals died after the extensive PDT treatment, no biologically significant lung edema could be demonstrated. These data indicate that lung edema and acute respiratory distress syndrome is not the cause of death in these animals and that the toxicity is related to other mechanisms including circulatory shock after extensive muscle damage.

In order to obtain milligram amounts of the enantiomers of a series of compounds to be tested for binding to the melatonin binding site, a system for semipreparative enantiomeric separation was set up using tri-acetylcellulose as the chiral stationary phase. Interactions of this class of compounds with tri-acetylcellulose were examined on an analytical scale with a series of 20 compounds. Apparently, both steric and electrostatic interactions determine retention behavior on tri-acetylcellulose. Semipreparative separations were carried out for a subset of seven compounds. The purity of the first eluting enantiomer usually was around 99%, whereas the purity of the second eluting enantiomer was slightly less. The system described is easy to use and has the major advantage that a series of compounds can be separated with one technique. The purities obtained are sufficient for a first screen of their affinity.

The hormone melatonin (N-acetyl-5-methoxytryptamine) has been implicated in the regulation of several neural and endocrine processes that are cued by the daily change in photoperiod. The conformational properties of melatonin and two conformationally restricted agonists, 8-methoxy-2-acetamidotetralin and cis-1-methyl-8-methoxy-2-acetamidotetralin, were examined as a starting point for SAR studies. The conformational analysis was carried out by means of molecular mechanics calculations (MM2-85 force field) using a step-wise build-up procedure and the molecular modelling program MacroModel (which has a modified version of the MM2 force field) for Monte Carlo and systematic tree searches. NMR spectroscopy was used to evaluate the conformational behaviour in solution. The three search methods were complementary and produced a good description of the conformational characteristics. The two force fields produced different geometries of some low energy conformations and also different relative steric energies. When using the MM2-85 force field, an intra-molecular interaction between the amide-H and the aromatic system lowers the relative energies of several conformations of both melatonin and the 2-amidotetralins. However, NMR experiments indicated that these interactions, which may be quite important in vacuo, are not important in solution.

Derivatives of the potent dopamine D2-selective agonist 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin (N-0437) were designed, aimed at producing drugs with less sensitivity towards metabolic inactivation (in particular glucuronidation at the 5-OH position). Since aminotetralins with a 5-methoxy substituent or lacking the 5-hydroxy group have been reported to retain dopaminergic activity, the non-5-hydroxylated N-0437 (N-0918) and two ethers of N-0437 [5-methoxy-N-0437 (N-0724) and 5-cyclopentoxy-N-0437 (N-0953)] have been prepared and tested. Three indices for activity at central dopamine receptors are considered: (1) the displacement of (3H)-SCH-23390 and (3H)-spiperone from calf caudate membranes, (2) the effects on dopamine release and metabolism in the striatum of freely moving rats after systemic and intrastriatal administration as assessed by brain microdialysis, and (3) the ability to elicit contralateral turning in rats with a unilateral 6-OH-dopamine lesion of the nigrostriatal pathway. In order to differentiate between direct dopaminergic activity and metabolic activation, brain and plasma levels of N-0437 after administration of N-0724 and N-0953 were measured. The results show the necessity of the 5-OH group for direct dopaminergic activity: N-0918, N-0724 and N-0953 are all inactive after intrastriatal administration in the microdialysis model and all three drugs show a weak in vitro affinity for both D1 and D2 receptors. Although N-0918 is also inactive after systemic administration in the microdialysis and turning model, N-0724 and N-0953 do exhibit dopaminergic activity after systemic administration in these models.(ABSTRACT TRUNCATED AT 250 WORDS)

Fasting and meal-stimulated serum gastrin and serum pepsinogen I levels were determined in 8 healthy volunteers before, during, and after administration of 30 mg of omeprazole daily for 14 days. Fasting levels and the integrated increment of serum gastrin were significantly increased after 7 and 14 days of treatment with omeprazole, but not after a single dose. Fasting levels measured 2, 4, 7, 14, and 21 days after stopping treatment with omeprazole and the integrated increment of serum gastrin determined 7 and 14 days after discontinuation of omeprazole were not significantly different from pretreatment levels. Fasting serum pepsinogen I levels increased progressively during omeprazole treatment. This increase was significant after 7 and 14 days of treatment and 2 and 4 days after discontinuing omeprazole. These levels were not significantly different from pretreatment levels 7, 14, and 21 days after omeprazole treatment. Serum pepsinogen I did not significantly change after the test meal. It is concluded that fasting and meal-stimulated serum gastrin levels and fasting serum pepsinogen I levels increase significantly during treatment with 30 mg of omeprazole daily for 14 days, but after stopping treatment there is a rapid return to pretreatment levels.

Omeprazole 60 mg once daily was compared with ranitidine 150 mg twice daily in an endoscopically-controlled, double-blind randomised trial in 51 outpatients with erosive or ulcerative reflux oesophagitis (grade 2 or 3). Endoscopy was repeated after 4 weeks and, in the absence of healing, again after 8 weeks. Symptoms were assessed before entry and after 2, 4, and 8 weeks. Patients who were unhealed after 8 weeks were blindly switched to the other drug and treatment was continued for another 4 to 8 weeks. The healing rate (change to grade 0 or 1 oesophagitis) after 4 weeks was 19 of 25 patients treated with omeprazole and 7 of 26 patients treated with ranitidine (p = 0.002). The corresponding figures after 8 weeks were 22 of 25 and 10 of 26 (p = 0.001). The higher healing rate with omeprazole was reflected in a significantly faster and stronger improvement of reflux symptoms. 13 patients, who were unhealed after 8 weeks on ranitidine, were healed after switching treatment. Healing was achieved in 1 of 3 patients who were switched to ranitidine. There were no adverse events or changes in laboratory variables of clinical importance. Omeprazole is superior to ranitidine in the short-term treatment of reflux oesophagitis.

To assess their value for early recognition of airway abnormalities, forced expiration slope ratios as recently defined by Mead, were measured at 5 lung volumes in 114 healthy nonsmokers and in 76 cigarette smokers. In healthy nonsmokers, slope ratios were independent of sex and body height, but were significantly correlated with age. They tended to be higher at low lung volume, particularly in older subjects. In male smokers with a tobacco consumption of less than 5 pack-years, slope ratios were increased at both ends of the volume range, suggesting nonhomogeneous lung emptying and peripheral airway obstruction. With increasing tobacco consumption, slope ratios tended to return to normal values at low lung volume, perhaps because of airway closure. In female smokers, slope ratios were decreased at high lung volume and increased at low lung volume, suggesting that both central and peripheral airways were abnormal. Mead's analysis appeared to be a useful tool for discussing the data in terms of functional abnormalities. However, because of their large variability, slope ratios were not as successful as transit time indices for recognizing abnormal subjects.

A Dutch family (family A) with inherited antithrombin-III deficiency and an increased incidence of venous thrombosis was investigated. Antithrombin-III levels were measured by means of a coagulation assay in plasma and by single radial immunodiffusion in plasma and serum.THREE GROUPS COULD BE DISTINGUISHED: group I comprised the relations-in-law of family A, group II the members of family A with a plasma antithrombin-III level higher than 90% of normal, when determined by the immunoassay, and group III the members of family A with an antithrombin-III level of less than 60%. To group III belonged all eight adults with an abnormal tendency to thrombosis, and furthermore nine children, all having a parent with abnormally low antithrombin-III levels. Mean plasma and serum antithrombin-III levels were significantly decreased in group III. However, the results of the coagulation assay showed some overlap between groups II and III. In addition, the immunoassay appeared to be much less laborious than the coagulation assay. Therefore, the former assay is recommended in any search for similar families. The results of our family investigation confirm the findings of Egeberg (1965) that inherited antithrombin-III deficiency, giving rise to plasma levels between 50 and 60% of normal, causes thrombophilia and that the pattern of inheritance is autosomal dominant.