Optimization of the High-Shear Wet Granulation Wetting Process Using Fuzzy Logic Modeling

A fuzzy model has been developed for the optimization of high-shear wet granulation wetting on a plant scale depending on the characteristics of pharmaceutical active substance particles. The model optimized on the basis of experimental data involves a set of rules obtained from expert knowledge and full-scale process data. The skewness coefficient of particle size distribution and the tapped density of the granulated mixture were chosen as the model input variables. The output of the fuzzy ruled system is the optimal quantity of wetting liquid. In comparison to manufacturing practice, a very strong sensitivity of the optimal quantity of the added wetting liquid to the size and shape of the active substance particles has been identified by fuzzy modeling.     

Operative treatment of infective endocarditis in children

A retrospective review of 11 children, aged 2 months to 15 years, demonstrates the feasibility of surgical treatment for infective endocarditis in childhood. Except for one case of perinatal infection, in all instances the infective endocarditis was a complication of a congenital heart defect. As medical treatment was not successful, surgery was indicated. Debridement of infected tissue and repair of the congenital heart defect was performed. There were no septic complications postoperatively although 8 patients were operated upon during the active stage of infection. One 2-month-old child did not survive excision of an infected tricuspid valve. The follow-up period of 8 years to 5 months (median 39 months) showed a good haemodynamic result (NYHA class I) in the remaining 10 patients. This included 4 patients with prosthetic valves.     

Post-pyloric enteral nutrition in septic patients: effects on hepato-splanchnic hemodynamics and energy status

Objective To evaluate the effects of post-pyloric enteral nutrition (EN) on hepato-splanchnic and systemic hemodynamics, metabolism and gastric mucosal energy balance in septic patients.Design Prospective clinical study.Setting Medical intensive care unit (ICU) in a university hospital.Patients Ten hemodynamically stable, mechanically ventilated patients with severe sepsis. Eight patients required norepinephrine.Intervention Low dose post-pyloric EN (Survimed, 40 ml bolus, 40 ml h^–1 continuously).Measurements and results Three data sets: F1 = baseline fasting, EN₁₂₀ = after 120 min of EN, F2=120 min after EN cessation. In addition to global hemodynamics and gastric mucosal PCO₂, we measured hepato-splanchnic blood flow (HSBF) using continuous primed indocyanine green dye infusion with hepatic venous sampling. The mean arterial pressure remained unchanged. During EN systemic vascular resistance decreased (p<0.05), while cardiac index increased (p<0.001). Simultaneously, HSBF increased during EN and decreased again at F2 (1.54 [0.88; 1.66] l min^–1 m^–2 at F1; 1.72 [1.18; 1.83] l min^–1 m^–2 at EN and 1.38 [0.91; 1.63] l min^–1 m–² at F2, p<0.001). Hepatic venous acid base status, lactate/pyruvate ratio and splanchnic lactate balance remained unchanged. There was also no change in splanchnic oxygen extraction ratio or in gastric mucosal to arterial PCO₂ difference.Conclusion The initiation of low dose post-pyloric EN in medical ICU patients with severe sepsis led to the parallel increase of systemic and hepato-splanchnic blood flow. Hepato-splanchnic energy metabolism, oxygen kinetics and gastric mucosal energy balance did not deteriorate during EN, suggesting that EN during sepsis may not be harmful even in patients requiring norepinephrine.Electronic Supplementary Material Supplementary Material is available in the online version of this article at Presented in part at 15th Annual ESICM congress, Geneva, October 2001     

Bioactive substances with anti-neoplastic efficacy from marine invertebrates: Porifera and Coelenterata

An ever increasing demand for new lead compounds in the pharmaceutical industry has led scientists to search for natural bioactive products. Based on this extensive research, marine invertebrates now represent a rich source of novel substances with significant anti-neoplastic activities. As the current approach of synthesizing new and chemically modifying old drugs seems to have slowed down, and the identification of new anticancer drugs is not too promising, a new approach is clearly needed. The objective of this review is to present up-to-date data on these newer compounds. Based on the data summarized in this short review, it is clear that marine invertebrates represent an extremely important source of compounds with potential anti-cancer effects. Considering that we tested only a tiny number of Porifera and Coelenterata, the best is yet to come.     

Autoimmune diseases as comorbidities for liver,gallbladder, and biliary duct cancers in Sweden

Background

Autoimmune diseases are associated with many cancers but there is a lack of population-based studies with different autoimmune diseases that have a long follow-up. This is also true of hepatobiliary cancers, which include hepatocellular cancer (HCC) and rarer entities of gallbladder cancer (GBC), intra- and extrahepatic cholangiocarcinoma (iCCA and eCCA), and ampullary cancer.

Methods

Diagnostic data on 43 autoimmune diseases were collected from the Swedish Inpatient Register from 1987 to 2018, and cancer data were derived from the national cancer registry from 1997 onward. Relative risks were expressed as standardized incidence ratios (SIRs).

Results

In a population of 13.6 million, 1.1 million autoimmune diseases were diagnosed and subsequent hepatobiliary cancer was diagnosed in 3191 patients (17.2% of cancers). SIRs for HCC were 2.73 (men) and 2.86 (women), 3.74/1.96 for iCCA, 2.65/1.37 for GBC, 2.38/1.64 for eCCA, and 1.80/1.85 for ampullary cancer. Significant associations between autoimmune disease and HCC were observed for 13 autoimmune diseases, with the highest risks being for autoimmune hepatitis (48.92/73.53, men/women) and primary biliary cirrhosis (38.03/54.48). GBC was increased after six autoimmune diseases, with high SIRs for ulcerative colitis (12.22/3.24) and men with Crohn disease (9.16). These autoimmune diseases were also associated with a high risk of iCCA, which had seven other associations, and eCCA, which had five other associations. Ampullary cancer occurrence was increased after four autoimmune diseases.

Conclusion

An autoimmune disease is a common precursor condition for hepatobiliary cancers. This calls for careful control of autoimmune disease symptoms in each patient and encouragement to practice a healthy lifestyle.     

Paravaginal defect: A new classification of fascial and muscle tears in the paravaginal region

The lateral support of the vaginal wall depends on the integrity of the paravaginal section of the visceral pelvic fascia, levator ani, and their connection. Various defects of the muscle and fascia can result in identical clinical findings—ie, the descent of the lateral vaginal sulcus. In this study, we created a realistic scheme for classifying paravaginal defects, based on the complex relationship of the pelvic fascia with the levator ani. Surgical observations, cadaver examinations, and a complex magnetic resonance imaging (MRI)‐based 3‐dimensional (3D) model were used to analyze the spatial relationships of normal and defective anatomy of the female pelvic floor. Descent of the lateral vaginal sulcus can result from a defect in the paravaginal visceral pelvic fascia, levator ani, or both. The fascial defect can be partial or complete, and the muscle defect can vary in location. A detailed illustrated classification is presented. We present a new model of the pathology that underlies a common clinical finding. Clin. Anat. 29:524–529, 2016. © 2016 Wiley Periodicals, Inc.     

Facial pillars in dogs: an anatomical study

This study describes the facial pillar system in dolichocephalic and brachycephalic breeds of dogs, and highlights its differences. Knowledge of facial pillar system anatomy is imperative to carry out successful fracture repair. The aim of our study was to describe the pillar system of the facial skeleton in dogs, and compare different shapes of dog skulls using native skulls, radiographs and computed tomography (CT). The heads of brachycephalic and dolichocephalic dogs were investigated following a maceration process using trans-illumination, radiography and CT. Ground sections were created from bones of the facial skeleton for investigation of osteon directions. This study has revealed that the facial skeleton of the dog has numerous sinuses supported by vertically and horizontally oriented bone pillars. These pillars can be divided into five principal regions in dolichocephalic skulls and six principal regions in brachycephalic skulls. Radiographic imaging of both the brachiocephalic and dolichocephalic skulls was not capable of discerning bone pillars. Computed tomography transverse and horizontal section images discerned all pillars observed in the illuminated skulls.     

Fetal anemia,thrombocytopenia, dilated umbilical vein,and cardiomegaly due to a voluminous placental chorioangioma. A case report

We report a case of voluminous placental chorioangioma diagnosed by ultrasound and color Doppler imaging during the 20th week of pregnancy. The size of the tumor was enlarging progressively (up to 10 cm in the 32nd week), and during this time the signs of fetal intrauterine volume overload and blood cell consumption, such as cardiomegaly, umbilical vein dilation, hydramnios, anemia, and thrombocytopenia, were observed. In the 32nd week of pregnancy, the signs of uteroplacental insufficiency and fetal hypoxia appeared; therefore, the pregnancy was terminated by cesarean section, and a female infant weighing 1,870 g was delivered. She was discharged, fully recovered, after 48 days. Histopathological examination of the placental tumor showed a benign, vascular-type chorioangioma.     

High-resolution melting analysis for detection of MYH9 mutations

May-Hegglin anomaly (MHA), Sebastian (SBS), Fechtner (FTNS) and Epstein (EPS) syndromes are rare autosomal dominant disorders with giant platelets and thrombocytopenia. Other manifestations of these disorders are combinations of the presence of granulocyte inclusions and deafness, cataracts and renal failure. Currently, MHA, SBS, FTNS and EPS are considered to be distinct clinical manifestation of a single illness caused by mutations of the MYH9 gene encoding the heavy chain of non-muscle myosin IIA (NMMHC-IIA). As the MYH9 gene has a high number of exons, it takes much time and material to use this method for the detection of MYH9 mutations. Recently, a new method has been introduced for scanning DNA mutations without the need for direct sequencing: high-resolution melting analysis (HRMA). Mutation detection with HRMA relies on the intercalation of the specific dye (LC Green plus) in double-strand DNA and fluorescence monitoring of PCR product melting profiles. In our study, we optimized the conditions and used HRMA for rapid screening of mutations in all MYH9 exons in seven affected individuals from four unrelated families with suspected MYH9 disorders. Samples identified by HRMA as positive for the mutation were analysed by direct sequencing. HRMA saved us over 85% of redundant sequencing.     

Acute mesenteric ischemia

BACKGROUND/AIMS: Acute mesenteric ischemia (AMI) is a serious disease in old age with low incidence but with a very high mortality rate (60-70%). The etiology is either primary (embolism or thrombosis of mesenteric arteries or veins, non-occlusive mesenteric ischemia) or secondary (mechanical obstruction such as intestinal volvulus, intussusception, tumor-caused compression). Independent of the origin of the illness, the clinical-pathological picture is the same: intestinal ischemia with subsequent necrosis. The aim of this study was to ascertain which underlying conditions lead to increased probability of development of acute mesenteric ischemia. METHODS: Two hundred and fifteen patients with a primary form of AMI were treated in the years 1991-2007, in the 1st Clinic of Surgery in Brno, Czech Republic and in the Department of General Surgery, Derer's University Hospital in Bratislava, Slovak Republic; the results of the treatment have been statistically evaluated. CONCLUSION: The probability of arterial mesenteric ischemia development rises significantly (p < 0.05) in patients with a history of atrial fibrillation and/or myocardial infarction. This probability is also significantly higher in smokers with symptoms of hypertension and clinical signs of abdominal angina (p < 0.05).