Compressed collagen sponges as gastroretentive dosage forms: in vitro and in vivo studies.

The objective of the present investigations was to develop oblong tablets which expand after contact with gastrointestinal fluids within a few minutes to a length of 4-6 cm and which should remain in the stomach for a prolonged period of time due to their size. The tablets were prepared from riboflavin-containing collagen sponges using a computer controlled single punch tablet machine. The collagen material was compressed to oblong tablets with dimensions of 3.5 mm x 9 mm x 18 mm. In vitro investigations were carried out to characterise drug release. The model drug riboflavin was released from the collagen tablets over 12h. The gastrointestinal retention time of the new dosage form was indirectly estimated by determining the duration of riboflavin excretion after oral intake of the tablet. A crossover in vivo study with 12 healthy male and female subjects was performed. The renal excretion of riboflavin was measured after oral administration of collagen tablets and small sustained release hydrocolloid tablets as reference preparation. The amount of riboflavin excreted into the urine was enhanced after administration of the expanding collagen tablets in comparison with the hydrocolloid tablets. The differences were statistically significant after 5, 6, 8, 9, 10 and 12 h.     

Predominant pathogenic role of tumor necrosis factor in experimental colitis in mice

Antibodies to tumor necrosis factor (TNF)-α have been recently proposed as effective treatment for patients with Crohn's disease. Here, we analyze the functional role of TNF-α in a mouse model of chronic intestinal inflammation induced by the hapten reagent 2,4,6,-trinitrobenzene sulfonic acid (TNBS) that mimics some characteristics of Crohn's disease in humans. Macrophage-enriched lamina propria (LP) mononuclear cells from mice with TNBS-induced colitis produced 10–30-fold higher levels of TNF-α mRNA and protein than cells from control mice. When mice with chronic colitis were treated by intraperitoneal injection of antibodies to TNF-α, an improvement of both the clinical and histopathologic signs of disease was found. Isolated macrophage-enriched LP cells from anti-TNF-α-treated mice produced strikingly less pro-inflammatory cytokines such as interleukin (IL)-1 and IL-6 in cell culture. The predominant role of TNF-α in the mouse TNBS-induced colitis model was further underlined by the finding that striking colonic inflammation and lethal pancolitis was induced in TNF-α-transgenic mice upon TNBS treatment. Conversely, no significant TNBS-induced colitis could be induced in mice in which the TNF-α gene had been inactivated by homologous recombination. Complementation of TNF-α function in TNF^?/? mice by the expression of a mouse TNF-α transgene was sufficient to reverse this effect. Taken together, the data provide direct evidence for a predominant role of TNF-α in a mouse model of chronic intestinal inflammation and encourage further clinical trials with antibodies to TNF-α for the treatment of patients with Crohn's disease.     

Electrode Placement and Prolactin Response to Electroconvulsive Therapy

Study of serum prolactin during electroconvulsive therapy (ECT) in depressive patients revealed a greater prolactin increase after bilateral than after unilateral ECT. A linear correlation between the two types of prolactin response was found for a group of 10 patients, a finding that suggests a quantitative rather than a qualitative difference between bilateral and unilateral ECT with regard to their prolactin-releasing properties. The magnitude of prolactin response did not differ between right and left unilateral ECT, nor in a systematically studied case of postictal dysphoric excitement that occurred after right, but not after left, unilateral ECT. In this case, maximal prolactin response occurred earlier with right than with left unilateral ECT. Prolactin increase after ECT was not correlated with such factors as severity of depression nor seizure duration.     

FGFR3 and Tp53 mutations in T1G3 transitional bladder carcinomas: independent distribution and lack of association with prognosis.

FGFR3 and Tp53 mutations have been proposed as defining two alternative pathways in the pathogenesis of transitional bladder cancer. FGFR3 mutations are associated with low-grade tumors and a favorable prognosis. Tp53 alterations are associated with advanced tumors and, possibly, with a poor prognosis. We focus here on the subgroup of T1G3 superficial tumors because they are a major clinical challenge. Patients (n = 119) were identified from a prospective study of 1,356 cases. Mutations in FGFR3 (exons 7, 10, and 15) and Tp53 (exons 4-9) were analyzed using PCR and direct sequencing. All cases were followed for recurrence and death. Survival was analyzed using Kaplan-Meier curves and multivariable Cox regression. FGFR3 mutations were detected in 20 (16.8%) tumors; 100 mutations in Tp53 were found in tumors from 78 (65.5%) cases. Multiple alterations in Tp53 were present in 19 tumors (16%). Inactivating mutations were present in 58% of tumors. The combined mutation distribution (FGFR3/Tp53) was: wt/wt (34.5%), mut/wt (7.6%), wt/mut (48.7%), and mut/mut (9.2%), indicating that the presence of either mutation did not depend on the other (P value = 0.767). FGFR3 and Tp53 mutations were not associated with clinicopathologic characteristics of patients and did not predict, alone or in combination, recurrence or survival. Taking the risk of the wt/wt group as reference, the mutation-associated risks of cancer-specific mortality were: mut/wt 1.42 (0.15-13.75), wt/mut 0.67 (0.19-2.31), mut/mut 1.62 (0.27-9.59). These molecular features support the notion that T1G3 tumors are at the crossroads of the two main molecular pathways proposed for bladder cancer development and progression.     

“Heart failure in COVID-19 patients: Critical care experience”: A letter to the editor

Coronavirus disease 2019 (COVID-19) is associated with poor cardiovascular outcomes in patients with heart failure (HF) of all categories of ejection fraction (EF), but mainly in patients with HF with reduced EF. Moreover, cardiac transplant patients exhibit worse cardiovascular prognosis, high mortality, and more admissions to the intensive care unit. In general, COVID-19 seems to de-teriorate the clinical status of HF and favors the development of acute respiratory distress syndrome and multiorgan failure, especially in the presence of cardiovascular comorbidities such as diabetes mellitus, kidney dysfunction, and older age. COVID-19 may induce new-onset HF with complex mechanisms that involve myocardial injury. Indeed, myocardial injury comprises a large category of detrimental effects for the myocardium, such as myocardial infarction type 1 or type 2, Takotsubo cardiomyopathy, microvascular dysfunction and myocarditis, which are not easily distinguished by HF. The pathophysiologic mechanisms mainly involve direct myocardial damage by severe acute respiratory syndrome coronavirus 2, cytokine storm, hypercoagulation, inflammation, and endothelial dysfunction. The proper management of patients with COVID-19 involves careful patient evaluation and ongoing monitoring for complications such as HF.     

Occupation, smoking, and chronic obstructive respiratory disorders: a cross sectional study in an industrial area of Catalonia, Spain

Background  

Few studies have investigated the independent effects of occupational exposures and smoking on chronic bronchitis and airflow obstruction. We assessed the association between lifetime occupational exposures and airflow obstruction in a cross-sectional survey in an urban-industrial area of Catalonia, Spain.     

A fatal case of Ludwig's angina and mediastinitis caused by an unusual microorganism, Gemella morbillorum

We present a case of Ludwig's angina in a 48-y-old immunocompetent male caused by an unusual pathogen, Gemella morbillorum. The infection was complicated with mediastinitis and despite aggressive management of the disease the patient died after 12 d of hospitalization. This is the first reported case of Ludwig's angina caused by G. morbillorum and emphasizes that the disease remains a potentially lethal infection.     

Atrial fibrillation-induced tachycardiomyopathy and heart failure: an underappreciated and elusive condition

Heart Failure Reviews - Many patients with persistent, chronic, or frequently recurring paroxysmal atrial fibrillation (AF) may develop a tachycardiomyopathy (TCM) with left ventricular (LV)...     

Reduced incidence of clinical restenosis with newer generation stents, stent oversizing, and high-pressure deployment: single-operator experience

BACKGROUND: Over the last 4 years, several newer generation stents have become available, promising to change the scenery of coronary angioplasty (PTCA) with its attendant restenosis rate. HYPOTHESIS: The aim of this study was to review prospectively the results of a single operator adopting a uniform approach with approximately 0.5 mm stent oversizing and high-pressure (> or = 12-16 bar) deployment and compare them with conventional PTCA in a series of 244 consecutive patients. METHODS: The study included 203 men and 41 women, aged 59 +/- 11 years, who presented with stable angina and/or positive exercise testing (n = 75), unstable angina (n = 161), or acute myocardial infarction (n = 8). Dilated vessels included the left anterior descending artery (n = 139), the right coronary artery (n = 86), the left circumflex artery (n = 47), the ramus branch (n = 4), or venous grafts (n = 2). Stents were implanted for dissection, suboptimal PTCA result, and electively. Two groups were compared: 83 patients who underwent balloon PTCA alone and 161 patients who also received stent(s). RESULTS: The two groups had similar demographics, age (58 +/- 10 vs. 59 +/- 11 years), initial vessel stenosis (92 +/- 7 vs. 93 +/- 6%), and left ventricular ejection fraction (51 +/- 9 vs. 51 +/- 8%). Procedural success was also similar (97.6 vs. 99.4%), but as expected the residual stenosis was much lower in the stent group (< or = 0 vs. 17%). The following stents were employed: J & J (n = 1), NIR (n = 117), ACS (n = 59), AVE (n = 9), Inflow GoldFlex (n = 9), Crossflex (n = 5), Wictor (n = 1), Jostent (n = 16), R stent (n = 9), Seaquence (n = 2) and Wallstent (n = 1). Single stents were used in 118 patients, two stents in 31 patients, three in 6 patients, and four in 6 patients. There was one in-hospital death at 3 days unrelated to the procedure. There were no events of subacute stent thrombosis; all patients in the stent group received combined therapy with aspirin and ticlopidine, the latter for 1 month. During 18 +/- 14 months, the clinical restenosis rate was significantly lower in the stent group (6.9%) than in the PTCA group (28.4%) (p = 0.001). CONCLUSION: In a series of 244 consecutive patients, newer generation stents and a consistent approach of stent oversizing and high-pressure stent deployment by a single operator resulted in high procedural success (99%), lack of stent thrombosis (0%), and a very low clinical restenosis rate (7%).