What parameters are relevant for the histological diagnosis of gastroesophageal reflux disease without Barrett's mucosa?

BACKGROUND/AIMS: There are still ongoing controversies as to which histological parameters allow the diagnosis of gastroesophageal reflux disease (GERD). The aim of the present analysis was to relate histological changes of the esophageal squamous epithelium to different severities of GERD. METHODS: Data were obtained from patients participating in the ProGERD study, who had either erosive reflux disease (ERD, n = 3,245) or non-erosive reflux disease (NERD, n = 2,970). 1,475 patients fulfilled our requirement of having complete biopsy data from two sites (2 cm above the z-line and at the z-line). Changes in the squamous epithelium were assessed by measuring the thickness of the basal cell layer and elongation of the papillae as a percentage of the whole epithelial thickness and counting interepithelial inflammatory cells. RESULTS: The most useful parameters for histological assessment of GERD (given as means, 2 cm above the z-line and at the z-line, respectively) were elongation of the papillae: NERD 40.7 and 48.9%; ERD 46.1 and 54.9% and basal cell hyperplasia: NERD 12.7 and 17.9%; ERD 15.7 and 23.0%. The occurrence of intraepithelial lymphocytic infiltrates, however, is dependent on the severity of GERD, and they are more common than neutrophilic and eosinophilic granulocytes. CONCLUSION: This study shows that both NERD and ERD can be diagnosed histologically if biopsies are obtained from the distal esophagus or from the z-line. Intraepithelial inflammatory cells are rare and show a high specificity, but very low sensitivity.     

Applying cultural safety beyond Indigenous contexts: Insights from health research with Amish and Low German Mennonites

People who identify as members of religious communities, such as the Amish and Low German Mennonites, face challenges obtaining quality health care and engagement in research due in part to stereotypes that are conveyed through media and popular discourses. There is also a growing concern that even when these groups are engaged in research, the guiding frameworks of the research fail to consider the sociocultural or historical relations of power, further skewing power imbalances inherent in the research relationship. This paper aims at discussing the uses of cultural safety in the context of health research and knowledge translation with groups of people that are associated with a specific religion. Research with the Amish and Low German Mennonites is provided as examples to illustrate the use of cultural safety in this context. From these examples, we discuss how the use of cultural safety, grounded in critical theoretical perspectives, offers new insight into health research with populations that are traditionally labeled as minority, vulnerable, or marginalized, especially when a dominant characteristic is a unique religious perspective.     

Toxic optic neuropathies: an updated review

Toxic optic neuropathy (TON) is caused by the damage to the optic nerve through different toxins, including drugs, metals, organic solvents, methanol and carbon dioxide. A similar clinical picture may also be caused by nutritional deficits, including B vitamins, folic acid and proteins with sulphur‐containing amino acids. This review summarizes the present knowledge on disease‐causing factors, clinical presentation, diagnostics and treatment in TON. It discusses in detail known and hypothesized relations between drugs, including tuberculostatic drugs, antimicrobial agents, antiepileptic drugs, antiarrhythmic drugs, disulfiram, halogenated hydroquinolones, antimetabolites, tamoxifen and phosphodiesterase type 5 inhibitors and optic neuropathy.     

The effect of the intramolecular C–H⋯O interactions on the conformational preferences of bis-arylsulfones – 5-HT6 receptor antagonists and beyond

The development of compounds with enhanced activity and selectivity by a conserved spatial orientation of the pharmacophore elements has a long history in medicinal chemistry. Rigidified compounds are an example of this concept. However, the intramolecular interactions were seldom used as a basis for conformational restraints. Here, we show the weak intramolecular interactions that contribute to the relatively well-conserved geometry of N1-arylsulfonyl indole derivatives. The structure analysis along with quantum mechanics calculations revealed a crucial impact of the sulfonyl group on the compound geometry. The weak intramolecular C–H⋯O interaction stabilizes the mutual "facing" orientation of two aromatic fragments. These findings extend the pharmacological interpretation of the sulfonyl group role from the double hydrogen bond acceptor to the conformational scaffold based on intramolecular forces. This feature has, to date, been omitted in in silico drug discovery. Our results should increase the awareness of researchers to consider the conformational preference when designing new compounds or improving computational methods.

The impact of weak intramolecular C–H⋯O interactions on the conformational stability of bis-arylsulfones is discussed, suggesting different role of sulfonyl group in the ligand – 5HT₆ receptor interaction.     

Prognostic value of angiographic markers of myocardial reperfusion in patients treated with primary coronary angioplasty for anterior wall acute myocardial infarction

BACKGROUND: Modern therapy of acute myocardial infarction (AMI) is aimed at rapid and persisting restoration of blood flow in an infarct-related artery (IRA). However, in some patients myocardial reperfusion is not achieved in spite of effective IRA recanalisation. Myocardial Blush Grade (MBG) is one of the angiographic markers useful for the detection of this phenomenon. AIM: To assess the prognostic value of MBG in patients with anterior AMI treated with primary angioplasty. METHODS: The study group consisted of 104 patients (74 males, 30 females, mean age 62+/-13 years) treated with primary angioplasty due to anterior ST-segment elevation AMI. MBG was assessed after the procedure. The mortality and major cardiovascular event (MACE) rates were analysed one and six months after AMI. RESULTS: Patients with preserved myocardial reperfusion following angioplasty (MBG 2-3, n=64 (61.5%)) had a trend towards lower one-month mortality and significantly reduced six-month mortality compared with 40 (38.5%) patients with an impaired (MBG 0-1) myocardial reperfusion (3% vs 12.5%, NS; and 6.25% vs 20%, p<0.05, respectively). The rate of MACE was significantly lower in patients with rather than without reperfusion both after one and six months of follow-up (9.4% vs 27.5%, p=0.027 and 12.5% vs 42.5%, p<0.001, respectively). Compared with patients with a high MBG score, patients with altered reperfusion more frequently had diabetes (30% vs 12.5%, p=0.04), hypertension (67.5% vs 45%, p=0.043), longer time from the onset of symptoms to balloon inflation (355.9+/-199 min vs 215.5+/-113 min, p<0.001) and lower left ventricular ejection fraction, measured 3 days after AMI (43.3%+/-8 vs 47.4%+/-9, p=0.02). CONCLUSIONS: MBG has a significant prognostic value in patients with anterior AMI treated with primary angioplasty. Diabetes, hypertension and long delay of treatment are associated with the impairment of myocardial reperfusion.     

Subacute stent thrombosis following coronary angioplasty: incidence and risk factors

BACKGROUND: Subacute stent thrombosis was a significant complication in the early years of coronary stenting, often leading to myocardial infarction, need for urgent surgery or even death. The introduction of intracoronary ultrasound enabled the identification and proper treatment of the main causes of stent thrombosis, reducing the rate of this complication to 1%. AIM: To identify risk factors of subacute stent thrombosis. METHODS: Data concerning 845 procedures with a single stent implantation in patients with stable or unstable angina, undergoing this procedure between 1998 and 2000, were analysed. RESULTS: Subacute stent thrombosis occurred in 13 (1.54%) patients. Risk factors for this complication included urgent procedures (so-called bailout stenting), improper pre-treatment with drugs ("ad hoc" procedures), dissection uncovered by stent, and poor final result of procedure (higher degree of residual stenosis). The majority of these patients developed myocardial infarction in spite of the fact that the patency of stented vessel was quickly achieved in all but one patient. CONCLUSIONS: Urgent stenting, improper drug pre-treatment and suboptimal result of the procedure are the risk factors of subacute stent thrombosis.