Inhibition of chemokines prevents intraperitoneal adhesions in mice

BACKGROUND: The present study evaluates the efficacy of a broad-spectrumchemokine inhibitor, NR58-3.14.3, in the prevention of adhesionformation after i.p. surgery in mice. METHODS: A total of 110eight week old female Balb/c mice underwent laparotomy. Fortyanimals were randomly assigned to receive daily i.p. injectionsof either vehicle (control) or NR58-3.14.3. Time-course of adhesionformation was assessed. A titration of NR58-3.14.3 was conductedfor i.p. and s.c. administrations. The effectiveness of a singleintra-operative dose of NR58-3.14.3 was evaluated. Number, extent,location and type of adhesions were recorded. Immunohistochemistryof adhesions was done with leukocyte common antigen, CD45. RESULTS:Adhesion scores peaked on post-operative days 6–8. Onboth days 6 and 8, there were smaller adhesion size and lowercumulative adhesion scores in NR58-3.14.3-treated group. Moreover,on day 8, there were significantly fewer adhesions in NR58-3.14.3-treatedgroup compared to controls. The least effective dose for i.p.administration of NR58-3.14.3 was 0.45 mg/animal. Subcutaneousand single intra-operative i.p. administrations were also effectivein the prevention of i.p. adhesions. Although NR58-3.14.3 decreasedthe number of CD45⁺ inflammatory cells in the adhesions by 22.5%compared to control group, this was not significant. CONCLUSIONS:Our results show that this broad-spectrum chemokine inhibitorprevents post-operative adhesions in mice and may have a potentialclinical use.     

Single-Center Study of 72 Patients with Severe Combined Immunodeficiency: Clinical and Laboratory Features and Outcomes

Journal of Clinical Immunology - Severe combined immunodeficiency is an inborn error of immunity characterized by impairments in the numbers and functions of T and B lymphocytes due to various...     

Complex Müllerian malformation: report of a case with a hypoplastic non-cavitated uterus and two rudimentary horns

Various classifications have been used for congenital anomalies of the Müllerian system. We report a case of a previously unknown anomaly of the uterus, and propose its possible embryological causes. The patient presented with primary amenorrhoea and infertility, and during laparoscopy three distinct uterine horns were observed. The tubes were connected to the two most lateral horns, each juxtaposed to a normal ovary. The middle horn had a seemingly normal attachment to the right uterosacral ligament, whereas its attachment to the left uterosacral ligament appeared attenuated and less normal. Furthermore, the right horn was immediately attached to the middle horn, whereas the left horn was, like its ipsilateral uterosacral ligament, attached to the middle horn by a more attenuated, stretched fibrous bridge. Only the middle horn, with its uterosacral ligaments, had an attached, although obstructed, cervix. Ultrasonographic examination revealed no endometrium echogeneity in any of these uterine bulbs. No etiologic factors were noted in the patient's history; her mother denied known ingestion of estrogens or other drugs while carrying her daughter. The pathogenesis of this anomaly cannot be clearly defined, but may involve sequential embryological errors of duplication of the Müllerian tracts, failure of fusion of each set of the Müllerian tracts with expected failed canalization of each tract and, finally, agenesis of the medial horn of the left duplicated tracts.     

The significance of beta-catenin, E-cadherin, and P-cadherin expressions in neoplastic progression of colorectal mucosa: an immunohistochemical study

BACKGROUND AND STUDY AIMS: The purpose of the current study was to investigate the role of beta-catenin, E-cadherin and P-cadherin in colorectal carcinogenesis using tissue array method. PATIENTS AND METHODS: Core tissue biopsies were taken from paraffin-embedded tissue blocks of 167 cases including 26 normal mucosae (NM), 99 colorectal polyps (10 hyperplastic polyps (HP), 8 traditional serrated (TSA), 17 tubular (TA), 37 tubulovillous (TVA), and 27 villous adenomas (VA)), 14 adenomas with intramucosal carcinoma (ACA), and 28 colorectal cancers (CCA). Immunohistochemistry was performed using antibodies to beta-catenin, E-cadherin, and P-cadherin. Distribution of positivity was assessed using percentage expression while an arbitrary grading scale was used for staining intensity. RESULTS: beta-catenin expression was cytoplasmic, membranous, and nuclear. Both E-cadherin and P-cadherin expressions were confined to cytoplasmic-membranous compartments. Membranous expression of beta-catenin significantly decreased in CCA (p < 0.01). Nuclear beta-catenin expression significantly increased in close correlation with neoplastic sequence reaching its highest expression in ACA and CCA (p < 0.001). Polyps with intraepithelial neoplasia (IEN) showed significantly higher nuclear beta-catenin expression in parallel with increasing grades of IEN (p < 0.001). E-cadherin and P-cadherin expression increased in polyps, whereas a significant decrease in their expression was observed in CCA (p < 0.001) while E-cadherin expression significantly increased in CCA compared to NM (p < 0.001), no such difference was observed in P-cadherin expression. CONCLUSIONS: Nuclear beta-catenin expression correlating with the grade of IEN in polyps and carcinomas supports its role in colorectal carcinogenesis. E-cadherin and P-cadherin expressions in adenomas suggest that these molecules might have role in adenoma formation though not necessarily be involved in neoplastic progression.     

The usefulness of chromoendoscopy with methylene blue in Barrett’s metaplasia and early esophageal carcinoma

Background Barrett’s esophagus is a condition that is premalignant for adenocarcinoma of the esophagus and the esophagogastric junction. Early detection of Barrett’s metaplasia and dysplasia is very important to decrease the mortality and morbidity from esophageal adenocarcinoma cancer. This study aimed to evaluate the effectiveness of methylene blue–targeted biopsies in the differential diagnosis of intestinal metaplasia, dysplasia, and superficial esophageal carcinoma. Methods A total of 109 patients (43 women and 66 men; average age, 62.32 ± 10.61 years; range, 33–82 years) were enrolled for the study. Four groups were designed before endoscopic examinations. The patients for these groups were selected at the conventional endoscopy, and then chromoendoscopy was performed. The esophagus was stained with methylene blue, after which six biopsies were taken from stained and unstained areas. Results Conventional and chromoendoscopic assessments were compared with histopathologic examination. The sensitivity of chromoendoscopy for Barrett’s epithelium was superior to that of conventional endoscopy (p < 0.05). However, there was no statistical difference between the two methods in the diagnosis of esophagitis or esophageal carcinoma (p > 0.05). Stained biopsies were superior to unstained biopsies in terms of sensitivity for Barrett’s epithelium and esophageal carcinoma (p < 0.001). Conclusion Chromoendoscopy is useful for delineating Barrett’s epithelium and for indicating the correct location for securing biopsies where dysplasia or early esophageal cancer is suspected.     

Evaluation of 28 cases of mucormycosis

Mucormycosis is a rare but invasive fungal disease with high mortality. The present study aimed to retrospectively investigate the demographic characteristics, as well as the clinical, radiological and laboratory features and the results of treatment, in the patients followed in our hospital because of mucormycosis. The present study retrospectively evaluated 28 cases, which were followed in our hospital because of mucormycosis between January 2002 and July 2013. The clinical form was rhinocerebral in 27 cases (rhinoorbital in 12, nasal in 8 and rhinoorbitocerebral in 7) and disseminated in one case. With regard to predisposing factors, diabetes mellitus (n = 20), haematological malignancy (n = 6) and chronic renal insufficiency (n = 5) were the leading concomitant diseases. Seventeen (61%) of 28 cases showed atypical clinical picture. With regard to the therapeutic outcomes; it was found that 14 (50%) cases died and six cases recovered with sequel. Today, when particularly the prevalence of immunosuppressive diseases and conditions are gradually increasing, the incidence of mucormycosis is also increased. Considering that the majority of our cases had atypical clinical involvement and complications, being familiar with the characteristics of this disease could be life‐saving together with early diagnosis and treatment.     

Reversible cerebral vasoconstriction syndromes and primary angiitis of the central nervous system: clinical,imaging, and angiographic comparison

Reversible cerebral vasoconstriction syndromes (RCVS) and primary angiitis of the central nervous system (PACNS) are invariably considered in the differential diagnosis of new cerebral arteriopathies. However, prompt and accurate diagnosis remains challenging. Here we compared the features of 159 RCVS to 47 PACNS patients and developed criteria for prompt bedside diagnosis. Recurrent thunderclap headache (TCH), and single TCH combined with either normal neuroimaging, border zone infarcts, or vasogenic edema, have 100% positive predictive value for diagnosing RCVS or RCVS‐spectrum disorders. In patients without TCH and positive angiography, neuroimaging can discriminate RCVS (no lesion) from PACNS (deep/brainstem infarcts). Ann Neurol 2016;79:882–894     

The Use of a Single-Pill Calcium Channel Blocker/Statin Combination in the Management of Hypertension and Dyslipidemia: A Randomized, Placebo-Controlled, Multicenter Study

Poor control of hypertension or dyslipidemia may at least in part be due to these risk factors being treated in isolation. The Caduet in Untreated Subjects Population (CUSP) trial was an 8-week, randomized, double-blind, placebo-controlled trial evaluating the efficacy/safety of the combination of a calcium channel blocker (amlodipine besylate) and a statin (atorvastatin calcium) in a single-pill form (5/20 mg) plus therapeutic lifestyle changes (TLC) compared with placebo plus TLC in patients with comorbid hypertension and dyslipidemia without evidence of cardiovascular disease. At week 4, additional antihypertensive/lipid-lowering medication was permitted. The primary end point was the proportion of patients in whom the dual goal of blood pressure (<140/90 mm Hg) and low-density lipoprotein cholesterol control (<100 mg/dL) was met at week 4. This dual goal attainment was significantly greater with amlodipine/atorvastatin plus TLC compared with placebo plus TLC at week 4 (47.6% vs 1.7%; P <.001), with further improvements at week 8. Most adverse events were mild to moderate. Therapy with single-pill amlodipine/atorvastatin plus TLC in these patients significantly increased dual blood pressure/low-density lipoprotein cholesterol goal attainment compared with placebo plus TLC.     

Amlodipine/Atorvastatin Single-Pill Therapy for Blood Pressure and Lipid Goals in African Americans: Influence of the Metabolic Syndrome and Type 2 Diabetes Mellitus

African Americans with diabetes ± the metabolic syndrome are at high risk for cardiovascular disease. This subanalysis of the Clinical Utility of Caduet in Simultaneously Achieving Blood Pressure and Lipid End Points (CAPABLE) trial studied attainment of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) and the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) goals by 8 flexibly titrated doses (5/10–10/80 mg) of amlodipine/atorvastatin single pill in 494 African Americans with hypertension and dyslipidemia, according to the presence of diabetes ± the metabolic syndrome. In 169 diabetic patients, the metabolic syndrome was associated with poorer BP goal attainment (38.5% vs 48.5% in diabetic patients without the metabolic syndrome). Among diabetic patients (± the metabolic syndrome) 61% to 62% reached LDL-C goal. More than 60% of patients with diabetes uncontrolled for LDL-C were maintained on suboptimal atorvastatin therapy (mean final dose: 29.9 mg vs maximum of 80 mg). Reluctance to intensify therapy to attain accepted targets in high-risk individuals suggests a degree of clinical inertia not explained by objective evidence of dose-dependent intolerance.