Cyclooxygenase-2 in normal,hyperplastic and neoplastic follicular cells of the human thyroid gland

This study was undertaken to investigate cyclooxygenase-2 (COX-2) expression in follicular cells of the human thyroid. COX-2 expression was studied immunohistochemically in a total of 174 samples. COX-2 immunoreactivity was confined to the cell cytoplasm with the nuclei remaining unlabelled. COX-2 expression was observed in five cases (17.2%) of normal follicular cells and in one case (16.6%) of solid cell nests. Follicular carcinoma expressed COX-2 more frequently than follicular adenoma (93.4% vs 21.1%) (p0.001). A higher percentage of cases of papillary microcarcinomas up-regulated COX-2 in comparison with all papillary carcinomas (p0.05). However, we could not establish any relationships among COX-2, patients ages or lymph node metastases in papillary carcinomas. COX-2 expression was found in 12 (92.3%) poorly differentiated carcinomas and in 13 (92.8%) undifferentiated carcinomas. We found that COX-2 is not always useful as a marker of malignancy. Our results suggest that COX-2 plays a role in progression of all thyroid carcinomas, but in papillary carcinomas, seems more important only in the early stages. COX-2 expression in the undifferentiated carcinoma deserves special consideration due to its prognosis and to the fact that selective COX-2 inhibitors were found to enhance tumour response to radiation in some studies.     

Comparison of the allergenicity and Ole e 1 content of 6 varieties of Olea europaea pollen collected during 5 consecutive years.

BACKGROUND: Numerous varieties of Olea europaea have been described in Mediterranean countries. OBJECTIVE: To investigate the immunochemical characteristics of 6 varieties of Olea europaea collected during 5 consecutive years. METHODS: The varieties Carrasquefio, Manzanillo, Acebuche (wild olive), Hojiblanco, Picual, and Nevado were analyzed. Pollen samples from each variety were collected for 5 consecutive years from the same cultivars by trained personnel. The antigenic and allergenic profiles of these extracts were evaluated by means of sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot using the serum of 29 O. europaea-allergic individuals. Ole e 1 was measured using enzyme-linked immunosorbent assay and purified Ole e 1 and rabbit polyclonal antibodies. Allergenic potency was determined using enzyme-linked immunosorbent assay inhibition and is expressed in histamine equivalent prick units per gram of raw material. RESULTS: Hojiblanco and Acebuche had the lowest mean +/- SD Ole e 1 content in the 5 years (0.045 +/- 0.029 and 0.059 +/-0.031 microg/microg of freeze-dried material, respectively). The variety with the highest mean +/- SD Ole e 1 content was Picual (0.19 +/-0.075 microg/microg). Hojiblanco had the lowest total biological potency throughout the study. A positive correlation was obtained between rainfall in the winter months and total allergenicity of the 6 varieties. CONCLUSIONS: The different varieties of O. europaea pollen demonstrated great differences in allergenic potency and Ole e 1 content. These differences were maintained throughout the study, suggesting that they are due to genetic differences intrinsic to the varieties, although certain climatic effects may also play a role.     

Aberrant cellular retinol binding protein 1 (CRBP1) gene expression and promoter methylation in prostate cancer

AIMS: Retinoids are involved in cell growth, differentiation, and carcinogenesis. Their effects depend on cytosolic transport and binding to nuclear receptors. CRBP1 encodes a protein involved in this process. Because altered CRBP1 expression and promoter hypermethylation occur in several tumours, these changes were investigated in prostate tumorigenesis. METHODS: The CRBP1 promoter was assessed by methylation specific polymerase chain reaction on tissue samples from 36 radical prostatectomy specimens (paired normal tissue, adenocarcinoma, and high grade prostatic intraepithelial neoplasia (HGPIN)), 32 benign prostatic hyperplasias (BPHs), and 13 normal prostate tissue samples from cystoprostatectomies. Methylation of DNA extracted from microdissected tissue was examined blindly. CRBP1 expression was assessed by immunohistochemistry on formalin fixed, paraffin wax embedded tissue. RESULTS: Loss of CRBP1 expression was seen in 15 of 36 adenocarcinomas and 18 of 36 HGPINs. Fifteen adenocarcinomas and nine HGPINs showed overexpression, whereas the remainder showed normal expression. BPH displayed normal expression. No significant associations were found between CRBP1 expression and Gleason score or stage. CRBP1 promoter hypermethylation was found in 17 of 36 adenocarcinomas, three of 35 HGPINs, one of 36 normal prostate tissues from the same patients, none of 32 BPHs, and none of 13 normal prostate tissues from cystoprostatectomies. Loss of expression and hypermethylation of CRBP1 were not significantly associated. CONCLUSIONS: Altered CRBP1 expression and hypermethylation are common in prostate carcinoma, although CRBP1 hypermethylation is not an early event in tumorigenesis. Moreover, both adenocarcinoma and HGPIN show frequent CRBP1 overexpression. The molecular mechanisms underlying altered CRBP1 expression in prostate cancer deserve further study.     

Postoperative assessment of nosocomial transmission of COVID-19 after robotic surgical procedures during the pandemic

ObjectivesTo assess potential nosocomial coronavirus disease-2019 (COVID-19) transmission in patients who underwent robot-assisted laparoscopic procedures during the pandemic.Material and methodsProspective study in patients undergoing robot-assisted laparoscopy in urology or gynaecology within 2 academic hospitals. Patients underwent local preoperative COVID-19 screening using a symptoms questionnaire. Patients with suspicious screening underwent coronavirus real time-polymerase chain reaction (RT-PCR) and were excluded from robotic surgery if positive. Patients with symptoms postsurgery were systematically tested for coronavirus by RT-PCR. One-month postsurgery, all patients had a telephone consultation to evaluate COVID-19 symptoms.ResultsSixty-eight patients underwent robotic surgery during the study period (median age: 63-years [IQR: 53–70], 1.8 male: female ratio). Oncology was the main indication for robotic surgery (n = 62, 91.2%) and 26 patients (38.2%) received a chest CT-scan prior to surgery. Eleven patients (16.2%) were symptomatic after surgery of whom only 1 tested positive for coronavirus by RT-PCR (1.5%) and was transferred to COVID-19 unit with no life-threatening condition. No attending surgeon was diagnosed with COVID-19 during the study.ConclusionsRobot-assisted laparoscopic surgery seemed safe in the era of COVID-19 as long as all recommended precautions are followed. The rate of nosocomial COVID-19 transmission was extremely low despite the fact that we only used RT-PCR testing in symptomatic patients during the preoperative work-up. Larger cohort is needed to validate these results.     

Antitumor activity of novel <Emphasis Type="Italic">N</Emphasis>-sulfonylpyrimidine derivatives on the growth of anaplastic mammary carcinoma in vivo

Purpose: The purpose of this study was to investigate in vivo antitumor activity of newly synthesized N-sulfonylpyrimidine derivatives 1-(p-toluenesulfonyl)cytosine (4H), 1-(p-toluenesulfonyl)cytosine hydrochloride (4H×HCl) and zinc(II) complex of 1-(p-toluenesulfonyl)cytosine (4K). Materials and methods: In order to do that we have used mouse anaplastic mammary carcinoma (AMCa). Tumor cells (10⁶) in a volume of 0.02 ml were transplanted into the thigh of the right hind leg of CBA mice. All compounds were dissolved in distilled water immediately before injecting to animals. Results: Antitumor effect of these compounds depends on drug doses and time interval between tumor transplantation and drug application. Further the efficacy of these compounds depends on number of drug injections, i. e. whether drug was given in single or in multiple doses. Multiple doses of 400 mg/kg of 1-(p-toluenesulfonyl)cytosine (4H) showed good antitumor effect when applied on day 1, 3, 5, 7 and 9 after tumor transplantation. Still good but slightly lower antitumor effect was also achieved when that compound was given in a single dose (1,200 mg/kg) on day 1 after tumor transplantation. The longest period of tumor growth time was obtained after application of 1-(p-toluenesulfonyl)cytosine hydrochloride (4H×HCl) given as a single dose (300 mg/kg) on day 1 or on day 6 after tumor implantation. However, antitumor effect of zinc(II) complex of 1-(p-toluenesulfonyl)cytosine (4K) was very strong when 300 mg/kg was given on day 1 or day 6, while this effect was slightly lower when drug (200 mg/kg/inj) was given on day 1, 3, 5, 7 and 9 or on day 6, 8, 10, 12 and 14. Conclusion: In this work it has been found that N-1-sulfonylcytosine derivatives have strong antitumor activity against mouse mammary carcinoma which is a good reason for further research of these compounds both in experimental and preclinical studies.     

Monitoring age-dependent effect of anticoagulation treatment in patients with atrial fibrillation

Oral anticoagulation treatment with dicumarol preparations (warfarin sodium) is the standard in patients with atrial fibrillation. The effect of treatment depends on many factors, especially in elderly patients. In the study, we assessed the effect of treatment in patients with atrial fibrillation hospitalized in our cardiology ward from 2004 to 2005, in the form of a telephone survey (who controlled the treatment--general practitioner or internist?, the last 2 INR results, complications). INR 2.0-3.5 is considered an efficient therapeutic range. The proportion of permanently correctly anticoagulated patients is approximately 47% across the whole age range, the hypothesis of lower efficiency of treatment in elderly patients does not apply (48% of efficiently anticoagulated patients younger than 75 years vs. 46% of older patients--however, the study does not include polymorbid patients who could not take warfarin at all!) The fact whether a patient is monitored by a general practitioner or an outpatient specialist does not make any difference (49% of anticoagulated patients monitored by a general practitioner vs. 52% of patients monitored by an internist). The percentage of severe complications is relatively low (3.4%).     

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

ObjectivesThe objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters.MethodsA cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs).ResultsIn all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22–0.47; p < 0.001) for tocilizumab, 0.82 (0.71–1.30; p 0.82) for IHDC, 0.61 (0.43–0.86; p 0.006) for PDC, and 1.17 (0.86–1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02–0.17; p < 0.001).ConclusionsTocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situation.     

Diagnostic accuracy of a rapid urine-screening test (Multistix8SG) in cirrhotic patients with spontaneous bacterial peritonitis

OBJECTIVE: To assess the diagnostic accuracy of a rapid urine-screening test (Multistix8SG) for spontaneous bacterial peritonitis (SBP) in cirrhotic patients. METHODS: Seventy-two consecutive patients (44 males, 28 females; mean age 61.6 years) with cirrhosis and ascites were included in the study. A diagnostic paracentesis was performed on hospital admission in all patients and 2 days after antibiotic treatment in the case of SBP (polymorphonuclear [PMN] count over 250/mm in ascitic fluid). Each fresh sample of ascitic fluid was also tested using the Multistix8SG urine test, and the results were scored as negative, trace or positive. RESULTS: Nine of the 72 patients had SBP and the Multistix8SG urine test was positive. After 48 h of antibiotic therapy, the PMN count of three of these nine patients was still above 250/mm and the Multistix8SG test remained positive. In three other patients with SBP, the PMN count dropped below 250/mm and the Multistix8SG test result had become negative. Two of the nine SBP patients died before 48 h, and paracentesis was not performed in the ninth case. In the other 63 patients, the PMN count in ascitic fluid was below 250/mm; the Multistix8SG test revealed 17 trace results and 46 negative results. At the threshold of 250 PMN/mm in ascitic fluid, this test had a sensitivity and a specificity of 100%. CONCLUSION: A positive Multistix8SG urine test result in ascitic fluid appears to be an indication for antibiotic treatment.