Effect of pre-emptive analgesia on clinical parameters and tissue levels of TNF-α and IL-1ß in third molar surgery: a triple-blind, randomized, placebo-controlled study.

This study aimed to evaluate whether pre-emptive analgesia modifies the tissue expression of tumour necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1ß), and whether there is an association with postoperative surgical outcomes. A triple-blind, randomized, placebo-controlled study of patients undergoing mandibular third molar removal was performed. Volunteers were allocated randomly to receive etoricoxib 120 mg, ibuprofen 400 mg, or placebo 1h before surgery. Twenty-four surgical sites per group were required (95% confidence level and 80% statistical power). Pain scores differed significantly between groups (P<0.001). Etoricoxib and ibuprofen reduced pain scores compared to placebo (P<0.05). Pain scores peaked at 4h postoperative in the experimental groups, but at 2h postoperative in the placebo group (P<0.05). A significant reduction in TNF-α concentration from time 0' to time 30' was seen for ibuprofen (P=0.001) and etoricoxib (P=0.016). The ibuprofen group showed a significant reduction in IL-1ß levels from time 0' to time 30' (P=0.038). In conclusion, TNF-α and IL-1ß levels and the inflammatory events in third molar surgery were inversely associated with the degree of cyclooxygenase 2 selectivity of the non-steroidal anti-inflammatory drugs used pre-emptively. Patients given pre-emptive analgesia showed significant reductions in the clinical parameters pain, trismus, and oedema when compared to the placebo group.

Evaluation of the accuracy of serum MMP-9 as a test for colorectal cancer in a primary care population.

BACKGROUND: Bowel cancer is common and is a major cause of death. Meta-analysis of randomised controlled trials estimates that screening for colorectal cancer using faecal occult blood (FOB) test reduces mortality from colorectal cancer by 16%. However, FOB testing has a low positive predictive value, with associated unnecessary cost, risk and anxiety from subsequent investigation, and is unacceptable to a proportion of the target population. Increased levels of an enzyme called matrix metalloproteinase 9 (MMP-9) have been found to be associated with colorectal cancer, and this can be measured from a blood sample. Serum MMP-9 is potentially an accurate, low risk and cost-effective population screening tool. This study aims to evaluate the accuracy of serum MMP-9 as a test for colorectal cancer in a primary care population. METHODS/DESIGN: People aged 50 to 69 years, who registered in participating general practices in the West Midlands Region, will be asked to complete a questionnaire that asks about symptoms. Respondents who describe any colorectal symptoms (except only abdominal bloating and/or anal symptoms) and are prepared to provide a blood sample for MMP9 estimation and undergo a colonoscopy (current gold standard investigation) will be recruited at GP based clinics by a research nurse. Those unfit for colonoscopy will be excluded. Colonoscopies will be undertaken in dedicated research clinics. The accuracy of MMP-9 will be assessed by comparing the MMP-9 level with the colonoscopy findings, and the combination of factors (e.g. symptoms and MMP-9 level) that best predict a diagnosis of malignancy (invasive disease or polyps) will be determined. DISCUSSION: Colorectal cancer is a major cause of morbidity and mortality. Most colorectal cancers arise from adenomas and there is a period for early detection by screening, but available tests have risks, are unacceptable to many, have high false positive rates or are expensive. This study will establish the potential of serum MMP-9 as a screening test for colorectal cancer. If it is confirmed as accurate and acceptable, this serum marker has the potential to assist with reducing the morbidity and mortality from colorectal cancer.

[Prevalence of cancer in the Guadalajara health area]. / Prevalencia de cáncer en el área de salud de Guadalajara.

OBJECTIVE: To quantify the prevalence of cancerand its distribution in adults. DESIGN: Descriptive study of point prevalence through research into primary and secondary sources. SETTING: Primary care, Guadalajara Health Region. 133 539 people over 14 years old. PARTICIPANTS: Patients previously diagnosed with cancer, who had a health card in the health area in June 1999. MEASUREMENTS: Demographic and diagnostic details (location according to CIE-9, date and diagnostic method). DATA SOURCES: primary care clinical records, cancer morbidity records and attendance orders. Overall crude and adjusted rates, in function of sex and age group, and specific to locations, were calculated. They were compared with data from other studies and data calculated for Spain on the basis of WHO information. RESULTS: 2717 tumours (2595 patients). Mean age, 68.2 (95% CI, 67.6-68.7); diagnostic age, 62.8 (95% CI, 62.1-63.5), in both cases higher in men (P<.01). Most common tumours: prostate, bladder, colon and lung (men); breast, colon, endometrium and ovaries (women). Crude prevalence: men, 2303.8/100 000; women, 1763.8. Adjusted to world population: 1394.2 and 1227.4/100 000, respectively (prevalence ratio, 1.14; 95% CI, 1.03-1.25). Truncated rate higher in women than in men (1638/100 000 against 1308). Five-year period with highest prevalence: 75-79 years old in men (8763.5/100 000) and 80-84 in women (4558.7/100 000). CONCLUSIONS: Cancer prevalence in adults is slightly above 2%. Once adjusted for age, values are similar to other studies and as expected for our country. The most common tumours are in the digestive apparatus, breast and the genito-urinary system. The man/woman proportion is higher than that described in other studies.

Malignant epithelial tumors observed in hernia sacs.

INTRODUCTION: The study of a hernia sac rarely provides the evidence of a primary or metastatic malignant epithelial tumor. METHODS: We have reviewed our institutional experience with malignant epithelial tumors found in a hernia sac with the purpose of evaluating cases present/manifesting in the sac, gross appearance, histologic type, primary tumor sites, staging, and patient outcome. RESULTS: A total of 8,435 adult patients underwent inguinal, femoral, umbilical or abdominal hernia repair in our hospitals. Twelve (0.14 %) patients had a malignant epithelial tumor in the hernia sac. Only one of these tumors was primary and the rest metastatic. Six out of twelve tumors (50.0 %), all of them metastatic, were discovered after hernia repair (0.07 %). The mean age of the 12 patients was 68.7 ± 15.2 years (range 43-90 years). Eight patients were male (66.7 %). Six tumors were located in inguinal (50.0 %), five in umbilical (41.7 %), and one in abdominal (8.3 %) hernia sacs. Gastrointestinal cases comprised 50.0 % and gynaecologic cases 25 % of tumors. In three cases (25.0 %) the hernia sac showed no gross abnormalities. All tumors were found in an advanced stage of development and ten patients died. Mean survival of these patients after hernia repair was 275.1 ± 376.4 days (range 6-1,095 days; median 68 days). CONCLUSIONS: Gravity, inflammatory oncotaxis, and chemotactic agents are probably operative phenomena in the development of metastatic lesions in hernia sacs. Routine microscopic evaluation of hernia sacs is not justified by the high cost. It should be reserved for selected cases based on the gross findings. Since subtle lesions may be overlooked on gross examination, particular caution should be taken with the examination of hernia sacs from older patients.

Tephrosia toxicaria†Pers. reduces temporomandibular joint inflammatory hypernociception: the involvement of the HO-1 pathway.

BACKGROUND: We investigated both the efficacy and the sub-chronic toxicity of Tephrosia toxicaria Pers. in the zymosan-induced temporomandibular joint (TMJ) inflammatory hypernociception in rats evaluating the possible role of heme oxygenase-1 (HO-1). METHODS: Rats were pretreated with T. toxicaria (0.2, 2.0 or 20 mg/kg) 60 min before the intra-articular injection of zymosan (2 mg, 40 µL) in the left TMJ. In another series of experiments, rats were treated with ZnPP-IX (3 mg/kg), a specific HO-1 inhibitor, before T. toxicaria (20 mg/kg). Von Frey test was used to evaluate inflammatory hypernociception (g) 4 h after zymosan injection. Six hours after zymosan injection, the synovial lavage was collected for total cell count and myeloperoxidase (MPO) activity, and joint tissue for histopathological analysis and immunohistochemistry for HO-1. To evaluate the sub-chronic toxicity, mice received T. toxicaria (20 mg/kg) or saline once a day for 14 days to analyse body mass, organ weight and biochemical parameters. RESULTS: T. toxicaria partially reversed the zymosan-induced head withdrawal threshold, the number of cells and the MPO activity. T. toxicaria reduced the inflammatory cell influx in the synovial membrane. TMJ immunohistochemical analyses treated with T. toxicaria showed increased HO-1 expression. These effects of T. toxicaria were not observed in the presence of ZnPP-IX. T. toxicaria treatment for 14 days did not show significant signs of toxicity when administrated to mice. CONCLUSIONS: T. toxicaria did not produce any signs of toxicity and effectively decreased zymosan-induced TMJ inflammatory hypernociception dependent, at least in part, upon the HO-1 pathway integrity.

Disección coronaria espontánea en España: un estudio sobre bases administrativas realizado a partir del Conjunto Mínimo Básico de Datos español / Spontaneous coronary artery dissection in Spain: a study using the minimum data set of the Spanish National Health System

Introducción y objetivos La disección coronaria espontánea (DCE) es una causa poco común de infarto agudo de miocardio (IAM). En este estudio se comparan la mortalidad y los reingresos hospitalarios de los pacientes con IAM-DCE e IAM de otras etiologías (IAM-NDCE). Métodos Se calcularon las razones de mortalidad hospitalaria y de reingresos a los 30 días estandarizadas por riesgo (RAMER y RARER respectivamente) utilizando el Conjunto Mínimo Básico de Datos del Sistema Nacional de Salud español (2016-2019). Resultados Se hallaron 806 eventos de IAM-DCE y 119.425 de IMA-NDCE. Los IAM-DCE se produjeron en pacientes más jóvenes y más frecuentemente mujeres que los IAM-NDCE. La mortalidad bruta fue menor (el 3 frente al 7,6%; p<0,001) y la RAMER, mayor (el 7,6±1,7 frente al 7,4±1,7%; p=0,019) en los IAM-DCE. Tras emparejamiento por puntuación de propensión (806 parejas), la mortalidad fue similar en ambos grupos (AdjOR=1,15; IC95%, 0,61-2,2; p=0,653). La tasa bruta de reingresos de los pacientes con IAM-DCE a 30 días fue similar (el 4,6 frente al 5%; p=0,67), mientras que la RARER fue menor (el 4,7±1 frente al 4,8±1%; p=0,015). Tras el emparejamiento por puntuación de propensión (715 parejas), la tasa de ingresos fue similar en ambos grupos (AdjOR=1,14; IC95%, 0,67-1,98; p=0,603). Conclusiones La mortalidad hospitalaria y los reingresos a los 30 días de los pacientes con IAM-DCE es similar a la de los IAM-NDCE cuando el riesgo se ajusta a las características basales de la población. Estos datos resaltan la necesidad de optimizar el manejo, tratamiento y seguimiento clínico de los pacientes con DCE (AU)

Introduction and objectives Spontaneous coronary artery dissection (SCAD) is a rare cause of acute myocardial infarction (AMI). We sought to compare the results on in-hospital mortality and 30-day readmission rates among patients with AMI-SCAD vs AMI due to other causes (AMI-non-SCAD). Methods Risk-standardized in-hospital mortality (rIMR) and risk-standardized 30-day readmission ratios (rRAR) were calculated using the minimum dataset of the Spanish National Health System (2016-2019). Results A total of 806 episodes of AMI-SCAD were compared with 119 425 episodes of AMI–non-SCAD. Patients with AMI-SCAD were younger and more frequently female than those with AMI–non-SCAD. Crude in-hospital mortality was lower (3% vs 7.6%; P<.001) and rIMR higher (7.6±1.7% vs 7.4±1.7%; P=.019) in AMI-SCAD. However, after propensity score adjustment (806 pairs), the mortality rate was similar in the 2 groups (AdjOR, 1.15; 95%CI, 0.61-2,2; P=.653). Crude 30-day readmission rates were also similar in the 2 groups (4.6% vs 5%, P=.67) whereas rRAR were lower (4.7±1% vs 4.8%±1%; P=.015) in patients with AMI-SCAD. Again, after propensity score adjustment (715 pairs) readmission rates were similar in the 2 groups (AdjOR, 1.14; 95%CI, 0.67–1.98; P=.603). Conclusions In-hospital mortality and readmission rates are similar in patients with AMI-SCAD and AMI–non-SCAD when adjusted for the differences in baseline characteristics. These findings underscore the need to optimize the management, treatment, and clinical follow-up of patients with SCAD (AU)

C4d immunohistochemical staining is a sensitive method to confirm immunoreactant deposition in formalin-fixed paraffin-embedded tissue in membranous glomerulonephritis.

Although the diagnosis of membranous glomerulonephritis (MGN) may be suspected on routine histology of formalin-fixed paraffin-embedded tissue, fresh-frozen tissue must be used to show the immunologic nature of the process by direct immunofluorescence (IF). The efficiency of IF or immunoperoxidase (IP) detection of IgG and C3 using paraffin sections is controversial. This study was designed to evaluate whether glomerular C4d deposition using an IP method in formalin-fixed paraffin-embedded tissue may be a useful marker for MGN. We showed characteristic glomerular, granular basement membrane deposition of C4d in 31 (100%) cases of idiopathic MGN and in 5 cases (100%) of pure class V membranous lupus nephritis, in which we had a positive diagnosis of the lesions for conventional IF study. Control cases were negative. Nineteen cases of different glomerulopathies, including IgA nephropathy, primary type I membranoproliferative glomerulonephritis, focal segmental glomerulosclerosis and minimal change disease showed diverse reproducible patterns of C4d deposition, without intrinsic background. Our results indicate that staining of formalin-fixed paraffin-embedded tissue for C4d can be used for confirmation of granular basement membrane immunoreactant deposition in cases of MGN. This proved to be a reliable method that could potentially obviate the need for rebiopsy in cases with absence of glomeruli in renal frozen sections or when other adjunct IF or IP methods on paraffin sections are negative. C4d immunostaining, using an IP method, deserves a place as an adjunct method in the biopsy diagnosis of MGN.

An overview of the pale and clear cells of the nipple epidermis.

The stratified squamous epithelium of the nipple-areola complex may contain pale or clear cells including: Paget's disease cells (PDCs), Toker cells (TCs), and so-called clear cells (CCs). Paget's disease is an uncommon presentation of breast carcinoma. PDCs are large, atypical, have abundant, pale-staining cytoplasm that may contain mucin secretion vacuoles and bulky heterochromatic nuclei. They are commonly concentrated along the basal layer and stain for EMA, CAM5.2, cytokeratin 7, and HER2/neu oncoprotein. TCs are bland cells with roundish and scant chromatin nuclei. They are found incidentally and are reactive for EMA, CAM5.2, and cytokeratin 7, but show negativity for HER2/neu oncoprotein. So-called CCs show varied morphology, are found incidentally, and have been variably interpreted by different authors. The majority of cells that have been called epidermal CCs fit the features of pagetoid dyskeratosis. These cells are reactive for high molecular weight cytokeratin. Other CCs showing signet-ring morphology present negativity for mucins and correspond to a fixation artefact.

Cardiopatía isquémica en la mujer: ¿una asignatura pendiente? / Ischemic heart disease in women: a pending issue?

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In vivo evidence that S-adenosylmethionine and fatty acid synthesis intermediates are the substrates for the LuxI family of autoinducer synthases.

Many gram-negative bacteria synthesize N-acyl homoserine lactone autoinducer molecules as quorum-sensing signals which act as cell density-dependent regulators of gene expression. We have investigated the in vivo source of the acyl chain and homoserine lactone components of the autoinducer synthesized by the LuxI homolog, TraI. In Escherichia coli, synthesis of N-(3-oxooctanoyl)homoserine lactone by TraI was unaffected in a fadD mutant blocked in beta-oxidative fatty acid degradation. Also, conditions known to induce the fad regulon did not increase autoinducer synthesis. In contrast, cerulenin and diazoborine, specific inhibitors of fatty acid synthesis, both blocked autoinducer synthesis even in a strain dependent on beta-oxidative fatty acid degradation for growth. These data provide the first in vivo evidence that the acyl chains in autoinducers synthesized by LuxI-family synthases are derived from acyl-acyl carrier protein substrates rather than acyl coenzyme A substrates. Also, we show that decreased levels of intracellular S-adenosylmethionine caused by expression of bacteriophage T3 S-adenosylmethionine hydrolase result in a marked reduction in autoinducer synthesis, thus providing direct in vivo evidence that the homoserine lactone ring of LuxI-family autoinducers is derived from S-adenosylmethionine.

Pagetoid dyskeratosis of the lips.

Pagetoid dyskeratosis is an incidental finding in a variety of lesions of the skin and squamous mucosa. The lesion is considered a selective keratinocytic response in which a small part of the normal population of keratinocytes is induced to proliferate in response to friction. As far as we know, pagetoid dyskeratosis has not been reported in the lips. In this article, we describe the location of the lesion in the lips and its incidence in a group of 90 unselected patients who underwent biopsy or were surgically treated for diverse labial lesions. Histochemical staining and immunohistochemical studies were performed in selected cases. Pagetoid dyskeratosis was found in 38 cases (42.2%) but only in 6 cases (6.7%) the lesion was conspicuous. There was no significant difference between the upper and the lower lip in terms of incidence of the lesion. Labial pagetoid dyskeratosis was more frequent in younger patients (46.7 +/- 25.0 versus 58.5 +/- 20.5; p < 0.05) and in women (chi(2) = 3.89; p < 0.05). Pagetoid cells were more common in suprabasal location and in the labial mucosa. These cells showed positivity for high-molecular weight cytokeratin and negative reaction for low-molecular weight cytokeratin, epithelial membrane antigen, carcinoembryonic antigen, and human papilloma virus. The immunohistochemical profile is different from the surrounding keratinocytes, indicating premature keratinization. The main differential diagnoses include white sponge nevus, leukoedema, oral koilocytoses, hairy leukoplakia, pagetoid squamous cell carcinoma in situ, and extramammary Paget's disease of the oral mucosa. The morphologic features of dyskeratotic pagetoid cells are distinctive and easily recognized as an incidental finding, thus preventing confusion with other important entities including an intraepidermal tumor.

Yeast pyruvate carboxylase: identification of two genes encoding isoenzymes.

In Saccharomyces cerevisiae, pyruvate carboxylase [EC 6.4.1.1] has an important anaplerotic role in the production of oxaloacetate from pyruvate. We report here the existence of two pyruvate carboxylase isozymes, which are encoded by separate genes within the yeast genome. Null mutants were constructed by one step gene disruption of the characterised PYC gene in the yeast genome. The mutants were found to have 10-20% residual pyruvate carboxylase activity, which was attributable to a protein of identical size and immunogenically related to pyruvate carboxylase. Immunocytochemical labelling studies on ultrathin sections of embedded whole cells from the null mutants showed the isozyme to be located exclusively in the cytoplasm. We have mapped the genes encoding both enzymes and shown the previously characterised gene, designated PYC1, to be on chromosome VII whilst PYC2 is on chromosome II.