Moderate alcohol consumption is associated with increased radiological progression in women, but not in men, with early rheumatoid arthritis: results from the ESPOIR cohort (Étude et Suivi des Polyarthrites Indifférenciées Récentes).

OBJECTIVE: We conducted this study to determine whether alcohol consumption influences radiological progression in early rheumatoid arthritis (RA). METHOD: Patients fulfilling the European League Against Rheumatism/American College of Rheumatology 2010 criteria in the early arthritis cohort ESPOIR (Étude et Suivi des Polyarthrites Indifférenciées Récentes) were included in this study. Alcohol consumption was collected at baseline and at each visit. We classified alcohol consumption into three groups: abstinent (0 g/day), moderate (≤ 20 g/day for women, ≤ 30 g/day for men), and abuse (> 20 g/day for women, > 30 g/day for men). The primary outcome was the occurrence of radiological progression, defined as an increase ≥ 5 points in the total Sharp/van der Heijde score. We investigated whether alcohol consumption is predictive of radiological progression at 1, 3, and 5 years by univariate and multivariate analysis adjusted for age, baseline erosion, rheumatoid factor, anti-citrullinated peptide antibody, smoking status, body mass index, and treatment with leflunomide or methotrexate and biologics. RESULTS: The study included 596 patients. When considering the influence of gender on the interaction between alcohol consumption and radiological progression, we showed a deleterious effect of moderate consumption in women [odds ratio (OR) = 1.73, 95% confidence interval (CI) 1.01; 2.96, p = 0.045] and a trend towards a protective effect of moderate consumption in men (OR = 0.50, 95% CI 0.21; 1.16, p = 0.106) in multivariate analysis. CONCLUSION: Our data suggest a deleterious effect of moderate consumption of alcohol on radiological progression in women, but not in men, with early RA.

Management of penetrating abdominal and thoraco-abdominal wounds: A retrospective study of 186 patients.

This is a single center retrospective review of abdominal or abdomino-thoracic penetrating wounds treated between 2004 and 2013 in the gastrointestinal and emergency unit of the university hospital of Grenoble, France. This study did not include patients who sustained blunt trauma or non-traumatic wounds, as well as patients with penetrating head and neck injury, limb injury, ano-perineal injury, or isolated thoracic injury above the fifth costal interspace. In addition, we also included cases that were reviewed in emergency department morbidity and mortality conferences during the same period. Mortality was 5.9% (11/186 patients). Mean age was 36 years (range: 13-87). Seventy-eight percent (145 patients) suffered stab wounds. Most patients were hemodynamically stable or stabilized upon arrival at the hospital (163 patients: 87.6%). Six resuscitative thoracotomies were performed, five for gunshot wounds, one for a stab wound. When abdominal exploration was necessary, laparotomy was chosen most often (78/186: 41.9%), while laparoscopy was performed in 46 cases (24.7%), with conversion to laparotomy in nine cases. Abdominal penetration was found in 103 cases (55.4%) and thoracic penetration in 44 patients (23.7%). Twenty-nine patients (15.6%) had both thoracic and abdominal penetration (with 16 diaphragmatic wounds). Suicide attempts were recorded in 43 patients (23.1%), 31 (72.1%) with peritoneal penetration. Two patients (1.1%) required operation for delayed peritonitis, one who had had a laparotomy qualified as "negative", and another who had undergone surgical exploration of his wound under general anesthesia. In conclusion, management of clear-cut or suspected penetrating injury represents a medico-surgical challenge and requires effective management protocols.

Electronegative LDL induces priming and inflammasome activation leading to IL-1ß release in human monocytes and macrophages.

BACKGROUND: Electronegative LDL (LDL(−)), a modified LDL fraction found in blood, induces the release of inflammatory mediators in endothelial cells and leukocytes. However, the inflammatory pathways activated by LDL(−) have not been fully defined. We aim to study whether LDL(−) induced release of the first-wave proinflammatory IL-1ß in monocytes and monocyte-derived macrophages (MDM) and the mechanisms involved. METHODS: LDL(−) was isolated from total LDL by anion exchange chromatography. Monocytes and MDM were isolated from healthy donors and stimulated with LDL(+) and LDL(−) (100 mg apoB/L). RESULTS: In monocytes, LDL(−) promoted IL-1ß release in a time-dependent manner, obtaining at 20 h-incubation the double of IL-1ß release induced by LDL(−) than by native LDL. LDL(−)-induced IL-1ß release involved activation of the CD14-TLR4 receptor complex. LDL(−) induced priming, the first step of IL-1ß release, since it increased the transcription of pro-IL-1ß (8-fold) and NLRP3 (3-fold) compared to native LDL. Several findings show that LDL(−) induced inflammasome activation, the second step necessary for IL-1ß release. Preincubation of monocytes with K+ channel inhibitors decreased LDL(−)-induced IL-1ß release. LDL(−) induced formation of the NLRP3-ASC complex. LDL(−) triggered 2-fold caspase-1 activation compared to native LDL and IL-1ß release was strongly diminished in the presence of the caspase-1 inhibitor Z-YVAD. In MDM, LDL(−) promoted IL-1ß release, which was also associated with caspase-1 activation. CONCLUSIONS: LDL(−) promotes release of biologically active IL-1ß in monocytes and MDM by induction of the two steps involved: priming and NLRP3 inflammasome activation. SIGNIFICANCE: By IL-1ß release, LDL(−) could regulate inflammation in atherosclerosis.

[Treatment of head and neck squamous cell carcinoma of an unknown primary (HNCCUP): oncologic analysis of 35 cases]. / Traitement des adénopathies cervicales malignes en apparence primitive (AMAP): résultats carcinologiques à propos de 35 cas.

OBJECTIVE: The aim of our study was to perform an oncologic analysis of patients treated for head and neck squamous cell carcinoma of an unknown primary (HNCCUP). PATIENTS AND METHODS: 35 cases were included in our monocentric restrospective study (1999-2010). All patients had a complete clinical exam as well as head, neck and chest CT scans. The primary tumour remained undetected after panendoscopy 25 patients underwent a routine tonsillar biopsy ipsilateral to the lymphadenopathy. In 9 cases (36%), an invasive squamous cell carcinoma was detected on pathological examination. These patients were excluded from further study. Kaplan-Meier method was used for survival analysis. Univariate and multivariate analysis were also performed using Cox's regression model. RESULTS: The therapeutic management of patients' majority (73%) consisted of lymphadenectomy with frozen section examination which confirmed the presence of an invasive squamous carcinoma in the resected lymph node(s). This was followed by ipsilateral neck dissection and radiotherapy or radiochemotherapy. Patients with unresectable lymph node(s) underwent exclusive radiochemotherapy. Specific survival rates at 1, 3 and 5 years were respectively 77%, 52% and 47%. The median survival time was 3 years. The comparison of univariate and multivariate survival curves confirmed that the lymph node status is an important factor for survival (HR 8.3 [2.03-33.96]). CONCLUSION: Our results are consistent with those found in the medical literature. HNCCUP has a poor prognosis which correlates with the lymph node status.

[Prospective comparative study on 50 patients between microsurgical sublabial transsphenoidal approach and endoscopic endonasal transsphenoidal approach]. / Comparación del abordje transesfenoidal microquirúrgico frente al abordaje endonasal transesfenoidal endosócpico. Estudio prospectivo de 50 pacientes.

OBJECTIVE: Compare the standard transsphenoidal sublabial microscopic approach with the endoscopic transsphenoidal approach concerning the tumoral invasiveness and resection, complications of the approaches and time of post operative hospitalisation. MATERIAL AND METHODS: We realized a prospective, non randomised study with 50 patients. They were operated between 2002 and 2006. All the patients had sellar lesions with different grades of invasiveness of the cavernous sinus as classified by Knosp. The variables included in our study were tumoral invasiveness and operative resection (total, subtotal and partial), optic nerve lesion, postoperative panhypopituitarism, CSF fistula, cranial nerves deficits, epistaxis, meningitis, diabetes insipidus and carotid artery lesion. Our series included 27 males and 23 females ranging from 19 to 80 years old (48 mean). In 23 patients we used the standard sublabial microscopic approach (two patients were excluded) and for 25 patients we used the endoscopic approach. The mean follow up was of 12 months. RESULTS: In our experience the endoscopic technique presents a higher percentage of total resection comparing to the sublabial microscopic approach (60% versus 34.8%) and higher percentage of subtotal resections (32% versus 26%) with a statistical significant difference (p=0.033). The time of hospitalisation was significant shorter for the endoscopic approach group (p=0.001), diminishing by half of the time (3 days) of the microscopic approach group. Concerning the tumoral invasiveness and complications we did not appreciate any significant dissimilarity. We appreciated that a higher grade of invasiveness augments by 3.59 the risk of an unsuccessful surgery. DISCUSSION AND CONCLUSION: In our experience the endoscopic technique may favour a better tumoral resection and shorter time of hospitalisation. We did not appreciate differences concerning the complications.

Low frequency electromagnetic radiation and hearing.

OBJECTIVE: To analyse the possible impact of low and extremely low frequency electromagnetic fields on the outer hairs cells of the organ of Corti, in a guinea pig model. MATERIALS AND METHODS: Electromagnetic fields of 50, 500, 1000, 2000, 4000 and 5000 Hz frequencies and 1.5 microT intensity were generated using a transverse electromagnetic wave guide. Guinea pigs of both sexes, weighing 100-150 g, were used, with no abnormalities on general and otic examination. Total exposure times were: 360 hours for 50, 500 and 1000 Hz; 3300 hours for 2000 Hz; 4820 hours for 4000 Hz; and 6420 hours for 5000 Hz. One control animal was used in each frequency group. The parameters measured by electric response audiometer included: hearing level; waves I-IV latencies; wave I-III interpeak latency; and percentage appearance of waves I-III at 90 and 50 dB sound pressure level intensity. RESULTS: Values for the above parameters did not differ significantly, comparing the control animal and the rest of each group. In addition, no significant differences were found between our findings and those of previous studies of normal guinea pigs. CONCLUSION: Prolonged exposure to electromagnetic fields of 50 Hz to 5 KHz frequencies and 1.5 microT intensity, produced no functional or morphological alteration in the outer hair cells of the guinea pig organ of Corti.

[Tracheal infection following oncological surgery in larynx and pharynx]. / Colonización traqueal en cirugía oncológica de laringe y faringe.

Surgical wound infection is one of the most frequent complications in pharyngo-laryngeal external surgery. They are usually polimicro with gram-positive, negative both aerobial and anaerobial microrganisms. The trachea is usually sterile and contamination is due to the intoduction during intubation of germs from the oropharyngeal area. A retrospective study was performed including 40 patients with pharyngo-laryngeal carcinoma. When the tracheostomy was done a culture from the internal trachea wall was obtained for micro study. Only one patient had an sterile culture from the trachea. There were 3 patients with just one microorganism and all the rest had at least two, being mixed aerobial and anaerobial flora the most frequent.

[Hodgkin and Non-Hodgkin lymphomas in otorhinolaryngology]. / Linfomas Hodgkin y No-Hodgkin en otorrinolaringología.

Lymphomas of the head and neck arise in lymph nodes and extranodal areas as Waldeyer ring, nasal cavity, thyroid gland and salivary glands. Though anatomically in close proximity, lymphomas presenting at the ENT area have different clinical characteristics if they are Hodgkin or Non-Hodgkin. We included 31 patients with the diagnosis of lymphoma and diagnosed in our Department between 1999 and 2002. We studied all the different variables that differentiate Hodgkin and Non-Hodgkin's lymphoma. Both types of lymphoma usually present as a cervical mass. Non-Hodgkin lymphoma have extranodal involvement more frequently and also a more advance disease at diagnosis. It is important to include the lymphoma in the differential diagnosis of any cervical mass or ENT lesion.

[Usefulness of 201T1 gammagraphy in the diagnosis of carcinoma of the larynx]. / Utilidad de la gammagrafía con 201Tl en el diagnóstico del carcinoma de laringe.

For the evaluation of a patient with a laryngeal tumor we need the clinical exam and other exams as the CT scan or MRI. Those studies have a sensitivity of less than 80%. For that reason in the last years there has been a development of new techniques trying to increase the accuracy. The 201Tl SPECT is one of them although it was developed for cardiological purposes. We present our experience in 46 patients with laryngeal tumor in whom we did a 201Tl SPECT as part of the extension study. The sensitivity of the study was 81.6% in the diagnosis of the primary tumor and 46.1% for the neck adenopathies. The 201Tl SPECT can be a good method for the evaluation and detection of recurrences in patients with pharyngo-laryngeal tumor.

[Antibiotic prophylaxis in oncologic pharyngolaryngeal surgery: ceftriaxone versus clindamycin and gentamycin]. / Profilaxis antibiótica en cirugía oncológica faringolaríngea: ceftriaxona versus clindamicina + gentamicina.

There are many papers comparing two antibiotic protocols for the profilaxis of head and neck infections after laryngeal surgery. We present one prospective and randomised study in 60 patients comparing the efficacy of two protocols. The comparison was between ceftriaxone versus the association of clindamicyn and gentamicyn. In our database we included the risk factors for infection, the surgical approach, the duration of surgery and the patient characteristics. We observed an incidence of 28% of infection, with a 23.3% in the clindamicyn + gentamicyn group and a 33.3% in the ceftriaxone group. The differences between the two groups were not statistically significant. In this study we observed a small difference between the amount of alcohol comsuption, the effectiveness of the surgical drainage, the surgical approach and the presence of wound infection. The difference was not statistical significant due to the small group of patients. The profilaxis was adequate for the total laryngectomy and cordectomy group, with a higher incidence of wound infection in patients treated with a supraglottic laryngectomy.

[Reconstruction of oropharyngeal defects with lateral arm flap]. / Reconstrucción de defectos orofaríngeos con colgajo lateral de brazo.

The lateral arm flap, is a fasciocutaneous flap with great versatility, but underused in head and neck reconstruction. Its qualities include a intermediate thickness between the radial forearm flap and the pectoralis major, ideal to reconstruct oropharyngeal defect, a consistent vascular pedicle, a pliable soft tissue and a low donor site morbidity. Use of this flap does not require the sacrificing of a major feeding vessel to the arm. We have chosen this technique to reconstruct four cases with surgical defects in oral cavity and oropharynx. The anatomic and functional results have been satisfactory and the complications rate is comparable to other microvascular techniques. We think that the lateral arm free flap is a useful reconstructive technique in specific areas of head and neck.

Electronegative LDL from normolipemic subjects induces IL-8 and monocyte chemotactic protein secretion by human endothelial cells.

The presence in plasma of an electronegative LDL subfraction [LDL(-)] cytotoxic for endothelial cells (ECs) has been reported. We studied the effect of LDL(-) on the release by ECs of molecules implicated in leukocyte recruitment [interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1)] and in the plasminogen activator inhibitor-1 (PAI-1). LDL(-), isolated by anion-exchange chromatography, differed from nonelectronegative LDL [LDL(+)] in its higher triglyceride, nonesterified fatty acid, apoprotein E and apoprotein C-III, and sialic acid contents. No evidence of extensive oxidation was found in LDL(-); its antioxidant and thiobarbituric acid-reactive substances contents were similar to those of LDL(+). However, conjugated dienes were increased in LDL(-), which suggests that mild oxidation might affect these particles. LDL(-) increased, in a concentration-dependent manner, the release of IL-8 and MCP-1 by ECs and was a stronger inductor of both chemokines than oxidized LDL (oxLDL) or LDL(+). PAI-1 release increased slightly in ECs incubated with both LDL(-) and oxLDL but not with LDL(+). However, no cytotoxic effects of LDL(-) were observed on ECs. Actinomycin D inhibited the release of IL-8 and MCP-1 induced by LDL(-) and oxLDL by up to 80%, indicating that their production is mediated by protein synthesis. Incubation of ECs with N:-acetyl cysteine inhibited production of IL-8 and MCP-1 induced by LDL(-) and oxLDL by >50%. The free radical scavenger butylated hydroxytoluene slightly inhibited the effect of oxLDL but did not modify the effect of LDL(-). An antagonist (BN-50730) of the platelet-activating factor receptor inhibited production of both chemokines by LDL(-) and oxLDL in a concentration-dependent manner. Our results indicate that LDL(-) shows proinflammatory activity on ECs and may contribute to early atherosclerotic events.

Partial epiglottectomy as a possible treatment for globus pharyngeus?

Globus pharyngeus is a relatively common complaint in an ear, nose, and throat consulting room and may account for 3-4% of outpatient referrals. The cause is still unknown, although a number of hypotheses have been suggested. Between 40% and 75% of the patients remain symptomatic despite any treatment regimen. Thirteen patients from a group of 124 with the diagnosis of globus pharyngeus and no response to medical treatment were treated with partial epiglottectomies. One year after the surgery all but one patient were free of symptoms. Our experience indicates that partial epiglottectomy can be a good treatment for those patients with globus pharyngeus in whom no cause is found after all studies are performed or when medical treatment fails.

[Positron-emission tomography (PET) in the diagnosis of malignancy, recurrence, and staging in patients with head and neck tumors]. / Tomografía por emisión de positrones (PET) en el diagnóstico de malignidad, recurrencia y el estadiaje en pacientes con tumores de cabeza y cuello.

We report a prospective study with 15 patients with the diagnosis of head and neck tumors. They underwent two types of studies, the radiological one with computed tomography or magnetic resonance image scan and the positron emission tomography (PET) with 18-fluorodeoxyglucose (FDG). Five patients did not receive any treatment before, and the PET was performed to evaluate the possibility of malignancy, to determine the stage of the disease and if a recurrence was suspected. The study with the PET has the advantage of detecting small lesions and it is not influenced by radiotherapy or surgery.

Effect of simvastatin treatment on the electronegative low-density lipoprotein present in patients with heterozygous familial hypercholesterolemia.

Most described modifications of low-density lipoprotein (LDL) cholesterol share an increase in its negative electric charge; in fact, an electronegative form of LDL can be identified and isolated from plasma. Although the exact nature of the chemical modification of electronegative LDL is still controversial, its toxicity on endothelial cells has been demonstrated. Statins have protective effects against cardiovascular disease that are independent of their lipid-lowering action and which could be due, at least in part, to the prevention of LDL modification. We evaluated the effect of 6 months of simvastatin therapy (40 mg/day) on electronegative LDL proportion and LDL susceptibility to in vitro induced oxidation in 21 patients with heterozygous familial hypercholesterolemia (FH). Eleven normolipemic subjects were analyzed as a control group. Total cholesterol as well as LDL and very low density lipoprotein cholesterol, triglycerides, and apoprotein B decreased 30% after the first month of therapy, with no further decreases thereafter. LDL susceptibility to oxidation was similar in FH patients and controls and did not change throughout the treatment. Electronegative LDL proportion was 35.1 +/- 9.9% in FH patients and 9.1 +/- 2.4% in control subjects (p <0.0001) but, in contrast to total LDL cholesterol and the rest of lipid parameters, it decreased to 28.6 +/- 9.1% in the third month and to 21.2 +/- 7.7% in the sixth month of therapy. The decrease in these cytotoxic particles may be a relevant mechanism by which simvastatin protects against cardiovascular disease.

[Nitric oxide synthase activity in nasal mucosa]. / Actividad óxido nítrico sintasa en la mucosa nasal.

Nitric oxide (NO) plays an important regulatory role in airway function and seems to be implicated in the pathophysiology of several airway diseases. We studied the presence of NO synthase activity in human nasal mucosa and nasal polyp tissues obtained from patients undergoing septoplasty or polypectomy, respectively. NO synthase activity was quantified in tissue homogenates using citrulline release assay and was located in tissue sections using NADPH-diaphorase histochemistry. The results indicated that nasal polyps contain higher levels of total NO synthase activity than nasal mucosa tissue. In addition, nasal polyps contained mainly inducible NO synthase activity whereas all NO synthase activity detected in the nasal mucosa was in constitutive form. In both cases, NO synthase activity was localized in epithelial cells. In view of these results, we conclude that NO may be an important inflammatory mediator in the respiratory system and that the epithelium may be a source of NO production.

Fractions of calcium in the plant-soil system affected by the application of olive oil wastewater.

A pot experiment using calcareous soil was conducted in a growth chamber to examine the effects of olive oil wastewater applications on Ca fractions in the plant and on exchangeable Ca in soil after plant growth. The experimental treatments consisted of two rates of olive oil wastewater, two mineral fertilizer treatments including K, which supplied K in amounts equivalent to the K supplied by the olive oil wastewater treatments, a mineral fertilizer without K treatment (F), and a control. The pots were sown with ryegrass which was harvested 3 times at monthly intervals. The high rate of olive oil wastewater resulted in a prolonged increases in dry matter production. It also resulted in a reduction in the concentrations of soluble Ca, bound Ca, inorganic insoluble Ca and organic insoluble Ca in the plant shoots relative to the control and the F treatment. The low rate of olive oil wastewater produced similar but less marked effects, with decreases being observed in the soluble Ca and bound Ca fractions. After 3 months of plant growth, soil exchangeable Ca was higher in the control and F treatment soils than in the soils receiving olive oil wastewater or K fertilizer. At this time, there were no significant differences in exchangeable Ca between the soils receiving olive oil wastewater and those treated with K fertilizer.

LDL from aerobically-trained subjects shows higher resistance to oxidative modification than LDL from sedentary subjects.

We studied the effect of regular intense aerobic exercise on the LDL susceptibility to oxidation and the electronegative LDL-proportion (LDL(-)). A group of 38 well-trained athletes was compared to a group of 38 age-BMI-matched sedentary individuals. Athletes showed higher concentration of total cholesterol (athletes 5.08 +/- 0.70 versus controls 4.65 +/- 0.75 mmol/l, P = 0.0229) and HDL cholesterol (athletes 1.72 +/- 0.47 versus controls 1.46 +/- 0.39 mmol/l, P = 0.0068); total plasma triglyceride, LDL cholesterol and VLDL cholesterol did not differ between trained and untrained subjects. The susceptibility of LDL to oxidation, determined by conjugated dienes formation and expressed as lag phase, was lower in athletes than in sedentaries (trained subjects 47.0 +/- 5.6 versus sedentary subjects 41.9 +/- 5.0 min, P = 0.0002). LDL(-) was similar in both groups (athletes 10.32 +/- 4.70 versus controls 10.26 +/- 3.71%). The antioxidant content in total plasma and isolated LDL (alpha-tocopherol, retinol, lycopene, alpha-carotene and beta-carotene) was quantitated by HPLC in a subgroup of 32 athletes and 32 control subjects. Athletes showed higher amounts of alpha-tocopherol and retinol in plasma, but not in LDL. However, none of these antioxidants correlated with the lag phase time. Trained subjects showed lower prevalence of smoking. However, no differences were observed between smokers and non-smokers concerning lag phase. No significant difference between athletes and sedentaries concerning LDL density, or composition was observed. We conclude that LDL from trained subjects is more resistant to oxidative modification than LDL from sedentary subjects. This observation could not be attributed to conventional antioxidants as alpha-tocopherol and carotene content of LDL was unchanged in trained subjects. Thus, although none of the variables studied appear as a single predictor of the LDL susceptibility to oxidation, an additive effect of the antioxidant content, the presence of some undetermined co-antioxidant, HDL and/or smoking habits cannot be discarded as responsible for the increased resistance to oxidation of LDL in trained subjects.