Allergy and occupational exposure to hydroquinone and to methionine.

Respiratory manifestations have been reported after exposure to hydroquinone and to methionine. One hundred and three men in the same chemical plant were divided into three groups according to their exposure and compared by questionnaire, respiratory functional tests with methacholine then salbutamol challenges, and measurements of serum immunoglobulins G and E. Group H included 33 workers exposed to hydroquinone, trimethyl-hydroquinone, and retinene-hydroquinone. Group M included 15 workers exposed to methionine. Group C was a control group of 55 workers. The prevalence of respiratory symptoms was higher in the two exposed groups. Before challenges, pulmonary function values were significantly lower in groups H and M than those in group C. The challenges induced significant variations in the three groups but these variations were less pronounced in group M than in the other groups. The level of immunoglobulin G in group H (m +/- SD = 12.5 gram/liter +/- 2.6) was significantly higher than in group C (10.6 gram/liter +/- 2.4; p less than 0.002). The level of immunoglobulin E in group H (m = 140 IU/l) was also higher in group C (109 IU/l) but this difference was not significant. These findings suggest that exposure to methionine and to hydroquinone and its derivatives induce ventilatory impairment, perhaps by an immunological mechanism.     

Human TLR-7-, -8-, and -9-mediated induction of IFN-alpha/beta and -lambda Is IRAK-4 dependent and redundant for protective immunity to viruses

Five TLRs are thought to play an important role in antiviral immunity, sensing viral products and inducing IFN-alpha/beta and -lambda. Surprisingly, patients with a defect of IRAK-4, a critical kinase downstream from TLRs, are resistant to common viruses. We show here that IFN-alpha/beta and -lambda induction via TLR-7, TLR-8, and TLR-9 was abolished in IRAK-4-deficient blood cells. In contrast, IFN-alpha/beta and -lambda were induced normally by TLR-3 and TLR-4 agonists. Moreover, IFN-beta and -lambda were normally induced by TLR-3 agonists and viruses in IRAK-4-deficient fibroblasts. We further show that IFN-alpha/beta and -lambda production in response to 9 of 11 viruses tested was normal or weakly affected in IRAK-4-deficient blood cells. Thus, IRAK-4-deficient patients may control viral infections by TLR-3- and TLR-4-dependent and/or TLR-independent production of IFNs. The TLR-7-, TLR-8-, and TLR-9-dependent induction of IFN-alpha/beta and -lambda is strictly IRAK-4 dependent and paradoxically redundant for protective immunity to most viruses in humans.     

Is laparoscopic treatment of adhesions a valid approach for postoperative abdominal pain?

The role of post-operative adhesions in chronic abdominal pain remains controversial. The aim of this study was to assess the value of laparoscopic treatment of adhesions for chronic post-operative abdominal pain in 32 patients. Over a period of 8 years, 32 patients (25 women and 7 men) with a mean age of 41.5 years (18-69) were hospitalized for chronic abdominal pain of more than 6 months duration, without an obvious underlying neoplasm or psychiatric disorder. They had all undergone at least one previous abdominal operation (mean, 1.9; range, 1-5), with a mean follow-up of 28 months (6-82). The mean duration of the pain was 18 months (6-65) and in 24 of the 32 cases it was mainly hypogastric. Other than the presence of a scar, the clinical examination was completely normal. Prior to hospitalization, 163 different laboratory tests, 162 radiological investigations, including 13 CT scans and 3 MRIs, and 25 endoscopies had been performed. A pneumoperitoneum was made by "open laparoscopy" in 23 cases and with Verres needle in 9 cases. Eight patients (25%) did not have any adhesions, but 6 of them were found to have a gynecological problem (endometriosis). In this group, the laparoscopy lasted 34 minutes (15-45) and the mean hospital stay was 48 hours. In 24 cases, adhesions were found and selected. This was thought to be complete in 22 cases (91.6%). There was a strict correlation between the adhesions and the scar in 85% of cases. In 5 cases, the adhesions were associated with another intervention. There were no conversions. The mean duration of surgery and hospitalization was respectively 56 minutes (32-120) and 3.2 days. There was no mortality and the morbidity rate was 4.1% (1 monopolar injury). The average follow-up was 26.7 months: 22 of the 24 patients who had freeing of adhesions were evaluated after at least 6 months of follow-up. In 10 cases, the pain had completely resolved (45%), in 6 it had decreased (27%) and in 6 cases it was unchanged or had even worsened (1 case of endometriosis). Laparoscopic exploration for chronic post-operative abdominal pain, after an extensive work-up performed after a suitably long delay post-surgery, can be used to detect and treat adhesions in 3/4 cases. In the absence of another lesion, the pain is lessened in 72% cases. However, if there is another lesion, laparoscopic treatment of adhesions is less effective with respect to the pain, but it nevertheless can identify an.     

Laparoscopic splenectomy for hematologic diseases. Study of 275 cases. French Society of Laparoscopic Surgery

AIM OF THE STUDY: To evaluate the results of laparoscopic splenectomy for hematologic diseases by a multicenter retrospective study. PATIENTS AND METHODS: Between 1991 and 1998, 275 patients (mean age: 40.4 years [18-93]) underwent splenectomy for idiopathic thrombocytopenic purpura (ITP) (n = 209, 76%), for hemolytic anemia (HA) (n = 37) including hereditary spherocytosis (n = 13) and auto-immune anemia (n = 24), lymphoma (n = 12), tumor (n = 6) and uncommon hematologic syndromes (n = 11). Laparoscopic splenectomy was attempted in every patient. The lateral approach was most commonly used with an anterior approach to the splenic hilar vessels, which were cut after hemostasis using a stapling gun; other techniques were also employed. RESULTS: The mean operating time was 165 minutes (45-360); it was shorter in the case of conversion (144 minutes) and became shorter with the operator's experience. Conversion was necessary in 55 patients (20%), due to hemorrhage in 2/3 of cases, related to splenic vessels (20 cases), short gastric vessels (9 cases), or injury of the spleen (8 cases). In ten cases (2%), conversion was necessary for extraction of the spleen. Conversion rate varied from 5.3 to 46.7%, depending on the surgical team. Univariate analysis of factors predisposing to conversion identified four causes: obesity; technique used to achieve hemostasis of the splenic hilar vessels; operator's experience; and presence of splenomegaly. An accessory spleen was found in 44 patients (16%). The weight of the spleen was more than 350 g in 43 patients (15.6%). There were no deaths. There were no significant complications in 236 patients (85.8%) and the mean hospital stay was 6.4 days. In comparison with patients who had a conversion, bowel function returned significantly earlier, use of analgesia was reduced and hospital stay was shorter. The overall morbidity rate was 13.8% (n = 38); morbidity rate was only 10.4% (n = 22) for laparoscopic splenectomy. In these 22 patients, the complications were: subphrenic collections (n = 5, 2.2%), abdominal wall infections (n = 5), thromboembolic events (n = 2), anemia (n = 2), pneumonia (n = 1), peptic ulcer (n = 1), bowel obstruction (n = 1), splenic vein thrombosis (n = 1). Re-operations were required in 4 patients (1.8%) because of hemorrhage, pancreatitis and bowel obstruction. Morbidity rate was significantly increased in the case of conversion (27%), obesity (20%), malignant disease (30%) and splenomegaly (21.8%). Forty-four patients (16%) received perioperative or postoperative blood transfusion and 23 (8.3%) received platelet transfusion. Mean time to return to normal activity was 21 days and was shorter in the absence of conversion (18.5 days versus 35 days). In patients with ITP, the mean platelet count was 240,000 after 3 months, and the failure rate was 8.3%. CONCLUSION: Laparoscopic splenectomy is a real alternative to conventional splenectomy for some hematologic diseases, particularly ITP and HA. The advantages are an uneventful postoperative course, a lower morbidity rate, a shorter hospital stay and an earlier return to normal activity. The limits of this technique are related to the operator's experience, the size of the spleen, the nature of the underlying disorders and patient characteristics, mainly obesity.     

Bruton's tyrosine kinase regulates TLR9 but not TLR7 signaling in human plasmacytoid dendritic cells

Plasmacytoid dendritic cells (PDCs) represent a key cell type for both innate and adaptive immunity. PDCs express both TLR7 and TLR9 and the recognition of nucleic acids by these two receptors triggers the production of a large amount of type‐I IFN and the induction of PDC maturation into APCs. This unique feature of PDCs is at the basis of clinical development of both TLR7 and TLR9 agonists for infectious diseases, allergy, cancer, and asthma. However, TLR7 and TLR9 recognition of self‐nucleic acids is linked to many autoimmune diseases including lupus, and a better understanding of the signaling pathways of these two receptors in PDCs is thus important. We have identified Bruton's tyrosine kinase (Btk) as an important player for TLR9 but not TLR7 signaling in human PDCs. Blocking Btk using a specific inhibitor leads to the reduction of all TLR9‐induced responses in PDCs, including cytokine production and expression of costimulatory molecules, while this has no impact on the TLR7 response. This identifies Btk as a key molecule in TLR9 signaling in PDCs and is the first demonstration that the TLR7 and TLR9 pathways can be dissociated in human PDCs.     

Multicenter prospective randomized study comparing the technique of using a bovine pericardium biological prosthesis reinforcement in parietal herniorrhaphy (Tutomesh TUTOGEN) with simple parietal herniorrhaphy,in a potentially contaminated setting

The use of parietal synthetic prosthetic reinforcement material in potentially contaminated settings is not recommended, as there is a risk that the prosthesis may become infected. Thus, simple parietal herniorrhaphy, is the conventional treatment, even though there is a significant risk that the hernia may recur. Using new biomaterials of animal origin presently appears to offer a new therapeutic solution, but their effectiveness has yet to be demonstrated. The purpose of this multicenter prospective randomized single‐blind study was to compare the surgical treatment of inguinal hernia or abdominal incisional hernia by simple parietal herniorrhaphy without prosthetic reinforcement (Group A), with Tutomesh TUTOGEN biological prosthesis reinforcement parietal herniorrhaphy (Group B), in a potentially contaminated setting. We examined early postoperative complications in the first month after the operation, performed an assessment after one year of survival without recurrence and analyzed the quality of life and pain of the patients (using SF‐12 health status questionnaire and Visual Analog Pain Scale) at 1, 6, and 12 months, together with an economic impact study. Hundred and thirty four patients were enrolled between January 2009 and October 2010 in 20 French hospitals. The groups were comparable with respect to their enrollment characteristics, their history, types of operative indications and procedures carried out. At one month post‐op, the rate of infectious complications (n(A) = 11(18.33%) vs. n(B) = 12(19.05%), p = 0.919) was not significantly different between the two groups. The assessment after one year of survival without recurrence revealed that survival was significantly greater in Group B (Group A recurrence: 10, Group B: 3; p = 0.0475). No difference in the patients' quality of life was demonstrated at 1, 6, or 12 months. However, at the 1 month follow‐up, the “perceived health” rating seemed better in the group with Tutomesh (p = 0.022). No significant difference between the two parietal repair groups was observed during the follow‐ups with respect to the criterion of pain (using a visual analog scale). There was a significant difference between the two parietal repair groups with regard to the number of days spent in intensive care unit, in favor of the Tutomesh technique (p = 0.010). The use of a Tutomesh bioprosthesis for hernia repair or postincisional hernia in a potentially contaminated workplace reduces the risk of short‐term recurrence without increasing overall comorbidity.