Hôpital Nestlé

The WHO Nomenclature Committee for Factors of the HLA System has met several times since the publication of the last major report in 2010.1 It met most recently in September 2023, to discuss additions to the serological defined HLA antigens. This report documents the additions and revisions to the nomenclature of HLA specificities following the principles established in previous reports.1-19 Links to these reports and details of HLA Nomenclature can be found on the website: hla.alleles.org The HLA-OLI pseudogene has been reported and officially named HLA-R. A full list of all recognised HLA genes is given in Table 1.20 Although at present it is only a recommendation that full-length sequences of the coding region of novel alleles be submitted, it was widely felt that in the future this should become a requirement for submission. Such requirement would remove many of the currently encountered ambiguities in the assignment of names to alleles for which partial sequences have been submitted and should not be burdensome as sequencing techniques have improved substantially since the submission conditions were first devised. In cases where novel mutations or polymorphisms are detected in non-coding regions of the gene, it will be a requirement that full-length sequences be submitted of both the novel allele and its most closely related allele. It should be noted with some caution that cells from which only partial sequences have been obtained may later be shown to have different or novel alleles when further sequencing is performed. This is of particular importance in cases where partial sequences of what appears to be the same allele have been obtained from several different cells. In such cases, all cells studied have been listed in this report. The list of those genes in the HLA region considered by the WHO Nomenclature Committee for Factors of the HLA System is given in Table 1. Current practice is that official designations will be promptly assigned to newly described alleles in periods between Nomenclature Committee meetings, provided that the submitted data and its accompanying description meet the criteria outlined above. A list of the newly reported alleles is published every three months in nomenclature updates in the journals HLA, Human Immunology and the International Journal of Immunogenetics. The listing of references to new sequences does not imply priority of publication. The use of numbers or names for alleles, genes or specificities which pre-empt assignment of official designations by the Nomenclature Committee is strongly discouraged. A total of 43,758 HLA alleles have been named as of December 2025. A complete listing of the numbers of alleles assigned for each HLA genes is given in Table 2. In September 2023, the WHO Nomenclature Committee for Factors of the HLA System met at the Stanford Blood Center located at Stanford University following the 18th International HLA and Immunogenetics Workshop held in Noordwijkerhout, the Netherlands in May 2022. The committee met to evaluate a proposal for the definition of additional and novel antigens defined in silico21. The in silico definition of HLA antigens was achieved by the systematic examination and cataloguing the amino acid (AA) replacements at specific residues determining epitopes (DEP) in all common HLA alleles at the classical HLA class I and class II loci [Common and Well Documented (CWD2.0) for alleles of HLA-DRB3, -DRB4, -DRB5, -DQA1 and -DPA1 and Common, Intermediate and Well Documented (CIWD3.0) for alleles of HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1].21-23 The committee voted to accept the proposed serologic nomenclature update provided that a validation study was conducted. The manuscript aiming to confirm these computationally predicted antigens defined by DEP residues for the 11 HLA loci was designed to assess and compare the antibody reactivity of patients' sera in solid phase assays with Single Antigen Bead (SAB) preparations from various HLA proteins24. The differences in correlation confirmed the distinctions between proposed associated antigens and identified a few additional antigens.21, 25 A full listing of all the serological specificities for HLA-A, -B, -C, -DR, -DQ, and -DP and cellular defined specificities for HLA-Dw and HLA-DPw are given in Table 3. The concept of an HLA Associated Antigen was introduced in 1991, with the understanding that serological types would be more closely associated with the allele sequence defining them. Thirteen associated antigens were named at this time: A203, A210, A2403, B703, B3901, B3902, B4005, B5102, B5103, B7801, DR103, DR1403, and DR1404.12 In 1996 the B2708 associated antigen was named and it was decided to shorten the B7801 antigen name to B78.15 Following the definition of novel associated antigens documented below, it has been necessary to update the names of four of these: A203, A210, B703, and DR103, have been updated to A0203, A0210, B0703, and DR0103. A full listing of all the Associated Antigens for HLA-A, -B, -C, −and -DR are given in Table 4. This report includes nomenclature for the serological specificities encoded by both the HLA-DQA1 and HLA-DQB1 genes. As such it is now possible to define a nomenclature for the paired combination of both subunits of HLA-DQ molecules. Table 5 lists those proteins encoded in cis by common DQ haplotype blocks. The specificities resulting from trans-encoded heterodimers should be presented in the same format. The newly assigned HLA antigens and associated antigens will be implemented in April 2026 and will be made available through the IPD-IMGT/HLA Database (www.ebi.ac.uk/ipd/imgt/hla) with the April 2026 release of the database.26-28 The IPD-IMGT/HLA Database continues to act as the official repository for HLA sequences named by the WHO Nomenclature Committee for Factors of the HLA System.26-28 The database contains sequences for all HLA alleles officially recognised by the WHO Nomenclature Committee for Factors of the HLA System and provides users with online tools and facilities for their retrieval and analysis. These include allele reports, alignment tools, and detailed descriptions of the source cells. The online IPD-IMGT/HLA Database submission tool allows both new and confirmatory sequences to be submitted directly to the WHO Nomenclature Committee. New releases of the database are made every three months, in January, April, July and October, with the latest version (release 3.63.0 January 2026) containing 43,758 HLA alleles. The database may be accessed via the worldwide web at www.ebi.ac.uk/ipd/imgt/hla. The IPD-IMGT/HLA Database is currently supported by the following organisations: NMDP, TxMiller Foundation, CareDx, DKMS, Gift of Life, Werfen, Scisco Genetics, the European Federation for Immunogenetics (EFI), GenDx, Pirche, ThermoFisher, the American Society for Histocompatibility and Immunogenetics (ASHI), LabCorp, Histogenetics, the Asia-Pacific Histocompatibility and Immunogenetics Association (APHIA), BAG Diagnostics, Protrans, Inno-train, and Anthony Nolan. The Committee would like to thank Dominic Barker, Michael Cooper, Sebastian Hopper and Surayia Akter for their work with the IPD-IMGT/HLA Database. Also thanked is Andy Yates and the staff at the European Bioinformatics Institute for their continued support of the IPD-IMGT/HLA Database. We would also like to thank the many organisations that provide financial support for the IPD-IMGT/HLA Database and Benjamin Hester of the ‘NMDP Foundation’ for his work in soliciting and coordinating the funding of this project. We are grateful to Stanford Blood Center for covering the cost for providing open access for this article. SGE Marsh, University College London, London, UK (Chairman) WF Bodmer, Oncology Department, Oxford University, Oxford, UK MN Carrington, Basic Science Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD, USA and Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA & Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA HA Erlich, Benioff UCSF Children's Hospital Oakland Research Institute, Oakland, USA M Fernández-Viña, Stanford Blood Center, Palo Alto, USA & Department of Pathology, Stanford University School of Medicine, Stanford, USA S Heidt, Erasmus Medical Center, Rotterdam, & Leiden University Medical Center, Leiden, The Netherlands R Holdsworth, University of Melbourne, Melbourne, Australia WR Mayr, University of Vienna, Vienna, Austria M Maiers, Center for International Blood and Marrow Transplant Research, (CIBMTR), NMDP, Minneapolis, USA P Parham, Stanford University School of Medicine, Stanford, USA EW Petersdorf, Fred Hutchinson Cancer Center, Seattle, USA J Robinson, Anthony Nolan Research Institute, & University College London, London, UK J Trowsdale, Cambridge University, Cambridge, UK RE Bontrop, Biomedical Primate Research Centre, Rijswijk, The Netherlands K Osoegawa, Stanford Blood Center, Palo Alto, USA New sequences should be communicated to the WHO Nomenclature Committee for Factors of the HLA System via the sequence submission tool of the IPD-IMGT/HLA Database to receive official names, www.ebi.ac.uk/ipd/imgt/hla. The data that support the findings of this study are available from the corresponding author upon reasonable request.

BACKGROUND: The Mini-Nutritional Assessment (MNA) is a validated assessment instrument for nutritional problems, but its length limits its usefulness for screening. We sought to develop a screening version of this instrument, the MNA-SF, that retains good diagnostic accuracy. METHODS: We reanalyzed data from France that were used to develop the original MNA and combined these with data collected in Spain and New MEXICO: Of the 881 subjects with complete MNA data, 151 were from France, 400 were from Spain, and 330 were from New MEXICO: Independent ratings of clinical nutritional status were available for 142 of the French subjects. Overall, 73.8% were community dwelling, and mean age was 76.4 years. Items were chosen for the MNA-SF on the basis of item correlation with the total MNA score and with clinical nutritional status, internal consistency, reliability, completeness, and ease of administration. RESULTS: After testing multiple versions, we identified an optimal six-item MNA-SF total score ranging from 0 to 14. The cut-point score for MNA-SF was calculated using clinical nutritional status as the gold standard (n = 142) and using the total MNA score (n = 881). The MNA-SF was strongly correlated with the total MNA score (r = .945). Using an MNA-SF score of > or = 11 as normal, sensitivity was 97.9%, specificity was 100%, and diagnostic accuracy was 98.7% for predicting undernutrition. CONCLUSIONS: The MNA-SF can identify persons with undernutrition and can be used in a two-step screening process in which persons, identified as "at risk" on the MNA-SF, would receive additional assessment to confirm the diagnosis and plan interventions.

This review has summarized some of the evidence suggesting that cytokines may play an important role in mediating pathophysiologic events in RA. However, these proteins are capable of mediating both stimulatory (agonist) and inhibitory (antagonist) effects in the rheumatoid synovium. GM-CSF, IL-1, TNF alpha, and PDGF are all produced in the rheumatoid synovium and may function to induce inflammation, enzyme release, fibroblast proliferation, and tissue destruction. Local release of IL-6 may alter the effects of IL-1 and TNF alpha, as well as induce Ig production and hepatic synthesis of acute-phase proteins. However, specific inhibitors of IL-1 and TNF alpha exist, which, if also released into the synovium, may antagonize the proinflammatory effects of these cytokines. In addition, IL-1 may have antiinflammatory effects, such as the induction of the synthesis of collagen and enzyme inhibitors by chondrocytes and synovial fibroblasts. Stimulation of these latter cells by TGF beta also may result in decreased matrix degradation and increased formation of scar tissue. The developing scenario is one of cell-cell interactions that are influenced in positive and negative manners by the local release of various mediators. A further understanding of cytokines and cytokine inhibitors in the rheumatoid synovium may lead to the development of more specific and effective therapeutic agents.

This review has summarized information published over the last 5 years on the presence and pathophysiologic role of IL-1 and TNF alpha in RA. The evidence to date shows that 5 of 6 criteria for identifying mediators of tissue damage in human autoimmune diseases are satisfied (Table 1). The last criterion, prevention of clinical progression in patients with RA, is currently being evaluated. Many new therapeutic approaches are currently being developed, including the use of soluble receptors to IL-1 or TNF, monoclonal antibodies to TNF alpha, a specific IL-1 receptor antagonist, and gene therapy with the latter molecule. It should be emphasized that both IL-1 and TNF alpha play important roles in normal host defense; the possible complications of blocking their production or effects need to be carefully evaluated in long-term studies. A recent review has emphasized that although IL-1 and TNF alpha have many overlapping biologic properties, each may exhibit distinct effects in joint disease (99). Anti-TNF treatment may be primarily antiinflammatory but blocking IL-1 may be more effective in preventing cartilage destruction (100). The possibility exists that simultaneous inhibition of TNF alpha and IL-1 may be more therapeutically efficacious than blockade of either agent alone, as was recently demonstrated with IL-1ra and soluble TNF receptors in bacterial cell wall-induced arthritis in rats (101). The next level of clinical studies in rheumatoid arthritis should include the use of two biologic response modifiers together, or one agent combined with a more traditional form of therapy.

Bioavailability is a key step in ensuring bioefficacy of bioactive food compounds or oral drugs. Bioavailability is a complex process involving several different stages: liberation, absorption, distribution, metabolism and elimination phases (LADME). Bioactive food compounds, whether derived from various plant or animal sources, need to be bioavailable in order to exert any beneficial effects. Through a better understanding of the digestive fate of bioactive food compounds we can impact the promotion of health and improvement of performance. Many varying factors affect bioavailability, such as bioaccessibility, food matrix effect, transporters, molecular structures and metabolizing enzymes. Bioefficacy may be improved through enhanced bioavailability. Therefore, several technologies have been developed to improve the bioavailability of xenobiotics, including structural modifications, nanotechnology and colloidal systems. Due to the complex nature of food bioactive compounds and also to the different mechanisms of absorption of hydrophilic and lipophilic bioactive compounds, unravelling the bioavailability of food constituents is challenging. Among the food sources discussed during this review, coffee, tea, citrus fruit and fish oil were included as sources of food bioactive compounds (e.g. (poly)phenols and polyunsaturated fatty acids (PUFAs)) since they are examples of important ingredients for the food industry. Although there are many studies reporting on bioavailability and bioefficacy of these bioactive food components, understanding their interactions, metabolism and mechanism of action still requires extensive work. This review focuses on some of the major factors affecting the bioavailability of the aforementioned bioactive food compounds.

The primary source for the blood supply of the head of the femur is the deep branch of the medial femoral circumflex artery (MFCA). In posterior approaches to the hip and pelvis the short external rotators are often divided. This can damage the deep branch and interfere with perfusion of the head. We describe the anatomy of the MFCA and its branches based on dissections of 24 cadaver hips after injection of neoprene-latex into the femoral or internal iliac arteries. The course of the deep branch of the MFCA was constant in its extracapsular segment. In all cases there was a trochanteric branch at the proximal border of quadratus femoris spreading on to the lateral aspect of the greater trochanter. This branch marks the level of the tendon of obturator externus, which is crossed posteriorly by the deep branch of the MFCA. As the deep branch travels superiorly, it crosses anterior to the conjoint tendon of gemellus inferior, obturator internus and gemellus superior. It then perforates the joint capsule at the level of gemellus superior. In its intracapsular segment it runs along the posterosuperior aspect of the neck of the femur dividing into two to four subsynovial retinacular vessels. We demonstrated that obturator externus protected the deep branch of the MFCA from being disrupted or stretched during dislocation of the hip in any direction after serial release of all other soft-tissue attachments of the proximal femur, including a complete circumferential capsulotomy. Precise knowledge of the extracapsular anatomy of the MFCA and its surrounding structures will help to avoid iatrogenic avascular necrosis of the head of the femur in reconstructive surgery of the hip and fixation of acetabular fractures through the posterior approach.

BACKGROUND: Biologic therapies such as adalimumab, a tumour necrosis factor antagonist, are safe and effective in the treatment of moderate to severe chronic plaque psoriasis. OBJECTIVES: To compare a biologic agent with methotrexate, a traditional systemic agent, to define clearly the role of biologics in psoriasis. METHODS: Patients with moderate to severe plaque psoriasis were randomized to adalimumab (80 mg subcutaneously at week 0, then 40 mg every other week, n=108), methotrexate (7.5 mg orally, increased as needed and as tolerated to 25 mg weekly; n=110) or placebo (n=53) for 16 weeks. The primary efficacy endpoint was the proportion of patients achieving at least a 75% improvement in the Psoriasis Area and Severity Index (PASI 75) after 16 weeks. Safety was assessed at all visits through week 16. RESULTS: After 16 weeks, 79.6% of adalimumab-treated patients achieved PASI 75, compared with 35.5% for methotrexate (P<0.001 vs. adalimumab) and 18.9% for placebo (P<0.001 vs. adalimumab). Statistically significantly more adalimumab-treated patients (16.7%) than methotrexate-treated patients (7.3%) or placebo-treated patients (1.9%) achieved complete clearance of disease. The response to adalimumab was rapid, with a 57% improvement in mean PASI observed at week 4. Adverse events were similar across treatment groups. Adverse events leading to study discontinuation were greatest in the methotrexate group, primarily because of hepatic-related adverse events. CONCLUSIONS: After 16 weeks, adalimumab demonstrated significantly superior efficacy and more rapid improvements in psoriasis compared with either methotrexate or placebo.

We have studied the mechanical properties of several current techniques of tendon-to-bone suture employed in rotator-cuff repair. Non-absorbable braided polyester and absorbable polyglactin and polyglycolic acid sutures best combined ultimate tensile strength and stiffness. Polyglyconate and polydioxanone sutures failed only at high loads, but elongated considerably under moderate loads. We then compared the mechanical properties of nine different techniques of tendon grasping, using 159 normal infraspinatus tendons from sheep. The most commonly used simple stitch was mechanically poor: repairs with two or four such stitches failed at 184 N and 208 N respectively. A new modification of the Mason-Allen suture technique improved the ultimate tensile strength to 359 N for two stitches. Finally, we studied the mechanical properties of several methods of anchorage to bone using typically osteoporotic specimens. Single and even double transosseous sutures and suture anchor fixation both failed at low tensile loads (about 140 N). The use of a 2 mm thick, plate-like augmentation device improved the failure strength to 329 N. The mechanical properties of many current repair techniques are poor and can be greatly improved by using good materials, an improved tendon-grasping suture, and augmentation at the bone attachment.

We investigated the antihypertensive effect of the angiotensin converting-enzyme inhibitor SQ 14225 in 12 hypertensive patients for periods of three to 24 weeks. Blood pressure decreased in all patients (from 177 +/- 8/110 +/- 2 to 136 +/- 6/88 +/- 2 mm Hg--mean +/- S.E.); oral doses ranged from 400 to 1000 mg daily. Concomitant effects noted were small increases in plasma potassium concentration and pulse rate. One patient experienced a transient febrile reaction. Plasma renin activity rose during treatment, plasma aldosterone decreased, and angiotensin-converting-enzyme activity was virtually eliminated. There was no significant correlation between pretreatment plasma renin activity and degree of blood-pressure fall with SQ 14225. The exact mechanisms contributing to the blood-pressure-lowering effect of this agent remain unclear. SQ 14225 is a promising new antihypertensive agent, effective in patients refractory to traditional medical therapy.

Sixteen consecutive patients were managed operatively for repair of an isolated traumatic rupture of the subscapularis tendon in the absence of avulsion of the lesser tuberosity. All of the patients were men. The diagnosis was made for each patient on the basis of the clinical examination and was confirmed by imaging studies and operative exploration. The operative treatment consisted of mobilization of the subscapularis after exploration and protection of the axillary nerve, transosseous reinsertion of the tendon to a trough created at the lesser tuberosity, closure of the rotator interval, and protection of the shoulder for six weeks postoperatively. The average duration of follow-up was forty-three months (range, twenty-four to eighty-four months). Thirteen patients subjectively rated the result as excellent or good. The average functional score of the shoulder, as assessed according to the system of Constant, was 82 per cent of the average age and gender-matched normal value. Active flexion was normal in twelve patients, was decreased by 15 degrees or less in three, and was severely limited in one patient. The capacity of the patients to work in their original occupations had increased from an average of 59 per cent of full capacity preoperatively to an average of 95 per cent postoperatively (p = 0.006). Operative treatment proved to be economically sound within the Swiss National Accident Insurance system. The quality of the result did not depend on the capacity for work at the time of the operation, on the type of work in which the patient was engaged, on the state of the biceps, or on the duration of follow-up. Conversely, the results were less successful when there was an increased delay from the time of the injury to the time of the operative repair.

Four mutants of Staphylococcus aureus strain Newman that were defective in the fibrinogen receptor (clumping factor) were isolated by transposon Tn917 mutagenesis. Southern hybridization analysis of the mutants identified transposon-host DNA junction fragments, one of which was cloned and used to generate a probe to identify and clone the wild-type clumping factor locus (clfA). The mutants failed to form clumps in soluble fibrinogen and adhered poorly to polymethylmethacrylate (PMMA) coverslips coated with fibrinogen. A single copy of the clfA gene, when introduced into the chromosome of the mutant strains, fully complemented the clumping deficiency of these strains and restored the ability of these mutants to adhere to fibrinogen-coated PMMA. In addition, the cloned clfA gene on a shuttle plasmid allowed the weakly clumping strain 8325-4 to form clumps with the same avidity as the wild-type strain Newman and also significantly enhanced the adherence of 8325-4 strains. Thus the formation of clumps in soluble fibrinogen correlated with adherence of bacteria to solid-phase fibrinogen. The clfA gene encodes a fibrinogen-binding protein with an apparent molecular mass of c. 130 kDa. The amino acid sequence of the protein was deduced from the DNA sequence; it was predicted that a 896 residue protein (molecular mass 92 kDa) would be expressed. The putative ClfA protein has features that suggest that it is associated with the cell surface. Furthermore it contains a novel 308 residue region comprising dipeptide repeats predominantly of Asp and Ser ending 28 residues upstream from the LPXTG motif common to wall-associated proteins. Significant homology was found between the ClfA protein and the fibronectin-binding proteins of S. aureus, particularly in the N- and C-termini.

BACKGROUND: Influenza causes lower respiratory tract complications (LRTCs), particularly bronchitis and pneumonia, in both otherwise healthy adults and those with underlying conditions. The aim of this study was to assess the effect of oseltamivir treatment on the incidence of LRTCs leading to antibiotic treatment and hospitalizations following influenza illness. METHODS: We analyzed prospectively collected data on LRTCs and antibiotic use from 3564 subjects (age range, 13-97 years) with influenzalike illness enrolled in 10 placebo-controlled, double-blind trials of oseltamivir treatment. RESULTS: In adults and adolescents with a proven influenza illness, oseltamivir treatment reduced overall antibiotic use for any reason by 26.7% (14.0% vs 19.1% with placebo; P<.001) and the incidence of influenza-related LRTCs resulting in antibiotic therapy by 55% (4.6% vs 10.3% with placebo; P<.001). In those subjects considered at increased risk of complications, 74 (18.5%) of 401 placebo recipients developed an LRTC leading to antibiotic use compared with 45 (12.2%) of 368 oseltamivir recipients (34.0% reduction; P =.02). Hospitalization for any cause occurred in 18 (1.7%) of 1063 placebo recipients compared with 9 (0.7%) of 1350 oseltamivir-treated patients (59% reduction; P =.02). In contrast, among subjects with an influenzalike illness but without a confirmed influenza infection, the incidence of LRTCs (6.7% vs 5.3%), overall antibiotic use (19.7% vs 19.3%), or hospitalizations (1.7% vs 1.9%) was similar between placebo and oseltamivir recipients, respectively. CONCLUSION: Oseltamivir treatment of influenza illness reduces LRTCs, antibiotic use, and hospitalization in both healthy and "at-risk" adults.

The oral perception of fat has traditionally been considered to rely mainly on texture and olfaction, but recent findings suggest that taste may also play a role in the detection of long chain fatty acids. The two G-protein coupled receptors GPR40 (Ffar1) and GPR120 are activated by medium and long chain fatty acids. Here we show that GPR120 and GPR40 are expressed in the taste buds, mainly in type II and type I cells, respectively. Compared with wild-type mice, male and female GPR120 knock-out and GPR40 knock-out mice show a diminished preference for linoleic acid and oleic acid, and diminished taste nerve responses to several fatty acids. These results show that GPR40 and GPR120 mediate the taste of fatty acids.

AIM: To examine adolescent food consumption trends in the United States with important chronic disease implications. METHODS: Analysis of dietary intake data from four nationally representative United States Department of Agriculture surveys of individuals 11-18 years of age (n = 12 498). RESULTS: From 1965 to 1996, a considerable shift in the adolescent diet occurred. Total energy intake decreased as did the proportion of energy from total fat (39% to 32%) and saturated fat (15% to 12%). Concurrent increases occurred in the consumption of higher fat potatoes and mixed dishes (pizza, macaroni cheese). Lower fat milks replaced higher fat milks but total milk consumption decreased by 36%. This decrease was accompanied by an increase in consumption of soft drinks and non-citrus juices. An increase in high fat potato consumption led to an increase in vegetable intake but the number of servings for fruits and vegetables is still below the recommended five per day. Iron, folate, and calcium intakes continue to be below recommendations for girls. CONCLUSIONS: These trends, far greater than for US adults, may compromise health of the future US population.

The clinical activity of rituximab has been evaluated in a phase 2 study in both untreated and relapsed mucosa-associated lymphoid tissue (MALT) lymphomas. Treatment consisted of 4 standard (375 mg/m2) weekly doses. Thirty-five patients were enrolled, and 34 completed the treatment program. The primary lymphoma location was stomach in 15 patients, and extragastric in 20. Eleven patients had previously been treated with chemotherapy. At study entry 12 patients had Ann Arbor stage IE, 3 had stage IIE, and 20 had stage IV disease. The overall response rate was 73% (95% confidence interval, 56%-87%), with 15 complete responses and 10 partial responses, and the response rate was significantly higher in the chemotherapy-naive patients, who had an 87% response rate compared with 45% of the previously treated patients (P =.03). The median response duration was 10.5 months. At a median follow-up of 15 months, 9 patients (26%) relapsed. The median time to treatment failure was 14.2 months in the whole series, but it was significantly longer (22 versus 12 months) in the chemotherapy-naive patients compared with those who had prior chemotherapy (P =.001). Most adverse events were of mild to moderate severity with no grade 4 toxicity. This study indicates that rituximab is safe with significant activity in MALT lymphomas.

A case-control study on larynx and hypopharynx cancer was carried out in 6 populations including the city of Turin and the province of Varese (Italy), the provinces of Navarra and Zaragoza (Spain), the canton of Geneva (Switzerland), and the département of Calvados (France). This report presents an analysis of the risk associated with alcohol and tobacco consumption based on 1,147 male cases and 3,057 male population controls. Special attention was given to the study of the risk at various sites of larynx and hypopharynx. The effect of tobacco is similar for all sites and the risk associated with ever smoking is on the order of 10. The risks from alcohol drinking depend on site. They are similar for epilarynx and hypopharynx (RR = 4.3, for more than 80 g/day) and lower for endolarynx (RR = 2.1, for more than 80 g/day). For all sites the risk decreases after quitting (RR = 0.3 after 10 years); exclusive use of filter cigarettes is protective (RR = 0.5 relative to smokers of plain cigarettes only) as is exclusive use of blond tobacco (RR = 0.5 relative to smokers of black tobacco only). Inhalation increases the risk of endolaryngeal cancer but not that of hypopharynx or epilarynx. The relative risks for joint exposure to alcohol and tobacco are consistent with a multiplicative model.

The primary source for the blood supply of the head of the femur is the deep branch of the medial femoral circumflex artery (MFCA). In posterior approaches to the hip and pelvis the short external rotators are often divided. This can damage the deep branch and interfere with perfusion of the head. We describe the anatomy of the MFCA and its branches based on dissections of 24 cadaver hips after injection of neoprene-latex into the femoral or internal iliac arteries. The course of the deep branch of the MFCA was constant in its extracapsular segment. In all cases there was a trochanteric branch at the proximal border of quadratus femoris spreading on to the lateral aspect of the greater trochanter. This branch marks the level of the tendon of obturator externus, which is crossed posteriorly by the deep branch of the MFCA. As the deep branch travels superiorly, it crosses anterior to the conjoint tendon of gemellus inferior, obturator internus and gemellus superior. It then perforates the joint capsule at the level of gemellus superior. In its intracapsular segment it runs along the posterosuperior aspect of the neck of the femur dividing into two to four subsynovial retinacular vessels. We demonstrated that obturator externus protected the deep branch of the MFCA from being disrupted or stretched during dislocation of the hip in any direction after serial release of all other soft-tissue attachments of the proximal femur, including a complete circumferential capsulotomy. Precise knowledge of the extracapsular anatomy of the MFCA and its surrounding structures will help to avoid iatrogenic avascular necrosis of the head of the femur in reconstructive surgery of the hip and fixation of acetabular fractures through the posterior approach.

This paper reports on a scientific workshop to study anterior cruciate ligament (ACL) reconstruction. The aim is to present recommendations for ACL reconstruction methods that will be of use for surgeons. A study of knee anatomy and graft placement concluded that the tibial attachment must be posterior enough to avoid graft impingement against the femur, and methods to attain this were presented. On the femur, poor graft placement leads to excessive changes of the graft attachment site separation distance as the knee flexes, and the worst case corresponds to the attachment being too far anterior. It was agreed that there were typical patterns of graft tension changes as the knee flexes, and that grafts should be tensioned close to full knee extension. A typical tensioning protocol would be 60 N tension applied at 10 degrees of flexion. It was recognised that graft remodelling caused uncontrollable tension changes post-operation. Graft twisting, to recreate the anatomical spiral of ACL fibres seen in the flexed knee, was also discussed.

Aldosterone controls sodium reabsorption and potassium secretion in the aldosterone-sensitive distal nephron (ASDN). Although clearance measurements have shown that aldosterone induces these transports within 30--60 min, no early effects have been demonstrated in vivo at the level of the apical epithelial sodium channel (ENaC), the main effector of this regulation. Here we show by real-time RT-PCR and immunofluorescence that an aldosterone injection in adrenalectomized rats induces alpha-ENaC subunit expression along the entire ASDN within 2 h, whereas beta- and gamma-ENaC are constitutively expressed. In the proximal ASDN portions only, ENaC is shifted toward the apical cellular pole and the apical plasma membrane within 2 and 4 h, respectively. To address the question of whether the early aldosterone-induced serum and glucocorticoid-regulated kinase (SGK) might mediate this apical shift of ENaC, we analyzed SGK induction in vivo. Two hours after aldosterone, SGK was highly induced in all segment-specific cells of the ASDN, and its level decreased thereafter. In Xenopus laevis oocytes, SGK induced ENaC activation and surface expression by a kinase activity-dependent mechanism. In conclusion, the rapid in vivo accumulation of SGK and alpha-ENaC after aldosterone injection takes place along the entire ASDN, whereas the translocation of alpha,beta,gamma-ENaC to the apical plasma membrane is restricted to its proximal portions. Results from oocyte experiments suggest the hypothesis that a localized activation of SGK may play a role in the mediation of ENaC translocation.

PURPOSE: This study was performed to determine the accuracy of correction in the frontal plane and to evaluate whether a frontal plane correction influences the sagittal slope of the proximal tibial surface in open-wedge high tibial osteotomy. TYPE OF STUDY: Retrospective review. METHODS: In this study, 30 patients (32 knees) with a mean age of 38 years (range, 20 to 66 years) were available for follow-up evaluation at a minimum interval of 24 months (mean, 42 months; range, 24 to 62 months). A normal axis was planned for a varus morphotype without evidence of osteoarthrosis. If one third of the thickness of the medial cartilage was lost, the new mechanical axis was planned to pass lateral to the center of the knee at the 10% position (where the 0% position is at the center of the knee joint and the 100% position is at the lateral border of the plateau). When two thirds were lost, the new mechanical axis was planned to pass through the 20% position. If total cartilage loss was present, the mechanical axis was planned to pass through the 30% position. The correction was estimated as good when the mechanical axis was found to be approximately +/- 5% of the width of the tibial plateau. The angle of the osteotomy and the size of the wedge-shaped bone graft were calculated using the "push" orthoradiogram. RESULTS: Consolidation of the osteotomy was obtained after a mean period of 8.4 weeks (range, 6 to 13 weeks). The mean amount of valgus correction was 5.9 degrees. Sixteen of 32 knees (50%) showed the desired position of the mechanical axis. Ten knees (31%) showed an undercorrection; 6 knees (19%) an overcorrection. The mean increase of the posterior tibial slope was 2.7 degrees (range, -8 degrees to 10 degrees ). CONCLUSIONS: The medial open-wedge osteotomy of the proximal tibia has a tendency to increase the posterior tibial slope. This effect is unfavorable in anterior knee instability because it increases the anterior translation of the tibia. Increasing the posterior slope can be favorable in posterior instability because it reduces the posterior sag. LEVEL OF EVIDENCE: Level IV.