Valgising angular stable plate fixation in the treatment of multifragmentary proximal humeral fractures in elderly patients.

INTRODUCTION: The frequency of proximal humeral fractures shows an increasing tendency, especially in the elderly, who are frequently affected by osteoporosis. The adequate treatment of complex, displaced fractures poses a serious challenge. Among surgical treatment options, osteosynthesis with an angular stable plate is preferred, however, the implant-related complication rate may be exceptionally high. In our present study, we report the short-term outcomes of our new method of valgising angular stable plate fixation which we use for multifragmentary, displaced proximal humeral fractures in elderly patients. MATERIALS AND METHODS: We retrospectively evaluated the clinical and radiological outcomes of 52 patients (46 female and 6 male, age: 71.9 ± 9.6) who suffered dislocated three- or four-part fractures and underwent valgising angular stable plate fixation. RESULTS: Mean follow-up time was 17.3 months, while the functional outcomes were as following: excellent in 26, good in 18, moderate in 5 and poor in 3 patients. The mean Constant-Murley Score was 82.5 ± 11.2. Functional outcomes only showed significant correlation (p = 0.031) with age and were proven unrelated to fracture type, BMI and known primary diseases. The cumulative complication rate was 9.6% and revision rate was 5.8%. Neurological deficit, pseudoarthrosis or avascular humeral head necrosis did not occur during the follow-up period. CONCLUSIONS: Valgising angular stable plate fixation that we apply for proximal humeral fractures provided favourable functional outcomes and a low postoperative complication rate due to the optimal head and plate placement. The method is especially effective for the treatment of displaced three- and four-part fractures with weakened, osteoporotic bone structure.

Comparison of clinical outcome of laparoscopic versus open appendectomy for complicated appendicitis.

BACKGROUND: Laparoscopic appendectomy is now the treatment of choice in uncomplicated appendicitis. To date its importance in the treatment of complicated appendicitis is not clearly defined. METHODS: From January 2005 to June 2013 a total of 1762 patients underwent appendectomy for the suspected diagnosis of appendicitis at our institution. Of these patients 1516 suffered from complicated appendicitis and were enrolled. In total 926 (61 %) underwent open appendectomy (OA) and 590 (39 %) underwent laparoscopic appendectomy (LA). The following parameters were retrospectively analyzed: age, sex, operative times, histology, length of hospital stay, 30-day morbidity focusing on occurrence of surgical site infections, intraabdominal abscess formation, postoperative ileus and appendiceal stump insufficiency, conversion rate, use of endoloops and endostapler. RESULTS: A statistically significant difference in operative time was observed between the laparoscopic and the open group (64.5 vs. 60 min; p = 0.002). Median length of hospitalization was significantly shorter in the laparoscopic group (p < 0.000). Surgical site infections occurred exclusively after OA (38 vs. 0 patients). Intraabdominal abscess formation occurred statistically significantly more often after LA (2 vs. 10 patients; p = 0.002). There were no statistical significances concerning the occurrence of postoperative ileus (p = 0.261) or appendiceal stump insufficiencies (p = 0.076). CONCLUSIONS: The laparoscopic approach for complicated appendicitis is a safe and feasible procedure. Surgeons should be aware of a potentially higher incidence of intraabdominal abscess formation following LA. Use of endobags , inversion of the appendiceal stump and carefully conducted local irrigation of the abdomen in a supine position may reduce the incidence of abscess formation.

Development of an open prospective observational multicentre cohort study to determine the impact of standardization of laparoscopic intraperitoneal onlay mesh repair (IPOM) for incisional hernia on clinical outcome and quality of life (LIPOM-Trial).

BACKGROUND: Incisional hernias are one of the most frequent complications in abdominal surgery. Laparoscopic repair has been widely used since its first description but has not been standardized. A panel of hernia experts with expertise on the subject "incisional hernia" was established to review existing literature and define a standard approach to laparoscopic IPOM-repair for incisional hernia. All involved surgeons agreed to perform further IPOM-repairs of incisional hernia according to the protocol. METHODS/DESIGN: This article summarizes the development of an open prospective observational multicentre cohort study to analyse the impact of a standardization of laparoscopic IPOM-repair for incisional hernia on clinical outcome and quality of life (health care research study). DISCUSSION: Our literature search found that there is a lack of standardization in the surgical approach to incisional hernia and the use of medical devices. The possibility of different surgical techniques, various meshes and a variety of mesh fixation techniques means that the results on outcome after incisional hernia repair are often not comparable between different studies. We believe there is a need for standardization of the surgical procedure and the use of medical devices in order to make the results more comparable and eliminate confounding factors in interpreting the results of surgical hernia repair. This approach, in our view, will also illustrate the influence of the operative technique on the general quality of surgical treatment of incisional hernias better than a "highly selective" study and will indicate the "reality" of surgical treatment not only in specialist centres. TRIAL REGISTRATION: The LIPOM-trial is registered at www.clinicaltrials.gov, with identifier: NCT02089958.

Laparoscopic pelvic mesh placement with closure of pelvic floor entrance to prevent small intestine radiation trauma - A retrospective cohort analysis.

BACKGROUND: In most pelvic malignancies radiation therapy is a main part of the treatment concept. The main dose limiting organ is the small intestine. Different mechanical methods to prevent radiation damage to the small intestine have been described. We herein report a retrospective study of laparoscopic placement of an absorbable vicryl mesh in patients requiring pelvic radiotherapy displacing the bowel out of the radiation field. PATIENTS/METHODS: The study included 6 consecutive patients requiring definitive radiotherapy due to locally advanced prostate cancer. All patients had small intestine within the radiation fields despite the use of non-invasive displacement methods. RESULTS: All patients underwent laparoscopic small bowel displacement from the pelvis and closure of the pelvic floor entrance using vicryl mesh placement. Peri- or postoperative complications were not seen. Postoperative radiotherapy planning CT scans confirmed displacement of the small intestine allowing all patients to receive the planned radiotherapy volume. CONCLUSION: Laparoscopic mesh placement represents a safe and efficient procedure in patients requiring high-dose pelvic radiation, presenting with unacceptable small intestine volume in the radiation field. As an alternate to native tissue, the vicryl mesh is a safe, effective substitute for small bowel exclusion from external-beam radiation therapy.

Effort, safety, and findings of routine preoperative endoscopic evaluation of morbidly obese patients undergoing bariatric surgery.

BACKGROUND: Obesity is becoming an epidemic health problem and is associated with concomitant diseases, such as sleep apnea syndrome and gastroesophageal reflux disease (GERD). There is no standardized diagnostic workup for the upper gastrointestinal tract in obese patients; many patients have no upper gastrointestinal symptoms, and few data are available on safety of endoscopy in morbidly obese patients. METHODS: Sixty-nine consecutive diagnostic upper gastrointestinal endoscopies in morbidly obese patients (26 men, 43 women; mean age 43.4 +/- 10.9 years) were prospectively evaluated from January to December 2008 in an outpatient setting before bariatric procedures. Sedation was administered with propofol. Data on sedation, critical events, and examination times were recorded, as well as pathological findings. RESULTS: The patients' mean body mass index was 47.6 +/- 7.9 (range, 35.1-73.3) kg/m(2); 17.4% reported GERD symptoms. The mean duration of the endoscopy procedure (including sedation) was 20.3 +/- 9.3 (range, 5-50) min, and the whole procedure (including preparation and postprocessing) took 58.2 +/- 19 (range, 20-120) min. The mean propofol dosage was 380 +/- 150 (range, 80-900) mg. Two patients had critical events that required bronchoscopic intratracheal O(2) insufflation due to severe hypoxemia (<60% SaO: (2)). Nearly 80% of patients had pathological findings in the upper gastrointestinal tract. Only 20% reported upper gastrointestinal symptoms. Pathologic conditions were found in the esophagus in 23.2% of the patients, in the stomach in 78.2%, and in the duodenum in 11.6%. The prevalence of Helicobacter pylori infection was 8.7%. CONCLUSIONS: Upper gastrointestinal endoscopy can be performed safely. However, careful monitoring and anesthesiological support are required for patients with concomitant diseases and those receiving sedation. Because 80% of the patients with pathological findings were asymptomatic, every morbidly obese patient should undergo endoscopy before bariatric surgery because there may be findings that might change the surgical strategy.

Dysfunction of the lower esophageal sphincter and dysmotility of the tubular esophagus in morbidly obese patients.

BACKGROUND: Morbid obesity is associated with gastroesophageal reflux (GERD). The aim of this prospective study was to determine esophageal motility in asymptomatic morbidly obese patients and compare it to non-obese individuals. METHODS: Forty-seven morbidly obese patients without GERD symptoms and 15 normal weight individuals were divided into four groups according to their body mass index (BMI; group I, <30 kg/m2; group II, 35-39.9 kg/m2; group III, 40-49.9 kg/m2; group IV, >or=50 kg/m2). Standard stationary water-perfused manometry was performed for the assessment of anatomy and function of the lower esophageal sphincter (LES). Twenty-four-hour ambulatory pH-metry and measurement of esophageal motility were performed with a microtransducer sleeve catheter. Data are given as mean+/-SD, and the results of groups II-IV were compared to the non-obese individuals from group I. RESULTS: Patients with morbid obesity had significantly lower LES pressures than non-obese individuals (I, 15.1+/-4.9; II-IV, 10.5+/-5.4, mmHg, p<0.05 vs. I) and showed an altered esophageal motility with respect to contraction frequency (I, 1.8+/-0.7/min; II-IV, 3.6+/-2.5/min; p<0.05 vs. I) and contraction amplitude (I, 38+/-12 mmHg; II-IV, 33+/-17 mmHg; p<0.05 vs. I). Furthermore, these patients had significantly higher DeMeester scores than non-obese individuals. Length and relaxation of the LES as well as propulsion velocity of the tubular esophagus did not differ. CONCLUSION: Patients with morbid obesity (=BMI>40 kg/m2) have a dysfunction of the LES and an altered esophageal motility, even when they are asymptomatic for GERD symptoms.

[Operative technique and outcome after laparoscopic adjustable gastric banding]. / Operative Technik und deren Outcome in der metabolischen Chirurgie: Adjustable Gastric Banding (AGB).

Laparoscopic gastric banding is an easy to perform procedure with low morbidity and mortality. The benefits of the operation on the metabolic outcome have been demonstrated in long-term studies and are directly proportional to the amount of weight loss. Beside a closely monitored interdisciplinary follow-up, patient compliance is an essential prerequisite for success.

[Ankylosing spondylitis. Therapy and complications of 34 spine fractures]. / Ankylosierende Spondylitis. Therapie und Komplikationen von 34 Wirbelsäulenfrakturen.

BACKGROUND: Spine fractures in ankylosing spondylitis (AS) are extremely unstable and associated with a high complication rate. The aim of this retrospective study was to evaluate the therapy and complications of these fractures in AS for a better understanding and management. PATIENTS AND METHODS: A total of 32 patients with 34 traumatic spine fractures were treated from 1981 to 2002. Cause of trauma, fracture site, and neurological examination were assessed. Analyses of the management of the treatment and complications were performed. RESULTS: Banal traumas resulted mostly in spinal fractures at the C 5/6 and C 6/7 level. Two patients were treated conservatively, while the others were stabilized operatively. Before therapy was undertaken, six patients suffered from a cervical radiculopathy, ten patients had an incomplete and two a complete paraplegia. After therapy, neurological status improved in eight patients, but one had a deterioration of neurological symptoms. CONCLUSIONS: Dorsal or combined dorsoventral stabilization of these fractures is necessary for better mobilization of these patients and to avoid further complications.

Complications in surgical treatment of thoracolumbar injuries.

The range of surgical methods for operative treatment of thoracolumbar injuries, with their different ways of approach, grafts and techniques, remains wide. The authors present sources of error and specific complications based on their own experience and on the results of a multicenter study of the Spine Study Group of the German Trauma Association (DGU). A systematic overview of possible mistakes and complications is first presented in anatomical order. A detailed analysis is then presented of the complications reported in a multicenter study, carried out prospectively between 1994 and 1996, on 682 patients operated for acute traumatic injuries of the thoracolumbar spine. In 101 cases (15%) at least one complication occurred intra- or postoperatively. In 41 patients (6%) a revision was performed, and in 60 patients (9%) complications without operative revision were observed. These complications were analysed according to the chosen method of initial treatment.

Fate of the transpedicular intervertebral bone graft after posterior stabilisation of thoracolumbar fractures.

The authors present a retrospective clinical and radiological study addressing the outcome after posterior stabilisation of thoracolumbar fractures with intervertebral fusion via transpedicular bone grafting. The study included computed tomographic (CT) scan after implant removal for analysis of the intervertebral fusion and incorporation of the intervertebral bone graft and its influence on postoperative re-kyphosing. Twenty-nine patients with acute fractures of the thoracolumbar spine, treated between 1988 and 1995 at the Department of Trauma Surgery, Hannover Medical School, underwent posterior stabilisation and interbody fusion with transpedicular cancellous bone grafting. This study group was followed clinically and radiologically for a mean of 3.5 years. All patients underwent spiral CT scan with sagittal reconstruction after implant removal. Twenty-four type A, four type B, and one type C lesion were posteriorly stabilised and transpedicular intervertebral bone grafting was performed. The operative time averaged 2 h 50 min, the intraoperative fluoroscopy time 4 min 7 s, and the mean intraoperative blood loss was 376 ml. Four patients out of six with an incomplete neurologic lesion (Frankel/ASIA D) improved to Frankel/ASIA grade E. Two complications were observed: one delayed wound healing and one venous thrombosis with secondary pulmonary embolism. Compared to the preoperative status, our follow-up examinations demonstrated permanent social sequelae: the percentage of individuals able to do physical labor was reduced, whereas the proportion of unemployed or retired patients increased. The assessment of complaints and functional outcome with the Hannover Spine Score reflected a significant difference ( P<0.001) between the status before injury (96.6/100 points) and at follow-up (64.4/100 points). The radiographic follow-up revealed a mean loss of correction of 7.8 degrees ( P<0.005). CT scans after implant removal showed an interbody fusion and incorporation of the transpedicular bone graft in ten patients (34%). In another ten patients (34%), the CT scans demonstrated the interbody fusion at the anterior and posterior walls of the vertebral body via direct contact due to collapse of the disc space. In these patients, the bone graft was not incorporated and no central interbody fusion could be found. In nine patients (31%) neither interbody fusion nor incorporation of the transpedicular graft was achieved. A frequent and reliable intervertebral fusion could not be achieved with the described technique of transpedicular bone grafting. The ineffectiveness of the intervertebral graft was found to be a reason for postoperative re-kyphosing.

[Development and validation of the Visual Analogue Scale (VAS) Spine Score]. / Entwicklung und Validierung des VAS-Wirbelsäulenscores.

The aim of the study was the development and validation of a new subjective rating scale for assessment of outcome in patients with thoracolumbar fractures and fracture dislocations. The VAS spine score consists of 19 score items, using 100-mm visual analogue scales. The items are answered by the patients independently of rater assessment. To measure the analogue scales and calculate the score, a computer-aided system was evolved consisting of self-developed software and digitizer board. The overall score is the mean of all items answered with values between 0 and 100. The individual score loss is calculated as the difference between the preinjury score and at follow-up with values between 0 and 100. The VAS spine score was tested for reliability with a group of 136 healthy volunteers. We performed a test-retest study with an interval of 24 h. For statistical analysis of the validity, we prospectively followed a group of 53 patients with the new outcome score. We chose patients with injuries of the thoracolumbar spine, all having been operatively treated by combined posterior-anterior stabilization and fusion between 1994 and 1996. In the reference group, the average test score was 91.95 (58-100) and 92.10 (58-100) at retest. The mean individual difference between test and retest scored 1.037 (0-8). A high reliability was proved by a strong correlation with a coefficient of 0.976 (p < 0.001). A high internal consistency of the VAS spine score was shown by a Cronbach-alpha of 0.9117. The mean score for the preinjury status of the patients was comparable to the reference group, amounting to 89.60 (21-100). The mean score at the time of implant removal was significantly (p < 0.001) decreased to 58.25 (13-97). Until the time of follow-up a significant (p < 0.001) increase was noted, and the group scored 66.08 (15-100) at follow-up. This was a significant (p < 0.001) difference compared with the preinjury status. The individual score loss averaged 24.1 (0-80). In the patient group we also noted a Cronbach-alpha > 0.95, indicating a high internal consistency. With the VAS spine score the authors have inaugurated a new tool for outcome measurement in the treatment of patients with thoracolumbar injuries. The study has proved the score to be both reliable and valid. The application of the score is helpful in analyzing the subjective outcome, and the results can be correlated with objective measures. The score is a useful tool for comparative clinical studies, addressing the outcome after different methods of treatment.

Osteomyocutaneous flap as a preclinical composite tissue allograft: swine model.

Composite tissue allotransplantation (CTA) constitutes one of the last frontiers of microsurgery. Prior to its clinical application, the long-term efficacy of modern immunotherapy must be tested in a pre-clinical CTA model. Based on the concept of osteomyocutaneous forearm flap, we developed a CTA flap model in swine. After identifying the vascular territory of the flaps in six pigs (vascular casting), flaps were transplanted from mismatched donor to recipient pigs (n = 6). Rejection was assessed daily by visual inspection and histopathology of biopsy specimens. Recipient pigs were able to ambulate immediately following surgery. There were no flap failures owing to technical or surgical complications. Rejection occurred over a period of 7 days as manifested by edema, cellular infiltration, epidermalysis, and thrombosis. This pre-clinical flap model is excellent for evaluating the effectiveness of modern immunotherapy because it is anatomically and immunologically relevant and because the minimal morbidity caused to the animal permits long-term studies.

[Post-traumatic osteolysis of the distal clavicle. A case report and review of the literature]]. / Posttraumatische Osteolyse des distalen Klavikulaendes. Ein Fallbericht und Literaturübersicht.

The post-traumatic osteolysis of the distal clavicle is very infrequent and the etiology and pathology is poorly understood. It is important to consider this possibility for differential diagnosis when continued pain in the acromio-clavicular joint (AC joint) follows blunt shoulder trauma. The course of the disease may result in a 3 cm loss of length of the distal clavicle. Months and years may pass until osteolysis becomes manifest, but the earliest radiological findings are present 4 weeks after trauma. The disease is self-limiting and usually does not leave residues. We report a case of a 35-year-old man with a post-traumatic osteolysis of the distal clavicle after blunt shoulder trauma. The diagnosis was determined several months after pain persisted in his shoulder. Using this case we discuss the possible pathogenic mechanism, differential diagnosis and treatment options for the post-traumatic osteolysis of the distal clavicle.

Long-term survival of an extremity composite tissue allograft with FK506-mycophenolate mofetil therapy.

BACKGROUND: High-dose tacrolimus (FK506) monotherapy has significantly prolonged rat hindlimb allograft survival. With an eye toward direct clinical application, we used a large-animal extremity composite tissue allograft model to assess the antirejection efficacy and systemic toxicity of combination FK506-mycophenolate mofetil (MMF) treatment. METHODS: Radial forelimb osteomyocutaneous flap transplants were performed between size-matched outbred pigs assigned to one of two groups: 5 control pigs received no immunosuppression and 9 animals received a once-daily oral FK506-MMF-prednisone regimen. Rejection was assessed by visual inspection of flap skin and was correlated with serial histopathologic examination of skin biopsy specimens. RESULTS: In all control pigs the flap was completely rejected on day 7. Of the 9 pigs receiving treatment, 3 died from pneumonia on days 29, 30, and 83 without signs of rejection and another died from gastric rupture on day 42 with persistent mild rejection. The remaining 5 animals were free of rejection at the end of the 90-day follow-up period (P < 0.005 vs controls). Overall, 5 pigs had pneumonia, 4 septic arthritis, 3 toe abscesses, and 5 diarrhea and decreased weight gain. CONCLUSIONS: Combination oral FK506-MMF treatment provided a superior antirejection effect but more produced more toxicity than that previously demonstrated with cyclosporin A-MMF therapy in our model. Our results suggest that reduction of FK506 or MMF doses might decrease both infectious and drug-specific side effects while still providing adequate prophylaxis against rejection.

Scoring of skin rejection in a swine composite tissue allograft model.

BACKGROUND: For the first time, we define and correlate visual and histologic grading systems of composite tissue allograft (CTA) skin rejection in a large-animal model and determine the utility of these grading systems for early diagnosis and monitoring of rejection. MATERIALS AND METHODS: Sixteen pairs of outbred swine underwent transplant of a forelimb osteomyocutaneous free flap. Group I (n = 6) did not receive immunosuppressive therapy. Group II (n = 10) received oral cyclosporin A, mycophenolate mofetil, and prednisone. The flap was visually inspected and protocol skin biopsies were taken at frequent intervals over a 90-day period. Visual Grades 0 (no rejection) to 4 (severe rejection) were assigned based on skin color, bleeding from biopsy site, and blister formation. Histologic Grades 0 to 4 were assigned based on the degree of vasculitis, folliculitis, dermal inflammation, and epidermal degeneration present. RESULTS: All Group I animals progressively rejected their graft by Day 7. Group II grafts survived from 19 and 90 days; 93% of 115 biopsy specimens were read to be within +/-1 histologic score of their assigned flap visual grade. Visual assessment carried an 8% false positive and 39% false negative rate with regard to biopsy-proven rejection. However, 81% of missed rejection specimens were histologic Grade 1. Biopsy, when visually indicated, would detect all rejection episodes when histologically Grade 1 or 2 and still potentially reversible. CONCLUSIONS: Visual scoring of CTA skin serves as a useful tool for initially detecting rejection, but repeated histologic evaluation is necessary for monitoring the subsequent course of the graft.

Long-term composite tissue allograft survival in a porcine model with cyclosporine/mycophenolate mofetil therapy.

BACKGROUND: Low-dose cyclosporine (CsA)/mycophenolate mofetil (MMF) therapy has significantly reduced the frequency of rejection and drug-induced side effects in rat hindlimb allograft recipients. With an eye toward direct clinical application, we developed a large-animal extremity composite tissue allograft model to assess the antirejection efficacy and systemic toxicity of combination CsA/MMF treatment. METHODS: Radial forelimb osteomyocutaneous flap transplants were performed between size-matched, outbred pigs assigned to one of two groups: 5 control pigs received no immunosuppression, and 10 pigs received a once-daily oral CsA/MMF/prednisone regimen. Rejection was assessed by visual inspection of flap skin and correlated with serial histopathologic examination of skin biopsies. RESULTS: In all control pigs, the flap was completely rejected on day 7. Of the 10 pigs receiving treatment, one died from pneumonia and an another from an anesthetic complication on days 19 and 30, respectively, without signs of rejection. Two flaps were lost on days 25 and 29 from severe rejection. Three pigs were free of rejection at the end of the 90-day follow-up period, and three had stable mild-to-moderate rejection at 90 days (P= 0.0007 vs. controls). White blood cell and platelet counts, serum creatinine values, and liver function tests remained normal in all animals receiving immunosuppressive therapy. CONCLUSIONS: Our results, to our knowledge, demonstrate for the first time that rejection can be significantly delayed in a large-animal composite tissue allograft model including skin using only orally administered agents dosed according to clinically relevant strategies without significant drug-specific systemic side effects.

Analysis of bcl-2+ lymphocyte subpopulations in inflammatory synovial infiltrates by a double-immunostaining technique.

We used a double-immunostaining technique to analyze the distribution of bcl-2+ B and T lymphocytes within the synovial membranes (SM) of 13 patients with rheumatic diseases: 11 with rheumatoid arthritis (RA), 1 with ankylosing spondylitis (AS), and 1 with osteoarthritis (OA). A high proportion (up to 50%) of the lymphocytes belonged to the B cell subset. Most of both T and B lymphocytes were positive for the bcl-2 protein. In germinal centers B lymphocytes were also negative for bcl-2 protein expression, comparable to the situation in germinal centers of secondary lymphatic organs. We conclude that bcl-2- B lymphocytes are submitted to antigen selection in the inflamed SMs while bcl-2 protein expression provides survival signals for their persistence in the infiltrates. The expression of bcl-2 may be an important factor in protecting lymphocytes in SM from apoptosis by glucocorticoids, cytostatic drugs, and irradiation.

The B lymphocyte in rheumatoid arthritis: analysis of rearranged V kappa genes from B cells infiltrating the synovial membrane.

The participation of the humoral immune system in rheumatoid arthritis (RA) is characterized by the production of rheumatoid factors (RF). RF are autoantibodies against the Fc part of IgG which are encoded by diverse germ-line genes. Most of the RF-encoding genes are unmutated, but in RA, a substantial quantity is encoded by somatically mutated genes. In addition, the synovial membranes (SM) of the diseased joints of RA patients are infiltrated by B lymphocytes which form germinal center-like aggregates. To analyze the local immune response, B cell foci from two RA SM were isolated by micromanipulation. From DNA of these foci, the rearranged kappa light chain variable region (V kappa) genes were amplified by polymerase chain reaction (PCR), cloned and sequenced. The amplification of different V kappa-J kappa combinations of different foci suggested oligoclonal expansion of B lymphocytes, which was confirmed by sequence analysis: each PCR product contained members of a single B cell clone. The sequence analysis of 29 different clones revealed rearrangements of diverse V kappa genes. Both frequent representatives of the V kappa 3 and the V kappa 1 family, as well as rarely used genes such as the L10 and B2 genes of the V kappa 2 and V kappa 5 families were found. Of the eleven potentially functional gene rearrangements, eight were significantly mutated, indicating their derivation from antigen-selected B cells. Intraclonal diversity in one of these clones may suggest ongoing mutation in the diseased synovial membrane of patients with RA.