Positive outcomes following Autologous Matrix-Induced Chondrogenesis (AMIC) in the treatment of retropatellar chondral lesions: a retrospective analysis of a patient registry.

BACKGROUND: The patellofemoral joint is a challenging environment for treating chondral defects. Among the surgical options for the treatment of chondral defects, the single-stage Autologous Matrix-Induced Chondrogenesis (AMIC) procedure uses a porcine collagen I/III membrane to enhance bone-marrow stimulation. However, longer term outcomes data are rare for this specific indication. In order to provide real-world information, an ongoing registry has been established to record patient data and outcomes when AMIC is used to treat chondral and osteochondral lesions. METHODS: Patient data were retrieved from an ongoing, prospective, multisite registry of patients who had undergone AMIC treatment of chondral defects. We identified 64 patients who had undergone AMIC for patellofemoral chondral defects and for whom pre-operative and at least 1 post-operative score were available were included in this retrospective data analysis. Outcomes were assessed via the KOOS, VAS pain, and the Lysholm scores. Outcomes at the post-operative time-points were analysed using a factorial ANOVA with post-hoc testing while linear regression was used to assess associations between the change in the Lysholm score and lesion size. RESULTS: There was a significant improvement in Lysholm, VAS pain, and KOOS scores from pre-operative to the 1st year post-operative (p < 0.001), and this was maintained during the follow-up. CONCLUSIONS: The forces exerted on the patellofemoral joint make this a challenging scenario for chondral repair. Our data demonstrates that the AMIC procedure with a collagen I/III membrane is an effective treatment for retropatellar cartilage lesions, and provides reliable results, with decreased pain and improved function. Importantly, these improvements were maintained through the follow-up period.

Comparison of hamstring and quadriceps tendon autografts in anterior cruciate ligament reconstruction with gait analysis and surface electromyography.

BACKGROUND: Anterior cruciate ligament (ACL) tear is the most frequent ligamentous injury of the knee joint. Autografts of hamstring (HS) or quadriceps tendons (QT) are used for primary ACL reconstruction. In this study, we planned to examine whether harvesting an HS graft is related to a deficit in dynamic knee stabilisation and strength revealed by dynamic valgus as compared with QT graft or the uninjured leg. Furthermore, if this deficit exists, is it compensated by higher neuromuscular activity of the quadriceps muscle? MATERIALS AND METHODS: Adult patients who had undergone ACL reconstruction with QT or HS autografts were included in this two-armed cohort study. Clinical outcome was assessed by clinical data analysis, physical examination and the Lysholm Score and Knee Injury and Osteoarthritis Score (KOOS). In addition, gait analysis and non-invasive surface electromyography were performed. RESULTS: A complete data set of 25 patients (QT: N = 8, HS: N = 17) was analysed. There was no significant demographic difference between the groups. Time between surgery and follow-up was significantly longer for the QT group. Significant differences regarding clinical outcome were not found between the treated and untreated leg or between the two groups, with excellent scores at the time of follow-up. Gait analysis revealed no significant differences of varus-valgus angles. Significant differences in surface electromyography were only found in the QT group with increased vastus medialis obliquus activity of the treated legs (p < 0.01). CONCLUSIONS: Our results suggest that harvesting of HS grafts for primary ACL reconstruction will not lead to a medial collapse and consequently impaired medial stabilisation of the knee when compared with QT grafts. LEVEL OF EVIDENCE: IV.

Mid-term outcome of arthroscopic AMIC for the treatment of articular cartilage defects in the knee joint is equivalent to mini-open procedures.

INTRODUCTION: We present the first retrospective study that compares two various autologous matrix-induced chondrogenesis (AMIC) surgical interventions to repair grade III-IV cartilage defects in the knee. Patients who underwent minimally invasive (arthroscopy) or open (mini-arthrotomy) AMIC were followed up to 2 years to investigate if minimally invasive AMIC is superior to open procedures. MATERIALS AND METHODS: Overall n = 50 patients with focal and contained grade III-IV articular cartilage defects in the knee joint were followed in a consecutive cohort study. 20 patients were treated arthroscopically (female 7, male 13; age: mean 38.2 years, range 18-70 years; BMI: mean 27.0, range 18.7-34.7; defect size: mean 3.1 cm2, range 1.0-6.0 cm2), and 30 patients via mini-arthrotomy (female 13, male 17; age: mean 34.4 years, range 14-53 years, BMI: mean 23.9, range 18.4-28.7; defect size: mean 3.4 cm2, range 1.5-12.0 cm2). The primary defect localization was the medial femoral condyle. RESULTS: AMIC led to a significant improvement of VAS pain, KOOS and Lysholm scoring for up to 2 years compared to pre-op. Outcome analysis revealed no significant differences between the two different surgical approaches. CONCLUSIONS: Our results suggest that mini-open AMIC is equivalent to the arthroscopic procedure. The anticipatory hypothesis that minimally invasive approaches bring greater patient benefit per se could not be confirmed. Therefore, we recommend to perform AMIC where indicated and suggest that the surgeon's personal skills profile guide the choice of surgical approach. LEVEL OF EVIDENCE: III.

[Management and Outcome of Surgery in Patients with Severe Pulmonary Hypertension--A Single-Center Experience]. / Management und postoperatives Überleben bei chirurgischen Eingriffen an Patienten mit schwerer pulmonaler Hypertonie--etrospektive Analyse eines Zentrums.

BACKGROUND: Patients with pulmonary hypertension (PH) are at high risk when undergoing surgery. Up to one-third of patients suffer complications; recent studies report a mortality rate of 1 to 7%. Frequent events are deterioration of right heart function and infectious or bleeding complications. METHODS: Data of patients (age ≥ 18) with precapillary PH who need to undergo elective surgery between January 2006 and March 2015 were included in this retrospective analysis. All patients who were planned for surgery underwent the same procedure. First, patients were evaluated in the PH center. Thereafter, PH-relevant data were discussed with the surgeon/anesthesiologist team for risk-adapted planning of anesthesia and intervention. The present analysis comprises patient characteristics and information about surgery and post-interventional course. RESULTS: This study analyzes 31 surgical procedures carried out in PH patients (male: n = 8; PH-group I: n = 23, group III: n = 3, group IV: n = 5, mean age: 59.5 ± 15.3 years). Patients were characterized by compromised hemodynamics and exercise capacity: pulmonary vascular resistance: 805.4 ± 328.5 dyn*s*cm(-5), mean pulmonary arterial pressure: 46.3 ± 9.3 mmHg, 6-minute walking distance: 350.3 ± 123.3 m.The majority of interventions were performed under general anesthesia (n = 24). In 25 cases, the intraoperative monitoring was complemented with right heart catheterization.Eight interventions were associated with complications, three of which were serious. One patient died postoperatively owing to sepsis and right heart failure. CONCLUSION: A careful and structured planning of surgical interventions in patients with PH and the choice of surgical procedure and anesthesia adapted to the conditions of PH might help avoid complications. Further multicentric studies are needed.

Expression cloning of a cDNA for the major Fanconi anaemia gene, FAA.

Fanconi anaemia (FA) is an autosomal recessive disorder characterized by a diversity of clinical symptoms including skeletal abnormalities, progressive bone marrow failure and a marked predisposition to cancer. FA cells exhibit chromosomal instability and hyper-responsiveness to the clastogenic and cytotoxic effects of bifunctional alkylating (cross-linking) agents, such as diepoxybutane (DEB) and mitomycin C (MMC). Five complementation groups (A-E) have been distinguished on the basis of somatic cell hybridization experiments, with group FA-A accounting for over 65% of the cases analysed. A cDNA for the group C gene (FAC) was reported and localized to chromosome 9q22.3 (ref.8). Genetic map positions were recently reported for two more FA genes, FAA (16q24.3) and FAD (3p22-26). Here we report the isolation of a cDNA representing the FAA gene, following an expression cloning method similar to the one used to clone the FAC gene. The 5.5-kb cDNA has an open reading frame of 4,368 nucleotides. In contrast to the 63-kD cytosolic protein encoded by the FAC gene, the predicted FAA protein (M(r) 162, 752) contains two overlapping bipartite nuclear localization signals and a partial leucine zipper consensus, which are suggestive of a nuclear localization.

Outcome of Autologous Matrix Induced Chondrogenesis (AMIC) in cartilage knee surgery: data of the AMIC Registry.

INTRODUCTION: Autologous Matrix-Induced Chondrogenesis (AMIC) is an innovative treatment for localized full-thickness cartilage defects combining the well-known microfracturing with collagen I/III scaffold. The purpose of this analysis was to evaluate the medium-term results of this enhanced microfracture technique for the treatment of chondral lesions of the knee. METHODS AND MATERIALS: Patients treated with AMIC (Chondro-Gide, Geistlich Pharma, Switzerland) were followed using the AMIC Registry, an internet-based tool to longitudinally track changes in function and symptoms by the Lysholm score and VAS. RESULTS: A series of 57 patients was enrolled. The average age of patients (19 females, 38 males) was 37.3 years (range 17-61 years). The mean defect size of the chondral lesions was 3.4 cm(2) (range 1.0-12.0 cm(2)). All defects were classified as grade III (n = 20) or IV (n = 37) according to the Outerbridge classification. Defects were localized at the medial (n = 32) or lateral (n = 6) condyle, at the trochlea (n = 4) and at the patella (n = 15). The follow-up period was 2 years. The majority of patients were satisfied with the postoperative outcome, reporting a significant decrease of pain (mean VAS preop = 7.0; 1 year postop = 2.7; 2 years postop = 2.0). Significant improvement of the mean Lysholm score was observed as early as 1 year after AMIC and further increased values were noted up to 2 years postoperatively (preop. 50.1, 1 year postop. 79.9, 2 year postop. 85.2). CONCLUSIONS: AMIC is an effective and safe method of treating symptomatic chondral defects of the knee. However, further studies with long-term follow-up are needed to determine if the grafted area will maintain structural and functional integrity over time. LEVEL OF EVIDENCE: Prognostic study, Level IV.

[Medical appraisal of anterior cruciate ligament ruptures]. / Begutachtung der vorderen Kreuzbandruptur.

BACKGROUND: Anterior cruciate ligament tears are one of the most common human ligament ruptures. The assessment of such ruptures is particularly difficult because most ACL injuries involve minimal to no contact. The steps of the assessment are presented with the necessary requirements. METHOD: Criteria for determining the cause of anterior cruciate ligament ruptures are discussed against the background of our experience and the literature. Different definitions of causality apply to German statutory accident insurance (workers' compensation) on the one hand and to private accident insurance on the other. RESULTS: The assessment of disability within the scope of workers' compensation in most cases results in "under 10 to 30%", while in private accident insurance it is rated as 1/10 to 1/20 degree of disablement.

Gross and ultrasonic morphology of the equine conceptus on days 10 to 40.

The gross and ultrasonic equine embryo morphology are described with emphasis on specific days after ovulation. Included are labeled colored photographs and detailed descriptions of the embryo proper (future fetus and foal) and of the entire embryonic vesicle on Days 21, 24, 30, 35/36, and 40. A few related aspects are included for the early fetus on Days 45 and 50. Regression lines for growth in the length of the embryo proper and diameter of the embryonic vesicle along with the mean days of the morphological event are included. Ultrasonograms of the embryonic vesicle are shown and discussed from Days 10 to 45. Major morphological changes in the embryo proper include: (1) appearance of forelimb and hindlimb buds, (2) appearance of the pontine flexure, (3) appearance of the genital tubercle, (4) closure of the pontine flexure, and (5) tapering of limbs toward the midline with hoof-shaped tips. Major changes in the embryonic vesicle are: (1) vascularization of mesoderm, (2) appearance of sinus terminalis, (3) emergence of allantoic sac, (4) formation of embryonic circulatory system, (5) formation and maturation of chorionic girdle, and (6) transition from yolk sac to allantoic sac.

[Antimicrobial treatment in burn injury patients]. / Antimikrobielle Therapie bei Patienten nach Verbrennungstrauma.

Infections are a great diagnostic and therapeutic challenge in intensive care patients with burn injuries. The major problems are due to bacteria with hospital-acquired multiresistance to antibiotics but fungal and viral infections may also be life-threatening. The main key points addressing pharmacotherapy with antibiotic, antifungal and antiviral agents in this special setting are exact diagnosis, early therapy with suitable drugs, adequate duration of treatment and adequate doses based on pharmacokinetic and pharmacodynamic characteristics of these compounds. The latter parameters are significantly altered in burn patients and show a wide interindividual and intraindividual variation in drug response as a result of the characteristic phases of burn injury. Drug concentration analysis may help to avoid inadequate dosing. In this review the main characteristics of burn injuries and the pharmacology of antibiotics, antifungal and antiviral agents in these patients are presented.

Correlation of the Histological ICRS II Score and the 3D MOCART Score for the Analysis of Aged Osteochondral Regenerates in a Large Animal Model.

OBJECTIVE: Reliable outcome measures are essential to predict the success of cartilage repair techniques. Histology is probably the gold standard, but magnetic resonance imaging (MRI) has the potential to decrease the need for invasive histological biopsies. The 3D magnetic resonance observation of cartilage repair tissue (MOCART) score is a reliable yet elaborate tool. Moreover, literature is controversial concerning the correlation of histology and MRI. DESIGN: To test the applicability of the International Cartilage Regeneration and Joint Preservation Society (ICRS) II and MOCART 3D score for the evaluation of aged osteochondral regenerates in a large animal model, and to identify correlating histological and MRI parameters. Osteochondral defects in medial femoral condyles of n = 12 adult sheep were reconstructed with biodegradable bilayer implants. About 19.5 months postoperation, n = 10 joints were analyzed with MRI (3D MOCART score). Histological samples were analyzed using the ICRS II score; both pre- and post-training. The intraclass correlation coefficient, the inter-rater reliability, and the 95% confidence interval were calculated. Matching histological and MRI parameters were tested for correlation. RESULTS: We found a statistically significant correlation of all histological parameters. MRI parameters reflecting "overall" assessments had very strong inter-rater correlations. Statistically significant strong correlations were found for the MRI parameters defect filling, cartilage interface, bone interface, and surface. For defect overall (MRI) and overall assessment (ICRS II), we found a significant yet mild correlation. CONCLUSIONS: The ICRS II and the 3D MOCART score are applicable to aged osteochondral regenerates. Prior training on the scoring systems is essential. Select MRI and histological parameters correlate; however, the only statistically significant correlation was found for overall assessment.

Renal cancer and pneumothorax risk in Birt-Hogg-Dubé syndrome; an analysis of 115 FLCN mutation carriers from 35 BHD families.

BACKGROUND: Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant condition caused by germline FLCN mutations, and characterised by fibrofolliculomas, pneumothorax and renal cancer. The renal cancer risk, cancer phenotype and pneumothorax risk of BHD have not yet been fully clarified. The main focus of this study was to assess the risk of renal cancer, the histological subtypes of renal tumours and the pneumothorax risk in BHD. METHODS: In this study we present the clinical data of 115 FLCN mutation carriers from 35 BHD families. RESULTS: Among 14 FLCN mutation carriers who developed renal cancer 7 were <50 years at onset and/or had multifocal/bilateral tumours. Five symptomatic patients developed metastatic disease. Two early-stage cases were diagnosed by surveillance. The majority of tumours showed characteristics of both eosinophilic variants of clear cell and chromophobe carcinoma. The estimated penetrance for renal cancer and pneumothorax was 16% (95% minimal confidence interval: 6-26%) and 29% (95% minimal confidence interval: 9-49%) at 70 years of age, respectively. The most frequent diagnosis in families without identified FLCN mutations was familial multiple discoid fibromas. CONCLUSION: We confirmed a high yield of FLCN mutations in clinically defined BHD families, we found a substantially increased lifetime risk of renal cancer of 16% for FLCN mutation carriers. The tumours were metastatic in 5 out of 14 patients and tumour histology was not specific for BHD. We found a pneumothorax risk of 29%. We discuss the implications of our findings for diagnosis and management of BHD.

PALB2 analysis in BRCA2-like families.

BRCA2 and PALB2 function together in the Fanconi anemia (FA)-Breast Cancer (BRCA) pathway. Mono-allelic and bi-allelic BRCA2 and PALB2 mutation carriers share many clinical characteristics. Mono-allelic germline mutations of BRCA2 and PALB2 are risk alleles of female breast cancer and have also been reported in familial pancreatic cancer, and bi-allelic mutations cause a severe form of Fanconi anemia. In view of these similarities, we investigated whether the prevalence of PALB2 mutations was increased in breast cancer families with the occurrence of BRCA2 associated tumours other than female breast cancer. PALB2 mutation analysis was performed in 110 non-BRCA1/2 cancer patients: (a) 53 ovarian cancer patients from female breast-and/or ovarian cancer families; (b) 45 breast cancer patients with a first or second degree relative with pancreatic cancer; and (c) 12 male breast cancer patients from female breast cancer families. One truncating PALB2 mutation, c.509_510delGA, resulting in p.Arg170X, was found in a male breast cancer patient. We conclude that germline mutations of PALB2 do not significantly contribute to cancer risk in non-BRCA1/2 cancer families with at least one patient with ovarian cancer, male breast cancer, and/or pancreatic cancer.

Peroxisome proliferator activated receptor-α agonists suppress transforming growth factor-α-induced matrix metalloproteinase-9 expression in human keratinocytes.

The peroxisome proliferator-activated receptors (PPARs), PPARα, PPARδ, and PPARγ, are nuclear ligand-activated transcription factors that are best known as regulators of glucose and lipid metabolism. PPARα agonists have been shown to have profound anti-inflammatory and antiproliferative effects on human keratinocytes, and are important for maintaining homeostasis of the skin. To better characterize the mechanisms underlying these phenomena, we analysed the effects of PPARα agonists on transforming growth factor (TGF)-α-induced expression of matrix metalloproteinase (MMP)-9. MMP-9 expression in keratinocytes has previously been linked to inflammatory skin diseases, regenerative skin mechanisms, and tumour development and metastasis. We found that PPARα agonists effectively inhibited TGF-α-induced MMP-9 expression in human keratinocytes via a post-transcriptional mechanism, revealing a novel and important aspect of the anti-inflammatory and anticarcinogenic action of these compounds.

Mid-term results after operative treatment of rockwood grade III-V acromioclavicular joint dislocations with an AC-hook-plate.

Acromioclavicular joint dislocations often occur in athletic, young patients after blunt force to the shoulder. Several static and dynamic operative procedures with or without primary ligament replacement have been described. Between February 2003 and March 2009 we treated 313 patients suffering from Rockwood III-V lesions of the AC joint with an AC-hook plate. 225 (72 %) of these patients could be followed up. Mean operation time was 42 minutes in the conventional group and 47 minutes in the minimal invasive group. The postoperative pain on a scale from 1 to 10 (VAS-scale) was rated 2.7 in the conventional group and 2.2 in the minimal invasive group. Taft score showed very good and good results in 189 patients (84%). Constant score showed an average of 92.4 of 100 possible points with 89 % excellent and good results and 11 % satisfying results. All patients had some degree of pain or discomfort with the hook-plate in place. These symptoms were relieved after removal of the plate. The overall complication rate was 10.6 %. There were 6 superficial soft tissue infections, 1 fracture of the acromion, 7 redislocations after removal of the hook-plate. We observed 4 broken hooks which could be removed at the time of plate removal, 4 seromas and 2 cases of lateral clavicle bone infection, which required early removal of the plate. We can conclude that clavicle hook plate is a convenient device for the surgical treatment of Rockwood Grade III-V dislocations, giving good mid-term results with a low overall complication rate compared to the literature. Early functional therapy is possible and can avoid limitations in postoperative shoulder function.

[Medium-term results of surgical treatment for osteitis of the clavicle]. / Mittelfristige Ergebnisse der operativen Behandlung bei Claviculaosteitis.

AIM: Osteitis of the clavicle is rare and not well described in the international literature. We describe a concept of surgical treatment with medium-term observations. METHOD: A total of 22 patients (12 women, 10 men; BMI Ø 24.6 kg/m(2), age Ø 48 years) with osteitis of the clavicle were included in the series. The treatment regime consisted of a surgical approach. Data collection was prospective. Data gathered preoperatively and at follow-up included clinical examination, laboratory findings, radiographs and the Constant scoring system. The mean follow-up period was 13.3 (3-53) months. RESULTS: The described surgical concept was able to permanently eliminate infection in all cases studied. Surgical revisions were required in six patients. The average Constant score showed a significant increase from 66 to 84 at follow-up. Patients also showed good functional results after total resection of the clavicle. CONCLUSION: The reported treatment regime provides reliable results in terms of eliminating infection with good clinical results. Neighboring joints were frequently also involved in the infection and needed to be surgically addressed.

Interferon enhances tumor necrosis factor-induced vascular cell adhesion molecule 1 (CD106) expression in human endothelial cells by an interferon-related factor 1-dependent pathway.

Tumor necrosis factor (TNF) and interleukin 1 are known to initiate endothelial vascular cell adhesion molecule (VCAM)-1 transcription primarily by activating nuclear factor (NF)-kappaB, which translocates to the nucleus. In addition to two NF-kappaB elements found within the minimal cytokine-inducible VCAM-1 promoter, an interferon-related factor (IRF) element (IRF-1) has been identified close to the transcription initiation site, suggesting that cytokines that induce IRF-1 might affect VCAM-1 expression levels. We therefore investigated the effects of interferons (IFNs), which strongly induce IRF-1, on VCAM-1 transcription and expression. We show that IFN-alpha and -gamma enhance TNF-induced VCAM-1 mRNA transcription and protein expression in human endothelial cells. IFN enhancement of TNF-induced expression is also seen using chloramphenicol acetyl transferase reporter genes linked to the minimal cytokine inducible VCAM-1 promoter. Nuclear IRF-1 is the molecular basis of IFN enhancement, because (a) IFN plus TNF-treated cells displayed increased nuclear IRF-1 levels and increased IRF-1 binding to the VCAM-1 promoter, compared with cells treated with TNF alone; (b) kinetics of nuclear IRF-1 levels correlated with VCAM-1 mRNA levels; (c) transfection with an IRF-1 construct substituted for IFN treatment; and (d) transfection with an expression construct encoding IRF-2, a competitive inhibitor of IRF-1, reduced TNF-induced VCAM-1 expression. Our experiments show that IFN amplifies TNF-induced VCAM-1 expression at the transcriptional level by an IRF-1-dependent pathway.

Posttraumatic severe infection of the ankle joint - long term results of the treatment with resection arthrodesis in 133 cases.

Although there is a clear trend toward internal fixation for ankle arthrodesis, there is general consensus that external fixation is required for cases of posttraumatic infection. We retrospectively evaluated the technique and clinical long term results of external fixation in a triangular frame for cases of posttraumatic infection of the ankle. From 1993 to 2006 a consecutive series of 155 patients with an infection of the ankle was included in our study. 133 cases of the advanced "Gächter" stage III and IV were treated with arthrodesis. We treated the patients with a two step treatment plan. After radical debridement and sequestrectomy the malleoli and the joint surfaces were resected. An AO fixator was applied with two Steinmann-nails inserted in the tibia and in the calcaneus and the gap was temporary filled with gentamicin beads as the first step. In the second step we performed an autologous bone graft after a period of four weeks. The case notes were evaluated regarding trauma history, medical complaints, further injuries and illnesses, walking and pain status and occupational issues. Mean age at the index procedure was 49.7 years (18-82), 104 patients were male (67.1%). Follow up examination after mean 4.5 years included a standardised questionnaire and a clinical examination including the criteria of the AOFAS-Score and radiographs. 92.7% of the cases lead to a stable arthrodesis. In 5 patients the arthrodesis was found partly-stable. In six patients (4,5%) the infection was not controllable during the treatment process. These patients had to be treated with a below knee amputation. The mean AOFAS score at follow up was 63.7 (53-92). Overall there is a high degree of remaining disability. The complication rate and the reduced patient comfort reserve this method mainly for infection. Joint salvage is possible in the majority of cases with an earlier stage I and II infection.

Mid-term results of Autologous Matrix-Induced Chondrogenesis for treatment of focal cartilage defects in the knee.

Articular cartilage defects heal poorly. Autologous Matrix-Induced Chondrogenesis (AMIC) is an innovative treatment for localized full-thickness cartilage defects combining the well-known microfracturing with collagen scaffold and fibrin glue. The purpose of this prospective study was to evaluate the medium-term results of this enhanced microfracture technique for the treatment of chondral lesions of the knee. Thirty-two chondral lesions in 27 patients were treated with AMIC. Within the context of clinical follow-up, these patients were evaluated for up to 5 years after the intervention. Five different scores (Meyer score, Tegner score, Lysholm score, ICRS score, Cincinnati score) as well as radiographs were used for outcome analysis. Articular resurfacing was assessed by magnetic resonance imaging (MRI). The average age of patients (11 females, 16 males; mean body mass index 26, range 20-32) was 37 years (range 16-50 years). The mean defect size of the chondral lesions was 4.2 cm(2) (range 1.3-8.8 cm(2)). All defects were classified as grade IV according to the Outerbridge classification. The follow-up period was between 24 and 62 months with a mean of 37 months. Twenty out of 23 individuals (87%) questioned were subjectively highly satisfied with the results after surgery. Significant improvement (P < 0.05) of all scores was observed as early as 12 months after AMIC, and further increased values were notable up to 24 months postoperatively. MRI analysis showed moderate to complete filling with a normal to incidentally hyperintense signal in most cases. Results did not show a clinical impact of patient's age at the time of operation, body mass index and number of previous operations (n.s.). In contrast, males showed significant higher values in the ICRS score compared to their female counterparts. AMIC is an effective and safe method of treating symptomatic full-thickness chondral defects of the knee in appropriately selected cases. However, further studies with long-term follow-up are needed to determine whether the grafted area will maintain structural and functional integrity over time.

Early onset of renal cancer in a family with Birt-Hogg-Dubé syndrome.

Birt-Hogg-Dubé syndrome is a hereditary syndrome characterized by benign disease of skin and lungs and a risk of malignant renal tumors. We describe a clinical and genetic study of a large Dutch family with a novel mutation in the FLCN gene. Renal cancer at very young age occurred in one branch of this family, while in other branches, cutaneous and pulmonary symptoms predominated. A variety of congenital anomalies and connective tissue abnormalities were observed, possibly associated with the gene mutation.

Observed ozone response to variations in solar ultraviolet radiation.

During the winter of 1979, the solar ultraviolet irradiance varied with a period of 13.5 days and an amplitude of 1 percent. The zonal mean ozone values in the tropics varied with the solar irradiance, with an amplitude of 0.25 to 0.60 percent. This observation agrees with earlier calculations, although the response may be overestimated. These results imply changes in ozone at an altitude of 48 kilometers of up to 12 percent over an 11-year solar cycle. Interpretation of ozone changes in the upper stratosphere will require measurements of solar ultraviolet radiation at wavelengths near 200 nanometers.