CD56+/CD16- Natural Killer cells expressing the inflammatory protease granzyme A are enriched in synovial fluid from patients with osteoarthritis.

OBJECTIVE: Natural killer (NK) cells have been involved in the pathology of different inflammatory and autoimmune disorders. Inflammation is an important regulator of osteoarthritis (OA), but the molecular and cellular mechanisms regulating this process are not well defined. DESIGN: To understand the role of NK cells in OA, we have compared the phenotype (CD56 subsets and perforin and granzyme expression) and cytotoxic function of NK cells in peripheral blood and synovial fluid from patients with OA undergoing total knee arthroplasty. RESULTS: In contrast to peripheral blood lymphocytes (PBLs), the majority of NK cells from the synovial fluid were CD56brightCD16(-) cells. As expected the expression of the cytolytic mediators perforin and granzyme B in CD56brightCD16(-) cells was low and correlated with a poor cytotoxic potential against K562 sensitive target cells. Surprisingly, this low cytotoxic NK cell subset expressed high levels of granzyme A (a protease recently characterized as a key modulator of inflammation in mouse models) in synovial fluid but not in peripheral blood. The presence of the CD56(+)brightCD16(-) cells expressing granzyme A correlated with increased levels of pro-inflammatory cytokines in synovial fluid from OA patients. CONCLUSION: Our results indicate that NK cells from the synovium of patients with OA, which present an immunoregulatory non-cytotoxic phenotype, show different phenotype comparing with NK cells from peripheral blood, especially expressing granzyme A, a pro-inflammatory molecule which may contribute to the establishment of chronic articular inflammation in this type of patients.

Pharmacological immunomodulation of surgical trauma.

Surgery and accidental trauma induce changes in the immune response, showing a predominant pattern of activation through the Th2 cell pathway to the detriment of Th1 cell pathway activation. Anapsos is a hydrosoluble extract obtained from Polypodium leucotomos. Anapsos has shown immunomodulating effects in vitro. On a rat experimental model (tibia and fibula fracture), cytokines (interleukin [IL]-2, IL-4, IL-6, IL-10, and IL-12) (enzyme-linked immunosorbent assay, ELISA) and cell percentages of CD4, CD8 CD25, CD122, and CD132 (monoclonal antibodies, MoAb) were determined in peripheral blood 7 days before surgery (PRE), 1 day after surgery (1PO), and 7 days after surgery (7PO). On postoperative day 1, rats undergoing fracture show an increase of CD8 percent expression and IL-6 and IL-10 levels, in contrast to rats undergoing fracture plus anapsos treatment. On postoperative day 7, rats undergoing fracture show an increase of IL-6 levels, whereas rats undergoing fracture plus anapsos do not. The IL-12 level decreases on postoperative day 7 in the group with fracture but not in the fracture plus anapsos group. Thus, we conclude that anapsos is able to modulate the immune response after trauma, inhibiting Th2 pathway activation with no effect on Th1 pathway activation. In trauma, Anapsos could prevent the shifting Th1/Th2 balance.

Fractography evolution in accelerated aging of UHMWPE after gamma irradiation in air.

We studied the fracture surface evolution of ultra high molecular weight polyethylene (UHMWPE) specimens, manufactured from GUR 1050 compression moulded sheets, after gamma sterilisation in air followed by different aging times after thermal treatment at 120 degrees C. Degradation profiles were obtained by FTIR and DSC measurements after 0, 7, 14, 24 and 36h aging. We observed by SEM the morphology patterns at these aging times, in surface fractographies after uniaxial tensile test of standardised samples. The results pointed out clear differences between short and long aging times. At shorter times, 7h, the behaviour was similar to non-degraded UHMWPE, exhibiting ductile behaviour. At longer times, 24-36h, this thermal protocol provided a highly degraded zone in the subsurface, similar to the white band found after gamma irradiation in air followed by natural aging, although closer to the surface, at 150-200mum. The microstructure of this oxidation zone, similarly found in gamma irradiated samples shelf-aged for 6-7 years, although with different distribution of microvoids, was formed by fibrils, associated with embrittlement of the oxidised UHMWPE. In addition, the evolution of the oxidation index, the enthalpy content, the mechanical parameters, and the depth of the oxidation front deduced from the fractographies versus aging time showed that a changing behaviour in the degradation rate appeared at intermediate aging times.

A simple infection model using pre-colonized implants to reproduce rat chronic Staphylococcus aureus osteomyelitis and study antibiotic treatment.

Staphylococcus aureus biofilms formed on medical implants represent a serious problem, being difficult to eradicate with antibiotic therapy and leading to chronic infections. Simplified in vivo and in vitro antibiotic susceptibility assays using biofilm bacteria are needed. In this work, a novel chronic osteomyelitis infection model was developed in rats in the absence of bacterial suspension, requiring the use of only 10(6) bacteria in biofilms at the site of surgery, with a full success in reproducing infection. Stainless-steel implants pre-colonized for 12 h with a highly adherent S. aureaus isolate were introduced into the rat tibiae. In animals not submitted to antibiotic treatment, infection was found in the implants and spread to bone in all cases, indicating the high efficacy of the model to reproduce osteomyelitis. The effect of a 21-day treatment with cefuroxime, vancomycin, tobramycin or ciprofloxacin on infection was studied in this model 42 days after surgery. Bone colonization was inhibited by vancomycin and cefuroxime. Cefuroxime (the most efficient antibiotic, able to sterilize 1 out of 8 implants) reduced the number of bacteria in biofilms adhered to implants at a higher extent than vancomycin, trobramycin and ciprofloxacin. Analogous observations were made in this work in vivo and in vitro on the relative antibiotic efficacy against S. aureus biofilm bacteria. suggesting the usefulness of both tests as a potential tool to study antibiotic suceptibility, and the need for new antimicrobials against these bacteria.

The increase in erythrocyte deformability in patients treated with nicardipine or nimodipine.

A study was made of a total of 50 patients, 36 females and 14 males, with an average age of 51.3 +/- 11.71 years (range 19-71). The group consisted of outpatients who came to the neurology clinic suffering from vascular headache or other symptomatic complaint of vascular type. In all cases, the existence of an organic neurological pathology had been considered and rejected. All patients who were smokers or suffering from hypertension were excluded, as well as those who had abnormal lipid or glucose values or who were on drug treatment for other reasons. The basal erythrocyte deformability value was determined and the patients divided into two random homogeneous groups. One of the groups was treated with nimodipine (90 mg/d) and the other with nicardipine (60 mg/d) for a period of two months. After this treatment period a further determination of the erythrocyte deformability was carried out. In the group treated with nimodipine, the erythrocyte deformability varied from 45.5 +/- 7.4 mcl/s to 50.35 +/- 12.02 mcl/s (p = 0.07123). In the group treated with nicardipine, these values varied from 45.96 +/- 7.35 mcl/s to 56.21 +/- 12.72 mcl/s (p = 0.00079). It was concluded that in both groups of patients, after two months treatment with these calcium antagonists, there was an improvement in erythrocyte deformability and, therefore, in blood fluidity, although only the nicardipine-treated group reached statistically significant levels.

Ganglion cysts associated with cruciate ligaments of the knee: a possible cause of recurrent knee pain.

Intraarticular ganglia of the knee are uncommon; however, these ganglion cysts may produce knee discomfort without a clear etiology. We present the cases of 10 patients with ganglion cysts arising from cruciate ligaments of the knee joint who underwent arthroscopic excision after MR examination. The MR findings, clinical features and arthroscopic findings were evaluated comparatively. Diagnoses were confirmed by means of a histological study after arthroscopic excision. The cysts were fluid-filled, with low T1-weighted signal intensity and high T2-weighted signal intensity. Except for two patients with recent accidents, the remaining eight presented chronic pain without any history of trauma. Pain was the most frequent clinical sign. It was associated with knee extension in 3 cases and with flexion in 3 cases. In 7 cases, cysts were exclusively associated with the anterior cruciate ligament (ACL). Only in one case was a cyst associated with an ACL rupture. Four patients presented meniscal lesions. All ganglia appeared solitary in each knee. Postarthroscopy evolution was painless in 8 patients. Histologic diagnoses corresponded to ganglion cysts. The tissues from the patient with the ACL rupture presented a fibrous reaction with myxoid degeneration forming intraligamentary ganglion cysts.

Primary hydatid disease in lumbar muscles.

The authors report a case of primary hydatid disease in the lumbar muscles of a 40-year-old male patient. The rarity of this disease in our regions and the low incidence of this location make primary diagnosis difficult. The tumor had been treated elsewhere five years previously by means of simple excision. Recurrence of the lesion was diagnosed five years after the first surgery. Wide excision of the cyst and pericyst with a 3.5-cm security margin was performed. Six years after the last surgery, no recurrence has been detected.

Results of the surgical treatment of Lisfranc fracture-dislocations.

The authors present a series of 25 patients with Lisfranc fracture-dislocation who were treated by reduction (open or closed) and stabilization with Kirschner wiring. Minimum follow-up was two years. The dislocations were divided based on the Quenu and Kuss classification system. Nonsurgical reduction was possible in 17 patients. Neither the type of dislocation nor the type of reduction influenced the results in progression in our series. Nonetheless, long-term functional results were better when the quality of the reduction was excellent.

Bizarre parosteal osteochondromatous proliferation. Difficulty in diagnosis.

Nora's tumor, also known as bizarre paraosteal osteochondromatous proliferation, is an exophytic outgrowth from the cortical surface that consists of a mixture of bone, cartilage, and fibrous tissue. It is a benign lesion with atypical microscopic features and a tendency to recur. Nora reported 35 cases emerging from the bones of the hands and feet. The largest published series is of 65 cases, with 17 lesions involving the long bones. With this exception, most authors report isolated cases. Age range from 8 to 74 years but most patients are between 20 and 35 years of age, and with the lesion affecting males and females in equal proportions. Usually the presenting symptoMs are due to bony mass, with a variable growth rate (months-years), and infrequent pain. In 15-20% of the cases there was trauma in the patient history: nevertheless, Fechner and Mills report no association with trauma. Radiography shows a calcified, rounded mass emerging directly from the surface of the bone. Isotope bone scans show intense tracer uptake in the lesion. With time, the appearance progresses to the more characteristic mature bone architecture.

Results in displaced radial neck fractures in children. Metaizeau technique versus arthrotomy.

The aim of the present article is to ascertain the differences between two surgical treatments commonly used in displaced radial neck fractures in children. We report the retrospective results of 20 displaced radial neck fractures with > 30 degrees of tilt (Judet grades 3-4) in children aged between 7 and 14 years treated with closed intramedullary pinning according to the Metaizeau technique (6 cases) or with arthrotomy and pinning (14 cases). Sex distribution was 14 girls and 6 boy. The average follow-up was 43 months. We found no relationship between delay in the surgical treatment and functional results. On the other hand, a relationship between residual final tilt and poorer functional results appears. The Metaizeau technique produced better results and fewer complications than arthrotomy and pinning, and, in our opinion, is the treatment of choice in this type of fracture.

Nonunion of the patella as a late chance observation after reconstructive surgery of the anterior cruciate ligament.

The use of autologous bone-tendon-bone grafts for reconstructive surgery of the anterior cruciate tendon is a widely diffused technique. Fracture of the donor patella constitutes an uncommon complication. It is the purpose of this study to present the clinical case of a patient submitted to reconstructive surgery of the anterior cruciate ligament where the existence of asymptomatic nonunion of the patella was by chance observed.

Risk factors for postoperative infections in patients with hip fracture treated by means of Thompson arthroplasty.

Specific conditions associated with surgery may predispose elderly people to septic complications after hip fracture surgery. This study investigated the risk factors predisposing infection in aged patients with subcapital hip fracture. We performed a prospective study of 290 patients with displaced subcapital hip fracture, operated by means of Thompson hip hemi-arthroplasty (83.5% fractures in women). The mean age was 85.42+/-6.06 years (ranging from 69 to 104). Follow-up was realized until death or at least for 2 years. The chi(2) test, analysis of variance, Kruskal-Wallis test, correlation analysis and the Spearman test were applied. Odds ratios (OR) were calculated. During the hospital stay, there were diagnosed 94 urinary tract infections, 25 pneumonias, 50 superficial wound infections, 11 deep wound infections. Transfusions were made in 120 patients (in average: 2.54+/-1.45 units of red cell concentrate/transfused patient). Transfusion appeared to be correlated with superficial wound infection (OR=1.96), urinary infection (OR=1.76) and pneumonia (OR=2.85). Higher number of days waiting for surgery were related significantly with pneumonia (9.8+/-7.44 days vs. 6.39+/-3.75), or urinary tract infection (7.76+/-4.39 days vs. 6.17+/-4.14). We concluded that the transfusion and longer waiting time for surgery have been associated with the septic complications in elderly patients treated surgically for hip fracture.

[Headache affecting the pigmented zones of Ota's naevus: clinical study in four cases (author's transl)]. / Etude clinique sur les céphalées pigmentaires des patients porteurs de naevus de Ota.

Four women, aged between 23 and 69 years, who had developed Ota's naevi either during the menarche (3 cases) or the first pregnancy (1 case), complained of headache in the frontal and orbital zones affected by the naevi. These headaches bore no relationship to those normally described as occurring in this region. They increased in severity, at the same time as the intensity of the pigmentation of the naevus, in each patient during the menstrual periods, and did not respond to conventional analgesics.

S-adenosylmethionine immunomodulator treatment in sepsis.

BACKGROUND: S-adenosylmethionine (SAMe) is a forerunner of glutathione. AIMS: The aim of the present study is to ascertain this drug effect on T-lymphocytes and cytokines in an experimental model of surgical sepsis. METHODS: Rats were allotted in two groups. In the control group, rats underwent anaesthesia and laparatomy with cecal ligation and puncture (CLP). In the second group, rats underwent the same CLP and received SAMe (14 mg/kg) i.m., on the 1st (1PO) and 2nd (2PO) postoperative days. A week before surgery (PRE), on the 1PO and on the 3PO: IL-1, IL-2, IL-4, IL-6, IL-10 and TNF levels (ELISA & MoAb), and CD3, CD4, CD8 cell and IL-2R percentages (%) (flow cytometry & MoAb) were determined in peripheral blood. RESULTS: Rats receiving SAMe do not show changes of CD3%, CD4% and IL-1 levels but show a significant increase of CD8% on the 3PO, showing a significant difference with regard to controls (p < 0.01). Both groups show a similar IL-2R variation pattern: increasing on 1PO (p < 0.05) and decreasing on 3PO (p < 0.05). CONCLUSION: In sepsis: SAMe inhibits the decrease of circulating immune-active cells and the IL-1 increase. This drug seems to have effects useful in avoiding immunological alterations in sepsis, that need to be tested in humans.

Autologous blood transfusion as an immunomodulator in experimental sepsis.

BACKGROUND: Homologous blood transfusion is associated with immunosuppressive consequences. Some clinical and experimental studies have suggested an immunostimulating action of autologous blood transfusion. The aim of this paper is to ascertain the effects of either homologous blood transfusion or autologous blood transfusion on the lymphocyte subsets and cytokines in a model of intra-abdominal sepsis. MATERIALS AND METHODS: There were three study groups. Group A: 10 Wistar-Furth (WF) rats underwent cecal ligation and puncture (CLP) aimed at causing an intra-abdomial sepsis; Group B: 10 WF rats underwent CLP plus 1 ml homologous blood perioperative transfusion obtained from Fisher-344 rat while Group C: 10 WF rats underwent CLP plus 1 ml autologous blood perioperative transfusion. Changes of peripheral lymphocyte subsets, percentages of total T-lymphocytes (CD3), Helper T-lymphocytes (CD4), supressor/cytotoxic T-lymphocytes (CD8), CD4/CD8 ratio, Interleukin-2 receptor expression (IL-2R) and cytokines IL-1 and TNF-alpha were measured in peripheral blood on the preoperative, 1st, 3rd and 7th postsepsis (PO) days. RESULTS: Rats in homologous transfused group showed a decrease of %CD4 on the 3rd PO (from preoperative to 3rd PO;p < 0.01; and from 1st to 3rd PO; p < 0.05) and on the 7th PO (from preoperative to 7th PO; p < 0.05); %CD8 increased from preoperative to 3rd PO (p < 0.05), from 1st to 3rd PO (p < 0.01) and from 1st to 7th PO (p < 0.05). An initial decrease on day 1 (p < 0.01) followed by an increase on the 3rd PO (p < 0.01) with regard to IL-2R and a significant increase of IL-1 levels within the first 24h (p < 0.01). Rats in autologous transfused group showed an increase of %CD3 from preoperative to 7th PO (p < 0.05), and from 3rd to 7th PO (p < 0.01). CONCLUSIONS: We observed that homologous blood transfusions induce a greater alteration in the cellular immune response and of the cascade of cytokines than autologous transfusions. This modulates the variations of the immune response induced by sepsis.

[The effect of cervical arthrosis in the etiopathogenesis of vertebrobasilar insufficiency]. / Influencia de la artrosis cervical en la etiopatogenia de la insuficiencia vertebrobasilar.

We studied four groups of one hundred patients older than forty years. A group with radiological signs of cervical arthrosis was statistically compared with another one without such signs. There was no significant difference between the two groups with regard to the presence of vertebrobasilar insufficiency. Then we compared one hundred patients diagnosed of vertebrobasilar insufficiency with another group without this disease. When cervical arthrosis cases in these two groups were statistically compared, we could not find any significant differences. We think cervical arthrosis is not an important etiologic factor in vertebrobasilar insufficiency. Our results point to atherosclerotic lesions as the main cause of this entity.