[Late hematogenous infection of prosthetic joint]. / Pozdní hematogenní infekce kloubních náhrad.

The importance of prevention in late hematogenous infection is well understood but, because responsibility lies with general practitioners and other specialists, the orthopedic surgeon is usually not much interested. In both our and other countries, discussions are taking place on whether and to what extent antibiotic prevention should be carried out. Antibiotic prophylaxis of hematogenous infection is not indicated for all patients with joint arthroplasty, but only for a limited, defined group of patients at high risk. In these, however, the present state of knowledge suggests that prevention is necessary. A preventive treatment of late hematogenous infection is used for a procedure or a disease associated with risks in all the patients involved within two years of prosthetic joint implantation and, after this period, only in immunosuppressed patients. Surgery on the urogenital tract associated with the risk of bacteremia includes prostate gland surgery, operations for urinary bladder tumors, nephrolithotomy, extracorporeal lithotripsy and prostate biopsy. Certain conditions, such as urinary catheter presence, intermittent catheterization, urethral stent presence, urine retention and a history of urinary tract infection or prostate inflammation, pose an increased risk of bacterial colonization for the urogenital system. Dental procedures associated with a risk of bacteremia include tooth extraction, surgery on the parodontium, surgical extraction of an impacted tooth, dental implant treatment, procedures in a tooth's apical region, initial application of an orthodontic apparatus, intraligamentous blocks and also cleaning teeth and implants expected to bleed. Gynecological surgery with a risk of bacteremia are abdominal, vaginal and laparoscopic hysterectomies, surgery for cancer contaminated with vaginal bacteria, reconstruction surgery, operations on the pelvic floor for defects associated with urinary incontinence and use of xenotransplants. In obstetrics, a cesarean section carries some risks. In general surgery, the preventive administration of antibiotics is indicated, apart from situations always requiring antibiotic therapy, also for advanced forms of acute appendicitis, perirectal abscess, invasive endoscopy procedures on the colon, soft tissue phlegmona or abscess, surgical treatment of venous ulceration and pressure sores, and limb amputation. When inserting any piercing in patients with joint replacement at risk, it is recommended to do it with antibiotic administration; also, it is necessary to responsibly treat any inflammatory complication. The system of prevention for the late hematogenous infections of prosthetic joints is not developed as thoroughly as, for instance, it is in cardiology for patients with valve reconstruction. Because of the reasons given above, it is advisable to set up unambiguous guidelines for the prevention of late hematogenous infection in patients with joint replacement.

[Total hip replacement after tuberculous coxitis. Twenty-seven-year experience (1980-2007)]. / 27leté zkusenosti s endoprotetikou po tuberkulózní koxitide (1980-2007).

PURPOSE OF THE STUDY: Tuberculous hip arthritis accounts for about 15 % of all orthopaedic forms of tuberculosis and ranks third after spinal and knee joint tuberculosis. The aim of this study was to present the results of total hip arthroplasty (THA) for treatment of post-infectious arthritis or ankylosis, or previous arthrodesis. MATERIAL: A group of patients, 16 women and 10 men, treated at the 1st Department of Orthopaedics, 1st Faculty of Medicine, Charles University in Prague, between 1980 and 2007, was evaluated. All patients had tuberculous hip arthritis in their history and subsequently underwent THA. The average age at the time of THA was 65 years. METHODS: Indications for THA following tuberculous coxitis were secondary post-infectious arthritis in 20 patient, ankylosis (fibrous or osseous) in four and conversion from arthrodesis in two. Intra-operative samples were taken for microbiological examination, polymerase chain reaction (PCR) and histological examination. Anti-tuberculous drugs (rifampicin and isoniazid) and cephalosporin were administered intra-operatively following the sample collection and continued post-operatively. Cephalosporin was discontinued on post-operative day 11, rifampicin and isoniazid were administered for further 3 to 5 months with regular laboratory tests. RESULTS: The average post-operative values for flexion ranged from 0 to 90 degrees, for abduction from 0 to 35 degrees and for both internal and external rotation from 0 to 30 degrees. At the end of treatment all patients walked without aid and with full weight-bearing on the operated leg. No complications were recorded. Intra-operative findings of microbiological, PCR and histological examinations were negative. No recurrent tuberculous disease was found. DISCUSSION: A total joint replacement in any post-infectious condition is a complex issue. The average time between achieving a steady state o tuberculous arthritis and the THA procedure was approximately seven years. The outcome was evaluated as good by 75 % of the patients, who would be willing to undergo the surgery again. The clinical picture and radiographic and laboratory findings were within norms at regular follow-ups, which is in agreement with the literature data. Our system of intra- and post-operative administration of anti-tuberculous drugs and antibiotics proved very efficient. CONCLUSIONS: In contrast to arthrodesis or Girdlestone resection arthroplasty, THA results in a marked improvement of painless joint motion. Before any patient is indicated for THA, a thorough medical history with laboratory, internal and pulmonary (including heart and lung radiographs) examination is necessary. When there is more than one tuberculous disease in the patient's medical history, other organ systems such as urinary or reproductive tracts should also be examined. In addition to conventional radiography, examination by computed tomography or magnetic resonance imaging is indicated. The priority is an individual approach of the phthisiology orthopaedist to the indications ensuing from this comprehensive examination, with assessment of both physical and psychic state of the patient in view of post-operative rehabilitation.

[Late hematogenous infection of prosthetic joints in our patients and proposal for a system of prevention]. / Výskyt pozdní hematogenní infekce kloubních náhrad v nasem souboru a návrh systému prevence.

PURPOSE OF THE STUDY: To design a prophylactic strategy for late hematogenous infection is not an easy task. It requires the assessment of risk factors for the patient as well as of a potential source of bacteremia. Cost effectiveness, efficacy of the antibiotic selected and complications associated with antibiotic treatment, such as allergic reactions and development of resistance to the antibiotic given, should also be considered. The aim of this retrospective study is to evaluate the occurrence of late hematogenous infection in our large group of patients, to analyze risk factors and to suggest an optimal system of antibiotic prophylaxis in order to prevent the development of this unwelcome complication. MATERIAL AND METHODS: Since our objective was to include a large number of patients, a retrospective study was chosen as the method used. The patients treated for infectious complications of total joint replacement at the 1st Department of Orthopaedics, Teaching Hospital in Motol, 1st Faculty of Medicine, Charles University, in the years 1991 through 2004, were evaluated with the use of a targeted questionnaire and complete medical records. The group comprised 229 patients, 149 women and 80 men. Of these, 123 were treated for infection of total hip replacement, 102 for total knee replacement, two had infection of prosthetic shoulder joints and two had infection of elbow joint alloplasty. RESULTS: Medical history of 37 patients (16.3 %) included infection of or a risk-associated procedure on the urogenital system (endoscopic or open surgery, prostate gland biopsy, extracorporeal lithotripsy). Six patients (2.6 %) underwent surgery with possible bacteremia (intestine resection for tumor, 2x; surgery for paronychium, 2x; cholecystectomy, 1x; and appendectomy, 1x). Dental surgery or mouth disease was recorded in 11 patients (4.8 %). DISCUSSION: The authors suggest that the orthopedic surgeons performing joint replacement should assume their deal of responsibility and should provide relevant, comprehensive information to both the patient and the attending physician. These surgeons should be ready to remain involved in their patients' further therapies and, after assessing all risks, should be able to recommend an optimal prophylactic treatment. The introduction of a new preventive approach requires a simple and uncomplicated scheme. Any complicated and expensive system of preventive antibiotic administration will only meet with lack of understanding and with trivialization. The requirement that antibiotic treatment should be selected according to the site and type of risk-associated disease is logical, but, in our opinion, rather formal and unrealistic. The authors prefer a simple system permitting a rapid and overall introduction of preventive measures. CONCLUSIONS: The groups of patients indicated for prevention of late hematogenous infection of prosthetic joints are clearly defined and, by no means, do they involve all patients with total joint replacement. Key words: prosthetic joint, infection, prevention, antibiotics, complication.

[Late hematogenic infection of joint replacements and its prevention in surgery]. / Pozdní hematogenní infekce kloubních náhrad a její prevence v chirurgických oborech.

INTRODUCTION: Late hematogenic infections of joint replacements represent a serious complication. The aim of the study is to assess a patient group with late hematgenic infections of allografts and to propose preventive measures. METHODS: The restrospective study included patients treated for infectious complications of their joint implants in the 1st Orthopaedic Clinic of the 1st LF UK and FN Motol during the 1991-2004 period. The study included 229 patients in total, of which 149 subjects were females and 80 were males. In 123 subjects their hip joint implant infection was managed, in 102 subjects the knee joint endoprosthesis infection and in two subjects the shoulder joint prosthesis infection was managed. The last two subjects sufferred from infections of their elbow joint alloplasty. RESULTS: Urinary infection or other procedures of urogenital tract were recorded in 37 patients (16.2%). Upper respiratory tract infections preceding deep joint implant infections were reported in 30 subjects (13.1%). Stomatological procedures or oral cavity disorders was diagnosed in 1 subjects (4.8%). Surgical proceudres with suspected bacteriemia was recorded in 6 subjects (2.6%). CONCLUSION: Late hematological infections of bone replacements are serious complications with imminent medical and economical consequences. The infection may be caused by a variety of conditions and medical procedures connected to bacteriemia. Provided the risk of the joint implant infection is high (immunocompromised patients, "recent" endoprosthesis implantation within the last two years), prophylactic antibiotic medication is strongly recommended in all conditions with increased risk of bacteriemia.

Inflammatory mediators in patients receiving long-term home parenteral nutrition.

This study was designed to examine circulating and urine cytokine levels in patients receiving long-term home total parenteral nutrition (TPN) support. Twelve patients who had been receiving home TPN for more than 1 year (range, 1.3-19.5 years) were enrolled for study. To avoid the potential confounding effects of intercurrent infection, patients were studied during periods of clinical stability without clinical evidence of infection. Ten normal healthy volunteers served as controls. Serum levels of albumin and C-reactive protein, temperature, body weight, and blood white cell counts were determined. The levels of soluble tumor necrosis factor receptor II (sTNF-RII) and interleukin 6 (IL-6) were measured in serum and 24-hr urine. The results showed that the concentrations of sTNF-RII and IL-6 in 24-hr urine and serum were significantly higher in patients, indicating that long-term home TPN may be associated with a persistent low-grade inflammatory state.

Nonviral transfer of the gene encoding coagulation factor VIII in patients with severe hemophilia A.

BACKGROUND: We tested the safety of a nonviral somatic-cell gene-therapy system in patients with severe hemophilia A. METHODS: An open-label, phase 1 trial was conducted in six patients with severe hemophilia A. Dermal fibroblasts obtained from each patient by skin biopsy were grown in culture and transfected with a plasmid containing sequences of the gene that encodes factor VIII. Cells that produced factor VIII were selected, cloned, and propagated in vitro. The cloned cells were then harvested and administered to the patients by laparoscopic injection into the omentum. The patients were followed for 12 months after the implantation of the genetically altered cells. An interim analysis was performed. RESULTS: There were no serious adverse events related to the use of factor VIII-producing fibroblasts or the implantation procedure. No long-term complications developed, and no inhibitors of factor VIII were detected. In four of the six patients, plasma levels of factor VIII activity rose above the levels observed before the procedure. The increase in factor VIII activity coincided with a decrease in bleeding, a reduction in the use of exogenous factor VIII, or both. In the patient with the highest level of factor VIII activity, the clinical changes lasted approximately 10 months. CONCLUSIONS: Implantation of genetically altered fibroblasts that produce factor VIII is safe and well tolerated. This form of gene therapy is feasible in patients with severe hemophilia A.

Inhibitors of the proteasome reduce the accelerated proteolysis in atrophying rat skeletal muscles.

Several observations have suggested that the enhanced proteolysis and atrophy of skeletal muscle in various pathological states is due primarily to activation of the ubiquitin-proteasome pathway. To test this idea, we investigated whether peptide aldehyde inhibitors of the proteasome, N-acetyl-leucyl-leucyl-norleucinal (LLN), or the more potent CBZ-leucyl-leucyl-leucinal (MG132) suppressed proteolysis in incubated rat skeletal muscles. These agents (e.g., MG132 at 10 microM) inhibited nonlysosomal protein breakdown by up to 50% (P < 0.01), and this effect was rapidly reversed upon removal of the inhibitor. The peptide aldehydes did not alter protein synthesis or amino acid pools, but improved overall protein balance in the muscle. Upon treatment with MG132, ubiquitin-conjugated proteins accumulated in the muscle. The inhibition of muscle proteolysis correlated with efficacy against the proteasome, although these agents could also inhibit calpain-dependent proteolysis induced with Ca2+. These inhibitors had much larger effects on proteolysis in atrophying muscles than in controls. In the denervated soleus undergoing atrophy, the increase in ATP-dependent proteolysis was reduced 70% by MG132 (P < 0.001). Similarly, the rise in muscle proteolysis induced by administering thyroid hormones was reduced 40-70% by the inhibitors. Finally, in rats made septic by cecal puncture, the increase in muscle proteolysis was completely blocked by MG132. Thus, the enhanced proteolysis in many catabolic states (including denervation, hyperthyroidism, and sepsis) is due to a proteasome-dependent pathway, and inhibition of proteasome function may be a useful approach to reduce muscle wasting.

Dietary protein deficiency reduces lysosomal and nonlysosomal ATP-dependent proteolysis in muscle.

When rats are fed a protein deficient (PD) diet for 7 days, rates of proteolysis in skeletal muscle decrease by 40-50% (N. E. Tawa, Jr., and A. L. Goldberg. Am. J. Physiol. 263 (Endocrinol. Metab. 26): E317-325, 1992). To identify the underlying biochemical adaptations, we measured different proteolytic processes in incubated muscles. The capacity for intralysosomal proteolysis, as shown by sensitivity to methylamine or lysosomal protease inhibitors, fell 55-75% in muscles from PD rats. Furthermore, extracts of muscles of PD rats showed 30-70% lower activity of many lysosomal proteases, including cathepsins B, H, and C, and carboxypeptidases A and C, as well as other lysosomal hydrolases. The fall in cathepsin B and proteolysis was evident by 3 days on the PD diet, and both returned to control levels 3 days after refeeding of the normal diet. In muscles maintained under optimal conditions, 80-90% of protein breakdown occurs by nonlysosomal pathways. In muscles of PD rats, this ATP-dependent process was also 40-60% slower. Even though overall proteolysis decreased in muscles of PD rats, their capacity for Ca(2+)-dependent proteolysis increased (by 66%), as did the activity of the calpains (+150-250%). Thus the lysosomal and the ATP-dependent processes decrease coordinately and contribute to the fall in muscle proteolysis in PD animals.