Overexpression of secretory leukocyte peptidase inhibitor (SLPI) does not modulate experimental osteoarthritis but may be a biomarker for the disease.

OBJECTIVE: Osteoarthritic cartilage destruction can be regulated by the balance between proteases and anti-proteases. Here, we sought to identify novel cellular protease inhibitors associated with osteoarthritis (OA) pathogenesis. METHODS: Candidate molecules were screened from microarray data of chondrocytes treated with OA-associated catabolic factors. The functions of candidate molecules in OA pathogenesis were examined in primary-culture mouse articular chondrocytes and mouse models of OA, such as those stimulated by destabilization of the medial meniscus (DMM) or intra-articular (IA) injection of adenovirus expressing the candidate gene. The value of the selected candidate molecule as a biomarker of OA was examined by measuring its circulating levels in human and mouse blood. RESULTS: Bioinformatic analysis identified secretory leukocyte peptidase inhibitor (SLPI) as a highly upregulated cellular protease inhibitor in chondrocytes treated with pathogenic catabolic factors, including interleukin (IL)-1ß, hypoxia-inducible factor (HIF)-2α, and zinc importer ZIP8. The adenovirus-mediated overexpression of SLPI in joint tissues did not cause any OA-like change or modulate DMM- or HIF-2α-induced experimental OA in mice. SLPI also did not markedly modulate the expression of OA-associated catabolic or anabolic factors in chondrocytes. However, SLPI was specifically upregulated in OA cartilage, and the serum SLPI levels were significantly elevated in human OA patients and experimental OA mice, suggesting that SLPI may be a biomarker of OA. CONCLUSION: Although SLPI is upregulated in OA chondrocytes, it does not appear to per se modulate OA development in mice. However, it may be a potential biomarker of OA in humans and animal models.

A ganglion cyst generated by non-absorbable meniscal repair suture material.

Arthroscopic meniscal repair has been a common procedure for the treatment of a torn meniscus, since the importance of meniscal preservation is widely understood. Over the years, the complications associated with suture material have been reported. Meniscal cyst is also one of those things. But ganglion cyst triggered by non-absorbable suture material was not documented in the literature. We report the case of a 19-year-old boy who underwent arthroscopic ACL reconstruction and repair of the medial meniscus by inside-out technique using 2-0 non-absorbable polyester sutures. The patient returned to our clinic at 4-year F/U with right knee pain due to medial meniscus tear and ganglion cyst. We suspect non-absorbable suture materials itself might have caused soft tissue irritation with repetitive trauma that lead to mucoid degeneration which results in ganglion cyst formation in the end.

Hypoxia-inducible factor-2α regulates Fas-mediated chondrocyte apoptosis during osteoarthritic cartilage destruction.

Apoptosis of articular chondrocytes is associated with the pathogenesis of osteoarthritis (OA). Recently, we demonstrated that hypoxia-inducible factor (HIF)-2α, encoded by Epas1, causes OA cartilage destruction by regulating the expression of various matrix-degrading enzymes. Here, we investigated the involvement of HIF-2α in chondrocyte apoptosis and OA cartilage destruction. HIF-2α levels in human and mouse OA chondrocytes were markedly elevated in association with increased apoptosis of articular chondrocytes. Overexpression or knockdown of HIF-2α alone did not cause chondrocyte apoptosis. However, HIF-2α expression markedly increased chondrocyte apoptosis in the presence of an agonistic anti-Fas (CD95) antibody. HIF-2α enhanced Fas expression and potentiated downstream signaling pathways, increasing the activity of initiator and executioner caspases. Overexpression of HIF-2α in mouse cartilage tissue, either by intra-articular injection of Epas1 adenovirus (Ad-Epas1) or in the context of chondrocyte-specific Epas1 transgenic mice, increased chondrocyte apoptosis and cartilage destruction. In contrast, chondrocyte-specific knockout of Epas1 in mice suppressed DMM (destabilization of the medial meniscus)-induced chondrocyte apoptosis and inhibited OA cartilage destruction. Moreover, Fas-deficient mice exhibited diminished chondrocyte apoptosis and OA cartilage destruction in response to Ad-Epas1 injection or DMM surgery. Taken together, our results demonstrate that HIF-2α potentiates Fas-mediated chondrocyte apoptosis, which is associated with OA cartilage destruction.

Effects of extremely low frequency magnetic fields on pain thresholds in mice: roles of melatonin and opioids.

1. We studied the effects of extremely low frequency (ELF, 60 Hz) magnetic fields (MFs) on pain thresholds using the hot plate test. The implication of opioid and benzodiazepine system in the MFs-induced alteration of pain thresholds was also studied. 2. There was an increase at night time and a decrease at daytime of pain thresholds in normal mice. Exposure of MFs (24 h, 20 gauss (G)) inhibited the increase of pain thresholds at night time and even produced hyperalgesia at daytime. 3. The increase of pain thresholds induced by melatonin at daytime was inhibited by exposure to MFs (24 h, 20 G) or opioid antagonist naloxone. The MFs and naloxone synergically inhibited hypoalgesia produced by melatonin. The hyperalgesia at daytime after MFs exposure was potentiated by the benzodiazepine agonist, diazepam, and inhibited by the benzodiazepine antagonist, flumazenil. There was no significant difference in all rotarod performance we tested. 4. From these results, it is suggested that exposure to MFs inhibits the increase of pain thresholds at night time and produces hyperalgesia at daytime with the involvement of opioid and benzodiazepine systems.

Modified step-cut osteotomy of the humerus.

Corrective osteotomy of the distal humerus for a posttraumatic cubitus varus was performed in 31 patients using a modified step-cut osteotomy. The average patient age was 14.3 years. Complete bony union was obtained between the 8th and 16th weeks. Twenty-one patients achieved excellent results, 7 achieved good results, and 3 achieved poor results on the basis of Oppenheim's criteria. Although the results for 28 patients (90.3%) were classified as excellent or good, 6 patients (19.3%) were subjectively disappointed due to bulging of the lateral condyle. We achieved an overall improvement in mechanical stability and established an easier technique in corrective osteotomy. However, this approach may not be appropriate if the correction angle desired is greater than 30 degrees.

Immediate ipsilateral fibular transfer in a large tibial defect using a ring fixator. A case report.

Massive segmental bony defects in open tibial fractures are generally treated with conventional bone grafting, a free vascularised fibular graft or the ring fixator technique. A vascularised fibular graft may be superior to a conventional bone graft, but it is technically difficult and occasionally impossible. In such circumstances, fibular transfer in conjunction with a ring fixator is an alternative method. This procedure can be accomplished by transferring the osteotomised part of the fibula to the tibia by means of olive wires. The authors have treated a 20-year-old male who presented with a Gustilo type IIIB open tibial fracture. The soft tissue defect was severe, only the tibialis posterior artery was patent and the peroneal artery was partially damaged. A latissimus dorsi flap was performed to cover the soft tissue defect. Since the patent tibialis posterior artery had already been used for the flap, it was difficult to perform a vascularised fibular graft. Moreover, it was technically difficult to accomplish a gradual transport using a ring fixator because the distal tibia was lost. For this reason, the fibular transfer was performed immediately after the ring fixator was applied. Good bony union and fibular hypertrophy were obtained even though these two procedures were undertaken simultaneously.

Treatment of tibial pilon fractures using ring fixators and arthroscopy.

Twenty-one patients with tibial pilon fractures were treated with ring fixators and arthroscopy. There were 2 Type I, 14 Type II, and 5 Type III fractures using the Ruedi classification. In Ruedi Types I and II fractures, ring fixators were applied to the tibia and foot, and closed reduction was performed, monitoring the quality of the reduction with an image intensifier. When the quality of the reduction was questionable, arthroscopy was used, and if necessary, the reduction was readjusted. Olive wires were used to achieve reduction and fixation. In all Ruedi Type III fractures and 4 Ruedi Type II injuries, a limited open reduction was performed instead of arthroscopy. Approximately 8 weeks after the operation, the foot mounting was removed. The ring fixators were removed between 16 and 28 weeks. Bony union was achieved in all but 1. At an average followup of 37 months, there were 15 good, 4 fair, and 2 poor results. There were 8 cases of pin tract infection, and 1 patient had loss of reduction. There were no cases of deep wound infection. It was concluded that ring fixator and adjunctive arthroscopy is safe and effective in the management of tibial pilon fractures.

[The history of small pox prevention in Korea].

The first record of small pox epidemics in Korea claims that the malignant pestilence came from China around the 4th-5th century. Records have been found indicating that this pestilence attacked Korea every few years and that the havoc it caused was beyond description. China was the first country in the orient to use Jenner's vaccine, 10 years after its invention in 1796. The effect of the vaccine had been widely recognized and it was introduced to Korea through Japan. Mr. Sok-Yong Chi, an educator who was much interested in modern medical science, with the cooperation of the public, introduced wide usage of the vaccine in December 1879. Through continued effort with vaccination by 1959 this pestilence had completely disappeared from this country. Before the introduction of vaccinations, the variolation method, which came from China was also practiced here. Its effect was not recognized by the public and the method did not become popular. In addition, a few other methods to prevent this pestilence were introduced. Methods such as inhalation of pox-liquid and insertion of scar-pills (a chinese style of intranasal inoculation) were also practiced. ...

Brain abscess. A study of 45 consecutive cases.

Clinical features, findings of diagnostic studies, results of therapy, and prognostic factors were analyzed in 45 patients with brain abscesses. The number of patients diagnosed yearly has increased since CT scanning became available, but despite the enhanced sensitivity, the time from either onset of symptoms or hospital admission until initiation of therapy was not decreased and there was no dramatic effect upon morbidity or mortality in this series. Infections of paranasal sinuses, ears, lungs, and odontogenic foci were predisposing factors in approximately 70% of cases. Single abscesses, present in 75% of patients, were distributed equally in both hemispheres, with more than half in the frontal and parietal lobes. Common signs and symptoms included headache, fever, chills, seizures, nausea, vomiting, altered sensorium, nuchal rigidity, and localizing neurologic signs. Blood cultures were positive in 11%. Lumbar puncture rarely provided data from which a diagnosis could be established; CSF cultures were positive in only 7% of patients, and there was a 15% temporally associated incidence of brain herniation and death. Diagnostic information was most readily obtained using imaging techniques such as CT and 99mTc scanning, and arteriography was invasive and of no added value. CT scans are however, often initially negative in patients presenting with clinical signs of meningitis presumably following rupture of an abscess into the subarachnoid space, and the average time for changes to appear on CT scan is 9 days. It is, therefore, recommended that when the clinical assessment suggests the possibility of brain abscess the patient be treated empirically with antibiotics and that lumbar puncture be performed only after thoughtful assessment of the risk-to-benefit ratio for each patient. Causative organisms were isolated from more than 80% of abscesses despite prior antibiotic treatment; more than half grew a single pathogen, most commonly streptococci. Anaerobic and microaerophilic bacteria accounted for 62% of all isolates, and were the only organisms in 33% of patients. Computerized tomographic scans in 30 patients showed "ring-enhancing" lesions, nodular enhancement, or areas of low attenuation. Complete resolution of abscesses on CT scans rarely occurred during hospitalization and took as long as 5 months. Decrease in the size of abscesses on CT scan correlated well with clinical improvement and was seen within a week when abscesses were excised, but was often not obvious for 6 to 8 weeks if antibiotics were used alone.(ABSTRACT TRUNCATED AT 400 WORDS)

Endogenous aspergillus endophthalmitis.

A 27-year-old man with a history of intravenous-narcotic abuse presented with signs and symptoms suggesting fungal endophthalmitis. He underwent core vitrectomy with intravitreal injection of amphotericin B. Aspergillus flavus grew from cultures of the vitreous aspirate. There was no evidence of extraocular infection, and the patient was treated postoperatively with subconjunctival amphotericin B and oral flucytosine. Unlike previously reported cases of endogenous aspergillus endophthalmitis in drug abusers, the patient described here recovered normal visual acuity.

Rhabdomyolysis associated with pneumococcal sepsis.

A case of pneumococcal sepsis associated with rhabdomyolysis is reported. Rhabdomyolysis is a rare complication of bacterial infections not directly involving muscle. Eleven cases of rhabdomyolysis associated with bacteremic infections were found in the literature and clinical data are summarized. The pathogenesis and frequency of this association remains unknown.

Splenic abscess complicating infectious endocarditis.

Infective endocarditis is the most common condition predisposing a patient to splenic abscess, and the conditions of 37 such patients are reviewed herein. Streptococci accounted for 18 abscesses, with six containing enterococci; 12 other contained staphylococci. Symptoms suggesting splenic abscess include abdominal distention, hiccups, and pain in the left flank, abdomen, and shoulder. Physical signs include recurrent or persistent fever and abdominal tenderness, with splenomegaly often inapparent. The most frequent finding on x-ray film is pleural effusion on the left side. Seventeen patients not undergoing splenectomy died; in these, the diagnosis of splenic abscess was established postmortem. Twenty patients underwent splenectomy, 19 of whom received antibiotics and survived; one patient who was not treated with antibiotics died. Physicians should suspect splenic abscess in patients with endocarditis, particularly those with staphylococcal or enterococcal endocarditis. Those patients with clinical evidence suggestive of splenic abscess should undergo specific diagnostic studies, and exploratory laparotomy may be necessary.

Metronidazole treatment of Bacteroides fragilis infections.

Seven patients with Bacteroides fragilis infections were treated with intravenous and/or oral metronidazole. Infections treated included endocarditis, osteomyelitis, lung abscess, empyema, peritonitis, septicemia, and pelvic infection. Some patients had failed to respond to therapy with chloramphenicol or clindamycin or both. Metronidazole was used alone or in combination with aminoglycosides. Serum levels of metronidazole several times in excess of the minimal inhibitory concentrations for the organisms were easily achieved and in one patient the CSF metronidazole level was equal to that of the serum. Response to therapy with metronidazole was considered to be excellent. The only serious side effect noted was hypotension, which occurred in the last patient. Therapy was discontinued, and therefore therapeutic results could not be evaluated. Metronidazole appears to be a safe and effective agent in the treatment of B fragilis infections.

Splenic abscess.

Fourteen cases of splenic abscess are reported and 159 cases previously cited in the literature are reviewed. The incidence, predisposing factors, pathogenesis, clinical features, bacteriology and radiologic findings are discussed. Infective endocarditis was the most common single antecedent infection. Hemoglobinopathies, non-penetrating abdominal trauma, and gastrointestinal malignancy appear to predispose the spleen to abscess formation. Emphasis is placed on clinical features and radiologic findings to aid practitioners in diagnosing this uncommon but often fatal infection. Also emphasized is the necessity for prompt surgical intervention when splenic abscess is suspected. An approach to the antimicrobial therapy in different clinical settings is outlined.

Erysipelas-like syndrome caused by Streptococcus pneumoniae.

Streptococcus pneumoniae produced an erysipelas-like eruption in a patient with the nephrotic syndrome. The eruption and accompanying fever resolved upon treatment with aqueous penicillin.

Endocarditis due to Hemophilus aphrophilus: report of a case with possible transmission from dog to man.

A 44-year-old man was treated for bacterial endocarditis due to Hemophilus aphrophilus. The characteristics of the organism are reviewed, along with other cases of endocarditis. There is an association of this organism with dogs and a potential for transmission from this source to man.