Effects of tibolone on osteoarthritis in ovariectomized rats: association with nociceptive pain behaviour.

BACKGROUND: To investigate the role of the synthetic steroid tibolone in the progression of osteoarthritis (OA) and in nociceptive behaviour in an experimental rat model of OA and ovariectomy (OVX)-induced osteoporosis. METHODS: OA was induced in Wistar rats by anterior cruciate ligament transection (ACLT) of the right knee. Osteoporosis was induced by bilateral OVX. Groups of animals were subjected to ACLT, OVX, sham or OVX + ACLT. In addition, two groups were subjected to OVX + ACLT surgeries and were orally administered 0.1 or 0.5 mg tibolone every other day for 14 consecutive weeks, starting 6 weeks after surgery. Nociceptive behaviours (secondary mechanical allodynia and weight-bearing distribution of the hind paws) were analysed prior to and every 3 weeks after surgery up to 24 weeks. At 24 weeks, histopathological studies were performed on the cartilage and synovial membranes of the knee joints, and bone metabolism was assessed by measuring serum concentrations of calcium, phosphorus and alkaline phosphatase. RESULTS: Rats undergoing ACLT or OVX + ACLT surgeries showed obvious OA changes in the joints. Animals subjected to ACLT + OVX and treated with tibolone had significantly less cartilage degeneration and synovitis and showed improved nociceptive tests compared with animals undergoing ACLT + OVX surgeries alone. OVX increased the severity of the ACLT-induced OA changes. There was a significant increase in serum alkaline phosphatase in the tibolone-treated ACLT + OVX groups. CONCLUSIONS: Treatment with tibolone attenuated the development of OA, concomitantly reduced nociception and increased serum alkaline phosphatase in ACLT + OVX rats.

Intra-articular injection of the selective cyclooxygenase-2 inhibitor meloxicam (Mobic) reduces experimental osteoarthritis and nociception in rats.

OBJECTIVE: To study the effect of intra-articular injection of meloxicam (Mobic) on the development of osteoarthritis (OA) in rats and examine concomitant changes in nociceptive behavior and the expression of mitogen-activated protein kinases (MAPKs) in articular cartilage chondrocytes. METHODS: OA was induced in Wistar rats by right anterior cruciate ligament transection (ACLT); the left knee was not treated. The OA + meloxicam (1.0 mg) group was injected intra-articularly in the ACLT knee with 1.0 mg of meloxicam once a week for 5 consecutive weeks starting 5 weeks after ACLT. The OA + meloxicam (0.25 mg) group was treated similarly with 0.25 mg meloxicam. The sham group underwent arthrotomy only and received vehicle of 0.1 mL sterile 0.9% saline injections, whereas the naive rats in meloxicam-only groups were treated similarly with 1.0- and 0.25-mg meloxicam. Nociception was measured as secondary mechanical allodynia and hind paw weight-bearing distribution at before (pre-) and 5, 10, 15, and 20 weeks post-ACLT. Histopathology of the cartilage and synovia was examined 20 weeks after ACLT. Immunohistochemical analysis was performed to examine the effect of meloxicam on MAPKs (p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK)) expression in the articular cartilage chondrocytes. RESULTS: OA rats receiving intra-articular meloxicam treatment showed significantly less cartilage degeneration and synovitis than saline-treated controls. Nociception were improved in the OA + meloxicam groups compared with the OA group. Moreover, meloxicam attenuated p38 and JNK but enhanced ERK expression in OA-affected cartilage. CONCLUSIONS: Intra-articular injection of meloxicam (1) attenuates the development of OA, (2) concomitantly reduces nociception, and (3) modulates chondrocyte metabolism, possibly through inhibition of cellular p38 and JNK, but enhances ERK expression.

Glucosamine sulfate reduces experimental osteoarthritis and nociception in rats: association with changes of mitogen-activated protein kinase in chondrocytes.

OBJECTIVE: To study the effects of oral glucosamine sulfate on the development of osteoarthritis (OA) and to examine concomitant changes in the nociceptive behavior of rats. METHODS: OA was induced in Wistar rats by anterior cruciate ligament transection (ACLT) of the right knee; the left knee was untreated. The OA+glucosamine group received oral glucosamine sulfate (250 mg/kg/day) in a 2-g wafer once a day for 10 consecutive weeks starting at week 5 after ACLT. The OA group was treated as above with 2-g wafers (placebo). The control group of naïve rats received 2-g wafers only. The glucosamine alone group comprised naïve rats receiving glucosamine sulfate only. Nociceptive behavior (mechanical allodynia and weight-bearing distribution of hind paws) during OA development was analyzed pre- and 3, 6, 9, 12, 15, and 18 weeks post-ACLT. Macroscopic and histologic studies were then performed on the cartilage and synovia. Immunohistochemical analysis was performed to examine the effect of glucosamine on expression of mitogen-activated protein kinases (MAPKs) in the articular cartilage chondrocytes. RESULTS: OA rats receiving glucosamine showed a significantly lower degree of cartilage degeneration than the rats receiving placebo. Glucosamine treatment also suppressed synovitis. Mechanical allodynia and weight-bearing distribution studies showed significant improvement in the OA+glucosamine group as compared to the OA group. Moreover, glucosamine attenuated p38 and c-Jun N-terminal kinase (JNK) but increased extracellular signal-regulated kinase 1/2 (ERK) expression in OA-affected cartilage. CONCLUSION: Our results indicate that treatment with oral glucosamine sulfate in a rat OA model (1) attenuates the development of OA, (2) concomitantly reduces nociception, and (3) modulates chondrocyte metabolism, possibly through inhibition of cell p38 and JNK and increase of ERK expression.

Intra-articular magnesium sulfate (MgSO4) reduces experimental osteoarthritis and nociception: association with attenuation of N-methyl-D-aspartate (NMDA) receptor subunit 1 phosphorylation and apoptosis in rat chondrocytes.

OBJECTIVE: To study the effects of intra-articular injection of magnesium sulfate (MgSO(4)) on the development of osteoarthritis (OA) and to examine concomitant changes in the nociceptive behavior of rats. METHODS: OA was induced in Wistar rats with intra-articular injection of collagenase (500 U) in the right knee; the left knee was left untreated. In the OA+MgSO(4) group (n=7), the treated knee was injected with 500-microg (0.1-ml) MgSO(4) twice a week for 5 consecutive weeks starting at 1 week after collagenase injection; in the OA group (n=7), the same knee was injected with the same amount of physiological normal saline. In the MgSO(4) group (n=6), naïve rats received only MgSO(4) injections; in the control group (n=6), naïve rats received only physiological normal saline injections. Nociceptive behavior (mechanical allodynia and thermal hyperalgesia) on OA development was measured before and at 1, 2, 4, 6, and 8 weeks after collagenase injection, following which the animals were sacrificed. Gross morphology and histopathology were examined in the femoral condyles, tibial plateau, and synovia. Immunohistochemical analysis was performed to examine the effect of MgSO(4) on N-methyl-D-aspartate (NMDA) receptor subunit 1 phosphorylation (p-NR1) and apoptosis in the articular cartilage chondrocytes. RESULTS: OA rats receiving intra-articular MgSO(4) injections showed a significantly lower degree of cartilage degeneration than the rats receiving saline injections. MgSO(4) treatment also suppressed synovitis. Mechanical allodynia and thermal hyperalgesia showed significant improvement in the OA+MgSO(4) group as compared to the OA group. Moreover, MgSO(4) attenuated p-NR1 and chondrocyte apoptosis in OA-affected cartilage. CONCLUSIONS: Our results indicate that local intra-articular administration of MgSO(4) following collagenase injection in an experimental rat OA model (1) modulates chondrocyte metabolism through inhibition of cell NMDA receptor phosphorylation and apoptosis, (2) attenuates the development of OA, and (3) concomitantly reduces nociception.

Increase in excitatory amino acid concentration and transporters expression in osteoarthritic knees of anterior cruciate ligament transected rabbits.

OBJECTIVE: The present study aimed to determine the role of excitatory amino acids (EAAs) and EAA transporters (EAATs) in an osteoarthritis (OA) model of rabbit knees. METHODS: OA was induced in New Zealand white male rabbits by anterior cruciate ligament transection (ACLT) in one knee of one hind limb; the other knee left unoperated. Rabbits that received ACLT of knee were assigned to the ACLT group (n=6), while a sham-operated group (n=6) underwent arthrotomy with no ACLT. Six naïve rabbits that received no surgery were used as normal control. The width of the knee joint was measured to determine the severity of joint inflammation. Before operation and at 10, 20, and 30 weeks after operation, knee joint dialysates were collected by microdialysis and assayed for EAAs by high-performance liquid chromatography. Gross morphology and histopathology and EAATs glutamate/aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1) expression in the articular cartilage of the knees were evaluated by immunohistochemistry and western blot analysis. RESULTS: In the ACLT knees, a significant increase in the joint width was observed (5.3+/-0.9 mm, P<0.05) at 30 weeks after operation, while the sham-operated and naïve knees showed no difference as compared with the basal values. The concentrations (microM) of aspartate and glutamate in knee dialysates at 30 weeks after ACLT in naïve, sham, and ACLT were 0.36+/-0.07 and 4.5+/-1.10; 0.38+/-0.09 and 4.61+/-1.11; 0.67+/-0.18 and 9.71+/-2.89, respectively. Levels of glutamate and aspartate in the dialysates obtained from the ACLT knees increased by 213.3+/-29.6% and 187.5+/-33.8% (P<0.05) when compared to those in the sham-operated knees. Both naïve and ACLT chondrocytes were positively stained by antibodies against GLAST and GLT-1. GLAST and GLT-1 protein expressions were significantly increased in the ACLT knees (P<0.05). CONCLUSION: Our findings indicate an involvement of EAAs and EAATs in the pathogenesis of OA in ACLT rabbits.

Intra-articular injection of the cyclooxygenase-2 inhibitor parecoxib attenuates osteoarthritis progression in anterior cruciate ligament-transected knee in rats: role of excitatory amino acids.

OBJECTIVE: Our present study examined the effect of intra-articular cyclooxygenase-2 (COX-2) inhibitor parecoxib on osteoarthritis (OA) progression and the concomitant changes in excitatory amino acids' (EAAs) levels of the anterior cruciate ligament-transected (ACLT) knee joint dialysates. METHODS: OA was induced in Wistar rats by anterior cruciate ligament transection of the knee of one hindlimb, the other was left unoperated and untreated. Rats were placed into four groups: Group ACLT/P received intra-articular parecoxib injection (100 microg) in the ACLT knee once a week for 5 consecutive weeks starting at 8 weeks after surgery. Group ACLT/S received the same procedure as group ACLT/P with saline injection instead. Naïve (Naïve/P) rats received only intra-articular parecoxib injection in one knee once a week for 5 consecutive weeks without surgery. The sham-operated rats underwent arthrotomy only without treatment. Twenty weeks after surgery, knee joint dialysates were collected and EAAs' concentration was assayed by high-performance liquid chromatography, and gross morphology and histopathology (Mankin and synovitis grading) were examined on the medial femoral condyles and synovia. RESULTS: Parecoxib alone had no effect on cartilage and synovium of normal knees in Naïve/P rats. In ACLT/P rats, parecoxib treatment showed a significant inhibition of cartilage degeneration of the medial femoral condyle at both the macroscopic level (1.15+/-0.17 vs 2.55+/-0.12, P<0.05) and the Mankin scores (3.03+/-0.28 vs 8.82+/-0.43, P<0.05). Intra-articular parecoxib injection also suppressed the synovial inflammation of ACLT joint compared to the ACLT/S group (3.92+/-0.41 vs 9.25+/-0.32, P<0.05). Moreover, glutamate and aspartate levels were also significantly reduced in the ACLT/P group compared to the ACLT/S group by parecoxib treatment (91.2+/-9.4% vs 189.5+/-17.0%, P<0.05 and 98.2+/-11.6% vs 175.3+/-12.4%, P<0.05, respectively). CONCLUSION: This study shows that intra-articular injection of COX-2 inhibitor parecoxib inhibits the ACLT-induced OA progression; it was accompanied by a reduction of glutamate and aspartate concentration in the ACLT joint dialysates. From our present results, we suggested that intra-articular parecoxib injection, in addition to the anti-inflammatory effect, inhibiting the EAAs' release, may also play a role in inhibiting the traumatic knee injury induced OA progression.

Pseudocyst formation after intertrochanteric fracture fixation: a case report.

We describe a 62-year-old woman who developed two pseudocysts, 25 x 15 cm and 20 x 12 cm, in the left proximal thigh as a complication 19 years after internal fixation of an intertrochanteric fracture. She received a 135 degrees dynamic hip screw and side plate in May 1979. She continued to live at home without major discomfort until May 1997. Two huge pseudocysts were noted in the left proximal thigh without trauma history. Angiography was normal. Computerized tomography scan revealed two voluminous cystic lesions without septa in the left proximal thigh, with accumulated fluid. During surgery, two huge cysts were found in the left proximal thigh, and their orifices were found slightly proximal to the curvature of the side plate. The pathology showed that the cysts consisted of a nonepithelialized wall of granulation tissue compatible with a pseudocyst. The patient had no further problems 2 years after surgery. We found no reports in the literature of this rare complication. The development of the pseudocysts may have been the result of chronic low-grade trauma due to irritation between the soft tissue and the implant. Orthopedic surgeons should be aware of the possible development of this rare complication following internal fixation of an intertrochanteric fracture.

Neonatal intracardiac rhabdomyomatosis: a case report.

Intracardiac tumors are rare in neonates. Most of these lesions are rhabdomyomas and they occur almost exclusively during infancy. Rhabdomyomas are commonly associated with tuberous sclerosis and often involve the brain, kidneys and pancreas; they are frequently multiple and originate most commonly from the ventricular septum. Surgical intervention is indicated for rhabdomyoma with either mechanical cardiac obstruction or dysrhythmias resulting in symptoms or sudden death. A newborn with diffuse rhabdomyomatosis over the right atrium, right ventricle and left ventricle of the heart complicated with congestive heart failure and intractable supraventricular tachycardia is reported herein. No tuberous sclerosis or other organ involvement was noted. The tumor was resected.

Retroperitoneal bronchogenic cyst: a case report.

Only a few subdiaphragmatic bronchogenic cysts are described, and their occurrence in the retroperitoneum is extremely rare. So far, only a few cases have been reported in the English-language literature. The pathogenesis is caused by the pinching off of irregular lung budding of the primitive ventral foregut, with aberrant migration into the abdomen before fusion of the diaphragm during embryonal development. A unique case with clinical, radiographic, surgical finding is presented. Final pathological findings confirmed the diagnosis of retroperitoneal bronchogenic cyst without other associated congenital anomalies. Retroperitoneal bronchogenic cyst, although rare, should be considered in the differential diagnosis in the retroperitoneal mass. This rare case is described and the relevant literature, reviewed.

Cutaneous Rosai-Dorfman disease manifestating as recurrent breast tumor: a case report.

A case of cutaneous Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy) manifestating as a recurrent breast tumor is reported. The tumor occurred on the left breast of a 35-year-old woman. Before arriving at the correct diagnosis, four biopsies had been performed with various diagnoses of chronic inflammation, plasma cell mastitis and inflammatory pseudotumor. Numerous typical histiocytes with lymphophagocytosis appeared in the final excised specimen, and a correct diagnosis was made. Ultrastructural examination revealed no evidence of Birbeck granule. The literature concerning Rosai-Dorfman disease manifestating as breast tumor is reviewed. Since the diagnosis is often overlooked in the absence of lymphadenopathy, a high index of suspicion is required to recognize this rare cutaneous Rosai-Dorfman disease.

Transitional cell and uncommon urothelial carcinoma of renal pelvis/ureter and bladder: low incidence of human papilloma virus.

BACKGROUND: Recently, it has been proposed that human papilloma virus (HPV) infection may play a role in the carcinogenesis of bladder urothelial malignancy. However, there is still controversy about the prevalence of HPV in such malignancies. With similar techniques of in situ hybridization (ISH) or polymerase chain reaction (PCR), either high or rare frequency have been detected. To evaluate the prevalence of HPV in the urothelial malignancies based on presentations here, 118 cases of urothelial malignancies were analysed, including those of the renal pelvis and ureter which have rarely been reported before. METHODS: Non-isotopic ISH technique was used to detect HPV on paraffin sections, including 51 bladder transitional cell carcinoma (TCC), 48 renal pelvic/ureter TCC, 5 bladder adenocarcinoma, 3 bladder small cell carcinoma, 2 bladder undifferentiated carcinoma, 1 multiple synchronous pelvic and ureteric squamous cell carcinoma (SCC) and 8 bladder SCC. An FITC-labelled probe of wide spectrum HPV was used for screening, and probes of HPV 6/11, 16, 18, 31, 33 were used for typing. RESULTS: By the technique of ISH, wide spectrum HPV was detected in only three of the eight cases of bladder SCC. Of the three positive cases, two were subsequently shown to be uterine cervical SCC with bladder invasion. Therefore, HPV was positive in only one case of primary bladder SCC, occurring in a patient with systemic lupus erythematosus under steroid and cyclophosphamide therapy. Further subtyping was negative for HPV 6/11, 16, 18, 31, and 33. The result indicated that the positive staining by wide spectrum probe was caused by types 30, 35, 45, 51, and/or 52. HPV was not detected in any of the 51 bladder TCC, 48 renal pelvic/ ureter TCC, 5 bladder adenocarcinoma, 3 bladder small cell carcinoma, and 2 bladder undifferentiated carcinoma. CONCLUSIONS: The results are in agreement with the majority of recent reports which suggest that HPV is unlikely to be involved in the etiology of urothelial malignancies; however, it seems probable that immunosuppressed patients are at greater risk for HPV-associated bladder SCC.

Cryptococcal meningitis and primary CNS lymphoma in a patient with acquired immunodeficiency syndrome: a case report.

This report describes a case of cryptococcal meningitis as the initial manifestation of acquired immunodeficiency syndrome (AIDS). During the admission, computed tomography (CT) of brain revealed multiple lesions with ring-enhancement over the cerebellum, frontal and temporal lobes. Autopsy findings showed diffuse cryptococcal meningoencephalitis and central nervous system (CNS) lymphoma forming multiple round ring abscesses. The case demonstrated that opportunistic cryptococcal infection and primary CNS lymphoma may coexist in a patient with AIDS.

Adult Wilms' tumor: a case report.

Wilms' tumor (nephroblastoma) is the most common intraabdominal tumor in children; its three primary components are blastemal, epithelial and stromal, with predominance of tri-phasic lesion. The tumor is rare in adults, in whom the Wilms' tumor accounts for less than 1%. The case presented here concerns a case of 46-year-old female with stage II, Wilms' tumor, composed of purely mono-phasic differentiated epithelial component with favorable histology. The patient received radical nephrectomy, than post-operative chemotherapy and radiotherapy as recommended by National Wilms' Tumor Study. With the advent of modern chemotherapy, the adult Wilms' tumor can have a better prognosis than previously. Because of the rarity of adult Wilms' tumor and its unusual histo-morphology, this case is described and the literature, reviewed.

Benign mesenchymoma of the mediastinum: a case report.

Benign mesenchymoma is an uncommon tumor containing at least two or more differentiated mesenchymal elements in addition to fibrous tissue. The case we presented here is a 60-year-old male who suffered from a superior posterior mediastinal mesenchymal tumor composed predominantly of mature adipose tissue separated by fascicular bundles of spindle cells admixed with cartilage and osseous tissue. The spindle cells were confirmed to be smooth muscle in nature by trichrome Masson stain and immunohistochemical studies, providing a picture consistent with that of benign mesenchymoma. Complete removal of this neoplasm proved possible, and no sign of recurrence or distant metastasis was present to date. This rare case of benign mesenchymoma in the mediastinum is described, and the literature is reviewed.

Human papillomavirus in cyclophosphamide and diverticulum-associated squamous cell carcinoma of urinary bladder: a case report.

The association of cyclophosphamide therapy with the development of urothelial malignancy has been documented. Bladder diverticula associated with squamous cell carcinoma were also identified. In addition, incorporation of human papillomavirus (HPV) deoxyribonucleic acid (DNA) has been previously shown in urothelial carcinoma by in situ hybridization technique. Here a case is reported of bladder squamous cell carcinoma occurring four years after intravenous pulse therapy with cyclophosphamide in a patient with bladder diverticula where HPV was identified in the lesion. To present knowledge, this is the first case report of bladder squamous cell carcinoma with simultaneous occurrence of three risk factors for urothelial malignancy: cyclophosphamide therapy, diverticulum, and HPV infection.

Plexogenic pulmonary vascular lesions in primary pulmonary arteriopathy--report of two autopsy cases.

Pulmonary hypertension is caused largely by an increase in pulmonary vascular resistance and is most frequently secondary to chronic pulmonary obstructive or interstitial diseases, recurrent pulmonary emboli, or antecedent heart diseases. Primary pulmonary hypertension (plexogenic pulmonary arteriopathy) is a rare disease and diagnosed only when the underlying causing factors are undetermined. Two autopsy cases of primary pulmonary hypertension, first documented at Taipei Veterans General Hospital, are reported. They showed apparent pulmonary vascular changes including medial hypertrophy, intimal proliferation and fibrosis and plexiform lesions of the muscular pulmonary arteries. The plexiform lesion has been considered to be characteristic in the histopathological diagnosis of primary pulmonary hypertension when there are no other associated diseases, such as cirrhosis of liver, pre- or post- tricuspid congenital cardiac shunts and portal vein thrombosis. The pathogenesis of the plexiform lesion is obscure. In the present report, we shall emphasize pathological changes of the "plexiform lesions" and discuss their pathogenesis.