Early surgical treatment using regional clinical pathways to reduce the length of postoperative hospital stay in hip fracture patients: A retrospective analysis using the Japanese Diagnosis Procedure Combination database.

Hip fracture is a common injury in older adults; however, the optimal timing of surgical treatment remains undetermined in Japan. Therefore, this retrospective study aimed to ascertain the rate of early surgery among hip fracture patients and investigate its effectiveness, along with "regional clinical pathways" (patient plan of care devised by Japanese clinicians), in reducing the length of hospital stay (LOS) postoperatively. We hypothesized that performing early surgery along with a regional clinical pathway is effective to reduce the postoperative LOS and complications among hip fracture patients. We examined the data of patients diagnosed with femoral neck and peritrochanteric fractures retrieved from the Japanese Diagnosis Procedure Combination database between April 2016 and March 2018. Patients were divided into the early (43,928, 34%; surgery within 2 days of admission) and delayed (84,237, 66%; surgery after 2 days of admission) surgery groups. The difference in postoperative LOS between the two groups was 3 days (early vs. delayed: 29 days vs. 32 days). The early surgery group had more cases of intertrochanteric fractures (57% vs. 43%) and internal fixation (74% vs. 55%) than did the delayed surgery group. In contrast, the delayed surgery group had more cases of femoral neck fractures (43% vs. 57%) and bipolar hip arthroplasty (25% vs. 42%) or total hip arthroplasty (1.2% vs. 3.0%). Moreover, the early surgery group showed a lower incidence of complications, except anemia (12% vs. 8.8%). Logistic regression analysis using the adjusted model revealed that early surgery and implementation of regional clinical pathways reduced LOS by 2.58 and 8.06 days, respectively (p<0.001). Early surgery and implementation of regional clinical pathways for hip fracture patients are effective in reducing postoperative LOS, allowing regional clinical pathways to have a greater impact. These findings will help acute care providers when treating hip fracture patients.

Clinical Outcomes and Return-to-Sport Rates following Fragment Fixation Using Hydroxyapatite/Poly-L-Lactate Acid Threaded Pins for Knee Osteochondritis Dissecans: A Case Series.

Osteochondritis dissecans (OCD) of the knee is an uncommon injury in young active patients. There is currently a lack of knowledge regarding clinical outcomes and return-to-sport rates after fragment fixation surgery using hydroxy appetite poly-L-lactic acid (HA/PLLA) threaded pins for knee OCD among athletes. Our purpose was to investigate the clinical outcomes and return-to-sport rates following osteochondral fragment fixation using HA/PLLA pins for the treatment of knee OCD lesions among athletes. A total of 45 patients were retrospectively reviewed. In total, 31 patients were excluded, and 14 patients were included. Pre- and postoperative patient-reported outcome scores (PROSs), including the International Knee Documentation Committee (IKDC) score and Knee Injury and Osteoarthritis Outcome Scale (KOOS), were compared. In addition, patients were categorized into four groups according to postoperative sports status: higher, same, lower than preinjury, or unable to return to sports. The mean age was 14.4 years (SD 1.67). All patients were male. All PROSs significantly improved at 6, 12, and 24 months postsurgery compared to presurgery. 50% of the patients returned to sports at the same or higher level after surgery. Fragment fixation using HA/PLLA pins leads to favorable clinical outcome scores and high return-to-sport rates in the treatment of athletes with knee OCD.

DAIR in treating chronic PJI after total knee arthroplasty using continuous local antibiotic perfusion therapy: a case series study.

BACKGROUND: Antimicrobial agents are administered via intramedullary antibiotic perfusion (iMAP)/intrasoft tissue antibiotic perfusion (iSAP) to infected lesions to control osteoarticular and soft tissue infections. Continuous local antibiotic perfusion (CLAP) has been reported to be useful. This study aimed to investigate the outcomes of DAIR combined with CLAP for chronic PJI after total knee arthroplasty performed at our hospital. SUBJECTS AND METHODS: Six patients (male; one case, female; five cases, mean age 79.5 years (70-94)) underwent CLAP for chronic PJI after TKA at our hospital between July 2020 and June 2022. They were followable for at least one year after surgery. Seven months (17-219), with a mean follow-up of 24.3 months (12-36). In addition to direct debridement and insert exchange, systemic antimicrobial treatment, and CLAP with gentamicin were performed using NPWT. We investigated the organisms causing the inflammation, the duration of iMAP/iSAP implantation, the maximum daily dose of GM, the maximum GM blood concentration, and the presence or absence of GM-induced adverse events. RESULT: Two of six patients had a recurrence of infection at five weeks and five months after initial CLAP and required repeat CLAP treatment, but all patients could preserve their components. The organisms responsible for the flare-ups were MSSA in three cases: ESBL-producing E. coli, mixed MSSA and streptococcal infection, Klebsiella pneumonia in one case each, and unknown pathogens in one case. CLAP therapy for all patients was administered eight times in 6 cases: iMAP, mean: 10.0 days (5-16); iSAP, mean: 19.3 days (15-28); GM dose, mean: 162.5 mg/day (80-240); and GM blood concentration, mean: 1.4 µg/mL (0.2-5.0). Adverse events included one case of reversible acute kidney injury during CLAP in a patient with recurrent infection. DAIR with CLAP for chronic post-TKA infection can be a useful treatment option to preserve components and allow the infection to subside, provided the implant is not markedly loosened.

Chemogenetic Activation of Oxytocin Neurons Improves Pain in a Reserpine-induced Fibromyalgia Rat Model.

Fibromyalgia (FM) is a syndrome characterized by chronic pain with depression as a frequent comorbidity. However, efficient management of the pain and depressive symptoms of FM is lacking. Given that endogenous oxytocin (OXT) contributes to the regulation of pain and depressive disorders, herein, we investigated the role of OXT in an experimental reserpine-induced FM model. In FM model, OXT-monomeric red fluorescent protein 1 (OXT-mRFP1) transgenic rats exhibited increased depressive behavior and sensitivity in a mechanical nociceptive test, suggesting reduced pain tolerance. Additionally, the development of the FM-like phenotype in OXT-mRFP1 FM model rats was accompanied by a significant reduction in OXT mRNA expression in the magnocellular neurons of the paraventricular nucleus. OXT-mRFP1 FM model rats also had significantly fewer tryptophan hydroxylase (TPH)- and tyrosine hydroxylase (TH)-immunoreactive (ir) neurons as well as reduced serotonin and norepinephrine levels in the dorsal raphe and locus coeruleus. To investigate the effects of stimulating the endogenous OXT pathway, rats expressing OXT-human muscarinic acetylcholine receptor (hM3Dq)-mCherry designer receptors exclusively activated by designer drugs (DREADDs) were also assessed in the FM model. Treatment of these rats with clozapine-N-oxide (CNO), an hM3Dq-activating drug, significantly improved characteristic FM model-induced pathophysiological pain, but did not alter depressive-like behavior. The chemogenetically induced effects were reversed by pre-treatment with an OXT receptor antagonist, confirming the specificity of action via the OXT pathway. These results indicate that endogenous OXT may have analgesic effects in FM, and could be a potential target for effective pain management strategies for this disorder.

A case of bone metastasis of hepatocellular carcinoma: Mallory hyaline bodies can lead to the correct cytological diagnosis.

Hepatocellular carcinoma (HCC) accounts for most primary tumors of the liver. Although bone metastasis does not occur in a high percentage of patients, bone metastasis is often found first, which leads to the diagnosis of HCC. In this report, we describe a case of bone metastasis from HCC in which bone lesions were detected incidentally, and in which a cytological diagnosis was difficult to make. The patient was a 78-year-old man with a history of renal dysfunction after orthopedic surgery. He underwent a thorough examination after a bone tumor was incidentally found on abdominal CT. Plasmacytoma was suspected. Fine needle aspiration cytology revealed irregular clusters of medium-to-large atypical epithelioid polygonal cells with relatively abundant eosinophilic, somewhat granular cytoplasm, and indistinct cell borders, which led to a diagnosis of malignancy. Histologically and immunohistochemically, the tumor was diagnosed as bone metastasis of HCC. Re-examination of the cytological specimen revealed characteristic Mallory hyaline bodies (MHBs). Immunohistochemistry using a cell transfer method revealed that they were positive for low molecular weight cytokeratin, Cam5.2, in a densely granular fashion. In this case, the cytological diagnosis of HCC was difficult to make due to the unclear cytoplasmic borders and absence of bile pigment. However, the identification of MHBs can potentially guide me to the correct cytological diagnosis.

Accurate cup placement using a portable navigation system during total hip arthroplasty based on pelvic orientation in the lateral decubitus position.

BACKGROUND: We previously proposed an accurate cup placement procedure using a portable navigation system (PNS) for total hip arthroplasty (THA) in the lateral decubitus position; however, the accuracy of our proposed procedure has not been shown, the aim of this study was to demonstrate the accuracy. METHODS: We prospectively analyzed 79 hips treated with primary THA; 40 hips treated until June 2020 were included in the conventional procedure (CP) group, and 39 hips treated from July 2020 were included in the modified procedure (MP) group. In the MP, pelvic orientation is considered to be the set coordinate axes in addition to the CP using the PNS. The accuracy was based on the difference between the navigation record (NR) and postoperative computed tomography measurement. RESULTS: The radiographic inclination (RI) and anteversion (RA) accuracies were 1.55° and 2.14°, respectively, in the MP group and 3.03° and 6.20°, respectively, in the CP group (p < 0.001). The error was within 5° of the NR for both the RI and RA in 34 in the MP group (87.2%) and 14 in the CP group (35.0%) (p < 0.001). The error was within 5° of the target angle (RI 40°, RA 15°) for both the RI and RA in 29 hips in the MP group (74.7%) and 12 in the CP group (30.0%) (p < 0.001). CONCLUSIONS: Our procedure with the consideration of pelvic orientation achieved dramatically improved the accuracy of PNS and was suitable to facilitate accurate cup placement.

Cytoplasmic-only Expression of Maspin Predicts Poor Prognosis in Patients With Oral Squamous Cell Carcinoma.

BACKGROUND/AIM: Maspin has tumor-suppressor functions; however, its prognostic value in patients with oral squamous cell carcinoma (OSCC) remains unknown. We aimed to assess the prognostic importance of the subcellular localization of maspin in patients with OSCC. PATIENTS AND METHODS: Eighty resected specimens were analyzed by immunohistochemistry. Cytoplasmic-only expression observed in >10% of the tumor was defined as maspin-positive. RESULTS: The maspin-positive status (25%) was significantly associated with a higher recurrence rate and shorter disease-free survival (DFS). Cox's multivariate analysis showed that maspin-positive status was an independent factor for shorter DFS. All OSCC cell lines (HSC2, HSC3, HSC4, Ca9-22 and SAS) showed maspin protein localization to both the cytoplasm and nucleus using western blot analysis. In HSC4 cells, cell invasion was significantly increased in response to maspin knockdown. CONCLUSION: Cytoplasmic-only expression of maspin could be an independent poor prognostic factor for patients with OSCC.

Factors associated with mortality among patients with necrotizing soft tissue infections: An analysis of 4597 cases using the Diagnosis Procedure Combination Database.

OBJECTIVE: This study aimed to determine the factors associated with mortality among patients with necrotizing soft tissue infection (NSTI) in Japan using inpatient data from the Diagnosis Procedure Combination (DPC) Database. METHODS: We conducted a cross-sectional study using a population retrieved from the Japanese DPC inpatient database of patients who underwent surgical operations from 2014 through 2017. The associations between the covariates and mortality were estimated using multivariate logistic regression models. RESULTS: In total, 4597 patients were registered in this study, with an overall mortality rate of 6.9%. Multilevel logistic regression analysis revealed that higher age, lower body mass index (BMI < 18.5 kg/m2), pre-existing cancer diagnosis, sepsis at admission, maintenance dialysis, antithrombin III use, and anti-methicillin-resistant Staphylococcus aureus (MRSA) antibiotic use were associated with a high mortality rate among NSTI patients. However, sex, underlying diabetes mellitus, ambulance use at admission, intravenous immunoglobulin use, higher hospital case volume, and frequency of operations were not associated with mortality. CONCLUSION: This study is the first to report the association of lower BMI, antithrombin III use, and anti-MRSA antibiotic use with a higher mortality rate among NSTI patients.

The posterior tibial slope is mainly created by the posterior rotation of the tibial condyles.

PURPOSE: Constitutional varus in the coronal plane is formed based on the Hueter-Volkmann's law. The varus deformity occurs at the proximal metaphysis of the tibia and the tibial condyle rotates medially. In the sagittal plane, we hypothesized that the posterior slope angle of the tibial articular surface may also occur at the proximal metaphysis and the tibial condyle rotates posteriorly. The purpose of this study was to verify the hypothesis. METHODS: A total of 208 patients who underwent TKA had lateral view proximal tibia digital radiograph on which seven parameters were analyzed. The posterior slope angle of the tibial articular surface relative to the anterior wall of the tibial condyle and that relative to the anterior cortex of the tibial shaft were assessed. Correlation between the position of the tibial condyle and the posterior slope angle of the articular surface were assessed. RESULTS: The proximal tibial condyle itself did not have a posterior slope in the 86.5% of the participants. Posterior rotation of the tibial condyle created posterior slope of the tibial articular surface relative to the anterior cortex of the tibial shaft. The more tibial condyle was posteriorly rotated, the more the tibial articular surface shifted posteriorly. CONCLUSION: Study findings showed that the posterior tibial slope occurs at the proximal metaphysis of the tibia, and the tibial condyle rotates posteriorly. The posterior tibial slope involves the posterior shift of the tibial articular surface. The posterior tibial slope is mainly created by the posterior rotation of the tibial condyle.

Clinical Features of Oral Multiple Primary Carcinomas Compared with Oral Single Primary Carcinoma.

BACKGROUND: Owing to the increase in the older population and the increased life span, the number of patients with oral multiple primary carcinomas will increase. Predicting the second and third carcinoma clinically is difficult, and the presence of second or third carcinomas is a factor that determines the prognosis of oral carcinoma. In this study, we examined the clinical features of oral multiple primary carcinomas treated in our department. METHODS: We retrospectively reviewed the medical records of patients with oral squamous cell carcinoma who underwent radical treatment at and were followed by the Department of Oral and Maxillofacial Surgery, Tottori University Hospital from January 2003 to October 2017. RESULTS: This study included 261 patients: 241 patients had oral single primary carcinoma and 20 patients had oral multiple primary carcinomas. Oral multiple primary carcinomas showed female predilection and occurred more frequently in the lower gingiva and significantly less frequently in the tongue (P < 0.01). Oral multiple primary carcinomas showed a significantly higher recurrence rate (P < 0.01). The 5-year overall survival of oral single primary carcinoma patients was 88.0% compared with 95% for oral multiple primary carcinomas, with no significant difference (log rank test, P = 0.54). However, the 15-year survival rate dropped to 28.1% in oral multiple primary carcinomas. The cumulative disease incidence rates of metachronous second primary carcinoma from first carcinoma at 5 years and 10 years were 3.45% and 5.36%, respectively. CONCLUSION: Oral multiple primary carcinomas rarely occur in the tongue. The 5-year survival rate showed no difference between single and multiple carcinoma patients, but over longer observation, the prognosis of multiple carcinoma was poor owing to a high recurrence rate. Because of the high recurrence rate and risk of further metachronous carcinoma in oral multiple primary carcinomas, longer-term follow-up is required.

Proximal tibia vara involves the medial shift of the tibial articular surface.

PURPOSE: According to the concept of the constitutional varus, the tibial articular surface (TAS) has varus inclination. On the other hand, it has been reported that proximal tibia vara involved medial shift of the TAS. However, it has not been assessed whether varus inclination of the TAS has a correlation with the medial shift. We investigated whether varus inclination of the TAS has a correlation with the medial shift. If there is a correlation between two parameters, the influence of the medial shift of the TAS on the value of the hip-knee-ankle (HKA) angle and the femorotibial angle should be considered. METHODS: A total of 112 patients who underwent total knee arthroplasty had anteroposterior view tibia digital radiograph on which five parameters were analyzed. Varus angle of the TAS, the distance between the mechanical axis and the anatomical axis on the articular surface, and the width of the articular surface were measured. RESULTS: The more the proximal tibia had varus deformity, the more the TAS shift medially would be. Therefore, the mechanical axis does not match the anatomical axis. Because the HKA angle was assessed based on the concept that the mechanical and anatomical axes match on the tibia, this angle may not express the true alignment of the lower extremity in knees with proximal tibia vara. CONCLUSION: In varus knees, the proximal tibia has a medial shift of the TAS that may influence the value of the HKA angle.

Neuropathic Pain Up-Regulates Hypothalamo-Neurohypophysial and Hypothalamo-Spinal Oxytocinergic Pathways in Oxytocin-Monomeric Red Fluorescent Protein 1 Transgenic Rat.

Despite the high incidence of neuropathic pain, its mechanism remains unclear. Oxytocin (OXT) is an established endogenous polypeptide produced in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus. OXT, which is synthesized by OXT neurons in the SON and the magnocellular part of the PVN (mPVN), is delivered into the posterior pituitary (PP), then released into the systemic blood circulation. Meanwhile, OXT-containing neurosecretory cells in the parvocellular part of the PVN (pPVN) are directly projected to the spinal cord and are associated with sensory modulation. In this study, the OXT system in the hypothalamo-neurohypophysial and hypothalamo-spinal pathway was surveyed using a rat neuropathic pain model induced by partial sciatic nerve ligation (PSL). In the present study, we used transgenic rats expressing an OXT-monomeric red fluorescent protein 1 (mRFP1) fusion gene. In a neuropathic pain model, mechanical allodynia was observed, and glial cell activation was also confirmed via immunohistochemistry. In this neuropathic pain model, a significant increase in the OXT-mRFP1 expression was observed in the PP, the SON, mPVN, and pPVN. Furthermore, OXT-mRFP1 granules with positive fluorescent reaction were remarkably increased in laminae I and II of the ipsilateral dorsal horn. Although the plasma concentrations of OXT did not significantly change, a significant increase of the mRNA levels of OXT and mRFP1 in the SON, mPVN, and pPVN were observed. These results suggest that neuropathic pain induced by PSL upregulates hypothalamic OXT synthesis and transportation to the OXTergic axon terminals in the PP and spinal cord.

[A Case of Consciousness Disorder Induced by the Syndrome of Inappropriate Antidiuretic Hormone Secretion Following Cisplatin and 5-Fluorouracil Chemotherapy in a Patient with Tongue Cancer].

We herein report a case of a consciousness disorder that was induced by the syndrome of inappropriate antidiuretic hormone secretion following cisplatin (CDDP) and 5 -fluorouracil (5-FU) chemotherapy in a patient with tongue cancer. A 72- year-old woman complained of tongue pain and was admitted to our hospital for neoadjuvant chemotherapy, under a diagnosis of tongue squamous cell carcinoma (T4aN2bM0). She was treated with CDDP and 5-FU. On the second day after administration, she complained of nausea and anorexia, and on the third day, she showed impaired consciousness. Laboratory studies revealed that the patient had a serum sodium concentration 112mEq/L, and no dehydration was noted. The patient was diagnosed with SIADH, using the appropriate diagnostic criteria based on serum and urine hypoosmolality. We subsequently discontinued chemotherapy and initiated fluid restriction and sodium supplements. Two days after this treatment, her consciousness level improved, and on the fifth day of treatment, laboratory studies revealed a serum sodium level of 134mEq/ L.

Role of Trpv1 and Trpv4 in surgical incision-induced tissue swelling and Fos-like immunoreactivity in the central nervous system of mice.

Pain management remains a major concern regarding the treatment of postoperative patients. Transient receptor potential (TRP) channels are considered to be new therapeutic targets for pain control. We investigated whether the genes Trpv1 and Trpv4 are involved in hind paw swelling caused after surgical incision in mice or in incision-induced Fos-like immunoreactivity (Fos-LI) levels in the central nervous system. Mice were divided into four groups: wild-type (WT) control, WT incision, Trpv1 knockout (Trpv1-/-) incision, and Trpv4 knockout (Trpv4-/-) incision. Mice were anesthetized, and only those in the incision, and not control, groups received a surgical incision to their right plantar hind paw. Changes in paw diameter and in Fos-LI levels in the dorsal horn of the spinal cord, paraventricular nucleus of the hypothalamus (PVN), paraventricular nucleus of the thalamus, and central amygdala were evaluated 2 h after the incision. There was no significant difference in the paw diameter among groups. In contrast, in laminae I-II of the dorsal horn of the spinal cord and PVN, Fos-LI was significantly higher in all incision groups than in the WT control group. A significant increase in Fos-positive cells was also observed in the dorsal horn laminae III-IV in Trpv1-/- and Trpv4-/- incision groups compared with the WT incision group. Our results indicate that surgical incision activates the PVN and that Trpv1 and Trpv4 might be involved in neuronal activity in the dorsal horn laminae III-IV after surgical incision.

Comparison of the induction of c-fos-eGFP and Fos protein in the rat spinal cord and hypothalamus resulting from subcutaneous capsaicin or formalin injection.

We evaluated whether a c-fos-enhanced green fluorescent protein (eGFP) transgenic rat line, which expresses the c-fos and eGFP fusion gene, can be useful for the study of nociceptive pathways and processing. Capsaicin solution (15%) or formalin (5%) was subcutaneously injected bilaterally into the hind paws (100µL per each paw) of adult male c-fos-eGFP transgenic or wild-type rats. Control rats were injected with ethanol or physiological saline respectively. Transgenic and wild-type rats were perfused at 1.5, 3 and 6h post injection, with some transgenic rats being perfused 24h post injection. A comparison of eGFP in transgenic rats and Fos-like immunoreactivity (LI) in wild-type rats was made in the dorsal spinal cord, paraventricular nucleus (PVN) and supraoptic nucleus (SON). Oxytocin-LI (OXT-LI) was carried out to examine the activation of OXT neurons in the PVN and SON. Following capsaicin or formalin treatment, eGFP was maximally expressed at 6h in the spinal cord and 3h in the PVN and SON, whereas, Fos-LI was maximally expressed at 1.5h in all the regions we analyzed. Induction of eGFP in the OXT neurons was observed after capsaicin or formalin treatment, while Fos-LI in the OXT neurons was observed only after formalin treatment. These results demonstrate that the peak induction of c-fos-eGFP following exposure to acute nociceptive stimuli was delayed by around 1.5-4.5h, but more sensitive than endogenous Fos, suggesting that the c-fos-eGFP rat line can be useful for the study of nociceptive pathways and processing.

Fifteen-Year Comparison of Wear and Osteolysis Analysis for Cross-Linked or Conventional Polyethylene in Cementless Total Hip Arthroplasty for Hip Dysplasia-A Retrospective Cohort Study.

BACKGROUND: Cross-linked polyethylene (XLPE) acetabular liners used in cementless total hip arthroplasty (THA) have demonstrated better wear resistance at 10 years compared with conventional polyethylene (CPE) liners. No clinical studies have compared XPLE to CPE liners beyond 10 years. METHODS: We performed a 15-year retrospective cohort study on cementless THA performed in patients with developmental hip dysplasia to measure the differences in polyethylene wear rates and the presence of osteolysis. Twenty-four THAs with XLPE and 17 THAs with CPE were evaluated. The mean age of patients was 55.9 years (41-68) in the XLPE group and 54.4 years (40-67) in the CPE group. The mean follow-up period was 15.1 years (13.9-16.1) in the XLPE group and 15.2 years (14.5-16.0) in the CPE group. RESULTS: The XLPE group had a significantly lower wear rate at 5 and 10 years compared with the CPE group; however, no significant difference was found at 15 years (XLPE group, 0.040 mm/y; CPE group, 0.034 mm/y). In addition, the incidence of osteolysis did not differ significantly between the groups. However, the incidence of excessive wear between 10 and 15 years after surgery in the XLPE group was significantly higher than that in the CPE group. CONCLUSION: XLPE demonstrated no advantage in the wear rate or the incidence of osteolysis at 15 years, despite having superior wear resistance up to 10 years. It is concerning that the incidence of excessive wear was higher in the XLPE group between 10 and 15 years, and this finding should alert the arthroplasty community to this possible problem with the more highly cross-linked polyethylene.

Possible involvement of TRPV1 and TRPV4 in nociceptive stimulation- induced nocifensive behavior and neuroendocrine response in mice.

Members of the transient receptor potential (TRP) family of ion channels play important roles in inflammation and pain. Here, we showed that both TRPV1 and TRPV4 might contribute to biphasic nocifensive behavior and neuroendocrine response following a formalin test. We subcutaneously injected saline, formalin, or the TRPV4 agonist, 4α-phorbol 12,13-didecanoate (4α-PDD) into one hindpaw of wild-type (WT), TRPV1-deficient (Trpv1(-/-)), and TRPV4-deficient (Trpv4(-/-)) mice to investigate nocifensive behaviors (phase I [0-10 min] and phase II [10-60 min]) and Fos expression in the dorsal horn of the spinal cord and other brain regions related to pain, in the paraventricular nucleus (PVN), paraventricular nucleus of the thalamus, the medial habenular nucleus, the medial nucleus of the amygdala and capsular part of the central amygdala. Subcutaneous (s.c.) injection of formalin caused less nocifensive behavior in Trpv1(-/-) and Trpv4(-/-) mice than in WT mice during phase I. In phase II, however, formalin induced less nocifensive behavior only in the Trpv1(-/-) mice, but not in the Trpv4(-/-) mice, relative to WT mice. The number of Fos-like immunoreactive (LI) neurons in laminae I-II of the dorsal horn increased in all types of mice 90 min after s.c. injection of formalin; however, there was no difference in the other regions between saline- and formalin-treated mice. Furthermore, s.c. injection of 4α-PDD did not induce nociceptive behavior nor influence the number of Fos-LI neurons in the all above mentioned regions in any of the mice. These results suggest that TRPV4-mediated nociceptive information from the peripheral tissue excluding the spinal pathway might be involved the formalin behavioral response during phase I. Only TRPV1 might regulate the formalin behavioral response in peripheral neuron.

Synovial cyst of the hip in a patient with rheumatoid arthritis.

A 67-year-old woman with rheumatoid arthritis (RA; Steinblocker stage IV, class 4) who had RA onset at 34 years of age had anterior thigh pain, femoral neuropathy and lower abdominal pain. Physical examination showed multidirectional limit of motion, and radiographic examination showed destruction of the hip joint. MRI and arthrography indicated a cystic lesion that communicated with the hip joint. The rheumatoid synovial cyst was removed during total hip arthroplasty. The symptoms were relieved, and the mass was reduced in size.

Expression of the c-fos-monomeric red fluorescent protein 1 fusion gene in the spinal cord and the hypothalamic paraventricular nucleus in transgenic rats after nociceptive stimulation.

We generated transgenic rats expressing the c-fos and monomeric red fluorescent protein 1 (mRFP1) fusion gene in the central nervous system after adequate stimulation. In the present study, the time-course of the induction patterns of mRFP1 fluorescence in the spinal cord and the paraventricular nucleus (PVN) was compared with that of Fos-like immunoreactivity (LI) within 24 h after subcutaneous (s.c.) injection of 0.9% saline and 5% formalin in both hind paws. Control rats were not treated. In the control and saline/formalin injected rats, scattered mRFP1 fluorescence in the spinal cord and the PVN was observed at 0 min, though there was little Fos-LI in the same region. The mRFP1 fluorescence in the spinal cord and the PVN was increased at 3h after formalin. On the other hand, the changes of Fos-LI in the spinal cord and the PVN were relatively shorter than those of the mRFP1 fluorescence after formalin. These results suggest that the c-fos-mRFP1 fusion gene expression is slightly upregulated in normal conditions and nociceptive stimulation-induced induction of the fusion gene may be maintained longer than the endogenous c-fos gene expression in the spinal cord and the PVN. Next, nocifensive behavior and mRFP1 fluorescence and Fos-LI in the spinal cord and the PVN after s.c. injection of formalin, 4α-phorbol 12,13-didecanoate (4α-PDD) and saline were compared. Although the 4α-PDD injected rats seldom displayed nocifensive behaviors like s.c. saline injection, 4α-PDD injection caused mRFP1 fluorescence and Fos-LI significantly in the spinal cord and the PVN unlike s.c. saline injection.

Cell-type specific oxytocin gene expression from AAV delivered promoter deletion constructs into the rat supraoptic nucleus in vivo.

The magnocellular neurons (MCNs) in the hypothalamus selectively express either oxytocin (OXT) or vasopressin (AVP) neuropeptide genes, a property that defines their phenotypes. Here we examine the molecular basis of this selectivity in the OXT MCNs by stereotaxic microinjections of adeno-associated virus (AAV) vectors that contain various OXT gene promoter deletion constructs using EGFP as the reporter into the rat supraoptic nucleus (SON). Two weeks following injection of the AAVs, immunohistochemical assays of EGFP expression from these constructs were done to determine whether the EGFP reporter co-localizes with either the OXT- or AVP-immunoreactivity in the MCNs. The results show that the key elements in the OT gene promoter that regulate the cell-type specific expression the SON are located -216 to -100 bp upstream of the transcription start site. We hypothesize that within this 116 bp domain a repressor exists that inhibits expression specifically in AVP MCNs, thereby leading to the cell-type specific expression of the OXT gene only in the OXT MCNs.