Predictors for onset of extended-spectrum beta-lactamase-producing Escherichia coli-induced bacteraemia: a systematic review and meta-analysis.

Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli bacteraemia can induce unfavourable clinical outcomes due to delay in appropriate antimicrobial treatment and limited therapeutic options. Therefore, elucidating the predictors of ESBL-producing E. coli-induced bacteraemia is crucial to improve clinical outcomes. However, a literature search did not reveal any studies that incorporate a meta-analysis of the predictors of ESBL-producing E. coli-induced bacteraemia. As such, this review was undertaken to assess current evidence on the predictors of ESBL-producing E. coli-induced bacteraemia. PubMed, Web of Science and Cochrane Library databases were searched for all relevant publications from January 2000 to September 2021. This systematic review evaluated 10 observational studies, comprising a total of 2325 patients with E. coli-induced bacteraemia and 850 (36.6%) ESBL-producing strains. In the meta-analysis, previous antibiotic therapy [pooled risk ratio (RR) 2.72; P<0.001], especially with cephalosporins (pooled RR 4.66; P<0.001) and quinolones (pooled RR 5.47; P<0.001), and urinary catheter use (pooled RR 3.79; P<0.001) were predictive of ESBL-producing E. coli-induced bacteraemia. Antibiotic therapy for patients with the above-mentioned risk factors should be selected considering the possibility of ESBL-producing E. coli-induced bacteraemia compared with non-ESBL-producing E. coli-induced bacteraemia. It is important to elucidate whether appropriate modulation of the identified risk factors can potentially mitigate the risk of ESBL-producing E. coli-induced bacteraemia compared with non-ESBL-producing E. coli-induced bacteraemia.

Predictors of hypervirulent Klebsiella pneumoniae infections: a systematic review and meta-analysis.

BACKGROUND: Hypervirulent Klebsiella pneumoniae (hvKp) infections confer notable morbidity and mortality. Differential diagnosis to determine whether the infections are caused by either the hvKp or classical K. pneumoniae (cKp) strain is particularly important for undertaking optimal clinical care and infection control efforts. AIM: To identify and assess the potential predictors of hvKp infections. METHODS: PubMed, Web of Science, and Cochrane Library databases were searched for all relevant publications from January 2000 to March 2022. The search terms included a combination of the following terms: (i) Klebsiella pneumoniae or K. pneumoniae and (ii) hypervirulent or hypervirulence. A meta-analysis of factors for which risk ratio was reported in three or more studies was conducted, and at least one statistically significant association was identified. FINDINGS: In this systematic review of 11 observational studies, a total of 1392 patients with K. pneumoniae infection and 596 (42.8%) with hvKp strains were evaluated. In the meta-analysis, diabetes mellitus and liver abscess (pooled risk ratio: 2.61 (95% confidence interval: 1.79-3.80) and 9.04 (2.58-31.72), respectively; all P < 0.001) were predictors of hvKp infections. CONCLUSION: For patients with a history of the abovementioned predictors, prudent management, including the search for multiple sites of infection and/or metastatic spread and the enforcement of an early and appropriate source control procedure, should be initiated in consideration of the potential presence of hvKp. We believe that this research highlights the urgent need for increasing clinical awareness of the management of hvKp infections.

p11 in Cholinergic Interneurons of the Nucleus Accumbens Is Essential for Dopamine Responses to Rewarding Stimuli.

A recent study showed that p11 expressed in cholinergic interneurons (CINs) of the nucleus accumbens (NAc) is a key regulator of depression-like behaviors. Dopaminergic neurons projecting to the NAc are responsible for reward-related behaviors, and their function is impaired in depression. The present study investigated the role of p11 in NAc CINs in dopamine responses to rewarding stimuli. The extracellular dopamine and acetylcholine (ACh) levels in the NAc were determined in freely moving male mice using in vivo microdialysis. Rewarding stimuli (cocaine, palatable food, and female mouse encounter) induced an increase in dopamine efflux in the NAc of wild-type (WT) mice. The dopamine responses were attenuated (cocaine) or abolished (food and female mouse encounter) in constitutive p11 knock-out (KO) mice. The dopamine response to cocaine was accompanied by an increase in ACh NAc efflux, whereas the attenuated dopamine response to cocaine in p11 KO mice was restored by activation of nicotinic or muscarinic ACh receptors in the NAc. Dopamine responses to rewarding stimuli and ACh release in the NAc were attenuated in mice with deletion of p11 from cholinergic neurons (ChAT-p11 cKO mice), whereas gene delivery of p11 to CINs restored the dopamine responses. Furthermore, chemogenetic studies revealed that p11 is required for activation of CINs in response to rewarding stimuli. Thus, p11 in NAc CINs plays a critical role in activating these neurons to mediate dopamine responses to rewarding stimuli. The dysregulation of mesolimbic dopamine system by dysfunction of p11 in NAc CINs may be involved in pathogenesis of depressive states.

Recurrent mutations of CD79B and MYD88 are the hallmark of primary central nervous system lymphomas.

AIMS: Primary central nervous system lymphoma (PCNSL) manifest aggressive clinical behaviour and have poor prognosis. Although constitutive activation of the nuclear factor-κB (NF-κB) pathway has been documented, knowledge about the genetic alterations leading to the impairment of the NF-κB pathway in PCNSLs is still limited. This study was aimed to unravel the underlying genetic profiles of PCNSL. METHODS: We conducted the systematic sequencing of 21 genes relevant to the NF-κB signalling network for 71 PCNSLs as well as the pyrosequencing of CD79B and MYD88 mutation hotspots in a further 35 PCNSLs and 46 glioblastomas (GBMs) for validation. RESULTS: The results showed that 68 out of 71 PCNSLs had mutations in the NF-κB gene network, most commonly affecting CD79B (83%), MYD88 (76%), TBL1XR1 (23%), PRDM1 (20%) and CREBBP1 (20%). These mutations, particularly CD79B and MYD88, frequently coincided within each tumour in various combinations, simultaneously affecting diverse pathways within the network. No GBMs had hotspot mutation of CD79B Y196 and MYD88 L265. CONCLUSIONS: The prevalence of CD79B and MYD88 mutations in PCNSLs was considerably higher than reported in systemic diffuse large B-cell lymphomas. This observation could reflect the paucity of antigen stimuli from the immune system in the central nervous system (CNS) and the necessity to substitute them by the constitutive activation of CD79B and MYD88 that would initiate the signalling cascades. These hotspot mutations may serve as a genetic hallmark for PCNSL serving as a genetic marker for diagnose and potential targets for molecular therapy.

The role of biomechanical factors in ankylosing spondylitis: the patient's perspective.

Biomechanical factors including occupational joint physical stressing and joint injury have been linked to spondyloarthritis. We explored such factors in ankylosing spondylitis (AS). A retrospective, online survey was developed alongside the UK National Ankylosing Spondylitis Society (NASS). Questions on early entheseal symptoms, potential precipitating trauma, sporting activity, and physiotherapy were asked. A total of 1026 patients responded with 44% recalling an instance of injury or trauma as a potential trigger for their AS. After symptom onset, 55% modified sporting activities and 28% reported that the initial AS recommended exercises exacerbated symptoms. Patients report physical trauma, exercise and physiotherapy as potential triggers for AS symptoms. These findings further support the experimental evidence for the role of biomechanical factors in disease.

Pharmacokinetic impact of SLCO1A2 polymorphisms on imatinib disposition in patients with chronic myeloid leukemia.

The purpose of this study was to explore the role of the organic anion-transporting polypeptide (OATP) 1A2, which is encoded by SLCO1A2, in the cellular uptake of the Bcr-Abl tyrosine kinase inhibitor imatinib, and the relationship between SLCO1A2 polymorphisms and the pharmacokinetics of imatinib in patients with chronic myeloid leukemia (CML). Imatinib uptake was significantly enhanced in OATP1A2-transfected human embryonic kidney (HEK) 293 cells (P = 0.002). Naringin, an OATP1A2 inhibitor, decreased the transport of imatinib in OATP1A2-transfected HEK293 cells, the human intestinal cell line Caco-2, and K562 CML cells. Linkage disequilibrium was found between the SLCO1A2 -1105G>A and -1032G>A genotypes in 34 CML patients and 100 healthy subjects. Imatinib clearance in CML patients was influenced by the SLCO1A2 -1105G>A/-1032G>A genotype (P = 0.075) and the SLCO1A2 -361GG genotype (P = 0.005). These findings suggest that imatinib is transported into cells by OATP1A2, and that SLCO1A2 polymorphisms significantly affect imatinib pharmacokinetics.

Comparative histopathological analysis between tenosynovitis and joint synovitis in rheumatoid arthritis.

AIMS: To clarify the histological and biological features of tenosynovitis accompanying rheumatoid arthritis (RA). METHODS AND RESULTS: Synovial tissue was obtained from the wrist joint and extensor tendon of the digits of six RA patients and the sections were examined by haematoxylin and eosin staining and immunohistochemical analysis. RA tenosynovitis exhibited the typical histological features of RA joint synovitis, including hyperplasia of the synovial lining and infiltration of leucocytes, largely CD4+ T cells and CD68+ macrophages. Notably, there was a significant correlation in the number of CD4+ T cells and CD68+ macrophages between the tenosynovium and joint synovium in each individual. Real-time reverse transcriptase-polymerase chain reaction analysis revealed similar mRNA expression patterns of various inflammatory mediators in tenosynovitis and joint synovitis. It was also observed that synovial fibroblasts isolated from the tenosynovium behaved in a manner similar to those isolated from the joint synovium with regard to proliferation and the production of inflammatory mediators. CONCLUSIONS: The histopathological features of RA tenosynovitis were indistinguishable from those of joint synovitis. Therefore, it is suggested that the ongoing inflammation is driven by similar mechanisms in the tenosynovium and joint synovium and that RA is probably a tissue-specific disease which targets systemic synovial tissues.

Microsurgery for vestibular schwannoma after gamma knife radiosurgery.

BACKGROUND: We evaluated the clinical characteristics of microsurgery for vestibular schwannoma (VS) after failed gamma knife radiosurgery (GKS). METHOD: Twelve patients, 5 men and 7 women aged 19 to 70 years (mean 54.5 years), who underwent microsurgery after failed GKS for VS were studied retrospectively. FINDINGS: The median interval between GKS and microsurgery was 28.8 months (range, 6.6-120 months) and 4 patients had undergone previous microsurgery. The mean volume of tumour at GKS was 6.9 cm(3) (range, 0.5-19.7 cm(3)) and the mean prescription dose to the tumour margin was 12.3 Gy. Microsurgery involved the lateral suboccipital approach in all patients. Tumour expansion involved solid enlargement in 7 patients, cystic enlargement in 3, and central necrosis in 2. Bleeding was slight in all patients except in one, probably because of the previous irradiation. Adhesion to the brain stem was severe in 7 patients. Identification of the facial nerve was easy in 5 operations and difficult in 7. Dissection of the tumour from the facial nerve was difficult in most interventions because of severe adhesions or colour change. Severe adhesions between the trigeminal nerve and the tumour was observed in 2 patients. The tumour was subtotally removed except around the internal auditory canal in most patients. Only one residual tumour increased in size and needed second GKS. The function of the facial nerve deteriorated in 3 patients, was unchanged in 7, and improved in 2. All patients had lost hearing on the affected side at the time of microsurgery. CONCLUSIONS: Microsurgery for VS after failed GKS presents some technical difficulties. Dissection of the tumour from the facial nerve or brain stem is likely to be difficult. We recommend subtotal resection without dissection of the facial nerve and tumour, because growth of the residual tumour was rare in our series.

Efficacy of gamma knife surgery for control of peritumoral oedema associated with metastatic brain tumours.

OBJECTIVES: To evaluate the efficacy of gamma knife surgery (GKS) for the control of peritumoral oedema associated with metastatic brain tumours. METHODS: A retrospective study of 280 consecutive metastatic brain tumours-100 from lung cancers, 100 from breast cancers and 80 from renal-cell carcinomas, associated with peritumoral oedema. The peritumoral oedema index was measured as A*B*C, where A (cm) was the maximum diameter of peritumoral oedema on the axial image, B (cm) was the maximum diameter perpendicular to A, and C (cm) was the maximum diameter on the coronal image. RESULTS: The oedema index of the renal cancer metastases was significantly larger than those of lung and breast cancer metastases (p<0.01). The oedema index of the renal cancer metastases at final imaging was also larger than those of lung (p<0.05) and breast (p<0.01) cancer metastases. The delivered marginal dose (22 Gy or more) was significantly correlated with tumour growth control by multivariate analysis (p = 0.03). Primary site (renal or not renal: p<0.01) and delivered marginal dose (25Gy or more: p = 0.04) were significantly correlated with control of peritumoral oedema by multivariate analysis. CONCLUSIONS: Brain oedema around metastatic brain tumours from renal-cell carcinomas was more extensive at the time of GKS and at final imaging compared with lung and breast cancer metastases. This paper suggests that the optimal doses for tumour growth control and brain oedema control may differ for metastatic brain tumours from renal-cell carcinomas.

Gamma knife radiosurgery for intracranial haemangioblastomas.

BACKGROUND: The results of gamma knife radiosurgery for haemangioblastomas were retrospectively studied to assess the efficacy for tumour growth control and clarify the clinical indications for gamma knife radiosurgery in these tumours. METHODS: The medical records of 22 patients with 67 tumours, 12 men and 10 women aged 20-73 years (mean 51.9 years), who underwent gamma knife radiosurgery for haemangioblastomas between January 1993 and January 2006, were retrospectively reviewed. Ten patients with 54 lesions had von Hippel-Lindau disease. The mean tumour volume was 1.69 cm(3) (range 0.0097-16.4 cm(3)). Nineteen patients had undergone 1-4 open surgery procedures (mean 1.5) before gamma knife radiosurgery. Tumours without a cystic component, (the solid type), were found in 54 lesions and tumours associated with cyst, (the mural nodule with cyst type), in 13 lesions. The marginal dose was 8-30 Gy (mean 14.0 Gy). FINDINGS: Follow-up magnetic resonance (MR) imaging was performed at 9-146 months (mean 63 months). The control rate for tumour growth was 83.6%. The only factor affecting tumour growth control was the presence of a cystic component at the time of gamma knife radiosurgery in both univariate and multivariate analysis. No complication such as radiation-induced peritumoural oedema or radiation necrosis occurred. CONCLUSION: The presence of cystic components at the time of gamma knife radiosurgery was the only factor significantly correlated with unfavourable tumour growth control by gamma knife radiosurgery for haemangioblastomas. Gamma knife radiosurgery is effective for solid type tumours, even if the marginal dose is relatively low. Surgical removal is recommended for mural nodule with cyst type tumours, when possible.

Role of adenosine A1 receptors in the modulation of dopamine D1 and adenosine A2A receptor signaling in the neostriatum.

Adenosine is known to modulate the function of neostriatal neurons. Adenosine acting on A(2A) receptors increases the phosphorylation of dopamine- and cAMP-regulated phosphoprotein of M(r) 32 kDa (DARPP-32) at Thr34 (the cAMP-dependent protein kinase [PKA] site) in striatopallidal neurons, and opposes dopamine D2 receptor signaling. In contrast, the role of adenosine A(1) receptors in the regulation of dopamine/DARPP-32 signaling is not clearly understood. Here, we investigated the effect of adenosine A(1) receptors on D(1), D(2) and A(2A) receptor signaling using mouse neostriatal slices. An A(1) receptor agonist, 2-chloro-N(6)-cyclopentyladenosine (100 nM), caused a transient increase, followed by a transient decrease, in DARPP-32 Thr34 phosphorylation. Our data support the following model for the actions of the A(1) receptor agonist. The A(1) receptor-induced early increase in Thr34 phosphorylation was mediated by presynaptic inhibition of dopamine release, and the subsequent removal of tonic inhibition by D(2) receptors of A(2A) receptor/G(olf)/cAMP/PKA signaling. The A(1) receptor-induced late decrease in Thr34 phosphorylation was mediated by a postsynaptic G(i) mechanism, resulting in inhibition of D(1) and A(2A) receptor-coupled G(olf)/cAMP/PKA signaling in direct and indirect pathway neurons, respectively. In conclusion, A(1) receptors play a major modulatory role in dopamine and adenosine receptor signaling.

Recurrence rate and transplantability after liver resection in patients with hepatocellular carcinoma who initially met transplantation criteria.

To understand the recurrence rate and transplantability after liver resection (LR), which are essential factors to predict the prognosis of initial resection and salvage transplantation for hepatocellular carcinoma (HCC), we reviewed the clinical records of 279 consecutive HCC patients who met the Milan criteria and underwent LR between 1990 and 2000. Recurrence-free survival rates after 1, 2, 3, 5, and 10 years following LR were 84%, 62%, 49%, 29%, and 17%, respectively. Multivariate analysis using clinical factors such as age, sex, histological differentiation, serum levels of alpha-fetoprotein and 7S domain of type IV collagen (7S collagen), platelet counts, indocyanin green retention test after 15 minutes, and type of LR (resection of one or more segments, or less than one segment) revealed 7S collagen to be a independent factor that significantly affects recurrence-free survival. Yearly recurrence rates up to 5 years after resection ranged from 14% to 27%, averaging 20%. Concerning 169 patients who underwent tests for 7S collagen, the average yearly recurrence rate (27%) in patients with 7S collagen levels 8.0 ng/mL or higher was remarkably greater than that in the patients with levels less than 8.0 ng/mL (16%). The transplantability rate at the time of recurrence meeting the Milan criteria was roughly 60%. There were no pre-LR factors that significantly predicted transplantability. This result indicates that patients with lower 7S collagen levels are more eligible for initial LR and then salvage LT rather than primary LT.

Repeated gamma knife radiosurgery for multiple metastatic brain tumours.

BACKGROUND: The effectiveness of repeated gamma knife radiosurgery (GKS) for the treatment of multiple metastatic brain tumours was evaluated. METHODS: This study included 16 patients with 242 tumours, 10 men and 6 women with a mean age of 60.3 years at initial GKS, who underwent GKS four times or more for newly developed metastatic tumours. FINDINGS: Sixteen patients underwent a total of 83 GKS procedures (range 4 to 8, mean 5.2). The mean number of metastases at each GKS procedure was 2.9 and the number of tumours tended to increase at the 5th GKS procedure compared with the 1st, but not significantly. The mean interval between each procedure was 4.8 months and was not significantly different. Median survival was 22.4 months (range 9.4-78.9 months) and the primary site was not correlated with survival time. The total number of treated tumours tended to correlate to survival time, but not significantly. Use of adjuvant whole brain radiation also had no significant effect on survival time. The Karnofsky performance status was maintained at more than 70 in most patients, but decreased significantly between initial and final GKS. Death due to progression of brain lesions occurred in only about 30% of patients regardless of the multiple newly developed brain metastases. CONCLUSIONS: Repeated radiosurgery for brain metastases is effective and relatively long survival can be expected in some patients associated with a low risk of radiation-induced injury.

Gamma knife radiosurgery for metastatic tumours in the brain stem.

BACKGROUND: Stereotactic radiosurgery has become important in the treatment of metastatic brain tumours and is often the first choice modality for eloquent or deep locations such as the brain stem. This study evaluated the efficacy of gamma knife radiosurgery (GKS) for the treatment of brain stem metastases. METHODS: The medical records of 25 patients with 31 tumours, 11 men and 14 women aged 42 to 78 years (mean 57.1 years), who underwent GKS for metastatic tumours in the brain stem were retrospectively reviewed. The results of GKS were evaluated according to the change in tumour size on neuro-imaging. FINDINGS: The most common location of the primary malignancy was the lung followed by the breast. Adenocarcinoma was found in 19 patients (24 lesions). No case of squamous cell carcinoma was found. The mean calculated tumour volume was 2.1 cm(3) and the mean prescription dose to the tumour margin was 13.0 Gy. Mean duration of neuro-imaging follow up was 5.2 months and the overall tumour control rate was 77.4%. There was a significant correlation between the marginal dose delivered and the effect on neuro-imaging. New radiation-induced injury in the surrounding brain occurred in only 2 patients. INTERPRETATION: GKS for brain stem metastases using a marginal dose of 15 Gy or less is effective and relatively safe. Accurate targeting of the tumour and safe dose planning are essential to obtain satisfactory results with GKS for brain stem metastases.

Cytokeratin-19 fragments in serum (CYFRA 21-1) as a marker in primary liver cancer.

Using an electrochemiluminescence immunoassay, CYFRA 21-1 concentrations were measured in sera from 187 patients with primary liver cancer (164 with hepatocellular carcinoma (HCC) and 23 with intrahepatic cholangiocarcinoma (ICC)) and 87 patients with benign liver diseases. Concentrations of CYFRA 21-1 were significantly higher in patients with ICC (5.0; interquartile range 3.1-10.7 ng ml(-1)) than in those with benign liver disease (1.4; 1.0-1.9; Mann-Whitney U-test, P<0.0001) or HCC (1.7; 1.1-2.7; Mann-Whitney U-test, P<0.0001). Using cutoff values selected for 95% specificity in the benign group (3.0 ng ml(-1)), CYFRA 21-1 showed higher sensitivity for ICC (87.0%) than three commonly used markers including alpha-fetoprotein (17.4%), carcinoembryonic antigen (34.8%), and carbohydrate antigen 19-9 (60.9%). Serum CYFRA 21-1 increased in ICC from stages I/II to IV (Kruskal-Wallis test, P=0.0102). CYFRA 21-1 concentration increased with extent of local invasion, but not nodal status. Serum CYFRA 21-1 represents a useful diagnostic test for ICC that offers high sensitivity. CYFRA 21-1 reflected differences in tumour burden, suggesting applicability to staging and follow-up.

Surgical management of synchronous hepatocellular carcinoma and gastric cancer.

BACKGROUND/AIMS: The improvement of diagnostic modalities and operative techniques has resulted in prolonged survival for cancer patients, but has also led to the diagnosis of an increasing number of patients with synchronous hepatocellular carcinoma (HCC) and extrahepatic primary cancer. It is necessary to determine the optimal surgical strategies for synchronous HCC and gastric cancer. METHODS: In this retrospective study, clinicopathologic findings, diagnostic methods, treatment and outcome were reviewed in 13 patients who underwent curative surgery for synchronous HCC and gastric cancer. RESULTS: Twelve of the 13 patients were men older than 60 years. All patients had chronic hepatic disease, and hepatitis viral infection was detected in 9 patients. Examinations of the esophagus to search for esophageal varices before liver resection for HCC, and imaging studies to rule out liver metastasis before gastrectomy for gastric cancer can lead to the incidental finding of a synchronous carcinoma. The most frequent postoperative complication was massive ascites, which occurred in 4 patients who underwent lymph node dissection, 1 of whom died of perioperative hepatic failure. HCC recurred in 7 patients, 4 of whom died of their disease; only 1 patient died of recurrence of gastric cancer. CONCLUSION: Careful follow-up for recurrence of HCC is necessary because the most common cause of death in patients with synchronous carcinoma is recurrence of HCC.

Randomized clinical trial of long-term outcome after resection of hepatitis C virus-related hepatocellular carcinoma by postoperative interferon therapy.

BACKGROUND: Interferon therapy seems to decrease the incidence of recurrence after resection of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). Effects of postoperative interferon therapy on the survival rate after resection of such HCC are still unclear. METHODS: A prospective randomized clinical trial of postoperative interferon therapy was performed. Thirty men were allocated randomly after liver resection to an interferon-alpha group (15 patients) or a control group. Patients in the interferon group received interferon-alpha 6 MIU intramuscularly every day for 2 weeks, then three times a week for 14 weeks and finally twice a week for 88 weeks. RESULTS: The response to interferon was complete in two patients, there was a biochemical response in six patients and no response in seven patients. Interferon administration was not completed in three patients because of adverse events. Liver function did not change or worsened after operation in the control group, and did not change or improved in the interferon group. The cumulative survival rate was higher in the interferon group than in the control group (P = 0.041). CONCLUSION: Postoperative interferon therapy seems to improve the outcome after resection of HCV-related HCC.

Fibroblasts from the inner granulation tissue of the pseudocapsule in hips at revision arthroplasty induce osteoclast differentiation, as do stromal cells.

BACKGROUND: It has previously been shown that many osteoclast precursors are included in the granulation tissue within the pseudocapsule obtained at revision arthroplasty from hips with osteolysis. In vitro culture of only cells isolated from the granulation tissue has been previously shown to generate many mature osteoclasts. OBJECTIVE: To investigate the presence or otherwise of supporting cells, similar to stromal cells, which differentiate osteoclasts within the granulation tissue. METHODS: Cells isolated from the granulation tissue were cultured alone, and after four weeks fibroblast-like cells (granulation fibroblasts) remained. Rat non-adherent bone marrow cells (NA-BMCs) were co-cultured with the granulation fibroblasts with or without 1alpha,25(OH)2D3 (10(-8) M) or heat treated ROS 17/2.8 cell conditioned medium (ht ROSCM), or both. Multinucleated cells (MNCs), which formed, were assessed by biochemical and functional characterisation of osteoclasts. Receptor activator of NFkappaB ligand (RANKL) was investigated by immunohistochemistry. RESULTS: Co-culture of NA-BMCs and granulation fibroblasts caused the formation of tartrate resistant acid phosphatase (TRAP) positive MNCs, which had the calcitonin receptor (CTR), the Kat-1 antigen, which is specific to the surface of rat osteoclasts, and the ability to form pits in the presence of both 1alpha,25(OH)2D3 and ht ROSCM or in the presence of just ht ROSCM. RANKL was detected in fibroblast-like cells in the granulation tissue. CONCLUSION: These data suggest that granulation fibroblasts support osteoclast differentiation, as do osteoblasts/stromal cells, and may play a part in aseptic loosening.

Multicentric reticulohistiocytosis with hydrarthrosis in both knee joints: disease stabilization with synovectomy, and medication with a steroid and low-dose methotrexate.

Abstract Multicentric reticulohistiocytosis is a rare systemic disease characterized by the infiltration of histiocytes and multinucleated giant cells with cutaneous nodules, and severe destructive arthritis. It is commonly the peripheral joints which are affected, and therefore symptoms in large joints have not been fully investigated. We describe the case of a 44-year-old woman with multicentric reticulohistiocytosis, who was suffering from swelling in both knee joints and cutaneous nodules, in addition to arthritis in the elbow, hip, and peripheral joints. Magnetic resonance imaging of both knee joints showed hydrarthrosis associated with a tumor-like overgrowth of synovial tissue. These symptoms were reduced following a resection of the synovial tissue and subsequent medication with prednisone and low-dose methotrexate. It should be noted that swelling in the knee joints can be one of the symptoms caused by multicentric reticulohistiocytosis, in addition to cutaneous nodules and arthritis in the peripheral joints. Resection of synovial tissue, and medication with prednisone and low-dose methotrexate were effective in the present case.

Relationship of the microvascular type to the tumor size, arterialization and dedifferentiation of human hepatocellular carcinoma.

Unlike normal liver with the sinusoids, hepatocellular carcinomas (HCCs) possess capillaries. Whether these capillaries derive from the sinusoids remains unclear in human HCCs. This study aimed to examine sinusoidal capillarization in human HCCs and its relationship to the tumor size, arterialization and dedifferentiation. Thirty-eight HCCs with a diameter of 10 - 140 mm were pathologically and angiographically examined. By electron microscopy, the microvasculature of tumors was classified into sinusoidal, intermediate and capillary types, which were all negative, partially positive and all positive, respectively, for four parameters, i.e., endothelial defenestration, continuous basement membrane, lack of Kupffer cells, and lack of lipid-containing hepatic stellate cells. Well-, moderately and poorly differentiated HCCs displayed sinusoidal / intermediate / capillary types, intermediate / capillary types and only capillary type, respectively, suggesting the transition from the sinusoids to capillaries in well-differentiated (and probably moderately differentiated) HCCs. Furthermore, well-differentiated HCCs with a diameter of less than 30 mm often received preferential portal venous blood, while moderately and poorly differentiated ones were all supplied with arterial blood, indicating a relationship between dedifferentiation and arterialization. In contrast, the microvascular type displayed no significant relationship with tumor size or arterialization in well-differentiated HCCs. The present study has demonstrated that sinusoidal capillarization occurs in human well-differentiated HCCs and seems to be related to dedifferentiation of parenchymal tumor cells, but not to tumor size or arterialization.