Spontaneous generation of functional osteoclasts from synovial fluid mononuclear cells as a model of inflammatory osteoclastogenesis

In osteoimmunology, osteoclastogenesis is understood in the context of the immune system. Today, the in vitro model for osteoclastogenesis necessitates the addition of recombinant human receptor activator of nuclear factor kappa‐B ligand (RANKL) and macrophage colony‐stimulating factor (M‐CSF). The peripheral joints of patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA) are characterized by an immune‐mediated inflammation that can lead to bone destruction. Here, we evaluate spontaneous in vitro osteoclastogenesis in cultures of synovial fluid mononuclear cells (SFMCs) activated only in vivo. SFMCs were isolated and cultured for 21 days at 0.5–1.0 × 10⁶ cells/mL in culture medium. SFMCs and healthy control peripheral blood monocytes were cultured with RANKL and M‐CSF as controls. Tartrate‐resistant acid phosphatase (TRAP) positive multinucleated cells were found in the SFMC cultures after 21 days. These cells expressed the osteoclast genes calcitonin receptor, cathepsin K, and integrin β3, formed lacunae on dentin plates and secreted matrix metalloproteinase 9 (MMP9) and TRAP. Adding RANKL and M‐CSF potentiated this secretion. In conclusion, we show that SFMCs from inflamed peripheral joints can spontaneously develop into functionally active osteoclasts ex vivo. Our study provides a simple in vitro model for studying inflammatory osteoclastogenesis.     

Trade Herbal Products and Induction of CYP2C19 and CYP2E1 in Cultured Human Hepatocytes

Abstract: The aim of this study was to evaluate in vitro the dose‐dependent induction potential of six commonly used trade herbal products on CYP2C19 and CYP2E1 metabolic activities in cultured human hepatocytes. S‐mephenytoin and chlorzoxazone were used as specific CYP substrates, respectively, and rifampicin was used as a positive induction control for both enzymes. The hepatocytes were exposed to herbal extracts in increasing and biological relevant concentrations for 72 hrs and CYP substrate metabolites were quantified by validated HPLC methodologies. The major findings were that St John's wort was the most potent CYP‐modulating herb, showing a dose‐dependent induction/inhibition of both CYP2C19 and CYP2E1, with induction at low dosages and inhibition at higher. Ginkgo biloba showed an induction/inhibition profile towards CYP2C19 which was similar but weaker than that observed for St John's wort. If cooperative mechanisms are involved is still an open question. Common sage induced CYP2C19 in a log‐linear dose‐dependent manner with increasing concentrations. Common valerian was a weak inducer of CYP2C19, while horse chestnut and cone flower were characterized as non‐inducers of CYP2C19. Only St John's wort showed an inductive effect towards CYP2E1. In addition to St John's wort, Gingko biloba and common sage should be considered as possible candidates for clinically relevant drug‐herb interactions with selected CYP2C19 substrates.     

Temporal Lobectomy for the Treatment of Intractable Complex Partial Seizures of Temporal Lobe Origin in Early Childhood

Eleven patients with intractable complex partial seizures underwent temporal lobectomy during their first decade. The mean age at onset of epilepsy was two years and at surgery was 5.5 years. On the basis of data from clinical evaluation, CT, MRI in six patients, and pathological examination of excised tissue, the aetiology of the epilepsy was thought to be mesial temporal sclerosis in four children, glioma in five, dysplasia in one and chronic progressive encephalitis in another. At follow-up eight children were seizure-free, two had reduced seizure frequency and only the child with chronic progressive encephalitis had not benefitted from surgery.     

Impact of smoking on cancer stage at diagnosis.

BACKGROUND: Studies evaluating the relationship between smoking and cancer spread are limited. METHODS: We studied the relationship between cancer stage at diagnosis (local, regional, or metastatic) and smoking history (current, previous, or nonsmoker). For lung cancer, patterns of spread were also studied. RESULTS: In a tumor registry for eastern North Dakota, northwestern Minnesota, and northern South Dakota, 11,716 cases were identified from 1986 to 2001. Current smokers (relative risk [RR], 2.11; 95% confidence interval, 1.93 to 2.32; P <.001) and previous smokers (RR, 1.56; 95% confidence interval, 1.42 to 1.72; P <.001) had an increased risk of metastatic disease at diagnosis. Current smokers (RR, 1.39; 95% confidence interval, 1.29 to 1.51; P <.001), but not previous smokers, also had an increased risk of regional disease. An increase in metastatic disease was most evident for prostate cancer (RR, 1.53; P =.003). An increase in regional disease was most evident for head and neck (RR, 3.53; P <.001), prostate (RR, 1.83; P =.030), and breast cancer (RR, 1.22; P =.005). Compared with previous smokers, current smokers with metastatic lung cancer were more likely to have involvement of the brain (33.6% v 23.0%; P =.004), bone marrow, adrenal gland, and pericardium (24.7% v 15.9%; P =.004). CONCLUSION: Previous or current smoking is a risk factor for increased cancer stage in a wide range of malignancies. Further study is required to determine whether this association is causal.     

Clinical trial of a prevention and treatment protocol for skin breakdown in two nursing homes.

OBJECTIVE: Our objective was to assess the effectiveness of skin care protocols, including a body wash and skin protectant, on skin breakdown in 2 nursing homes. DESIGN: This was a quasi-experimental pretest/posttest design study.Setting and subjects Adult residents (n = 136) of 2 skilled nursing homes consented to participate in this study. Seventy percent were women; the sample average age of 82 years. INSTRUMENTS: A researcher-designed data recording form documented resident demographics, incidence and type of skin breakdown or pressure ulcer, presence of urinary or fecal incontinence, and assessment of the effectiveness of body wash and skin protectant. METHODS: Baseline data on prevalence of pressure ulcers and skin protocol were collected weekly for a 3-month period followed by a week-long educational program by the researchers about skin care and the body wash and skin protectant. During the 3-month trial with the body wash and skin protectant incorporated into routine care, research assistants recorded resident data weekly and researchers again assessed prevalence and incidence of pressure ulcers and skin breakdown weekly. RESULTS: Incorporation of a body wash and skin protectant into a skin care prevention and early intervention protocol in 2 nursing homes documented a decrease in skin breakdowns from 68 pre-intervention to 40 postintervention; the decrease in agency B was statistically significant. There was a statistically significant decrease in stage I and II pressure ulcer incidence overall (pre-intervention = 19.9%, postintervention = 8.1%). Nurses evaluated the body wash and skin protectant as effective for 98% of the time used. CONCLUSION: Implementation of a protocol for skin care along with staff education, including the prophylactic use of a body wash and skin protectant, reduced the incidence of skin breakdown, including pressure ulcers and perineal dermatitis, in 2 long-term care facilities.     

THE SURGICAL MANAGEMENT OF OSSEOUS CRANIAL BASE TUMOURS IN CHILDREN

Background : Osseous cranial base tumours in children present as a diverse collection of both benign and malignant pathologies. Concerns raised by the difficulty in accurate diagnosis and local recurrence of benign lesions and by the long-term sequelae of radiotherapy for malignant cranial tumours (marked local growth disturbances, pituitary dysfunction, visual disturbances, late new tumour induction) prompted an evaluation of surgical resection of cranial base tumours in children, with specific regard to safety, efficacy and aesthetic result. Methods : A retrospective review was performed of 10 consecutive children presenting with tumours either arising from or eroding into bone of the cranial base who were managed by surgical resection in a 10-year period from 1986 to 1996. The patients demonstrated a great variation in both presentation and pathology. All underwent surgical resection of tumour with reconstruction where indicated. Results : There were no postoperative complications or mortality. All patients remained clinically free of disease at follow-up, which ranged from 17 months to 9 years (mean 6 years and 4 months). Conclusion : The aggressive surgical resection and craniofacial reconstruction of cranial base tumours in the paediatric population offers a safe and efficacious mode of treatment that obviates problems of diagnosis and local recurrence for benign lesions and of the long-term sequelae of radiotherapy for malignant lesions.     

Clinical characteristics of severe peripheral neuropathy induced by docetaxel (Taxotere)

Background: Docetaxel, a semi-synthetic taxane may cause a usuallymild sensory neuropathy. We describe the clinical characteristics of fivepatients who developed a more severe neuropathy following treatment withdocetaxel.Patients and methods: All patients were treated in phase II studieswith 100 mg/m² docetaxel in three weekly cycles, withoutsteroid administration.Results: The clinical picture in these patients was dominated by asensory neuropathy, but in one case severe weakness was present. Anotherpatient developed Lhermitte's sign. Signs and symptoms are usually reversibleafter discontinuation of docetaxel administration, but in three patientssymptoms worsened for some time after the end of treatment before improvementoccurred.Conclusion: Severe docetaxel neuropathy may especially occurfollowing treatment with cumulative dosage over 600 mg/m²; inpatients treated with this dosage a moderate or severe neuropathy may not berare.     

An investigation of the potential for laser nerve welding.

Suture repair of a severed peripheral nerve is cumbersome, presents a focus for infection and neuroma formation, and does not always produce adequate stump alignment. An alternative form of repair is laser nerve welding, which is attractive because it does not introduce foreign material into the anastomotic site, it forms a circumferential seal, and it can be performed in difficult-to-reach areas. Laser repair has not been widely accepted both because the effect of laser irradiation on intact nerves is not well documented, and the anastomotic strength of the weld has been inferior to suture repair. In the first part of the present study, rat sciatic nerves were exposed and irradiated with increasing intensities from a Sharplan CO2 and KTP laser to document nerve damage as recorded by decreases in the peak compound action potential. A new technique of laser repair (S-Q weld) was then developed that involved harvesting subcutaneous tissue from the adjacent dermis, wrapping it around the two opposed nerve stumps, and lasering it to the epineurium to effect a weld. The strength of the S-Q weld (6.1 grams) was considerably greater than that produced by laser welding alone. The third phase of the study compared regeneration at 2 months in severed rat sciatic nerves repaired by either microsuture or S-Q weld. Analysis of the compound action potential values indicated that the number of regenerating fibers after laser repair was greater than that after suture repair, although a significant difference could not be demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Erythropoietic protoporphyria and pretransplantation treatment with nonbiological liver assist devices.

Erythropoietic protoporphyria (EPP) is a disease of the heme metabolism due to a deficiency of ferrochelatase, leading to accumulation of protoporphyrin (PPIX) in the erythrocyte (red blood cell [RBC]). The major clinical manifestation in EPP is photosensitivity; however, in a small number of patients liver failure is a significant complication and liver transplantation is the only treatment option. Damage to both abdominal skin and organs occurs when exposed to operating light; however, this problem can be ameliorated by the use of filters that block the transmission of light with wavelength below 470 nm. A more unusual but very serious complication postoperatively is severe motor neuropathy, with few or no known acute available precautions. An effective treatment option is needed to manage EPP crises and to prevent complications after liver transplantation. We successfully treated a patient with EPP-induced liver failure with the molecular adsorbents recirculating system (MARS) and Prometheus in independent sessions. Following treatment with MARS we found a 9.1% reduction of the RBC-PPIX concentration and a 5.9% reduction after treatment with the Prometheus system. Plasmapheresis made a reduction in RBC-PPIX concentration of 0.8%. Following treatment sessions with MARS and Prometheus, the clinical condition was markedly improved and orthotopic liver transplantation was performed without further complications. In conclusion, extracorporeal therapy with MARS or Prometheus seems to be efficient in reducing RBC-PPIX concentration in comparison to plasma exchange.