In vitro comparison of clodronate, pamidronate and zoledronic acid effects on rat osteoclasts and human stem cell-derived osteoblasts

In the present study we compared the first generation non-nitrogen-containing bisphosphonate, clodronate with second and third generation nitrogen-containing bisphosphonates, pamidronate and zoledronic acid in dynamic rat osteoclast resorption and apoptosis assays and in human mesenchymal stem cell-derived osteoblast assay. We found that due to high bisphosphonate-bone binding affinity, bone surface exposure to clodronate for 3 min. had maximal resorption inhibition. The mechanism of action of both clodronate and zoledronic acid involved osteoclast apoptosis, whereas pamidronate had only minor apoptotic effect at dosages, which readily inhibited resorption. Zoledronic acid was not metabolised into an intracellular ATP-analogue in vitro in contrast to clodronate. All bisphosphonates had a dose-dependent inhibitory effect on the human bone marrow mesenchymal stem cell (hMSC)-derived osteoblast calcium deposition. None of the compounds had inhibitory effect on hMSC differentiation. Zoledronic acid was the most potent of all three bisphosphonates in terms of both apoptosis induction and resorption inhibition. Zoledronic acid efficacy might thus use its capacity to trigger osteoclast apoptosis in an unknown, but similar manner to that of the non-nitrogen-containing bisphosphonates. It appears that zoledronic acid has properties of both bisphosphonate classes and could well be the first member of a new class of bisphosphonates, by definition.     

Management of degenerative disk disease and chronic low back pain

Degenerative disk disease is a strong etiologic risk factor of chronic low back pain (LBP). A multidisciplinary approach to treatment is often warranted. Patient education, medication, and cognitive behavioral therapies are essential in the treatment of chronic LBP sufferers. Surgical intervention with a rehabilitation regime is sometimes advocated. Prognostic factors related to the outcome of different treatments include maladaptive pain coping and genetics. The identification of pain genes may assist in determining individuals susceptible to pain and in patient selection for appropriate therapy. Biologic therapies show promise, but clinical trials are needed before advocating their use in humans.     

Force platform measurements as predictors of falls among older people - a review

BACKGROUND: Poor postural balance is one of the major risk factors for falling. A great number of reports have analyzed the risk factors and predictors of falls but the results have for the most part been unclear and partly contradictory. Objective data on these matters are thus urgently needed. The force platform technique has widely been used as a tool to assess balance. However, the ability of force platform measures to predict falls remains unknown. OBJECTIVE: The purpose of this systematic review was to extract and critically review the findings of prospective studies where force platform measurements have been used as predictors of falls among elderly populations. METHODS: The study was done as a systematic literature review. PubMed, the Cochrane Central Register of Controlled Trials, and CINAHL databases from 1950 to April 2005 were used. The review includes prospective follow-up studies using the force platform as a tool to measure postural balance. Results: Nine original prospective studies were included in the final analyses. In five studies fall-related outcomes were associated with some force platform measures and in the remaining four studies associations were not found. For the various parameters derived on the basis of the force platform data, the mean speed of the mediolateral (ML) movement of the center of pressure (COP) during normal standing with the eyes open and closed, the mean amplitude of the ML movement of the COP with the eyes open and closed, and the root-mean-square value of the ML displacement of COP were the indicators that showed significant associations with future falls. Measures related to dynamic posturography (moving platforms) were not predictive of falls. CONCLUSION: Despite a wide search only a few prospective follow-up studies using the force platform technique to measure postural balance and a reliable registration of subsequent falls were found. The results suggest that certain aspects of force platform data may have predictive value for subsequent falls, especially various indicators of the lateral control of posture. However, the small number of studies available makes it difficult to draw definitive conclusions.     

Robotic-assisted laparoscopy is a feasible method for resection of deep infiltrating endometriosis,especially in the rectosigmoid area

ObjectiveThis study aimed to compare outcomes of mini-invasive surgical treatment of endometriosis, especially conventional laparoscopy with robotic-assisted laparoscopy, and to evaluate the quality of life.MethodsOne hundred three consecutive patients with endometriosis who had surgery from 2014 to 2017 owing to an indication of pain were enrolled in this retrospective study. The majority (n = 77, 75%) of patients underwent conventional laparoscopy and 18 (17%) had robotic-assisted laparoscopy. The quality of life was postoperatively assessed with a questionnaire.ResultsThe rates of parametrectomy (76% vs. 45%,) and rectovaginal resection (28% vs. 4%) were significantly higher in robotic-assisted laparoscopy than in laparoscopy. Additionally, the rate of bowel operations (50% vs. 17%), especially the shaving technique, was higher in robotic-assisted laparoscopy surgery than in laparoscopy (39% vs. 8%). There was no difference in the rate of postoperative complications between laparoscopy and robotic-assisted laparoscopy. Most (91%) of the patients who answered the questionnaire felt that surgical treatment had relieved their pain. In the laparoscopic and robotic-assisted groups, 88% of respondents felt that their quality of life had improved after surgery.ConclusionsThis study suggests that robotic-assisted laparoscopy is a feasible method to resect deep infiltrating endometriosis, especially in the rectosigmoid area.     

Hereditary gelsolin amyloidosis mimicking Sj?gren’s syndrome

Hereditary gelsolin amyloidosis (AGel amyloidosis) belongs to the wide group of amyloidotic diseases, which comprise various hereditary but also sporadic forms, such as inflammation-associated AA amyloidosis, primary or myeloma-associated AL amyloidosis and common Alzheimer's disease and type II diabetes-associated local amyloidoses. AGel amyloidosis caused by a gelsolin G654A gene mutation is autosomally dominantly inherited and presents typically in the 30s with progressive corneal lattice dystrophy, followed by cutis laxa and cranial polyneuropathy. Here, we present a case of sicca syndrome, originally diagnosed as primary Sjögren's syndrome (SS) but later found to represent an initial disease manifestation of AGel amyloidosis, not recognised earlier. This case emphasises both the importance of specific amyloid stainings and comprehensive salivary gland histopathology as well as family history in SS differential diagnostics.     

Screening of tumor necrosis factor receptor-associated factor 6 as a candidate gene for inflammatory bowel disease

OBJECTIVE: The two forms of inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC), are thought to arise because of an interplay of unfavorable genetic and exogenous factors. During a genome-wide linkage study of IBD, we observed a nominal linkage to chromosome 11p12-q13 that was further confirmed upon fine density mapping. This chromosomal region contains a functional IBD candidate gene coding for tumor necrosis factor receptor-associated factor 6 (TRAF6), a signal transducer regulating innate and adaptive immunity as well as bone homeostasis. MATERIAL AND METHODS: Using denaturing high-performance liquid chromatography (dHPLC) and DNA sequencing, all exons and exon-intron boundaries of the TRAF6 gene in probands of 95 IBD families were initially screened; this material comprised 20 CD, 39 UC and 36 mixed families. RESULTS: No nucleotide changes in the coding sequence of TRAF6 were detected, but a single-base insertion/deletion polymorphism in a polythymine stretch (containing 8 or 7 thymines, respectively) in intron 3 was identified. However, examination of an extended material of 290 unrelated CD patients, 416 UC patients and 320 healthy blood donors failed to show any association with this 7T/8T variation and IBD, nor was this polymorphism related to specific clinical features in IBD. CONCLUSIONS: Our study tends to exclude a good positional and functional candidate gene, TRAF6, as an IBD predisposing gene and lends support to the idea that the function of TRAF6 is important enough not to permit structural alterations of this mediator.     

Endoglin,VEGF, and its receptors in predicting metastases in endometrial carcinoma

Preoperative evaluation of the risk for metastases in endometrial carcinoma is challenging. The growth of new vessels, angiogenesis, is important for tumor growth and purported to be involved in the metastatic process. The aim of this study was to evaluate the significance of preoperative serum levels and immunohistochemical expression of angiogenic markers in predicting a metastasized disease. Preoperative sera from 98 consecutive women presenting with endometrial carcinoma were collected. Serum concentrations of VEGF, sFLT1, and CD105 were assessed by enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry was used to assess the expression of CD105, VEGF, FLT1, and KDR. The results were correlated to the presence of metastases, presence of deep (≥50 %) myometrial invasion, and the histological grade of the tumor. Tumors with other than endometrioid histology were excluded. Of the 80 evaluable patients, 11 had a metastasized disease. The serum concentration of VEGF was higher in the group with metastases than in the group without metastases (median [range], 743 pg/mL [546–1,183 pg/mL] vs. 383 pg/mL [31–1,524 pg/mL], p?<?0.001, respectively). In the multivariable analysis, the concentration of VEGF was the sole independent, albeit weak predictive factor for the presence of metastases (odds ratio, 1.004, 95 % confidence interval, 1.002–1.007; p?=?0.001). The immunohistochemical expression of the markers was not associated with any of the clinicopathological features of the tumors. The results of the present study suggest that preoperative serum VEGF concentration correlates with the presence of metastases in endometrioid endometrial carcinoma.     

Adolescent cholesterol metabolism predicts coronary risk factors at middle age: the Cardiovascular Risk in Young Finns Study

Atherosclerosis develops at an early age. We studied whether cholesterol metabolism in adolescence is related to coronary risk factors later during the adult years. A random population sample of 12-year-old (n=162), 15-year-old (n=158), and 18-year-old (n=148) boys who participated in the Cardiovascular Risk in Young Finns Study was studied for major coronary risk factors in 1980 and 2001. These values were related to noncholesterol sterols and their quartiles in 1980 (ie, markers of cholesterol absorption and synthesis). In 1980, serum triglycerides, body mass index (BMI), and systolic blood pressure were lower and high-density lipoprotein (HDL) cholesterol was higher in high absorbers versus low absorbers. This difference, except HDL cholesterol, was maintained after follow-up (eg, in 2001, systolic blood pressure was 123+/-1 mm Hg in low absorbers vs 119+/-1 mm Hg in high absorbers, P<0.01). Cholesterol synthesis (r = up to 0.470, P<0.001) and absorption (r = down to -0.347, P<0.001) were related to BMI at baseline and after follow-up. Significant associations were also found between cholesterol metabolism and serum triglycerides, blood pressure, and HDL cholesterol after follow-up. Cholesterol absorption was related to LDL cholesterol only in low absorbers (r=0.251, P<0.01). In conclusion, synthesis and absorption of cholesterol measured with serum noncholesterol sterols in adolescence were related to coronary risk factors later in adult life. High synthesis and low absorption of cholesterol are related to risk factors that determine the characteristics of the metabolic syndrome.     

Odour annoyance and physical symptoms among residents living near waste treatment centres

Waste treatment processes produce odours and biological emissions to the environment, but their health effects are controversial. The aim of our study was to assess odour-associated self-reported physical symptoms among residents living near waste treatment centres. The study was conducted in the surroundings of five large-scale Finnish waste treatment centres with composting plants. In 2006, 1142 randomly selected residents living within 1.5, 3.0 and 5.0 km of these centres were interviewed by telephone. A questionnaire with 102 items asked about respondent's personal characteristics, odour exposure and symptoms during the preceding 12 months. Physical symptoms were analysed by distance to the waste treatment centre and by the respondent's perception and annoyance of waste treatment odour. The residents who were classified as “annoyed of the odour” reported following physical symptoms more than the others did: unusual shortness of breath (OR 1.5, 95% CI 1.0–2.2), eye irritation (1.5, 1.1–2.1), hoarseness/dry throat (1.5, 1.1–2.0), toothache (1.4, 1.0–2.1), unusual tiredness (1.5, 1.1–2.0), fever/shivering (1.7, 1.1–2.5), joint pain (1.5, 1.1–2.1) and muscular pain (1.5, 1.1–2.0). Moreover, the ORs for almost all other physical symptoms were elevated among the annoyed respondents. Reported odour annoyance near the waste treatment centres showed an association with many physical symptoms among residents living in the neighbouring areas.