Prevention of Bone Loss by Clodronate in Early Postmenopausal Women with Vertebral Osteopenia: A Dose-Finding Study

This double-masked, placebo-controlled study was undertaken to determine the efficacy and safety of oral clodronate in the prevention of bone loss in early postmenopausal women with vertebral osteopenia. Altogether 610 women with a mean age of 53 years were recruited for the study. They were 1–5 years postmenopausal and their lumbar spine bone mineral density (BMD) was at least 1 standard deviation below the mean of premenopausal women (T-score ≤−1). The subjects were randomized into five study groups to receive either placebo, clodronate 65 mg, 400 mg or 800 mg daily, or intermittent clodronate in 3 month cycles with 400 mg daily for 15 days followed with no treatment for 75 days for 3 years. One hundred and eighty-seven of 509 women who completed the primary study continued in the extension study of 2 years in which previous placebo users were switched to clodronate 800 mg daily, while previous users of 400 mg or 800 mg of clodronate used either placebo or 800 mg of clodronate daily. In the primary study clodronate was administered in the evening, and in the extension 1 h before breakfast on an empty stomach. In the primary study mean changes in lumbar spine BMD were −3.4% in the placebo group and +0.4% in 800 mg clodronate group [difference between groups at 3 years 3.8% (95% CI 2.7% to 4.9%, p<0.0001)], and in the trochanter area BMD −1.1% in the placebo group, and + 0.4% in the 800 mg clodronate group [difference between groups at 3 years 1.5% (95% CI 0.05% to 2.9%)]. During the extension study mean changes in lumbar spine BMD were +1.5% in the clodronate group and −0.2 % in the placebo group [difference between groups 1.7% (CI 0.4% to 3.0%, p = 0.010)] and in trochanter BMD were +2.5% in the clodronate group and no change in the placebo group [difference between groups 2.1% (CI 0.3% to 3.9%, p = 0.007)]. No statistically significant differences between the placebo and 800 mg clodronate groups were found in the femoral neck BMD. In the primary study the urinary excretion of type I collagen aminoterminal telopeptide (NTX) decreased by 44% (p<0.0001 compared with placebo) and that of deoxypyridinoline by 18% (p<0.0001) in the clodronate 800 mg group. In the extension study urinary NTX decreased by 51% (p<0.0001) in those who were switched to 800 mg of clodronate and increased by 67% (p<0.0001) in those who stopped using that dose. There was no difference in the frequency of gastrointestinal complaints between clodronate- and placebo-treated patients in the primary study, but they were more common among women who received clodronate in the extension phase. Clodronate in daily doses of 400–800 mg caused a slight elevation of aminotransferase levels, usually within the reference range. In bone biopsies no defect in mineralization was found. In conclusion, clodronate in a daily dose of 800 mg prevents early postmenopausal bone loss at the sites of the skeleton in which cancellous bone predominates. It effectively reduces bone resorption and bone turnover rate. Antifracture efficacy of clodronate remains to be established by prospective, placebo-controlled trials. Received: 4 March 2002 / Accepted: 9 July 2002     

The relation of appraisal,coping efforts,and acuteness of trauma to PTS symptoms among former political prisoners

We examined how trauma-specific appraisals and coping efforts mediate between traumatic experiences, acuteness of trauma, and length of imprisonment and posttraumatic stress symptoms (PTS) among 103 Palestinian former political prisoners. The findings provide support for both direct and mediated models of trauma. The acuteness of trauma (time since release), appraisal of prison experience as harmful and involving loss, and use of both emotion- and problem-focused coping efforts were associated with high levels of PTS symptoms. Torture and ill-treatment had a direct association with intrusion, and recent release from prison with avoidance symptoms. Acuteness of trauma turned out to be important in the coping and symptom association: emotion-focused coping was associated with a low level of PTS symptoms in the long run, whereas problem-focused coping was associated with a low level of PTS symptoms in the short run.     

Determinants of bone strength and fracture incidence in adult Finns: Cardiovascular Risk in Young Finns Study (the GENDI pQCT study)

Summary

Peripheral bone strength and fracture risk were studied in young adult Finns. Peripheral bone measures were associated with risk factors of osteoporosis in young adults and discriminated between those with and without low-energy fractures. In men, trabecular bone loss at peripheral bone sites starts before the age of 40 years.

Purpose

This is a cross-sectional study of the determinants of bone strength and fracture risk in young Finns using peripheral quantitative computed tomography (pQCT) and quantitative ultrasound (QUS).

Methods

pQCT scans were performed in 1,884 subjects at distal and shaft sites of non-dominant radius and left tibia, and QUS measures (n?=?1,415) at the left calcaneus. Lifestyle factors and medical conditions affecting bone health were assessed with questionnaires.

Results

In men, the youngest age cohort had the lowest trabecular volumetric bone mineral density (vBMD) at radius and tibia (difference between the youngest and the oldest, 4.4% and 5.6%, respectively, P?<?0.001) and lowest speed of ultrasound at the calcaneus (difference 0.5%, P?=?0.016). In women, bone traits did not differ by age groups. When sexes were pooled, underweight (relative risk (RR)?=?2.95, P?<?0.001), excess alcohol intake (1.52, P?=?0.036), smoking (1.29, P?=?0.025), Crohn’s disease or inflammatory bowel syndrome (2.43, P?=?0.016), epilepsy (2.54, P?=?0.011), use of corticosteroids (2.01, P?<?0.001) and inactivity (1.34, P?=?0.045) increased the risk of low trabecular vBMD. RRs for low-energy fractures were excess alcohol intake (2.58, P?=?<0.001), anorexia (3.74, P?=?0.041) and hypogonadism (2.08, P?=?0.015). Same risk factors predicted BMD and fractures in both sexes. Trabecular bone mineral content, vBMD and bone strength index showed greatest differences (4–9%; P?<?0.05) between those with and without low-energy fractures.

Conclusions

Peripheral QCT traits are associated with common risk factors of osteoporosis in young Finns and discriminate between those with and without low-energy fractures. In men, trabecular bone loss at peripheral bone sites starts before the age of 40 years.     

Guidelenines in the management of obstructing cancer of the left colon: consensus conference of the world society of emergency surgery (WSES) and peritoneum and surgery (PnS) society

Background

Obstructive left colon carcinoma (OLCC) is a challenging matter in terms of obstruction release as well of oncological issues. Several options are available and no guidelines are established. The paper aims to generate evidenced based recommendations on management of OLCC.

Methods

The PubMed and Cochrane Library databases were queried for publications focusing on OLCC published prior to April 2010. A extensive retrieval, analyses, and grading of the literature was undertaken. The findings of the research were presented and largely discussed among panellist and audience at the Consensus Conference of the World Society of Emergency Surgery (WSES) and Peritoneum and Surgery (PnS) Society held in Bologna July 2010. Comparisons of techniques are presented and final committee recommendation are enounced.

Results

Hartmann's procedure should be preferred to loop colostomy (Grade 2B). Hartmann's procedure offers no survival benefit compared to segmental colonic resection with primary anastomosis (Grade 2C+); Hartmann's procedure should be considered in patients with high surgical risk (Grade 2C). Total colectomy and segmental colectomy with intraoperative colonic irrigation are associated with same mortality/morbidity, however total colectomy is associated with higher rates impaired bowel function (Grade 1A). Segmental resection and primary anastomosis either with manual decompression or intraoperative colonic irrigation are associated with same mortality/morbidity rate (Grade 1A). In palliation stent placement is associated with similar mortality/morbidity rates and shorter hospital stay (Grade 2B). Stents as a bridge to surgery seems associated with lower mortality rate, shorter hospital stay, and a lower colostomy formation rate (Grade 1B).

Conclusions

Loop colostomy and staged procedure should be adopted in case of dramatic scenario, when neoadjuvant therapy could be expected. Hartmann's procedure should be performed in case of high risk of anastomotic dehiscence. Subtotal and total colectomy should be attempted when cecal perforation or in case of synchronous colonic neoplasm. Primary resection and anastomosis with manual decompression seems the procedure of choice. Colonic stents represent the best option when skills are available. The literature power is relatively poor and the existing RCT are often not sufficiently robust in design thus, among 6 possible treatment modalities, only 2 reached the Grade A.     

Midbrain dopamine D2/3 receptor binding in schizophrenia

Several studies suggest that dysregulation of dopaminergic transmission in the midbrain and thalamus may contribute to the symptomatology of schizophrenia. The objective of this study was to examine the putative alteration of dopamine D_2/3 receptor densities in the thalamus and midbrain of drug-naïve schizophrenic patients. We used the high-affinity single-photon emission tomography ligand [¹²³I]epidepride for imaging D_2/3 receptor binding sites in six neuroleptic-naïve schizophrenic patients, and seven healthy controls. Schizophrenic symptoms were evaluated by the Positive and Negative Syndrome Scale. Significantly lower D_2/3 values were observed in the midbrain of patients with schizophrenia compared to controls (P = 0.02). No statistically significant difference was observed in the thalamus between two groups. Negative correlations were found between thalamic D_2/3 receptor binding and general psychopathological schizophrenic symptoms (r from ?0.78 to ?0.92). These observations implicate altered dopaminergic activity in the midbrain of schizophrenic patients.     

Mid-term survivorship results for a rotating-platform knee prosthesis

Interest in mobile-bearing knee prostheses is increasing in the US market. We studied results at 2 to 5 years with a mobile-bearing system that includes a cobalt-chrome tibial tray and femoral component with a polyethylene cruciate-retaining tibial component insert that allows rotation around a central axis and can be used with cruciate-retaining or posterior-stabilized femoral components. The inserts used in this study were cruciate retaining and did not include the posterior-stabilized design. The goal of this study was to demonstrate the function and safety of this prosthesis along with the lack of spinout, which is a major concern in the mobile-bearing knee. Four hundred thirty-five knees constituted the study cohort and underwent survivorship analysis and complication reporting. Routine clinic evaluations included pre- and postoperative radiographs and Knee Society knee and function scores at 6 and 12 weeks and every 2 years. The most recent follow-up data within 2 to 5 years was included for the study along with survey data. Flexion at most recent follow-up averaged 125°. Knee Society score at most recent visit averaged 88 of 100. Knee Society function score averaged 83 of 100. Radiographic results were available for 226 knees, with 97.3% assessed as normal and 6 with these issues: patella stress fracture (3), aseptic tibial loosening (1), patellar osteolysis (1), and patella aseptic loosening (1). In comparison with the fixed-bearing knee equivalent, this mobile-bearing knee demonstrated at least equivalent results in terms of survivorship, function, and patient satisfaction in the short- and mid-term.     

Early recurrence of congenital diaphragmatic hernia is higher after thoracoscopic than open repair: a single institutional study

Introduction

Experience in thoracoscopic congenital diaphragmatic hernia (CDH) repair has expanded, yet efficacy equal to that of open repair has not been demonstrated. In spite of reports suggesting higher recurrent hernia rates after thoracoscopic repair, this approach has widely been adopted into practice. We report a large, single institutional experience with thoracoscopic CDH repair with special attention to recurrent hernia rates.

Methods

We reviewed the records of neonates with unilateral CDH repaired between January 2006 and February 2010 at Morgan Stanley Children's Hospital. Completely thoracoscopic repairs were compared to open repairs of the same period. In addition, successful thoracoscopic repairs were compared with thoracoscopic repairs that developed recurrence. Data were analyzed by Mann-Whitney U and Fisher exact tests.

Results

Thirty-five neonates underwent attempted thoracoscopic repair, with 26 completed. Concurrently, 19 initially open CDH repairs were performed. Preoperatively, patients in the open repair group required more ventilatory support than the thoracoscopic group. Recurrence was higher after thoracoscopic repair (23% vs 0%; P = .032). In comparing successful thoracoscopic repairs to those with recurrence, none of the factors analyzed were predictive of recurrence.

Conclusions

Early recurrence of hernia is higher in thoracoscopic CDH repairs than in open repairs. Technical factors and a steep learning curve for thoracoscopy may account for the higher recurrence rates, but not patient severity of illness. In an already-tenuous patient population, performing the repair thoracoscopically with a higher risk of recurrence may not be advantageous.     

Temporary abdominal closure techniques

Open abdomen treatment (OAT) is increasingly used, most often to prevent intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) after emergency abdominal surgery. The goal of temporary abdominal closure (TAC) techniques no longer is abdominal coverage alone, but fluid control and facilitation of early fascial closure are now important aspects. Various methods are available, but negative pressure therapy seems to be best suited to achieve these goals. Fascial approximation techniques prevent lateral retraction of the abdominal muscles and can be combined with TAC techniques. Mesh-mediated vacuum-assisted wound closure is emerging as one of the most promising approaches for OAT. In the intensive care unit, continued attention to IAH/ACS and measures to prevent or treat these conditions is imperative.     

Delayed resolution of extensive T2-weighted intramedullary signal changes after oblique corpectomy for cervical spondylotic myelopathy

We report two cases of cervical spondylotic myelopathy (CSM) with extensive T2-weighted intramedullary changes noted on preoperative imaging extending far beyond the level of compression. A delayed resolution 2 years after cervical oblique corpectomy was noted in both cases. This short report cautions against diagnosing this unusual magnetic resonance imaging (MRI) finding as an intramedullary tumour, demyelination or an inflammatory process.     

A new biodegradable braided self-expandable PLGA prostatic stent: an experimental study in the rabbit

PURPOSE: The biodegradable PLGA (a copolymer of L-lactide and glycolide) urethral stent with a spiral configuration has been used clinically for the prevention of postoperative urinary retention after different types of thermal therapy for benign prostatic hyperplasia. A new braiding pattern for this stent has recently been developed by our group. The aim here was to investigate the in situ degradation and biocompatibility of the new braided stent in the rabbit urethra. MATERIALS AND METHODS: PLGA stents with a one-over-one braiding pattern and steel stents served as controls that were inserted into the posterior urethras of 24 male rabbits using a special delivery instrument. The animals were sacrificed after 1 week, 1 month, 2 months, or 4 months, and light microscopy and histologic analyses were performed. RESULTS: The delivery instrument worked well and cystoscopy was not needed in the insertion process. The braided PLGA stents degraded smoothly in 1 to 2 months. The metallic stents induced more epithelial hyperplasia and epithelial changes than the biodegradable stents at all time points analyzed. These differences increased during follow-up. CONCLUSION: The degradation process was well controlled and the biodegradable stents were more biocompatible than the metallic stents. The new stent can be inserted into the posterior urethra without cystoscopic aid.