Inhibition of cortical and cancellous bone formation in glucocorticoid-treated OVX sheep

INTRODUCTION: Little is known about the effects of steroids on cortical bone. The purpose of this study was to explore the effects of glucocorticoid treatment on cortical bone density, strength, and formation of new bone in ovariectomized sheep and to compare it to cancellous bone. MATERIALS AND METHODS: Sixteen ovariectomized merino sheep either received a 6-month glucocorticoid treatment (GLU; 0.45 mg/kg/day Methylprednisolone s.c.) or were left untreated (control). After 2 and 4 months, newly formed bone was labeled by the administration of calceingreen and Tetracycline-hydrochloride. After 12 months, the animals were sacrificed and cortical specimens were obtained from the tibial diaphysis. Cancellous bone specimens were harvested from the proximal tibia. All specimens were scanned for apparent BMD by pQCT and tested mechanically. Formation of new bone was analyzed using histological slices of the femoral condyles and cross-sections of the mid-diaphysis of the tibia. RESULTS: The intracortical formation of new bone in glucocorticoid-treated sheep was 70% lower after 2 months and 80% lower after 4 months. Six months after the termination of the steroid administration, the active bone area was 20% lower than in the control group. Cortical width and cortical bone area were reduced by 7-8% and marrow area increased by 8% in steroid-treated animals compared to control animals. Neither cortical apparent bone mineral density nor biomechanical parameters of cortical bone specimens differed between the groups. Cancellous bone formation in steroid-treated animals declined by 68% after 2 months and by 90% after 4 months. After 1 year, cancellous bone formation was reduced by 38% compared to control. The apparent cancellous bone mineral density and cancellous bone compressive stiffness were reduced by 34% and 55%, respectively. CONCLUSION: A six-month glucocorticoid treatment of ovariectomized sheep resulted in a substantial reduction of bone formation both in cortical and in cancellous bone and reduced cortical width by increased endosteal resorption. Beyond changes in cancellous bone, impaired cortical bone remodeling may add to the increased fracture risk at the hip or the distal radius in patients treated with steroids.     

The patient's choice of androgen-deprivation therapy in locally advanced prostate cancer: bicalutamide, a gonadotrophin-releasing hormone analogue or orchidectomy

OBJECTIVE: To investigate patient preference for three established androgen-deprivation therapies for locally advanced prostate cancer; the patient's capacity to decide his therapy; the reasons for selecting a certain mode of therapy; and patient satisfaction with the chosen therapy 3 months after initiation. PATIENTS AND METHODS: In all, 150 patients (mean age 75 years, range 57-89) with previously untreated locally advanced prostate cancer from 13 hospitals were consecutively given the chance to choose between the antiandrogenic oral drug bicalutamide, a gonadotrophin-releasing hormone analogue (GnRH) by injection, or surgical orchidectomy. After discussing the nature of their disease the patients took home written information about prostate cancer and the three different treatment options. After 1 week they were assessed using a questionnaire for biographical data, their attitude towards the different treatment alternatives and their choice of therapy. Three months later the patients completed a questionnaire about the treatment they had undergone. RESULTS: Sixty-three patients (42%) chose bicalutamide, 51 (34%) the GnRH analogue and 36 (24%) orchidectomy; 87% of those choosing bicalutamide, 84% GnRH and 94% orchidectomy, respectively, were sure about their choice but 12%, 17% and 3% of the patients, respectively, had some difficulty in deciding. The most important reasons for the therapy chosen were avoidance of injections and surgery, and a lower risk of impotence (bicalutamide), negative attitude to surgery and tablets (GnRH), and avoidance of injections and tablets (orchidectomy). Almost all patients (98%, 98% and 97%, respectively) were satisfied with their choice after 3 months of treatment. CONCLUSION: There are three equally effective forms of androgen deprivation for locally advanced prostate cancer without known metastases. There are major differences among these treatments in the mode of application and the likelihood and impact of side-effects. When patients are fully informed and play an active role in the treatment decision they are satisfied with their decision 3 months later.     

Preservation of Muscular and Elastic Artery Distensibility After an Intercontinental Cryoconserved Exchange: Theoretical Advances in Arterial Homograft Generation and Utilization

While the situation of tissue donation and transplantation differs between Latin American and European countries, a common problem is tissue deficiency. Hence, at present, there is a pressing need to generate alternatives so as to increase the possibilities of obtaining the requested materials. Consequently, it would be of significant interest to establish an intercontinental network for tissue exchange, to improve international cooperation, and to help patients that need tissue transplantation, and to evaluate the feasibility of using an intercontinental network for the exchange of cryopreserved arteries (cryografts), preserving the arterial distensibility and ensuring a reduced native artery–cryograft biomechanical mismatch. Distensibility was studied in ovine arteries divided into three groups: intact (in vivo tests, conscious animals), fresh control (in vitro tests immediately after the artery excision, Uruguay), and cryografts (in vitro tests of cryopreserved-transported-defrosted arteries, Spain). Histological studies were performed so as to analyze changes in the endothelial layer and elastic components. The comparison between fresh control and cryografts showed that neither the cryopreservation nor the exchange network impaired the distensibility, despite the expected histological changes found in the cryografts. The comparison between intact and cryografts showed that the cryografts would be capable of ensuring a reduced biomechanical mismatch. The cryopreservation and the intercontinental network designed for artery exchange preserved the arterial distensibility. It could be possible to transfer cryografts between Latin America and Europe to be used in cardiovascular surgeries and/or for tissue banking reprocessing, with basic biomechanical properties similar to those of the fresh and/or native arteries.     

Implication of glutamate in the kinetics of insulin secretion in rat and mouse perfused pancreas

It is intriguing that the kinetics of glucose-stimulated insulin secretion from the in situ perfused pancreas differ between the rat and the mouse. Here we confirm that insulin release in the rat is clearly biphasic, whereas in the mouse glucose essentially elicits a transient monophasic insulin release. Glucose-derived glutamate has been suggested to participate in the full development of the secretory response. The present report shows that the expression of glutamate dehydrogenase is lower in mouse than in rat or human islets, paralleling the insulin secretion profile. Addition of glutamic acid dimethyl ester mainly enhances insulin release at an intermediate glucose concentration in the rat pancreas. In the mouse preparation, glutamic acid dimethyl ester induces a sustained secretory response, both at 7.0 and 16.7 mmol/l glucose. These results are compatible with a role for glucose-derived glutamate principally in the sustained phase of nutrient-stimulated insulin secretion.     

Posterior transpedicular stabilisation of the infected spine

BACKGROUND: Six men and seven women, aged 62 years, bedridden due to back pain from a septic spondylitis in the thoracolumbar region and not responding to conservative treatment, were operated on with transpedicular stabilisation of the affected segments to enhance mobilisation. All patients experienced immediately reduced back pain, allowing them to leave their bed and start mobilisation during the first postoperative day. At follow-up after a mean of 29 months (range 13-60 months) only one was using analgesics. RESULTS: Nine of the 11 patients with pathological neurology at surgery had improved, none had deteriorated, and all were ambulatory without bladder or bowel disturbances. Seven had achieved a solid interbody fusion, with a continued radiographic decrease in the spondylitic change in the rest, indicating that a progressive interbody fusion was in progress. Three individuals had increased kyphosis, a mean of 11 deg compared with the postoperative radiographs.     

Pulmonary hemodynamics as predictors of mortality in patients awaiting lung transplantation.

Lung transplantation (LTx) is a therapeutic option for patients with end-stage lung disease. However, the mortality rate of patients on the waiting list is high. The purpose of this study was to examine the prognostic value of cardio-pulmonary hemodynamics for death in patients awaiting LTx. Retrospectively, 177 patients with advanced lung disease accepted for LTx at Sahlgrenska University Hospital from January 1990 through December 2003 were studied. Patient demographics, pulmonary function tests, gas exchange and hemodynamic variables were included in the analysis. Death while awaiting LTx was the primary endpoint for all analyses. Mean age was 49 +/- 9 years. Main diagnoses were alpha 1 antitrypsin deficiency (n = 56), chronic obstructive pulmonary disease (n = 61), cystic fibrosis (n = 14) and interstitial lung disease (n = 46). Thirty patients died (17%). LTx was performed in 143 cases. By univariate analyses, forced vital capacity (FVC) % of predicted, pulmonary vascular resistance (PVR) and diagnosis were associated with risk for death. In multivariate analysis PVR (HR, 1.22; 95% CI, 1.06-1.41; P = 0.006) and FVC% of predicted (HR, 0.97; 95% CI, 0.94-0.99; P = 0.01) were independently associated with death. Patients with increased PVR and a lower FVC % of predicted awaiting LTx should be considered for a higher organ allocation priority. Assessment of pulmonary hemodynamics needs to be considered during evaluation for LTx.     

Surgery for fulminating colitis during pregnancy

Two cases of fulminating colitis presenting during pregnancy are described. In both cases, resectional surgery was performed. In the first case, cesarean section was combined with subtotal colectomy and ileostomy during the 32nd week of gestation. In the second case, cesarean section was performed during the 33rd week of gestation and proctocolectomy in the puerperium. In both cases, histopathologic examination showed colitis more consistent with Crohn's disease. It is concluded that if fulminating colitis appears during pregnancy it should be treated in the same manner as in the nonpregnant state.     

Defecography

PURPOSE: This study was designed to analyze the frequency of different findings at defecography in patients with defecation disorders and see in what way the evaluation could be improved. METHODS: The reports of investigations in 2,816 patients were analyzed. RESULTS: Twenty-three percent of the investigations were considered normal. Thirty-one percent of the patients had rectal intussusception, 13 percent had rectal prolapse, 27 percent had rectocele, and 19 percent had enterocele. Twenty-one percent of the patients had a combination of two or three of these diagnoses. The combination of rectocele and enterocele was rare. The majority of patients with enterocele had other concomitant findings. Patients with or without abnormal perineal descent had similar frequencies of rectal prolapse, rectal intussusception, and enterocele. Rectocele was more common in patients with abnormal perineal descent. CONCLUSIONS: Defecography is valuable when investigating patients with defecation disorders. Pathologic findings were found in 77 percent of the patients. A standardized protocol should ensure a complete evaluation of defecography.Read in part at the 14th Biennial Congress of University Colon and Rectal Surgeons, Crete, Greece, October 25 to 29, 1992.