Nasal salmon calcitonin in osteoporosis

Conclusion Nasal sCT is a safe drug with few and mild side effects and compared with HRT is often more attractive to elderly, osteoporotic women. Under controlled conditions, nasal sCT reduces the rate of new fractures by two-thirds compared with calcium treatment alone [10] and increases spinal bone mass dose dependently.Conclusively, nasal sCT is indicated for treating women who have passed the menopause some years ago. The treatment should be administered discontinuously. The nasal formulation has been approved for treatment of osteoporosis in a variety of European and South American countries, and has also been filed with appropriate governmental authorities for consideration of approval in many countries throughout the world, including the US. Should calcitonin treatment be generalized in women who are 10–15 years postmenopausal, the costs will undoubtedly be reduced. Compared with the effect of HRT on early postmenopausal bone loss, the effect of nasal sCT is only marginal. Thus, HRT prevents both the cortical and trabecular bone loss throughout the entire treatment period [38]. Furthermore, HRT is inexpensive and its adverse event profile has been fully clarified except in respect to the possible change in the risk of breast cancer [39]. Nasal sCT can be effective in women soon after the menopause—by decreasing the rate of vertebral bone loss and lowering the bone turnover—as an alternative to hormone replacement therapy either when estrogens are contraindicated or for women who are not candidates for estrogen therapy.     

Stereological quantitation of human brains from normal and schizophrenic individuals

The complex organization and high density of nerve cells in the human brain presents a challenge to the estimation of total cell numbers. The first unbiased counting method, the disector, was described in 1984 and has since made it possible to accurately count total neuron numbers in any region that can be defined, while excluding artifacts of earlier counting methods. The disector method has been applied to normal neocortex and to four subcortical brain regions from schizophrenics and controls. The total neuron number in neocortex in 26 normal individuals was estimated to be 25·10⁹. A 40 and 50% reduction of total nerve cell number was found in the mediodorsal thalamic nucleus and nucleus accumbens in schizophrenics, respectively. Furthermore, the Cavalieri principle has been used to estimate the volume of human cortex, white matter, central grey regions and the volume of the ventricular system in both controls and schizophrenics. As shown by these studies, the introduction of unbiased stereological methods and subsequent modifications in recent years have made it possible to estimate a number of parameters in the human brain without the biases included in most classical works. By comparison, earlier conventional counting methods have been relatively time consuming, mostly biased to a smaller or larger degree, and generally less precise. The application of these new neurostereological methods will undoubtedly provide greater confidence for future brain studies.     

Studies on urinary bladder carcinoma by morphometry,flow cytometry,and light microscopic malignancy grading with special reference to grade II tumours

Summary Biopsies from 28 patients with urinary bladder carcinoma were investigated by flow cytometry and morphometry. Histopathological grading on 1.5 µm thick glycol methacrylate sections was also performed.Nuclear profile areas, nuclear volume densities and mitotic indices were usually larger in the higher grades of malignancy. All grade I tumours were diploid and all grade III tumours were aneuploid. Out of 13 grade II tumours 8 were diploid and 5 aneuploid. In these latter five cases nuclear profile areas were at the high end of the spectrum.The data show that flow cytometry and morphometry could be a valuable tool in the diagnosis of urinary bladder carcinoma. Our data also suggest that a subdivision of the grade II tumours might be possible and meaningful in the assessment of prognosis.     

RELAY,Ramucirumab Plus Erlotinib Versus Placebo Plus Erlotinib in Patients with Untreated,Epidermal Growth Factor Receptor Mutation-Positive,Metastatic Non-Small-Cell Lung Cancer: Safety Profile and Manageability

Drug Safety - RELAY was a global, double-blind, placebo-controlled phase III study that demonstrated superior progression-free survival (PFS) for ramucirumab plus erlotinib (RAM + ERL) versus...     

Translation,data quality,reliability, validity and responsiveness of the Norwegian version of the Effective Musculoskeletal Consumer Scale (EC-17)

Background  

The Effective Musculoskeletal Consumer Scale (EC-17) is a self-administered questionnaire for evaluating self-management interventions that empower and educate people with rheumatic conditions. The aim of the study was to translate and evaluate the Norwegian version of EC-17 against the necessary criteria for a patient-reported outcome measure, including responsiveness to change.     

Impact of Physical Inactivity on Subcutaneous Adipose Tissue Metabolism in Healthy Young Male Offspring of Patients With Type 2 Diabetes

OBJECTIVE

Physical inactivity is a risk factor for type 2 diabetes and may be more detrimental in first-degree relative (FDR) subjects, unmasking underlying defects of metabolism. Using a positive family history of type 2 diabetes as a marker of increased genetic risk, the aim of this study was to investigate the impact of physical inactivity on adipose tissue (AT) metabolism in FDR subjects.

RESEARCH DESIGN AND METHODS

A total of 13 FDR and 20 control (CON) subjects participated in the study. All were studied before and after 10 days of bed rest using the glucose clamp technique combined with measurements of glucose uptake, lipolysis, and lactate release from subcutaneous abdominal (SCAAT) and femoral (SCFAT) adipose tissue by the microdialysis technique. Additionally, mRNA expression of lipases was determined in biopsies from SCAAT.

RESULTS

Before bed rest, the FDR subjects revealed significantly increased glucose uptake in SCAAT. Furthermore, mRNA expression of lipases was significantly decreased in the SCAAT of FDR subjects. Bed rest significantly decreased lipolysis and tended to increase glucose uptake in the SCFAT of both CON and FDR subjects. In response to bed rest, SCAAT glucose uptake significantly increased in CON subjects but not in FDR subjects.

CONCLUSIONS

FDR subjects exhibit an abnormal AT metabolism including increased glucose uptake prior to bed rest. However, the differences between FDR and CON subjects in AT metabolism were attenuated during bed rest due to relatively more adverse changes in CON subjects compared with FDR subjects. Physical inactivity per se is not more deleterious in FDR subjects as compared with CON subjects with respect to derangements in AT metabolism.Type 2 diabetes is the product of a complex interplay between genetic susceptibility and environmental factors. The best known environmental modifiable risk factors for type 2 diabetes are obesity and a low level of habitual physical activity (1).Even though there is substantial evidence that a change toward a healthy lifestyle halts the progression of type 2 diabetes (2), certain groups, including first-degree relatives (FDRs) of patients with type 2 diabetes, are at increased risk of developing the disease (3). Type 2 diabetes has a major hereditary component (4), and FDR subjects show multiple abnormalities in intermediary metabolism and pancreatic islet cell function, displaying insulin resistance despite normal glucose tolerance (5). The metabolic defects include insufficient insulin secretion (6), decreased peripheral glucose uptake (7), and the impaired antilipolytic effect of insulin in subcutaneous adipose tissue (AT) (8).AT is an active compartment in the lipid and glucose metabolism of humans, but the role of AT metabolism in the development of type 2 diabetes is not clarified. AT, along with skeletal muscle, is a site of peripheral insulin resistance in type 2 diabetes (9). The role of AT in the pathophysiology of insulin resistance can partly be attributed to lipolytic activity resulting in the mobilization of free fatty acids (FFAs), which are deleterious for glucose utilization and insulin action (10). However, AT may play a more direct role since it is a site of deranged glucose metabolism. Although AT is of minor quantitative importance for whole-body glucose disposal, the tissue produces lactate (11), which functions as a gluconeogenic precursor in the liver (12). Previous studies have demonstrated increased plasma lactate (13) and lactate release from adipocytes (14) in FDR subjects.In this study, we investigated in vivo AT glucose uptake, lipolysis, and lactate release, as well as subcutaneous abdominal adipose tissue (SCAAT) mRNA expression of lipases and GLUT-4 in FDR and control (CON) subjects prior to and after 10 days of bed rest. We hypothesized that FDR subjects would show abnormalities in baseline AT metabolism and be more sensitive to the unhealthy effects of physical inactivity.