Relationship Among MRTA, DXA, and QUS

Dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound (QUS) are the accepted modalities for the evaluation of fracture risk in the clinical setting. However, neither method provides a direct measurement of bone mechanics. In this study, we investigated a prototype device, known as a mechanical response tissue analyzer (MRTA), which provides direct mechanical measurements of mechanical properties of bone. A total of 56 healthy volunteers (20 men and 36 women) between the ages of 18 and 83 were recruited. The MRTA was used to measure the cross-sectional bending stiffness (EI) of the ulna bone. Axial speed of sound (SOS) at the ulna bone was determined by QUS; bone mineral content (BMC) and bone mineral density (BMD) were determined by DXA. Correlations, regression analysis, and analyses of variance (ANOVAs) were used to compare the three modalities. These analyses revealed that although there are strong linear relationships among the data collected by the various technologies, the bone properties reflected by MRTA are not fully explained by DXA and QUS. We conclude that the total information conveyed by MRTA measurements is unique. Further research is needed to delineate the different qualities of bone strength that are captured by MRTA, but not by DXA or QUS.     

Changes in muscle morphology in dialysis patients after 6 months of aerobic exercise training.

BACKGROUND: In the present study we investigated the effect of a 6-month aerobic exercise programme on the morphology of the gastrocnemius muscle of end-stage renal disease (ESRD) patients. METHODS: Twenty-four ESRD patients volunteered to participate in the training programme and underwent muscle biopsy before training. Eighteen patients completed the training programme of whom nine agreed to a post-training biopsy (one woman and eight men, mean age 56 +/- 15 years). Data are presented for the nine subjects who were biopsied before (PRE) and after training (POST) and separately for the 15 subjects for whom we only have a biopsy before training (cross-sectional group). RESULTS: There were no significant differences (P > 0.05) in fibre type distribution or myosin heavy chain (MyHC) expression between the cross-sectional and PRE/POST groups. The mean cross-section fibre area after training (POST) increased by 46% compared with the PRE training status (P < 0.01). The proportion of atrophic fibres decreased significantly after training in type I, IIa and IIx fibre populations (from 51 to 15%, 58 to 21% and 62 to 32%, respectively). Significant differences were also found in capillary contact per fibre (CC/F), with the muscle having 24% (P < 0.05) more CC/F compared with the PRE training status. No significant differences in cytochrome c oxidase concentration were found between the groups. CONCLUSIONS: In conclusion, exercise appeared to be beneficial in renal rehabilitation by correcting the fibre atrophy, increasing the cross-section fibre area and improving the capillarization in the skeletal muscle of renal failure patients.     

Calcium Concentration-dependent Mechanisms through which Ketamine Relaxes Canine Airway Smooth Muscle

Background: Ketamine is a potent bronchodilator that, in clinically used concentrations, relaxes airway smooth muscle in part by a direct effect. This study explored the role of calcium concentration (Ca2+) in this relaxation.

Methods: Canine trachea smooth muscle strips were loaded with the fluorescent probe fura-2 and mounted in a spectrophotometric system to measure force and intracellular calcium concentration ([Ca2+]i) simultaneously. Calcium influx was estimated using a manganese quenching technique. Cyclic nucleotides in the airway smooth muscle strips were measured by radioimmunoassay.

Results: In smooth muscle strips stimulated with submaximal (0.1 micro Meter) and maximal (10 micro Meter) concentrations of acetylcholine, ketamine caused a concentration-dependent decrease in force and [Ca2+]i. The sensitivity of the force response to ketamine significantly decreased as the intensity of muscarinic receptor stimulation increased; the median effective concentration for relaxation induced by ketamine was 59 micro Meter and 850 micro Meter for tissue contracted by 0.1 micro Meter or 10 micro Meter acetylcholine, respectively (P < 0.05). In contrast, the sensitivity of the [Ca2+] sub i response did not depend on the intensity of muscarinic receptor stimulation. Ketamine at 1 mM significantly inhibited calcium influx. Ketamine did not significantly increase cyclic nucleotide concentrations.     

Diagnosing intramuscular myxoma by fine-needle aspiration: A multidisciplinary approach

The gross and microscopic appearances of aspirates from ten intramuscular myxomas are reported. The specimens were obtained from seven women and three men, ages 43 to 75, who had tumors involving the muscles of the thigh (7), upper arm (2), and forearm (1). Magnetic resonance (MR) imaging performed in six of the ten cases revealed well-defined, sharply demarcated tumors exhibiting low signal intensity relative to muscle on the T1-weighted images. The tumors were hyperintense to muscle on T2-weighted images. All aspirated tissues were clear, tenacious, and viscous. Smears contained few spindled and histiocytoid cells in an abundant mucoid background. Spindle cells demonstrated long cytoplasmic processes that in areas intertwined to form fibrillar tangles. Nuclei were oval to spindled with fine chromatin and inconspicuous nucleoli. Capillaries were sparse with simple (nonplexiform) branching. The differential diagnosis of myxoid lesions of the extremities includes benign entities such as myxoid schwannoma and neurofibroma, mesenchymal repair, and ganglion cyst, as well as malignant neoplasms such as myxoid liposarcoma, fibrosarcoma, malignant fibrous histiocytoma, and extraskeletal chondrosarcoma. The findings of this study revealed that, although the cytologic features were suggestive of intramuscular myxoma, a definitive diagnosis was often difficult, owing to scant cellularity and lack of distinctive cytologic features. The MR imaging findings may be utilized as an adjunct to the cytologic features to more confidently suggest a diagnosis of intramuscular myxoma. Diagn Cytopathol 1994;11:255–261. © 1994 Wiley-Liss, Inc.     

Prolactin responses to haloperidol in drug-free and treated schizophrenic patients

Summary The prolactin response to 5 mg haloperidol i.m. was studied in 12 schizophrenic patients in a drug-free state and after a month treatment with haloperidol, as a possible index of dopamine receptor sensitivity and occupancy. Blood samples were taken at times 0, 60, 90 and 120 minutes. The increase in PRL observed in the drug-free state disappeared after drug treatment. The PRL plasma levels after treatment with 60 mg haloperidol per os were higher than the maximal PRL responses after 5 mg i.m. The increases in baseline PRL caused by the treatment correlated positively to the reduction in the BPRS score. The test was also performed in a group of 11 patients chronically treated with haloperidol during a daily dose of 60 mg, and 15 days after reduction of the dose to 30 mg. PRL increases after 5 mg haloperidol i.m. were observed only after reduction of the dose. It is suggested that the prolactin response to haloperidol is an index of the occupancy of receptors that are involved in the PRL releasing mechanisms, and could be used to verify their blockade by the neuroleptics, especially in patients that do not respond positively to drug treatment.     

Systemic Absorption and Block after Epidural Injection of Ropivacaine in Healthy Volunteers

Background: For local anesthetics, the process of removal from the site of administration influences the duration of anesthesia and the risk for systemic toxicity to develop. The systemic absorption of epidural ropivacaine and the time profile of sensory and motor block were studied in healthy volunteers.

Methods: Nine persons simultaneously received 150 mg ropivacaine hydrochloride (7.5 mg/ml) epidurally and 40 mg deuterium-labeled (sup 2 H sub 3)ropivacaine hydrochloride (0.25 mg/ml) intravenously. Peripheral arterial and venous plasma samples were collected, and assessments of sensory and motor block were made.

Results: The arterial plasma concentrations increased faster than the venous concentrations, with 50% higher maximum concentrations after both intravenous and epidural administration. The absorption was biphasic. A correlation was seen between the duration of sensory block and the slower absorption half-life; that is, the longer the half-life, the longer the duration. The extent of spread varied among the volunteers, with the median upper block level not exceeding T12. The motor block (Bromage score 1) was of slower onset (median, 0.4 h) and of shorter duration (median, 4.1 h) than the sensory block (onset, 0.2 h; duration, 6.5 h at L2 medians).     

VASCULAR CONNECTIVE TISSUE CHANGES IN EXPERIMENTAL PORTACAVAL ANASTOMOSIS

Hepatic vascular changes are generally associated to fibrotic lesions of the liver but their role in the development and extension of fibrosis is not well known. By performing a portacaval anastomosis in rats, a proliferation of hepatic vessels was attained progressively, comparable to proliferations seen in cirrhosis and schistosomiasis. Such a modification of the hepatic vasculature was accompanied by changes in the connective matrix of the liver, mainly related to the vascular walls. Moreover, sinusoidal capillarization was detected at the electron microscopical level whereas no alterations could be seen neither in the distribution nor in the quality of the connective matrix proteins with Immunofluorescence technique. The only modification detected by light microscopy, at this zone, was the shrinked aspect of reticulin fibers which could be related to the important liver atrophy provoked by the anastomosis. It can be assumed that in liver pathology, selective changes occur in the connective matrix components depending on the type of injury. Necrotic and inflammatory processes lead mainly to the deposition of interstitial collagens and associated proteins, related to a diffuse stroma reaction resultant from activation of specific cell populations whereas in portacaval anastomosis, a selective increase of vascular connective matrix (mainly basement membrane components) occurs as a direct consequence of vessel proliferation.     

Regulatory aspects of drug dissolution from a European perspective.

The need for an early identification of formulation and manufacturing factors that are important for setting satisfactory specification limits for the dissolution rate of an active substance from a dosage form is emphasized. A discriminatory dissolution test has to be developed based on experiences from early drug development, bioavailability/bioequivalence studies and clinical trials. References are given to guidelines of the EU-system and to the monographs and chapters of the European Pharmacopoeia, which have to be considered. The dissolution test is expected to be an appropriate tool for checking that the manufacture of dosage forms is consistent and successful and that each dosage unit of a batch will have pharmaceutical qualities that correspond to those on which the safety and efficacy documentation of a product is based.