Three cases of successful stenting for radiation-induced carotid arterial stenosis

We report three cases of radiation-induced carotid arterial stenosis that underwent successful angioplasty with stenting. The patients had received radiation therapy for tongue or laryngeal cancers and developed minor completed strokes 6 to 14 years after irradiation. All patients had multiple and bilateral stenosis, measuring more than 50%, of the carotid arteries. The stenosis was located in the internal, external, and common carotid arteries. We performed percutaneous transluminal angioplasty with stenting. All interventions were successful and carotid stenosis decreased to less than 28%. No permanent complications occurred. During follow-up periods of up to 26 months, all of these cases were free from ischemic symptoms. Neither carotid angiography nor ultrasound sonography showed evidence of restenosis. The present results suggest the usefulness of angioplasty with stenting for radiation-induced carotid arterial stenosis.     

Cancer chemotherapy based on evidence--metastatic breast cancer

Breast cancer is relatively sensitive to chemotherapy. However, although response rate to chemotherapy is reported to be from 50 to 70% in metastatic breast cancer, it is incurable. Current standard chemotherapeutic regimens do not provide a large survival benefit according to the evidence obtained from clinical studies. Before developing a treatment program, we should therefore realize that the aims of chemotherapy for metastatic breast cancer are improvement of quality of life through relief of symptoms, and prolonging survival.     

Studies on a Factor Enhancing Colicin E3 Activity In Vitro

The mechanism of action of colicin E3 (E3) was investigated in an in vitro system. Purified ribosomes are less susceptible to E3 than crude or washed ribosomes. A factor was found in the supernatant fraction of normal Escherichia coli cells that stimulates inactivation of ribosomes by E3, and on addition of this factor, about one tenth as much E3 was required for inactivation of ribosomes. On heating a mixture of E3 and this factor above 60 degrees , the ribosome inactivating activity of E3 increased greatly, and an amount corresponding to 0.01 mug of E3 was sufficient to inactivate 1.0 A(260) unit of ribosomes completely. By this treatment bacteriocidal activity of E3 decreased considerably, as the ratio of the two activities of E3 (ribosome inactivating activity and bacteriocidal activity) increased to 6 x 10(4)-fold. It is evident that the two activities do not run in parallel.This heat-treated product cleaved 16S rRNA in the same way as E3. These results suggest that inactivation of ribosomes is not due to colicin molecules prepared by the standard procedure, but to a modified form of them.     

The role of regional research laboratories of the local government in administering regional EQA programs

In 1981, the Japanese Ministry of Health and Welfare revised the enforcement of regulations of the Medical Technologists' Act. The amendments stipulate that all independent laboratories are legally obliged to introduce laboratory quality assurance programs and are responsible for the quality of all test results. To ensure adherence to these regulations, regional research laboratories of local governments such as the Tokyo Metropolitan Research Laboratory of Public Health should conduct regional external quality assessment (EQA) programs. We did a survey, in the form of a questionnaire, of the regional research laboratories of public health across the country. We found that commitment to the regional EQA in almost all of these public laboratories is insufficient. The main problem is that restructuring of local governments has resulted in lower budgets and so they are short of human resources. Nationwide EQA programs are only able to detect gross errors and use invalid methods for evaluating routine performance. We conclude that the regional EQA should be further developed.     

Long-term effects of muscle-derived protein with molecular mass of 77 kDa (MDP77) on nerve regeneration

The long-term effects of the 77-kDa muscle-derived protein (MDP77) on motor and sensory nerve regeneration were examined in vivo. Fourteen-millimeter bridge grafts of the right sciatic nerve of SD rats were carried out with silicone tubes containing a solution of type I collagen together with 0, 5, 10, or 20 microg/ml recombinant human MDP77 (N = 10 in each group). Recovery of motor and sensory function was evaluated monthly by the maximal toe-spread index (TSI) and hot-plate test, respectively, for 6 months after the operation. Electrophysiology (nerve conduction velocity), histology (diameter and total number of the regenerated myelinated axons in the tube), and immunohistochemistry (total number of Schwann cells in the tube), as well as measurement of soleus muscle weight, were also performed at this time. Motor, but not sensory, function recovered rapidly in the MDP77-treated groups in a dose-dependent manner. Electrophysiological measurements and the ratio of soleus muscle weight corroborated the positive effects of MDP77 on motor nerve regeneration, but no facilitation of sensory nerve recovery was observed. Furthermore, histological and immunohistochemical evaluations suggested that MDP77 treatment accelerates Schwann cell migration, followed by enhanced maturation of regenerating axons, resulting in functional recovery of both the nerves and the atrophied, denervated muscle.     

Imaging of intraneural edema by using gadolinium-enhanced MR imaging: experimental compression injury

BACKGROUND AND PURPOSE: Compressive and entrapment neuropathies are diseases frequently observed on routine clinical examination. A definitive diagnosis based on clinical symptoms and neurologic findings alone is difficult in many cases, however, and electrophysiologic measurement is used as a supplementary diagnostic method. In this study, we examined to use protein tracers (Evans blue albumin or horseradish peroxidase) and gadolinium-enhanced MR imaging to determine the changes of blood-nerve barrier permeability in compressive neuropathies. METHODS: In dogs, the median nerve was compressed for 1 hour by using five kinds of clips with various strengths (7.5-90-g force). After clip removal, the combined tracers of Evans blue albumin and gadolinium or horseradish peroxidase was administered intravenously as a tracer. After the animals were euthenized, we compared gadolinium-enhanced MR images with Evans blue albumin distribution in the nerve under fluorescence microscopy. The horseradish peroxidase-injected specimens were observed by transmission electron microscopy. RESULTS: On enhanced MR imaging, intraneural enhancement was caused by 60- and 90-g-force compression after 1 hour. Marked extravasation of protein tracers in the nerve occurred where there was compression by 60- and 90-g-force compression, and capillaries in the nerve showed the opening of tight junction and an increase of vesicular transport under the electron microscopy. This situation indicated breakdown of the blood-nerve barrier, with consequent edema formation and was seen as enhancement on MR imaging. CONCLUSION: Gadolinium-enhanced MR imaging can detect morphologic and functional changes of blood-nerve barrier in the nerve induced by mechanical compression.     

Relation between vertical orientation and stability of acetabular component in the dysplastic hip simulated by nonlinear three-dimensional finite element method

In acetabular dysplasia, more vertical orientation of the acetabular component is often used to minimize the superolateral bone grafting. This study was designed to determine the effects of vertical orientation of the cup on the stability and polyethylene wear of the acetabular component in uncemented total hip arthroplasty (THA). Three-dimensional finite element models of the hemipelvis with dysplastic acetabulum were developed. Metal-backed hemispherical cups were placed in the true acetabulum with abduction angles of 35, 45, 55, and 65 degrees. It was found that more vertical orientation of the cup was associated with larger relative motion of the metal shell between the acetabulum and metal shell. Furthermore, tilting and torsional shear stresses in the model of the cup abduction angle of 65 degrees were found to be 1.7 times larger than that in the model with 35 degrees at the bone-metal shell interface. More vertically oriented cups caused larger contact stresses at the articulating surfaces of the polyethylene liners. The results suggest that the abduction angle of the acetabular component significantly influences cup loosening and polyethylene wear in THA.     

Mirtazapine increases dopamine release in prefrontal cortex by 5-HT1A receptor activation

Mirtazapine has a low affinity for 5-HT(1A) receptors but shows 5-HT(1A)-agonistic-like effects in behavioral pharmacology test. However, there is to date no clear evidence that mirtazapine enhances 5-HT(1A) neurotransmission. The object of the present study was to assess the effects of mirtazapine on dialysate levels of dopamine and 5-HT in the medial frontal cortex of freely moving rats and to determine whether this drug could modulate 5-HT(1A) neurotransmission. In vivo microdialysis was used to study the effects of mirtazapine on extracellular dopamine and 5-HT levels, and the effect of the 5-HT(1A) antagonist WAY100,356 on extracellular dopamine level increased by mirtazapine in the rat prefrontal cortex. Mirtazapine (4-16 mg/kg, i.p.) produced a dose-dependent increase in extracellular dopamine levels in the medial prefrontal cortex (mPFC) of freely moving rats without modifying those of 5-HT. In the presence of the selective 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazineyl]ethyl]-N-(pyridinyl)-cyclohexane-carboxamide (WAY100,635; 0.3 mg/kg; i.p.), the influence of mirtazapine on cortical levels of dopamine was markedly attenuated. These results indicate that mirtazapine induces the enhancement of the output of cortical dopamine mediated via blockade of alpha(2)-adrenergic receptors and facilitation of post-synaptic 5-HT(1A) function.     

Potentiation of proopiomelanocortin gene expression in cultured pituitary cells by benzodiazepines

BACKGROUND: Benzodiazepines are frequently used not only as a part of general anesthesia but also for the purpose of sedation during regional anesthesia. Effects of these drugs on the hypothalamic-pituitary-adrenal axis activity have been studied, but are still controversial. It is not known whether benzodiazepines affect expression of proopiomelanocortin, precursor protein of adrenocorticotropic hormone and related peptides. METHODS: AtT20PL cell line, a clone of AtT20/D16v mouse corticotroph tumor cells stably transfected with approximately 0.7 kilobases (kb) of the rat proopiomelanocortin 5' promoter-luciferase fusion gene, was used. In the presence or absence of diazepam or midazolam, cells were stimulated by corticotropin-releasing hormone (CRH) or forskolin. Proopiomelanocortin gene expression was estimated by measurement of luciferase activity. Furthermore, to study the mechanism of benzodiazepine effects, cyclic adenosine 3',5'-monophosphate (cyclic AMP) efflux was measured by enzyme immunoassay. RESULTS: Diazepam and midazolam dose-dependently increased the proopiomelanocortin gene expression induced by CRH or forskolin. The potentiating effect was not affected by benzodiazepine receptor antagonists flumazenil and PK11195, but was abolished by a cyclic AMP-dependent protein kinase inhibitor H89. Cyclic AMP efflux induced by CRH or forskolin was also enhanced by diazepam and midazolam. In the presence of isobutylmethylxanthine, a nonspecific phosphodiesterase inhibitor, potentiation of proopiomelanocortin gene expression and enhancement of cyclic AMP efflux by benzodiazepines were not observed. CONCLUSIONS: Benzodiazepines potentiate the effect of CRH or forskolin on proopiomelanocortin gene expression. The potentiating effect is not mediated by the benzodiazepine receptors, but its mechanism probably involves inhibition of phosphodiesterase.