Characterization of germanium linear kinoform lenses at Diamond Light Source.

The unprecedented brilliance achieved by third-generation synchrotron sources and the availability of improved optics have opened up new opportunities for the study of materials at the micrometre and nanometre scale. Focusing the synchrotron radiation to smaller and smaller beams is having a huge impact on a wide research area at synchrotrons. The key to the exploitation of the improved sources is the development of novel optics that deliver narrow beams without loss of brilliance and coherence. Several types of synchrotron focusing optics are successfully fabricated using advanced miniaturization techniques. Kinoform refractive lenses are being developed for hard X-ray beamlines, and the first test results at Diamond are discussed in this paper.

Characterization of the prostanoid receptor types involved in mediating calcitonin gene-related peptide release from cultured rat trigeminal neurones.

1. Prostaglandins and the vasodilator neuropeptide, calcitonin-gene related peptide (CGRP), have both been implicated in the pathogenesis of migraine headache. We have used primary cultures of adult rat trigeminal neurones to examine the effects of prostanoids on CGRP release in vitro. 2. CGRP release was stimulated by prostaglandin E2 (PGE2) and the IP receptor agonist, carbaprostacyclin (cPGI2). These responses were extracellular calcium-dependent, and the PGE2-induced CGRP release was unaltered by inhibition of nitric oxide synthase (NOS), ATP receptor blockade, or the addition of adenosine deaminase. 3. Increases in CGRP levels were also observed in response to prostaglandin D2 (PGD2), and the EP2 receptor selective agonist, butaprost. No increases in CGRP release were observed in response to prostaglandin F2alpha (PGF2alpha) or the TP receptor selective agonist, U46619, or the EP3 receptor selective agonist, GR63799X. 4. The selective DP receptor antagonist, BWA868C, antagonized the PGD2-, but not PGE2- or cPGI2-induced release. Furthermore, the EP1 selective antagonist, ZM325802, failed to antagonize the PGE2-induced CGRP release from these cells. 5. These data indicate that activation of DP, EP and IP receptors can each cause CGRP release from trigeminal neurones, and suggest that the predominant EP receptor subtype involved may be the EP2 receptor. Together with evidence that the cyclo-oxygenase inhibitor, aspirin, particularly when administered intravenously is effective in treating acute migraine, these findings further suggest a role for prostaglandins in migraine pathophysiology.

Adenosine A(1) receptor-mediated inhibition of protein kinase A-induced calcitonin gene-related peptide release from rat trigeminal neurons.

Calcitonin gene-related peptide (CGRP), a potent vasodilator, has been implicated in the pathogenesis of migraine. Its release from adult rat trigeminal neurons in culture was shown to be markedly increased by the activation of adenylate cyclase with forskolin. Modulation of this secretion was investigated by a number of agents with known inhibitory effects on cAMP generation mediated via receptor coupling to G(i/o) proteins. Significantly, forskolin-stimulated CGRP release could be closely correlated with the phosphorylation of the protein kinase A (PKA) substrate cyclic AMP response element-binding protein (CREB). Forskolin-stimulated CGRP release could be potently and effectively inhibited by the adenosine A(1) receptor-selective agonist GR79236X (pIC(50) = 7.7 +/- 0.1, maximal inhibition 65 +/- 2.5% at 300 nM), whereas the A(2A) (CGS21680) and the A(3) (2-chloro-N(6)-(3-iodobenzyl)-adenosine-5'-N-methyluronamide) receptor-selective agonists were without effect. GR79236X-mediated inhibition was abolished by the A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine. Immunocytochemical studies and Western analysis revealed the presence of adenosine A(1) receptors on trigeminal neurons. However, despite the additional detection of 5-hydroxytryptamine (5-HT)(1B) receptors on these cells, the clinically effective antimigraine 5-HT(1B/1D) agonist sumatriptan did not inhibit forskolin-stimulated CGRP release nor did it show any effect on the concomitant CREB phosphorylation. In contrast, the mu-opioid agonist fentanyl elicited a 74 +/- 4% reduction in CGRP levels. Forskolin-stimulated CGRP release and CREB phosphorylation could be mimicked by incubation of the cells with chlorophenylthio-cAMP and blocked by pretreatment with the PKA inhibitor myrPKI(14-22). Taken together, the present data confirm the PKA-dependence of forskolin-stimulated CGRP release and suggest that A(1) adenosine agonists may warrant further investigation in models of migraine and neurogenic inflammation.

Retained digital foreign body after a pellet gun injury.

A symptomatic foreign body embedded in the human body can be a frustrating problem for physician and patient alike. A unique case of a retained foreign object resulting from a pellet gun injury has been presented. Although the course of treatment in this case was uncomplicated, it is important to understand the complexities of the human body's response to foreign bodies.

The Syme's amputation: a correlation of surgical technique and prosthetic management with an historical perspective.

In 1843, James Syme introduced an amputation which he believed had numerous advantages over more proximal amputations. Despite these claims, utilization of the Syme's amputation has been limited due to a less than ideal compatibility of the surgical result with prosthetic design and function. In this article, the history of the Syme's amputation is reviewed along with indications and surgical technique. Modifications to the original surgical procedure are discussed as well as advantages and disadvantages inherent to the Syme's amputation. A description of the biomechanical function of the residual limb/prosthesis and management of the Syme's amputee is provided emphasizing the quest for an ideal prosthesis which is found, could very well allow Dr. Syme's amputation to reach the potential as he had originally envisioned.

The effect of lower-limb anatomy on knee loads during seated cycling.

Overuse knee joint injuries are the primary injuries to cyclists. Overuse injuries have been intuitively linked to the anatomic structure of the foot because external loads are applied to the foot in cycling. Thus, the structure and function of the foot should dictate in part how the loads are transmitted to the knee joint. Therefore, it was hypothesized that patterns in knee loads are related to the anatomic structure of the foot. To test this hypothesis, peak knee loads (dependent variables) were related to anatomical variables (independent variables) through statistical analyses. This required first the detailed evaluation (i.e. measurement) of the anatomical structure of the foot and leg for 23 subjects. Next, three-dimensional knee joint loads were determined for a standardized riding condition. The results of the statistical analyses indicated that a group of cyclists with the most extreme inversion of the forefoot relative to the transverse plane developed significantly greater average posterior knee force and extensive knee moment. In addition, a number of anatomical variables significantly accounted for the variability in peak values of the posterior force, the extensive moment, the varus/valgus moment and the external axial moment. Based on these results, the hypothesis is accepted.

Three cases of alpha 1-antitrypsin deficiency: a review of diagnostic and therapeutic strategies.

Deficiency of alpha 1-antitrypsin is an unusual cause of emphysema. This deficiency may be suspected when the age of onset and severity of disease are out of proportion to the history of inhaled agents (usually cigarette exposure). Three patients seen during a relatively short time in a private practice underscore the variability of presentation. Proper diagnosis offers such patients several benefits, particularly in view of new potential therapies.

Product safety in Great Britain and the Consumer Protection Act 1987.

The Consumer Protection Act 1987 imposes new demands on manufacturers regarding the safety of their products. They can be sued directly by any person injured by their defective goods and prosecuted if they fail to meet the new comprehensive general safety requirement and any other safety provision. Product designers and ergonomists need a sound understanding of and involvement in the legal aspects of product safety. It is now essential to take into account what may reasonably be done with goods, or foreseeable conditions of use, in order to satisfy the test of what is "reasonably safe" and meet the level of safety which "persons generally are entitled to expect" under the law. Any significant progress in product safety will now come through developments in technical standards which will be harmonised throughout the European Community. It is essential that ergonomics considerations be taken into account during the drafting of product specifications if users' interests are to be safeguarded more effectively. Ergonomists will be required to make an even greater contribution in the field of product safety, therefore, by assisting in the determination of the new statutory safety criteria. They are uniquely qualified to ensure that the product user is fully considered at the design and assessment stages which can now be looked upon as an essential pre-requisite of the law and not just sound engineering policy.

Minor salivary gland tumors: the role of radiotherapy.

Previous analyses of minor salivary gland tumors (MSGTs) have not clearly established the role of radiotherapy in their treatment. The following is a retrospective review of 44 patients treated from 1956 to 1984 with MSGT of the maxillary sinus (15 of 44), nasal cavity/ethmoid complex (six of 44), or hard palate (23 of 44). Histological findings included adenocarcinoma (18), adenoid cystic (17), high-grade mucoepidermoid (six), and mixed malignant (three). Treatment was by surgery (18 of 44), radiotherapy (eight of 44), or a combination of both (18 of 44). Patients treated with radiotherapy, either alone or combined with surgery, had disease that was inoperable, marginally resectable, or residual after surgery. Despite this handicap, 3-year local control rates for all treatment modalities were similar (surgery, 78%; radiotherapy, 63%; and combined treatment, 83%). Absolute 3-year survival rates were 94% for surgery, 63% for radiotherapy, and 78% for combined therapy, with death attributable to distant metastases a significant factor in the advanced cases treated with radiotherapy. A dose response relationship was apparent in those patients whose treatment involved radiotherapy. Clearly, MSGTs are radioresponsive lesions and radiotherapy can play an important role in their management.

Accuracy of radionuclide ventriculography for estimation of left ventricular volume changes and end-systolic pressure-volume relations.

Estimation of left ventricular end-systolic pressure-volume relations depends on the accurate measurement of small changes in ventricular volume. To study the accuracy of radionuclide ventriculography, paired radionuclide and contrast ventriculograms were obtained in seven dogs during a control period and when blood pressure was increased in increments of 30 mm Hg by phenylephrine infusion. The heart rate was held constant by atropine infusion. The correlation between radionuclide and contrast ventriculography was excellent. In the individual animals, the average r value for left ventricular volume was 0.96 +/- 0.03 (+/- SD) (p = 0.001, n = 7) and the mean r value for end-systolic volume changes was 0.90 +/- 0.08 (n = 7, range 0.76 to 0.99). For the entire series, there were 33 end-systolic volume changes, and there was an equally strong radionuclide-contrast correlation (r = 0.89, p less than 0.001, n = 33), even though the volume changes averaged only 11.9 +/- 8.2 ml (range 0.3 to 38.1). The systolic pressure-volume relations were linear for both radionuclide and contrast ventriculography (r = 0.98 and 0.97, respectively, n = 7). The mean slope for radionuclide ventriculography (2.9 +/- 1.4) was lower than the mean slope for contrast ventriculography (4.8 +/- 1.7) (p = 0.004); however, the slopes correlated well (r = 0.81, n = 7, p = 0.026). The radionuclide-contrast volume relation was compared using background subtraction, attenuation correction, neither of these or both. By each method, radionuclide ventriculography was valid for measuring small changes in left ventricular volume and for defining end-systolic pressure-volume relations.

Lipoid pneumonia caused by an Oriental folk medicine.

With recognition of the problem of aspiration, mineral oil has been removed from nose drops. We have described a Thai woman who had lipoid pneumonia after instillation of a common Oriental folk medicine. At 2 1/2-year follow-up, she had persistent cough, interstitial disease, air trapping, and widened A-aDO2.

Veres needle in the pleural space.

The Veres needle is designed to allow entry into body cavities without trauma to underlying organs. Its major use has been in the induction of a pneumoperitoneum for peritoneoscopy. An initial successful evaluation of its use was in the pleural space of dogs. A subsequent analysis of complications in 69 thoracenteses using the Veres needle and 152 thoracenteses using a conventional needle favored the Veres needle (P = .05). We believe that the Veres needle is a safe and technically superior instrument for thoracentesis and that it deserves further application and study.

Pulmonary sarcoidosis. Long-term follow-up of the effects of steroid therapy.

Fifteen years ago we began a prospective study using alternate case treatment with prednisone in patients with pulmonary function abnormalities due to sarcoidosis. Twenty-five patients were divided into treatment and control groups that were similar in sex, age, race, degree of pulmonary dysfunction, and duration of disease. Evaluation included complete spirometric studies, single-breath carbon monoxide diffusion capacity, and arterial blood gases. Follow-up studies at six months, one to two years, and ten to 15 years show no difference between the treated and untreated groups. Improvement or deterioration in pulmonary function of individual patients in the treated group was reflected in the control group, even in those patients with a diffusing capacity and forced vital capacity less than 65 percent of predicted. Data from this long-term study fail to show any benefit of short-term use of steroids in therapy for pulmonary sarcoidosis.

Cyanosis following right pneumonectomy: importance of patent foramen ovale.

A patient with chronic lung disease became cyanotic following right pneumonectomy for cancer. He was found to have right-to-left shunting through a patent foramen ovale in the absence of pulmonary hypertension, and he improved remarkable after surgical therapy. This case vividly illustrates the subtlety with which acquired right-to-left shunting may appear in the setting of chronic hypoxemia. The frequency of patent foramen ovale in the general population (20 percent) and the ease and efficacy of treatment for this lesion underscore the need for general awareness of this potential problem in the chronically or critically ill.