Problems associated with mechanical heart valve sounds.

A cross-sectional study of 50 randomly selected patients 12-36 months following mechanical heart valve replacement with Bjork-Shiley tilting disc valves was undertaken to investigate the factors which affect perception of, and reaction to, sounds generated by mechanical heart valves implanted in patients. Numerous problems were generated by the valves, including annoyance (68%), sleep disturbance (52% in patients; and 46% in patients' partners), interference with concentration (36%) and social embarrassment (28%). These findings are not affected by the measured level of sound or any variation in the number or anatomical position of the valve(s), though age and sex do seem to matter, more problems being reported by younger patients and those of the female sex. Aspects of the patient's personality did not seem to alter the difficulties experienced, though a high level of psychological morbidity was identified in the group as a whole. Most patients experience problems due directly to the noise generated by their valve and should be adequately warned of this before operation. This should also be taken into consideration in designing and evaluating new valve prostheses.


Aortic valve replacement in cardiac ochronosis.

Two patients with generalized ochronosis developed cardiovascular symptoms related to cardiac ochronosis with aortic valvular stenosis. One patient with a transvalvular pressure gradient of 150 mm Hg underwent emergency aortic valve replacement. The other patient with a transvalvular pressure gradient of 96 mm Hg underwent successful elective aortic valve replacement. Cardiac ochronosis is a rare disease that might be encountered, with the typical signs, during an elective, planned cardiac operation. The most frequent presenting feature of this disease seems to be aortic valvular stenosis.


Mouse peritoneal macrophages contain an acylating system specific for twenty-carbon polyunsaturated fatty acids. A study with intact cells.

It is widely recognized that in addition to regulating the expression and activity of arachidonic acid (AA)-metabolizing enzymes, the availability of free AA limits eicosanoid biosynthesis. AA participates in a deacylation/reacylation cycle of membrane phospholipids in which the fatty acid is cleaved by phospholipase A2 and reesterified by acyltransferase. Thus, free AA can become available either by phospholipase A2 activation or by inhibition of fatty acid reincorporation. We observed that exposure of [3H]AA-prelabeled macrophages to micromolar concentrations of unlabeled AA resulted in a net release of 3H-radioactivity into the extracellular medium. This was not the consequence of phospholipase A2 activation, but of impaired reesterification of previously liberated [3H]AA. The eicosanoid precursors eicosatrienoic acid (ETA) and eicosapentaenoic acid (EPA) mimicked the effect of unlabeled AA on 3H-radioactivity release from [3H]AA-prelabeled macrophages, but all other fatty acids tested were ineffective. Similarly, only AA, ETA and EPA were able to inhibit [3H]AA uptake by macrophages, all other fatty acids being ineffective. From these data, it is concluded that intact macrophages contain an acylating system specific for the eicosanoid precursors AA, ETA and EPA. Altogether, the results of this study underscore the importance of fatty acid reacylation in controlling free AA levels in macrophages.


Lipopolysaccharide priming potentiates calcium ionophore stimulated human placental prostaglandin E2 release in vitro.

In this study, the effect of bacterial endotoxin (lipopolysaccharide; LPS) and of LPS priming on the in vitro release of PGE2 from human placental explants was investigated. Both LPS and the calcium ionophore A23187 significantly stimulated PGE2 release (P less than 0.05). Simultaneous exposure of placental explants to both LPS and A23187 revealed no additive or synergistic stimulation of PGE2 release. LPS priming of placental tissue significantly increased A23187-stimulated PGE2 release when compared to non-LPS-primed tissues. The addition of exogenous arachidonic acid (the substrate for PGE2 synthesis) also significantly (P less than 0.05) stimulated PGE2 release. There was, however, no significant further stimulation of PGE2 release following LPS priming in arachidonic acid treated explants. These data suggest that LPS not only increases basal PGE2 release in human placentae, but also potentiates agonist-stimulated PGE2 release, possibly by increasing tissue capacity for endogenous arachidonic acid liberation.


Effect of glutathione content on cellular uptake and growth inhibitory activity of prostaglandin A2 in L-1210 cells.

Prostaglandin A2 (PGA2) is known to be actively incorporated into mammalian cells and thereby evokes its biological effects. To explore the transport mechanism of PGA2 and the possible role of cellular glutathione (GSH) in the transport process, we prepared GSH-enriched and -depleted L-1210 cells and then incubated with [3H] PGA2. In GSH-depleted cells, the total amount of PGA2 incorporated was reduced to about 50% of that in the control and GSH-enriched cells, accompanied by marked reduction of the PG in the cytosol but not in the nuclei. The kinetics of uptake revealed that the apparent Vmax was reduced by GSH depletion. Subsequent study of L-1210 cells under culture conditions provided similar results; GSH-depletion caused suppression of PG uptake and a reduction in the amount of PGA2 in cytosol, while its nuclear accumulation was little influenced. Comparison of the effect of PGA2 on the growth of control and GSH-depleted cells showed that the PG suppressed cell proliferation to the same extent. Our results suggest that, though uptake of PGA2 may be significantly influenced, its accumulation, and hence the manifestation of its biological effects are not influenced by GSH status.


Prostaglandin photoaffinity probes: synthesis and binding affinity of C-18 substituted PGF2 alpha prostanoids bearing a perfluorinated aryl azide.

C-18 Phenoxy analogs of prostaglandin F2 alpha (PGF2 alpha) that possessed a perfluorinated aryl azide and an aryl iodide substituent were synthesized and evaluated as potential photoaffinity probes for PGF2 alpha. Prior studies indicated that only hydrophobic modifications in the omega-side chain of PGF2 alpha were compatible with high binding affinity, and this finding excluded the use of a hydroxyl-substituted C-18 phenoxy group as an activated aryl ring capable of radioiodination. Consequently, an alternate means of introducing the iodine substituent using an ipsosubstitution of a trimethylsilyl arene was developed. Although this strategy was successful from a synthetic perspective, the potential PGF2 alpha photoaffinity probe, (15S)-18-[3'-((4''-azido-2'',3'',5'',6''-tetrafluorophenyl)- methoxy) methyl-5'-iodophenoxy]-19,20-bisnorprostaglandin F2 alpha, exhibited only marginal competitive binding with [3H]-PGF2 alpha to ovine luteal cells and to plasma membranes of bovine corpora lutea. The hydrophobic but bulky C-18 substituent was presumably incompatible with effective receptor binding.


Prostaglandin photoaffinity probes: synthesis and binding affinity of aryl azide-substituted C-1 esters of prostaglandin F2 alpha.

In seeking prostaglandin F2 alpha (PGF2 alpha) photoaffinity probes possessing both an efficient, photoactive cross-linking substituent and a radiolabel of high specific activity, the synthesis and binding affinity of PGF2 alpha C-1 esters in which the alcohol component possessed either an aryl azide or a perfluorinated aryl azide was investigated. These derivatives showed great promise due to their ability to compete for the binding of [3H]-PGF2 alpha in both a luteal membrane binding assay and in a whole luteal cell binding assay. Identification of the C-1 site in PGF2 alpha as a site for modification of the PGF2 alpha molecule with photoactive alcohol derivatives represented a logical step toward the goal of developing a useful PGF2 alpha photoaffinity probe.


Platelet signal transduction mechanisms induced by eicosanoids.

Platelets are in many ways involved in the pathogenesis of artherosclerosis and the development of coronary heart disease, and play a role in acute myocardial infarction (8). They are also an useful model to study cellular activation mechanisms: their isolation from peripheral venous blood is simple and rapid and their physiological responses such as shape change, aggregation and secretion can be easily measured (10). This chapter is focused on our results on the mechanisms of platelet activation and inhibition induced by eicosanoids.


Annexins and phospholipase A2 inhibition.

Annexins of human placenta have been purified and characterized. In addition to annexins I to VI and II complex, two novel species of 45 and 68 kDa were obtained. Annexins V and II are most abundant. Phospholipase A2 inhibitory activity of annexin V is low in contrast to that of annexins I to VI, and it is best for annexin II complex. In vitro, annexins bind to liposomes to extents which depend on the type of phospholipid used. This induces liposome aggregation whereby Mix, PI, and PC liposomes preferably aggregate. This hinders PLA2 from its access to the substate. Our data suggest that substrate-depletion by annexins is rather the result of liposome cross-bridging than pure liposome surface coating.


LDL receptor-dependent polyunsaturated fatty acid transport and metabolism.

It is widely assumed that eicosanoid biosynthesis is initiated by an increase in the intracellular concentration of unesterified arachidonic acid (AA) as a consequence of the activation of cellular phospholipases and/or inhibition of AA reacylation reactions. Here, we describe a mechanism of eicosanoid formation that is entirely dependent on low density lipoprotein (LDL) receptor-mediated delivery of AA to eicosanoid producing target cells. This LDL AA pathway introduces a new regulatory component into the provision of unsaturated fatty acids to mammalian cells.


Cleavage of phosphatidylcholine: an additional mechanism for stimulation of macrophage eicosanoid synthesis?

Cleavage of phosphatidylcholine (PtdChol) as putative mechanism leading to enhanced eicosanoid synthesis was investigated in mouse peritoneal macrophages. Addition of 12-O-tetradecanoylphorbol 13-acetate (TPA) to intact [3H]choline-labelled cells did not enhance radioactivity release above control levels. Membrane-bound PtdChol-specific phospholipase (PL) activity was then measured in a cell-free assay using [3H]choline-labelled membranes as endogenous substrate. Preincubation of macrophages with TPA increased PL activity in a time course resembling the one observed for protein kinase C (PKC) activation. Diacylglycerol (DAG) species derived from PtdChol might therefore serve as additional stimulator of rapid macrophage eicosanoid synthesis via PKC.


Prostaglandin 9-ketoreductase from pig and human kidney: purification, properties and identity with human carbonyl reductase.

Prostaglandin 9-ketoreductase has been purified to apparent homogeneity from pig and human kidney with an overall yield of 6%. The enzyme has a molecular mass of 34 kDa, it is present as an active monomer in diluted solution and contains approx. 2 equivalents Zn++/mole enzyme. It is stereoselective for the pro(S) hydrogen of NADPH and reduces the prostaglandin 9-keto group to yield 90% prostaglandin F2 alpha and 8% of the beta-form. An extensive study of the catalytic properties was carried out, which leads to the conclusion that the enzyme function in vivo is unlikely a catalysis of oxidation/reduction at the prostaglandin 9-position. Five peptides from the pig kidney enzyme were sequenced and compared with the sequence of carbonyl reductase from human placenta. The identity is > 90% and this, together with the immunological cross-reactivity with human brain carbonyl reductase, most strongly suggests that prostaglandin 9-ketoreductase and carbonyl reductase are the same enzyme.


Priming mechanisms and induction of heat shock proteins in human polymorphonuclear granulocytes induced by eicosanoids and cytokines.

Priming of human polymorphonuclear granulocytes (PMNs) with cytokines (IL-3, IL-6, TNF-alpha) followed by a subsequent stimulation (FMLP) led to an enhanced polymerization of actin and GTPase-activity which correlated to a loss of ras immunoreactivity and an increased expression of Rab proteins. Furthermore TNF-alpha and 12-HETE induced the heat shock proteins (hsp 70 family) in PMNs as was demonstrated by metabolic radiolabeling and Western blotting (anti-hsp 72). This activation of the stress response exerted a protective function towards a subsequent lytic attack by a bacterial cytolysin (leukocidin).


The role of prostanoids in pediatric diseases employing mass spectrometric techniques.

Urinary excretion rates of primary prostanoids and their metabolites are useful parameters to assess as well renal as systemic prostanoid activity under clinical conditions. Children with renal diseases with systemic involvement, such as Bartter syndrome, renal diabetes insipidus, postobstructive hydronephrosis, and acute renal allograft rejection, have exclusively elevated excretion rates of primary prostanoids. In patients with systemic diseases and additional renal involvement, such as hyperprostaglandin E syndrome and hemolytic uremic syndrome, rates of primary prostanoids and of their metabolites are elevated. In contrast, systemic vascular diseases without renal involvement, such as Henoch-Schönlein purpura and persistent pulmonary hypertension in the newborn, are associated only with increased systemic prostanoid activity indicated by elevated excretion rates of prostanoid metabolites, whereas excretion rates of primary metabolites are in the normal range.


The role of leukotriene D4 in septic shock models.

Septic shock is a major complication during the treatment of intense care patients. A similar pathologic state can be experimentally induced in rodents by application of endotoxins. There is circumstantial as well as direct evidence for a participation of leukotriene D4 in this experimental multiorgan failure. Due to liver-specific sensitivation by galactosamine endotoxin-induced multiorgan failure can be experimentally transposed to a single organ, i.e. hepatic failure. Data presented here show a participation of the eicosanoid leukotriene D4 in either model of sepsis. We have recently described a cellular system modelling endotoxin-induced hepatic failure. In this system based on the coculture of hepatocytes and nonparenchymal liver cells leukotriene D4 is required for the development of cytotoxicity. It is concluded that the three models share pivotal mechanistic principles and might be used complementary to each other in order to study underlying molecular events.


Lipoxygenase inhibitors but not site specific 5-lipoxygenase blockers protect against endotoxic shock and inhibit production of tumor necrosis factor.

In the present study it was found that lipoxygenase inhibitors prevent LPS-, but not tumor necrosis factor alpha (TNF alpha)-evoked lethality. The specific 5-lipoxygenase inhibitors (MK-886, CGS-8515) were uneffective in endotoxin-induced shock. The 5-lipoxygenase inhibitors interfered with LTC4 formation in macrophages while they did not affect endotoxin induced TNF alpha-formation, neither in cell cultures nor in mice. The potency of other, less specific lipoxygenase blockers to suppress TNF alpha formation correlated quantitatively with their ability to interfere with 13-HODD synthesis. Based on the fact that a tight correlation exists between inhibition of TNF alpha synthesis and 13-HODD formation, this product might be important for TNF alpha formation.


Epidermal derived growth factor stimulates the prostaglandin F2 alpha-synthesis in rabbit luteal cells.

Isolated rabbit luteal cells from day 6 and 12 of pseudopregnancy were cultured with hCG, EGF, and EGF together with arachidonic acid (AA) in serum-free culture medium for 96 hours. The hCG stimulation of the progesterone (P) synthesis was more pronounced on day 6 then on day 12. EGF alone did not change significantly the production of either P or PGF2 alpha. AA increased the production of PGF2 alpha on day 6 and 12 significantly (3.9-fold on day 6, P < 0.005; 7-fold on day 12, P < 0.001). AA together with EGF increased the level of PGF2 alpha more pronounced when compared with AA alone (7.2-fold on day 6, P < 0.025; 9.8-fold on day 12, P < 0.05). The progesterone production of the cells remained unchanged during EGF exposure. We conclude that EGF together with AA is able to stimulate the PGF2 alpha biosynthesis in cultured rabbit luteal cells. Therefore, EGF could be relevant as an additional regression factor in rabbits. This mechanism seems to be independent from the progesterone synthesis.


Endogenous eicosanoids modulate cell growth and the expression of immediate early response genes.

Experiments were performed in rat mesangial cells indicating that endogenous non-cyclooxygenase metabolites of AA act to modulate the mitogenic response. Irrespective of the mitogen used, metabolism of AA by LO and/or CP 450 influences induction of cell growth and expression of the immediate early response genes c-fos and Egr-1. In accordance with other reports (3,4) on the influence of eicosanoids on gene expression, our observations indicate that endogenous eicosanoids may act as intracellular mediators. In the mitogenic response, at least two mechanisms of modulation seem possible: i) AA and its metabolites may act by modulating other 2nd messenger systems or ii) eicosanoids may directly regulate the expression of growth-related genes, e.g. by interacting with a fatty acid response element in the promoter region of respective genes.


Thromboxane as diagnostic tool and therapeutic target in cardiovascular disease.

Our studies were first directed to improvements in analytical methodology of thromboxane metabolism in man. These methods were then applied in a variety of clinical settings to better define the clinical spectrum and timecourse of platelet related pathomechanisms. They were also applied in studies aiming at optimized therapeutic interventions. Such biochemical guidelines are essential for the optimal planning of future clinical studies.


The role of eicosanoids in reproduction.

The central role of eicosanoids in reproduction was studied in areas of important clinical interest. First, their involvement in pregnancy-induced hypertension was investigated. Urine of normotensive and hypertensive pregnant women was analysed for 6-keto-PGF1 alpha, TXB2 and PGE2 by HPLC/RIA. PGE2 and 6-keto-PGF1 alpha excretion was markedly reduced in the preeclamptic subgroup of hypertensive patients during the last two trimesters. A reduced urinary excretion of 6-keto-PGF1 alpha, TXB2 and PGE2 was also found in a hypertension animal model (rat). Further, tissue cultures of human placentas, deciduas and fetal membranes from hypertensive pregnancies displayed a reduced prostaglandin production. Secondly, in the same in-vitro model the central role of PGE2 of fetal membrane origin for the beginning or parturition was shown. Thirdly, concerning endometrial function, the enhancement of PGF2 alpha and PGE2 formation in secretory endometrial cells by estradiol-17 beta and progesterone was documented. Fourthly, lipoxygenase product content in peritoneal fluid of endometriotic patients did not differ from controls.


[Biologic markers in multiple sclerosis (I). Clinical correlations].

Seven biological markers were studied in a population of 236 patients (144 females, 92 males) with multiple sclerosis as was the relation with the different degrees of diagnostic certainty (Rose and Poser scales), the time of evolution and number of bouts of the disease. The IgG concentrations, IgG ratio and the quantification of the intrathecal IgG synthesis by the Tourtellotte formula isolatedly constituted the most sensitive biological markers for the diagnosis of multiple sclerosis. Altogether, the determination of the number of cells, IgG and the IgG ratio achieved diagnostic sensitivity of 94% for defined multiple sclerosis. The IgG ratio was the most closely related biological marker related with the number of bouts and the time of evolution of the disease.


[Biologic markers in multiple sclerosis (and II). Neurophysiologic and imaging correlations].

The relation between the results of 7 biological markers (cells, total protein, albumin, IgG, IgG ratio, Tibbling ratio, and Tourtellotte's formula) and 4 paraclinical tests (PEV, PEATC, CT and MR) in 236 patients with multiple sclerosis (MS) not selected by the localization of symptoms were studied. One hundred forty-one had clinically defined MS, 22 had defined MS supported by a laboratory and 68 had clinically probable MS. The existence of a relation between PEV and MRI abnormality and the increase in the concentration and the ratios of intrathecal IgG synthesis and the degree of certainty of disease diagnosis was demonstrated. The most sensitive test was MRI (93%) followed by VEP (83%) and BAEP (60%) and the sensitivity of the study with high resolution CT including 59 patients explored by double enhancement and delayed cut off was very low (33%). It was considered that for the lack of a specific diagnostic test the use of biological markers PEV and MR constituted a necessary aid in the diagnosis of MS.


Conferencia Cotzias de 1991 de la Sociedad Española de Neurologá. The genetic etiology of Parkinson's disease. A review of the evidence.

It has been amply documented that Lewy body PD can occur on genetic basis. The pedigrees described thus far have constantly shown an autosomal dominant pattern of inheritance. It remains to be determined what proportion of PD generally is familial? Accumulating clinical data indicate the proportion is quite large. The clinical data now available confirm the observations and conclusions of Mjones' pioneering study and are most consistent with the hypothesis that PD is an autosomal dominant disorder with reduced penetrance, markedly age-related expression and a broad range of clinical manifestations extending beyond our traditional clinical concepts of PD and including many atypical cases and formes frustes as Mjones had suggested. As a practical matter of research strategy the study of pedigrees offers the most promising approach available today to clarifying the etiology of PD for they make possible DNA linkage-mapping studies in search of gene loci.


[Primary intraventricular hemorrhage in a patient with unilateral moyamoya disease].

According to the diagnostic criteria currently in use, the so-called "unilateral" forms of the moyamoya disease, or rather those in which the disorders of the disease itself--such as occlusion of the internal supraclinoid carotid artery or its terminal branches and development of abnormal collateral circulation in the region of the basal ganglia--are only found in one hemisphere and should be considered as "probable" forms of the disease with a much lower incidence than the bilateral or "defined" forms of the same. One patient with a primary intraventricular hemorrhage (PIVH) in whom an occlusion of the right internal carotid artery was angiographically demonstrated and in whom collateral type moyamoya circulation was found as was the presence of an aneurysm in the right coroid territory is presented. The association of PIVH, unilateral moyamoya disease and aneurysm is infrequent in the literature, with the origin of the bleeding, in some cases, having been attributed to rupture of the aneurysm. Since angiographic control was not available in the patient presented it cannot be excluded that the aneurysm was really a pseudoaneurysm therefore being a consequence, rather than a cause, of the arterial rupture. Thus one of the other mechanisms proposed must be invoked to explain the pathogenesis of the PIVH: rupture of a perforating artery or of a microaneurysm located in the subependimary periventricular region. The treatment recommended for these case of PIVH associated to aneurysm is chirurgical if persistence is demonstrated in successive arteriographies.


Lung infection with alginate-producing, mucoid Pseudomonas aeruginosa in cystic fibrosis.

Progressive pulmonary insufficiency is the major cause of morbidity and mortality in patients with the inherited disease cystic fibrosis. The basic defect involves a disturbed ion transport across cells, but it is not known how this leads to the airways becoming highly susceptible to recurrent respiratory tract infection with S. aureus, H. influenzae and P. aeruginosa as the dominating pathogens. P. aeruginosa is not a primary pathogen in CF and some degree of lung damage generally has taken place before colonization begins at approximately 10 years of age. Cross-infection occurs and the incidence of P. aeruginosa infection can be reduced by interrupting person-to-person spread. P. aeruginosa infection is a chronic infection that is never permanently eradicated. However, intensive antipseudomonal chemotherapy has contributed to improved survival rates. 90% of patients remain alive more than 10 years after onset of chronic P. aeruginosa and, on an average, they can maintain an almost unchanged lung function during that period. Diagnosis of chronic infection rests on bacteriological examination and demonstration of a specific antibody response. Immunological assays to detect an early antibody response were developed. It is characteristic, but not specific for CF, that chronic lung infection is caused by alginate producing mucoid P. aeruginosa. Alginate biosynthesis is under complex genetic control and possibly regulated by environmental factors. Alginate was purified from mucoid P. aeruginosa and characterized and it was shown to be immunologically heterogenous. It is generally assumed that the infection begins with strains that are nonmucoid, but serological analysis show that these strains probably also produce the mucoid substance, alginate, in vivo. Patients infected with mucoid strains demonstrate a significantly higher antibody response to all P. aeruginosa antigens and have a lower lung function when compared to patients infected with nonmucoid strains. Despite the pronounced humoral antibody response efficient immune clearance of P. aeruginosa does not occur. Mucoid P. aeruginosa are organisms that are deficient in most of the classical virulence factors. In vivo it grows in a protected biofilm as mucoid microcolonies, where bacteria are enmeshed in a loosely bound, highly hydrated extracellular matrix of alginate. Purified alginate was shown to inhibit chemotaxis of neutrophil leukocytes and unable to activate complement. A deficient SIgA antibody response to alginate has been observed in bronchial secretions and it was hypothesized to be associated with the epithelial transport defect.(ABSTRACT TRUNCATED AT 400 WORDS)


Diagnostic accuracy and observer performance in the diagnosis of abnormalities in the anterior maxilla: a comparison of panoramic with intraoral radiography.

An investigation was undertaken to assess the reliability of radiographic diagnosis of abnormalities of orthodontic significance in the anterior region of the maxilla from intraoral and dental panoramic tomograph (DPT) views. DPT films of 200 patients were scrutinised by two observers on two separate occasions, who also examined intraoral radiographs of the same patients. Sixty-three of these patients were selected because they had previously been diagnosed as presenting with a defined abnormality of orthodontic relevance, such as supernumerary teeth, absent incisors, etc. The remaining cases had been assessed as depicting normal radiographic appearances. Each radiograph was allocated a unique, randomly selected code number as the only means of identification. It was not possible for the observers to match the DPT to the corresponding intraoral films, and this information was only available to the principal investigator (JWF). Both observers were asked to record the presence or otherwise of any abnormalities at each observation of each radiograph, and to record their findings. The overall level of diagnostic accuracy and reproducibility was fairly high, and in general terms the DPT views were as reliable as the intraoral films with regard to the detection of abnormalities; however, there were significant differences between the observers. It was concluded that in many instances supplementary intraoral films would not contribute any additional information compared to the DPT and that selection criteria should be defined for the former.


Permanent retention in orthodontic patients with reduced levels of bone support: a pin stabilised resin bonded splint.

Bone loss resulting from periodontal disease can precipitate spontaneous tooth migration. Teeth repositioned by orthodontic means are frequently inherently unstable and may need to be permanently retained by some form of splint. A new technique for permanent anterior splinting is described.


Characterisation of the ultrastructure of glass-ionomer (poly-alkenoate) cement.

Set glass-ionomer cements were sectioned with a diamond knife and examined in the transmission electron microscope. Their appearance was in accordance with the theoretical structure of these materials, close examination revealing glass particles surrounded by a siliceous layer set in a hydrogel matrix. The elemental composition of each region was determined by X-ray microanalysis (energy dispersive). The results of microanalysis supported the ultrastructural observations, with ions that originated from the glass particles being detected throughout the matrix of the set cement. It was suggested that the mobility of these ions in the matrix phase was important in determining the biocompatibility and adhesive properties of glass-ionomer cements.


Teaching integrated treatment at Newcastle upon Tyne Dental School.

This article explains the educational policy decisions that lay behind the development of a teaching and training programme of integrated dentistry at the Dental School at Newcastle upon Tyne. The development and organisation of a specially designed clinic is described. The pattern of work undertaken during the first 2 years of operation is analysed and the means of clinical assessment of this work discussed.


Quality development.

The problem with improving quality in dental practice is not so much a difficulty with understanding exactly what quality means, but more a lack of clear guidance as to how to take the simple, practical steps to achieving that improvement in the daily pressures of practice life. This article describes Quality Development, a simple and practical method that can be used in general practice to help the dental team achieve the objectives in quality care that are appropriate to them.


What are Section 63 and 'approved' courses and how are they organised?

Although Section 63 courses for general dental practitioners in the NHS have been running for many years, there seems to be poor understanding of what 'Section 63' means and how it operates. To some extent this is because of the changes which have taken place since it was introduced and the tremendous expansion in postgraduate dental education (and its objectives) in recent years. The introduction of other 'approved' courses and postgraduate education allowances have created further uncertainties. This paper gives an overview of Section 63, the source of the funds, how they are allocated, how they may be used and who is eligible, and outlines details of other 'approved' courses and the various allowances which GDPs can claim in relation to these different categories of courses.


Intra-oral carcinoma simulating benign oral disease.

Intra-oral carcinoma can present in a variety of ways. Whilst carcinoma classically presents as an irregular, indurated, painless mass or ulcer, it is also recognised as being a great 'mimic' of benign lesions. A series of four cases of intra-oral squamous cell carcinoma is presented in which the initial presentation suggested a lesion of benign or dental origin. Factors which raise the index of suspicion are discussed.


Self-inflicted mutilation of the dentition in a schizophrenic patient.

A case is presented in which a patient performed mechanical self-mutilation of her dentition during an episode of psychotic illness. The management of this case is described and discussed.


Computer-based learning in orthodontics--a hypertext system.

The computer hypertext system which is described is being used at Birmingham dental hospital to complement the undergraduate training programme in orthodontics. The system is a database of orthodontic information which can be accessed and read in any order. Text screens are linked to numerous graphic images, many of which are interactive. Associated question routines provide a means for student self assessment. The scores from these routines are used to give feedback on student performance and the efficacy of teaching methods. A strength of the programme is the ease of authoring material for inclusion in the database.


Comparison of 12-bit and 8-bit gray scale resolution in MR imaging of the CNS. An ROC analysis.

A reduction in gray scale resolution of digital images from 12 to 8 bits per pixel usually means halving the storage space needed for the images. Theoretically, important diagnostic information may be lost in the process. We compared the sensitivity and specificity achieved by 4 radiologists in reading laser-printed films of original 12-bit MR images and cathode ray tube displays of the same images which had been compressed to 8 bits per pixel using a specially developed computer program. Receiver operating characteristic (ROC) curves showed no significant differences between film reading and screen reading. A paired 2-tailed t-test, applied on the data for actually positive cases, showed that the combined, average performance of the reviewers was significantly better at screen reading than at film reading. No such differences were found for actually negative cases. Some individual differences were found, but it is concluded that gray scale resolution of MR images may be reduced from 12 to 8 bits per pixel without any significant reduction in diagnostic information.


Ultrasound guided needle biopsy of brain tumors using an automatic sampling instrument.

All ultrasound (US) guided needle biopsies of brain tumors performed during an 8-year period were reviewed. Tissue samples were obtained in 112 of 115 biopsy procedures, and a histologic diagnosis was established in 99 cases (88.4%). The rate of major complications was 8.0%. The mortality is similar as in reports on stereotactic and CT-guided biopsy procedures while the morbidity is higher in our material. There are no large series available on US guided intracranial biopsy with adequate reports of complications. A modified biopsy technique is introduced here using a cutting needle and an automatic sampling instrument. The modified technique, which has been used in all cases since 1985, yielded diagnostic material in 91.5%. This method consistently provides a tissue core which is essential for a confident histopathologic diagnosis.


CT and MR imaging of primary tumors of the masticator space.

A retrospective study of CT and MR examinations in 14 patients with benign and malignant tumors originating in the masticator space is presented. At presentation, 12 patients revealed tumor extension to adjacent regions and spaces. Perineural tumor spread along trigeminal nerve branches to the cavernous sinus and orbits was combined with facial pain, and/or numbness, ophthalmoplegia, and exophthalmus. Detailed analysis of tumor growth and spread, enhancement and signal features at CT and MR imaging indicated the tumor histology was, with a few exceptions, nonspecific. More extensive growth and bone destruction was noted only among malignant tumors. MR imaging was found superior to CT in delineating tumor extension due to better soft tissue contrast resolution and multiplanar imaging. Posttreatment examinations were available in 11 patients and showed long-standing regional edema of the adjacent temporal lobe and masticator muscles in 4 out of 5 patients without clinical evidence of tumor. In 6 patients, CT and MR features were found almost unchanged with only small size differences after various forms of treatment.


Comparison of CT findings in non-Hodgkin lymphoma and squamous cell carcinoma of the maxillary sinus.

The findings at CT in 11 patients with primary non-Hodgkin lymphoma (NHL) of the maxillary sinus were compared with the CT findings in 21 patients with squamous cell carcinoma (SCC) of the maxillary sinus. In NHL, the segmental bone destruction was in alignment with the bony wall with a massive tumor infiltration into the neighboring structures. In contrast, all patients with SCC were characterized by a soft tissue mass with aggressive bone destruction. About half of the patients with NHL had cervical lymphadenopathy. Post-treatment recalcification of previous bone destruction was seen in 4 out of 5 NHL patients on follow-up CT. In the patients with SCC, only a few had metastatic lymphadenopathy, and no recalcification occurred after treatment. CT is therefore of importance in differentiating NHL from SCC of the maxillary sinus.


Large vein sampling for intact parathyroid hormone in preoperative localization of enlarged parathyroid glands.

Unilateral neck exploration for primary hyperparathyroidism (pHPT) of old and high risk patients can be safely performed under local anesthesia, provided there is a correct preoperative side localization of the enlarged parathyroid gland. We performed large vein sampling and measured intact parathyroid hormones (PTH) with a new, highly sensitive immunoradiometric assay. The method was used before operation in 20 patients with pHPT. A unilateral positive gradient of serum PTH levels was obtained in 15 patients. At surgery, 13 of these (87%) proved to be correct, i.e., the adenoma was localized on the same side. Thus, the technique correctly lateralized the parathyroid adenoma in 65% of the patients. We conclude that large vein sampling with measurement of intact PTH is a potentially useful investigation for preoperative side localization of parathyroid adenomas in pHPT patients scheduled for unilateral surgery under local anesthesia. However, prior to routine bilateral neck exploration large vein sampling is not justified.


Intravascular ultrasonographic appearance of angiographically normal arteries related to age and the occurrence of vascular disease.

In 22 individuals (mean age 52 years) the ultrasonographic images of arteries defined as normal by arteriography were studied and related to the age and medical history of the patients. The series was divided into 2 groups: patients with clinical manifestation of atherosclerosis and patients without a history of arterial disease. The study included 6 young patients (mean age 14 years) referred for angiographic documentation of abolished intracranial circulation. A typical 3-layered appearance of the arterial wall was found in young healthy individuals as well as in adult and elderly subjects. There was no difference in the ultrasonographic appearance of muscular and elastic arteries. In patients with extensive obstructive atherosclerosis affecting other parts of the arterial tree, a segment of the iliac artery can have the same appearance as seen in young healthy individuals. There are indications that severe hypertension can result in a thickening of the middle low-echogenic layer of the arterial wall. In patients with chronic renal insufficiency, small calcifications in the middle layer were a typical finding.


Holmium:YAG laser angioplasty. Experimental ablation of vascular tissue via flexible ring catheters.

This experimental study was designed to define the potential value of a mid-infrared holmium laser in the free running mode for angioplasty. Immediately after removal, fresh normal and diseased human cadaveric arteries were irradiated under saline with a Ho:YAG laser (wavelength 2.13 microns). The laser was pulsed at 3 Hz, 250 microseconds pulse width and fluences of 10 to 40 J/cm2. The laser beam was coupled to ring catheters with multiple low-OH quartz fibers. The tip of the delivery device was held in direct contact with the vessel surface with the laser beam oriented perpendicularly. Ablation of atherosclerotic plaque was accomplished at an ablation threshold of 10 J/cm2. The ablation rate was 2.1 to 8.3 microns/pulse. Removal of calcified plaque was only partially effective. There were marked thermal effects with vacuolizations extending up to 1505 +/- 178 microns into the adjacent tissue. Laser light at the mid-infrared wavelength of 2.13 microns is supposed to be attractive as it is readily absorbed in water and can easily be transmitted through optical fibers. However, Q-switching seems to be essential to minimize thermal side effects and to make effective ablation of calcium possible.


Visual interpretation compared with caliper and computerized measurements in experimental vessel stenosis.

To explain visual interpretation errors on angiograms, visual interpretation, caliper measurement, and computerized measurement of cine film were compared using each of 10 graphic models and 10 acrylic models with "stenotic vessels". Stenosis > 40% was overestimated and stenosis < 40% underestimated by visual interpretation. In caliper measurement, stenosis > 40% at exposure of 90 kV was greatly overestimated by a degree similar to the estimation by visual interpretation, and stenosis > 40% at exposures of 74 kV and 58 kV was slightly overestimated. In computerized measurement, the estimation was consistent with the actual degree of stenosis. Therefore, visual interpretation was not reliable for estimation, and computerized measurement was indispensable for estimation of vessel stenosis. Moreover, we consider the most common cause of error in visual interpretation to be optical illusions.


Diagnosis of tracheal carcinoma at chest radiography.

All of the 95 primary tracheal carcinomas registered in Finland during 1967 to 1985 were reviewed. Chest radiographs of 44 patients were available. A tracheal tumor was detected in 8 cases (18%) in the primary examination and according to the review all the detected tumors were larger than 15 mm. However, when the same radiographs were reexamined by a senior radiologist, the tumor was identified in the correct site in 66%. This percentage parallels the results of high kV tracheal radiography (69%) performed on 32 patients. Tumors involving anterior or posterior wall and tumors near the bifurcation were the most difficult to detect.


High resolution CT in children with cystic fibrosis.

High resolution CT (HRCT) was performed in 24 children (median age 57.9 months) suffering from cystic fibrosis (CF). In 23 patients (one examination unacceptable because of motion artifacts) the most frequent finding was bronchial wall thickening, shown in 21 patients (91%), followed by bronchiectasis in 15 patients (65%). Less frequent findings were mucus plugging and patchy consolidations, which could be demonstrated in 11 patients each (48%). Findings were classified using a CT scoring system and including only irreversible pulmonary changes; a statistically significant correlation with lung function tests (FEV1/FVC; MEF50) could be established. HRCT to date seems to be the most valuable method to determine extent and severity of lung involvement in children with CF and should therefore be routinely used for the staging of this disease.


CT compared to angiography for staging of tumors of the pancreatic head.

A retrospective study of 32 patients with malignant tumor of the pancreatic head and ampullary region is presented. The aim of the study was to compare the ability of CT and angiography to evaluate the peripancreatic vessels, and to correlate the results of tumor staging based upon CT criteria to angiographic and surgical findings. In 5 patients (16%) CT disclosed contiguous tumor growth around vessels not discernible at angiography and, in contradiction to previous reports, angiography added no valuable information regarding main vessel involvement. In terms of sensitivity, specificity, and positive predictive value CT was more accurate in predicting unresectable than resectable tumors, the former with a sensitivity of 92% and a specificity and positive predictive value of 100%.


Splenic abscess. Imaging and intervention.

We reviewed the imaging findings of 14 splenic abscesses in 13 patients. All patients underwent chest radiography, 12 ultrasonography (US), 9 CT, 4 plain abdominal radiography, 2 99mTc-HMPAO leukocyte scan and 2 99mTc-HIG scan. Three patients were treated with percutaneous catheter drainage, and 5 with diagnostic or therapeutic fine-needle aspiration (FNA). At US the abscess was hypoechoic (n = 9), anechoic (n = 2), or anechoic with gas-bubbles (n = 1), or the entire spleen was inhomogeneous with gas-bubbles (n = 1). At CT the abscesses appeared as low density (18-30 HU) lesions with (n = 2) or without (n = 7) gas. In 2 cases 99mTc-HMPAO leukocyte scan, and in one case 99mTc-HIG scan showed an intrasplenic defect, and in one case 99mTc-HIG scan was considered normal. At plain abdominal radiography extraintestinal gas was suggested in 2 patients, and the findings were normal in 2. US-guided FNA confirmed infectious etiology of the lesion in 4 patients, and a necrotic specimen suggested infection in one. One patient was cured with repeated aspirations. Catheter drainage was successful in all 3 patients who underwent the procedure. We conclude that US and CT are accurate in detecting splenic abscesses. Our results in splenic interventions advocate wider use of the procedures.


CT evaluation of compensatory renal growth in relation to postnephrectomy time.

In 27 patients nephrectomized for renal carcinoma, the compensatory hypertrophy of the remaining kidney was assessed by 72 CT examinations performed one month before and during 32 months after nephrectomy. Kidney size was estimated on CT by multiple measurements of the renal parenchymal thickness. Kidney growth was evaluated by comparing the amount of renal parenchyma before and after contralateral nephrectomy. Renal compensatory hypertrophy varied with postnephrectomy time. Kidney enlargement was 15% in the first 3 months, reached maximum 30% about a year later, and was reduced to 5%, 2 1/2 years postoperatively.


Acute renal failure secondary to rhabdomyolysis. MR imaging of the kidney.

MR imaging of the kidney was performed in 6 patients with acute renal failure (ARF) secondary to rhabdomyolysis caused by snake bite (n = 4), crush injury (n = 1), and carbon monoxide poisoning (n = 1). A test for urine myoglobin was positive in all 6 patients and MR imaging was done 6 to 18 days after the causative event of the rhabdomyolysis. MR images in all 6 patients showed globular swelling of the kidneys, preserved corticomedullary contrast on T1-weighted images, and obliteration of corticomedullary contrast on T2-weighted images. Unlike other medical renal diseases in which corticomedullary contrast is lost on T1-weighted images, preservation of the corticomedullary contrast on T1-weighted MR images with globular renal swelling was a constant finding in patients with ARF secondary to rhabdomyolysis.


MR imaging with STIR technique and air insufflation for local staging of bladder neoplasms.

Fifty-six patients with bladder carcinoma were studied with MR imaging for the assessment of the local stage, using the inversion recovery pulse sequence with fat suppression (STIR) with air in the bladder. With this technique images of the inner and the outer parts of the bladder wall were obtained, showing high contrast between the latter and the tumor (tumor/muscle contrast 89.9%). Four tumor stages were recognized: superficial neoplasms (Tis, Ta, and T1), partial wall infiltrating neoplasms (T2); total wall infiltrating neoplasms (T3a, T3b), and neoplasms involving other pelvic organs (T4). MR imaging was compared with histopathologic diagnosis obtained at transurethral resection or cystectomy. True-positive diagnosis was obtained in 80.4%; false-positive in 14.3% of cases; false-negative in 5.3%. Despite the relatively high incidence of overstaged neoplasms, STIR technique combined with air in the bladder allowed a good accuracy in local staging.


MR pelvimetry--a practical alternative.

Pelvimetry remains a useful technique as part of the assessment of the term breech pregnancy where vaginal delivery is planned. MR pelvimetry is accurate, well tolerated and shows soft-tissue structures as well as bone. It avoids the potentially carcinogenic effects of ionising radiation and is thought to be completely safe for mother and fetus. A technique of MR pelvimetry is described which uses gradient-echo sequences. This quick, practical method makes minimal inroads into valuable scanning time, and may therefore be considered a potentially cost-effective alternative to conventional pelvimetry.


One or two samples for determination of total plasma clearance of a nonionic contrast medium in patients undergoing enhanced CT.

Plasma clearance of nonionic iopamidol (300 mg I/ml) was measured in 50 patients in connection with enhanced CT. Before injection of either 50 or 100 ml of the contrast medium, S-creatinine and urine osmolality were measured. Employing Renalyzer PRX 90, the plasma concentration of iodine was determined in blood samples drawn approximately 3 and 4 h after injection of iopamidol. The glomerular filtration rate was calculated by the Renalyzer using 2 different formulas, one requiring only a single sample, and one requiring at least 2 samples (standard). Both the 3- and 4-h single sample values correlated well with the glomerular filtration rate expressed by the standard sample value. The result was independent of whether 50 or 100 ml had been administered and whether or not water soluble contrast medium had been given orally before CT. As could be expected S-creatinine and urine osmolality correlated poorly with the clearance values. It is concluded that in patients receiving either 50 or 100 ml contrast medium for enhanced CT, the glomerular filtration rate can be determined in a single sample as well as with 2 samples taken between 3 and 4 h after contrast medium injection.


Comparison of intravenous contrast agents for CT studies in children.

One hundred and eighty children undergoing CT examination were randomly allocated to receive meglumine diatrizoate, iohexol, or iopamidol as their i.v. contrast agent. Minor side effects were detected in 85% of children receiving meglumine diatrizoate, in 18% of those receiving iohexol, and in 36% of those receiving iopamidol. Because many of these minor side effects cause patient motion or delay scanning after contrast medium injection, they potentially degrade image quality. These findings are an indication for the use of low osmolarity contrast agents for i.v. use in pediatric CT imaging.


Influence of contrast media on single nephron glomerular filtration rate in rat kidney. A comparison between diatrizoate, iohexol, ioxaglate, and iotrolan.

The effects of slow (10 min) i.v. infusions of contrast media (CM, 1,600 mg I/kg b.w.) on single nephron glomerular filtration rate (SNGFR) in the rat kidney were investigated using a micropuncture technique. Diatrizoate, iohexol, or ioxaglate did not change SNGFR, although a tendency towards a transient suppression was seen during the infusion phase. Iotrolan infusion, however, decreased SNGFR (p < 0.05) and the value still remained below the control value 25 min after the start of infusion. Iotrolan is a nonionic dimeric CM and has a lower osmotic effect in the tubules than the ionic dimeric CM and the monomeric CM when given in iodine equivalent doses. These characteristics of iotrolan have probably some influence on the depression of SNGFR after iotrolan injection.


Viscosity of some contemporary contrast media before and after mixing with whole blood.

The viscosity of 7 contrast media was measured using a rotational viscometer. When solutions with similar iodine concentrations were compared, the highest viscosities were found for the nonionic dimers iodixanol and iotrolan, the lowest for diatrizoate, iopamidol, and iopromide, and intermediate values for iohexol and ioxaglate. The viscosity of iohexol and ioxaglate was found to vary linearly with temperature and quadratically with concentration. Whole-blood viscosity was measured for 5 subjects at high and low shear rates before and after mixing with contrast media in various proportions. Low-shear viscosity was found to decrease and high-shear viscosity to increase with contrast medium concentration. It is concluded that the contrast media currently used may affect blood rheology less than previous agents, despite their higher viscosity.


Motion associated susceptibility artifacts.

A bowel labeling agent is important for improving abdominal MR. Besides providing contrast between the bowel and other organs, the contrast agent itself is a potential source of artifacts. The artifacts created by superparamagnetic particles (SPP) subjected to motion have been studied in vitro at 0.5 T, and compared to artifacts created by a paramagnetic compound. Apart from the expected static effects of the SPP, movement induced additional artifacts were seen as signal displacements in the phase-encoding direction. The artifacts were obvious at an iron concentration of 1 mg Fe/ml, barely visible at 0.2 mg Fe/ml, and completely absent at 0.1 mg Fe/ml. Artifacts were also evident with the SPP outside the imaging slice. This further emphasizes the importance of choosing the lowest effective dose when using SPP contrast agents. For the paramagnetic agent, motion propagated artifacts consisted of high and low signal regions in a mosaic pattern.


Iodixanol--a new nonionic dimer--in aortofemoral angiography.

In 26 patients iodixanol, a new nonionic dimer, isotonic to blood in all concentrations, was used as contrast medium in aortofemoral angiography. Half of the patients received contrast medium in a concentration of 270 mg I/ml and the other half 320 mg I/ml. The aim of the trial was to evaluate the safety and tolerability of iodixanol and the radiographic efficacy of the two concentrations. The degree of discomfort, adverse events, changes in serum chemistry parameters, and diagnostic information were assessed. There were no changes or trends of clinical importance in serum chemistry parameters. The side effects were mild and consisted mostly of some sensation of warmth of short duration. No other adverse events were seen. The overall radiographic efficacy did not show any significant difference between the two concentrations. This indicates that iodixanol is safe and well tolerated when used in adult femoral angiography.


The function of the 5-hydroxymethyl group of lactose in enzymatic hydrolysis with beta-galactosidase from E. coli.

A series of 6-substituted methyl lactoside derivatives together with methyl allolactoside and (6S)-methyl [6-2H]lactoside have been synthesized and characterized by NMR spectroscopy. All compounds were tested as substrates for the enzyme beta-galactosidase from E. coli using progress curve kinetic methology both in single-substrate and competition experiments. The results show that the hydrolysis of methyl lactoside to a large extent takes place through an intramolecular transglycosidation reaction via allolactoside. Furthermore, methyl 6-amino-6-deoxy-D-glucopyranoside proved to be an ihibitor for the enzymatic hydrolysis.


Two-dimensional nuclear Overhauser enhancement NMR experiments on pelargonidin-3-glucopyranoside, an anthocyanin of low molecular mass.

Pelargonidin-3-glucoside has been isolated from the acidified methanolic extract of strawberries (Fragaria anannassa variety Corona) by successive application of an ion-exchange resin, droplet-counter chromatography and gel filtration. The pigment in acidified methanolic solution was studied by means of the two-dimensional nuclear Overhauser enhancement NMR technique, and the sugar unit was found to be attached to the 3-position on the aglycone. At +20 degrees C the pigment was found to be in the extreme narrowing limit where the NOESY cross-peaks are negative. However, at -20 degrees C this low-mass anthocyanin could be studied in the slow motion regime where the NOESY cross-peaks are positive. With a mixing time of 0.3 s, the glucose H1"-H4" proton pair was measured in the initial cross-relaxation rate and their cross-peak volume corresponded to the H1"-H4" distance found in a 4C1 chair conformation.


Changes in left ventricular function and wall thickness in heart transplant recipients and their relation to acute rejection: an assessment by digitised M mode echocardiography.

Assessment of changes in left ventricular diastolic function and wall thickness after heart transplantation to verify whether these changes predicted acute rejection assessed by endomyocardial biopsy. Follow up according to a predefined protocol of consecutive patients from the first week after transplantation. Heart transplantation unit of the Thoraxcentre, University Hospital Rotterdam Dijkzigt, The Netherlands. All 32 patients undergoing orthotopic heart transplantation from 1 January 1989 to 31 March 1990 were examined. Two were excluded from the analysis. Patients were treated with cyclosporin and low dose steroids. Data obtained by digitised M mode echocardiography were compared with the results of endomyocardial biopsy (Billingham classification). Mean values for left ventricular wall thickness, internal dimension, and their standardised rates of change and fractional shortening were determined from 4-6 consecutive expiratory beats. Mean values and individual trends during follow up were also investigated for each ultrasound variable. The results of these average values were compared with values in a group of 10 healthy volunteers. Median follow-up was 177 days (range 10-399). Two hundred and sixty three consecutive M mode studies were examined in relation to concurrent biopsy results. No significant differences were observed between the ultrasound variables at the time of moderate acute rejection (Billingham class 2, n = 37) and other biopsy classes (n = 226). Nor did changes in individual patients predict (moderate) acute rejection episodes. Twenty six of the 30 patients had an abnormal (slow) left ventricular relaxation pattern throughout follow up. Digitised left ventricular M mode echocardiography did not predict the presence of acute rejection. In most patients there was a persistent slow left ventricular relaxation pattern.


Fall in pulmonary vascular resistance in patients awaiting heart transplantation.

Raised pulmonary vascular resistance is associated with decreased survival after orthotopic heart transplantation and patients with this risk factor are usually denied transplantation. In a proportion of cases raised pulmonary vascular resistance may fall with time and medical treatment. Seven patients with high pulmonary vascular resistance (range 3.9-6.6 Wood units) at initial assessment for cardiac transplantation were restudied by right heart catheterisation after a period of seven to 17 months. In five of the seven patients the pulmonary vascular resistance had fallen, allowing orthotopic heart transplantation to be performed in four. In one patient the resistance was static and in one it had risen. The mean fall in pulmonary vascular resistance for the group was (mean (SD)) 2.6 (2.7) Wood units, p < 0.05. Patients who have been denied transplantation on the basis of their raised pulmonary vascular resistance should be reassessed after four to six months if they remain otherwise clinically suitable.


Early vasodilator treatment in myocardial infarction: appropriate for the majority or minority?

To assess the influence of vasodilator treatment started early after myocardial infarction on left ventricular size and function. Coronary care unit, Royal Infirmary, Edinburgh. 105 patients with acute myocardial infarction (systolic blood pressure > 90 mm Hg) were randomised within 24 hours of the start of pain. Unlike previous studies 88% of the patients received thrombolysis. Double blind randomised placebo controlled study with either 12.5 mg of captopril three times daily or 20 mg of isosorbide mononitrate three times daily for 28 days. Clinical outcome and left ventricular size and function assessed by echocardiography, radionuclide ventriculography, and magnetic resonance imaging. There was no difference in left ventricular size or function in either treatment group as measured one week after the end of the trial. Even the placebo group tended to decrease left ventricular diameter over the four week study period (one week: 5.0 (0.1) v, five weeks: 4.8 (0.1) cm, NS). Four patients had an adverse clinical outcome in the placebo group whereas no adverse outcome was seen in the captopril group. Vasodilator treatment may be of limited value or of no benefit for most infarct patients, particularly those treated with thrombolytic agents. Captopril, however, may benefit patients at high risk.


Evidence of increased platelet activation after thrombolysis in patients with acute myocardial infarction.

To assess platelet activation after thrombolysis in patients with acute myocardial infarction. Platelet function was assessed by measurement of the in vivo synthesis of thromboxane by gas chromatography-mass spectrometry of thromboxane's major urinary metabolite, 2,3-dinor-thromboxane-B2. Coronary care unit of Huddinge University Hospital. 30 patients with acute myocardial infarction given either streptokinase 1.5 million units intravenously over one hour + 500 mg aspirin (n = 10), 500 mg aspirin (n = 10), or neither thrombolysis nor aspirin (n = 10). Patients treated by thrombolysis had a 20-fold increase in thromboxane formation during thrombolysis compared with control patients not treated by thrombolysis (p = 0.0001). Until two days after thrombolysis thromboxane production in patients treated with streptokinase did not decrease to a value comparable with patients treated with aspirin but not given thrombolysis. Thromboxane production increased considerably during thrombolysis, possibly reflecting greatly enhanced platelet activation. The slow decrease in thromboxane formation after treatment with aspirin suggests that the efficacy of thrombolysis might be improved by more efficient antiplatelet treatment.


Left atrial and left ventricular diastolic function during acute myocardial ischaemia.

To study indices of diastolic left ventricular function during the first few seconds of myocardial ischaemia. Isovolumic and total relaxation times and left atrial and left ventricular dP/dt were identified from high fidelity (micromanometer) pressure recordings in the left ventricle and left atrium during percutaneous transluminal angioplasty of the left anterior descending coronary artery. 20 patients with isolated disease of the left anterior descending artery and normal left ventricular function. The isovolumic relaxation time lengthened during the first seven to nine seconds of ischaemia; then it shortened by an average of 15% up to the twentieth second, initially as a result of increased left atrial contractility and subsequently because of impaired ventricular relaxation. Ventricular ischaemia resulted in impaired left ventricular diastolic compliance, as shown by an increase in the total relaxation time, before there was evidence of systolic impairment. Minimum dP/dt decreased progressively (by -37% at the twentieth second of ischaemia), whereas maximum dP/dt fell only after 20 seconds of ischaemia (by -11%). Relaxation and filling of the left ventricle (indices of diastolic function) are more sensitive to myocardial ischaemia than myocardial contractility and systolic function. Left atrial contractility increases during left ventricular ischaemia.


Nocturnal hypoxia and arrhythmias in patients with impaired left ventricular function.

To document the incidence of hypoxic episodes in a series of patients with impaired left ventricular function, and to correlate the occurrence of hypoxia with severity of arrhythmia. 34 patients with breathlessness and clinical evidence of left ventricular dysfunction. Simultaneous overnight finger oximetry and electrocardiographic monitoring. High grade arrhythmias (Lown grade > III) occurred in 20/34 (59%) of patients, and frequent dips in oxygen saturation were noticed (mean dip frequency 4.8/h, range 0.1-20.0). 20/34 (59%) of patients had episodic hypoxaemia, including 13/34 (38%) with a classical Cheyne Stokes pattern. There was a correlation between dip frequency and the presence of high grade arrhythmias (those with high grade arrhythmia had mean (SD) 6.7 (5.5) dips/h v 2.2 (3.4) in those without, p < 0.01); there was also a correlation between the presence of arrhythmias and episodic hypoxaemia (episodic hypoxaemia in those with high grade arrhythmias occurred in 17/20 (85%) v 3/14 (21%) of those without arrhythmias, p < 0.002). There was no correlation between the presence of high grade arrhythmias or dip frequency and the extent of left ventricular impairment, which was present in all patients (mean (SD) ejection fraction 26% (13%)). Noticeable abnormalities of nocturnal oxygen saturation occur in patients with impaired left ventricular function, and these are associated with high grade arrhythmias. Interventions that limit desaturation may have valuable anti-arrhythmic effects.


Increased circulating atrial natriuretic factor concentrations in patients with chronic heart failure after inhibition of neutral endopeptidase: effects on diastolic function.

+/- Candoxatrilat was used to raise atrial natriuretic factor (ANF) concentrations in patients with heart failure, and the effects on left ventricular systolic and diastolic function were studied to determine the contribution of peripheral and central mechanisms to the haemodynamic effects. This was a single blind, randomised comparison of +/- candoxatrilat and placebo in patients with mild heart failure. All patients received two intravenous doses of +/- candoxatrilat and two placebo doses on four consecutive days. A teaching hospital department of cardiology. Six men (mean age 52 years) with mild heart failure (New York Heart Association class II) due to ischaemic heart disease (four patients) or dilated cardiomyopathy (two patients) were included. Mean ejection fraction was 37.5% and mean peak oxygen consumption was 20.4 ml/min/kg. Plasma ANF concentrations, haemodynamic indices and left ventricular diastolic function measured by early to atrial filling rate (E:A ratio) with Doppler echocardiography were determined before and after +/- candoxatrilat and placebo. +/- Candoxatrilat caused a threefold rise of plasma ANF compared with placebo (p < 0.005), but there was no significant change in heart rate, blood pressure, or cardiac output. Mean right atrial pressure fell from 6.7 to 4.7 mmHg (NS) and pulmonary artery wedge pressure fell from 9.2 to 6.7 mmHg (p < 0.05). Doppler echocardiographic measurements of transmitral blood flow showed a significant fall in peak early left ventricular filling velocity from 39.5 to 34.2 cm/s (p < 0.05), along with a non-significant rise in peak atrial filling velocity from 39.7-41.6 cm/s after +/- candoxatrilat. The E:A ratio, a Doppler index of left ventricular diastolic function, fell from a mean of 1.04 to 0.87 (p < 0.05). +/- Candoxatrilat increased plasma ANF concentrations and reduced right atrial and pulmonary artery wedge pressures. No evidence of an improvement in left ventricular systolic or diastolic function was found, so the fall in preload was due to peripheral effects, either an increase in venous capacitance or a fall in circulating blood volume.


Efficacy of flecainide, sotalol, and verapamil in the treatment of right ventricular tachycardia in patients without overt cardiac abnormality.

A comparison of the efficacy of verapamil, sotalol, and flecainide to suppress right ventricular tachycardia (VT) in patients with a clinically normal heart. Patients underwent treatment serially with verapamil (360 mg daily), sotalol (240 or 320 mg daily), and flecainide (200 or 300 mg daily), (the larger dose was for patients heavier than 80 kg) to suppress tachycardia. Each drug was given orally for five half lives before testing. 23 patients with right VT associated with a clinically normal heart were studied. The effects of drug treatment were examined by the number of ventricular events on 24 hour Holter monitoring, and the ability of tachycardia to be induced by treadmill exercise testing (Bruce protocol) and programmed ventricular stimulation (Wellens protocol), compared with drug free baseline tests. Patients were studied in a tertiary referral centre. All three drugs suppressed ventricular salvos (> 3, < 5 consecutive ventricular premature contractions) (p < 0.01) and VT (p < 0.05) on Holter monitoring and did not differ statistically in effect. Exercise induced VT was also suppressed by all three drugs (p < 0.01), and of these sotalol was the most effective although this was not statistically significant (14/23 inducible when drug free, 4/23 on flecainide, 2/23 on sotalol, 5/23 on verapamil). Sustained and non-sustained VT induced by programmed stimulation was also suppressed by the three drugs (p < 0.01) and again sotalol was the best of these though the differences did not achieve statistical significance (17/23 inducible when drug free, 4/17 on flecainide, 2/17 on sotalol, and 6/17 on verapamil). Proarrhythmic effects of drugs were found in a few patients. There was no difference in the efficacy of the drugs in patients with histological abnormalities of the myocardium when compared with those of normal histology. Ventricular tachycardia associated with a clinically normal heart can be suppressed by flecainide, sotalol, or verapamil. In individual patients sotalol was the most frequently effective drug (effective in > 89% of patients) and is a suitable choice for first line treatment.


Comparison of unipolar and bipolar ventricular paced evoked responses.

To study the differences between endocardial bipolar and unipolar ventricular paced evoked responses and surface electrocardiograms. 10 patients with conduction system disease awaiting insertion of a permanent pacemaker were studied with temporary ventricular pacing from the right ventricular apex. Comparison of the durations of the QRS complexes and QTa and QTe intervals of the endocardial bipolar paced evoked response and the surface electrocardiogram with those of the reference unipolar paced evoked response. By comparison with the unipolar reference, the mean durations of the QRS complexes of the bipolar signal and the surface electrocardiogram were 41.8% and 132.1% respectively. The mean QTa interval was 85.9% and 112.2% respectively and the mean QTe interval was 86.9% and 109.5% respectively. All these differences were significant. The amplitudes of the unipolar QRS complexes and T waves were significantly larger than those recorded in the bipolar configuration. Differences between the unipolar and bipolar ventricular paced evoked responses are significant. The time course of the unipolar signal is closer to that of the surface electrocardiogram. This indicates that the unipolar paced evoked response does not reflect local electrophysiological events, as has been suggested previously.


Effects of abnormal activation on the time course of the left ventricular pressure pulse in dilated cardiomyopathy.

To investigate the effects of QRS duration on characteristics of the left ventricular pressure pulse derived from the time course of functional mitral regurgitation by continuous wave Doppler. Retrospective and prospective study of 50 patients with dilated cardiomyopathy, by electrocardiography, echocardiography, and Doppler cardiography. Tertiary cardiac referral centre. 50 patients (mean age (SD) 58 (16)) with dilated cardiomyopathy, all with functional mitral regurgitation. The values of QRS duration ranged widely, from 70 to 190 ms with a mean value of 110 ms, and were unimodally distributed. The overall duration of mitral regurgitation correlated positively with QRS time (r = 0.65) over the entire range of values. When the duration of mitral regurgitation was divided into contraction, aortic ejection, and relaxation times, increased QRS duration prolonged contraction (r = 0.51) and relaxation (r = 0.52) times. Aortic ejection time was affected by RR interval (r = 0.74). Duration of QRS correlated negatively with peak rate of rise in left ventricular pressure (+dP/dt) (r = -0.48), and positively with the time intervals from Q to peak pressure (r = 0.49) and to peak +dP/dt (r = 0.72), and also with those from the start of mitral regurgitation to peak pressure (r = 0.49) and to peak +dP/dt (r = 0.76). Duration of QRS did not directly affect the peak rate of left ventricular pressure fall (-dP/dt), or the isovolumic relaxation period. Values of QRS duration are unimodally distributed in patients with dilated cardiomyopathy, without evidence of a discrete group of patients with left bundle branch block. Prolonged QRS duration reduces peak +dP/dt, prolongs overall duration of the pressure pulse, the time to peak +dP/dt, and relaxation time. Duration of QRS must therefore be taken into account in assessing standard measurements of myocardial function in patients with dilated cardiomyopathy.


Mitochondrial DNA deletion diagnosed by analysis of an endomyocardial biopsy specimen from a patient with Kearns-Sayre syndrome and complete heart block.

Defects of mitochondrial DNA have been found at necropsy in the myocardium of patients with Kearns-Sayre syndrome. A patient with characteristics typical of Kearns-Sayre syndrome and a complete heart block is described. Southern blot analysis showed a deletion of 3.3 kb in the mitochondrial DNA in an endomyocardial biopsy specimen and in skeletal muscle. The deletion led to the disappearance of the genes for four transfer RNAs and four subunits of complex I (NADH:ubiquinone oxidoreductase) in the mitochondrial respiratory chain. The defect could not be demonstrated in whole blood despite amplification of the mitochondrial DNA region of interest by the polymerase chain reaction technique. There can be heteroplasmy--that is, normal and abnormal mitochondrial DNA populations in one cell--in different tissues, and the degree of heteroplasmy may be crucial in the development of organ-specific symptoms. This patient raises the possibility that some tissues can be specifically enriched with mitochondria with DNA defects and emphasises the need for elective sampling of the target tissue and polymerase chain reaction technique to exclude these defects. The role of mitochondrial DNA defects in idiopathic cardiomyopathies could perhaps be studied by analysis of mitochondrial DNA from endomyocardial biopsy specimens.


Apparent obstruction of the superior vena cava and a continuous murmur: signs of a fistula between a vein graft aneurysm and the right atrium.

A previously undescribed complication of a saphenous vein aortocoronary bypass graft, namely formation of a fistula between a vein graft aneurysm and the right atrium is reported. A patient presented with a continuous murmur and a combination of signs suggesting superior vena cava obstruction. This pathology was shown by both echocardiography and angiography. Surgical treatment was attempted.


A posteroseptal accessory pathway located in a coronary sinus aneurysm: diagnosis and radiofrequency catheter ablation.

A coronary sinus aneurysm was diagnosed by means of echocardiography, coronary sinus contrast angiography, coronary angiography, and nuclear magnetic resonance imaging in a patient with Wolff-Parkinson-White syndrome caused by a posteroseptal accessory pathway. Percutaneous radiofrequency current catheter ablation performed in the isthmus of the coronary sinus aneurysm was successful.


Effect of increasing heart rate on Doppler indices of left ventricular performance in healthy men.

To investigate the effects of heart rate on the Doppler measurements of left ventricular function and to determine the normal pattern of rate dependency. University hospital specialising in internal medicine. 14 healthy male volunteers 10 of whom were studied. Transoesophageal atrial pacing. At paced rates of 70, 80, and 90 ppm the ratio of early to late peak transmitral flow velocity (E/A) was 1.97 (0.28), 1.49 (0.21), and 0.95 (0.11) respectively; the ratio of early to late time-velocity integrals of transmitral flow (Ei/Ai) was 3.03 (0.51), 2.11 (0.24), and 1.14 (0.30) respectively; and the atrial filling fraction (AFF) was 0.17 (0.03), 0.21, (0.04), and 0.24 (0.04) (mean (SD)). Heart rate showed a linear correlation with E/A (r2 = 0.806), Ei/Ai (r2 = 0.838), and AFF (r2 = 0.343). Neither the peak aortic flow velocity or the mean aortic flow acceleration showed significant changes during pacing at rates of 70, 80, 90, and 100 ppm. E/A and Ei/Ai can be expected to decrease by 0.5 and 0.9 for each increase of 10 beats/min in heart rate. Knowledge of this relation may be useful for the development of algorithms to correct for heart rate when diastolic function is assessed.


Cardiac surgery: moving away from intensive care.

To evaluate outcome in patients managed outside an intensive care unit after open heart surgery. The high cost of cardiac surgery is mainly due to the needs of traditional postoperative care. The requirements for intensive care and treatment has decreased with improvements in techniques of cardiac surgery and anaesthesia. In this setting the need to continue to depend on intensive care units for the recovery of cardiac surgical patients is questionable on clinical and economic grounds. Postoperative outcome in 245 patients over a four month period was studied prospectively. Mean age of the patients was 63.2 years. They underwent a wide variety of operative procedures. Ninety percent of them recovered in a dedicated three bed cardiac surgical recovery area where the management protocol led to rapid extubation and step down in dependency care. Median time for ventilatory support was 90 minutes after transfer to the area. Only five patients were subsequently admitted to the general intensive care unit for prolonged respiratory and cardiac support. Ten patients were electively admitted to the general intensive care unit. Two deaths occurred in hospital in this group (0.8%). Four patients were ventilated for 24 hours in the recovery area itself and made an uncomplicated recovery. This study confirms that over 90% of patients undergoing cardiac surgery would recover safely and be treated effectively in a more economical area than intensive care.


Simple bone cysts. A review of 59 cases with special reference to their treatment.

In a retrospective study, 21 simple bone cysts (SBC) treated by curettage (with or without bone grafting) are compared to 20 SBC treated by intralesional injections of methylprednisolone. Curettage led to 43% favourable results and 29% recurrences. Cortisone injections led to 90% favourable results and 5% recurrences. Combined therapy (curettage and injections) led to results comparable to injections only. In our experience, curettage and hydroxyapatite grafting led to 100% complete healing (only 2 cases). We recommend intralesional methylprednisolone injections because the method is easy, effective and safe.


Effect of cup geometry and the presence of cement on acetabular component fixation.

Two series of implanted conical, polyethylene Ring cups were studied clinically and radiographically. In one series the cups were uncemented while in the second cement was used. The results using cemented conical cups were then compared with results using a cemented cup of hemispherical design to study the effect of cup geometry. At 7-8 years a total of 3.8% of the cemented conical series and 2.9% of the uncemented were revised for aseptic loosening. At 9 years survivorship was identical. Migration of the sockets occurred in approximately 25% of both series and was directly related to cup cover of less than 80% (P < 0.001). The series of cemented hemispherical cups were reviewed after an identical period. Although the numbers revised for loosening were comparable in this and the cemented conical group, radiological migration was statistically greater in the latter (P < 0.001). Alternative methods of socket preparation and cement technique were thought to be the most likely explanation for the observed differences.


Clinical results and radiologic findings after cementless implantation of PCA stems in total hip replacement.

The results of radiologic and clinical follow-up of 81 PCA (porous coated anatomie) hip joint prostheses implanted in our clinic between 1986 and 1988 are presented. One of the prostheses had to be explanted because of aseptic loosening after 2.5 years' implantation. Contrary to the fixation concept of the prosthesis, which requires both proximal osseointegration and free axial shifting of the distal part of the prosthesis, our follow-up radiographs showed proximal lysis of 2 mm and more as well as distal hypersclerosis of 3 mm and more in the form of endosteal bone formation in 70% of cases 3 years after implantation. On the basis of our data, the question whether these bone reactions will finally lead to aseptic loosening of the implant cannot be answered yet.


The modified Mayo procedure combined with basal valgus osteotomy of the first metatarsal for severe hallux valgus.

The modified Mayo procedure corrects valgus deformity of the great toe secondary to osteoarthritis in the first metatarsophalangeal joint. Basal osteotomy of the first metatarsal to correct metatarsus primus varus and to maintain correction of the valgus deformity may be performed simultaneously. We retrospectively reviewed the results in 55 of 70 feet treated by this combined procedure. The average duration of follow-up was 4.2 years (range 0.5-6 years) and the average age at operation was 63 years (range 45-80 years). The results were either very good or good in 82%, moderate in 14%, and poor in 4%. Our technique of basal osteotomy of the first metatarsal is a simple and effective procedure to correct metatarsus primus varus and may restore the distal transverse arch. It should be considered as a possible method of treatment when the intermetatarsal angle is greater than 10 degrees.


The pelvic compartment syndrome.

In the pelvic region three major compartments (gluteus medius-minimus compartment, gluteus maximus compartment, and iliopsoas compartment) can be distinguished from the smaller compartment of the tensor fasciae latae muscle. Pelvic compartment syndromes are rare. A clear history of trauma is often lacking. Association with drug and alcohol abuse is common, as is the association with the widespread use of anticoagulant therapy. From 1982 to 1990 six patients with acute buttock compartment syndrome were treated in the Department of Trauma Surgery of Hannover Medical School. In five patients fasciotomy of the gluteal compartment was performed. Two patients with a compartment syndrome secondary to necrotizing fasciitis died of septic multiple organ failure. The mean follow-up of the four other patients was 29 months (7-48 months). Three of these four patients revealed a decrease of gluteal muscle volume. Ergometric tests showed a decrease in gluteal muscle force in all patients.


Aneurysmal bone cyst. A review of 52 primary and 16 secondary cases.

Authors report on the results of treatment of 52 primary and 16 secondary aneurysmal bone cysts (ABC). ABC grow rapidly; 84% of them have already destroyed more than the half of the bone width at recognition. En bloc resection is preferred when the ABC is growing superficially and eccentrically and more than half of the bone width is intact. Careful curettage and bone grafting still remains the surgical method of choice in the majority of cases, when the ABC is more destructive and affects the subchondral bone of the joints. Segmental resection is only indicated when removal of the affected bone does not influence the function of the extremity. Superselective embolization of the cyst was performed in seven cases with excellent results. This method is suggested for ABC in certain locations inaccessible to surgical intervention, e.g., the pelvis, or to avoid excessive bleeding in hypervascularized tumors. In one case, however, an incomplete rebuilding of the ABC could only be achieved by the administration of calcitonin. The 16 cases of secondary ABC were observed mostly in association with osteoblastomas, giant-cell tumors, and osteosarcomas. The incidence of the secondary ABC was 23% in the whole ABC group but not more than 2-4% among the osteosarcomas and giant-cell tumors. Secondary ABC may confuse the histological and clinical diagnoses and that, especially in cases of osteosarcoma, may have fatal consequences.


Diagnosis and treatment of retroperitoneal hematoma in multiple trauma patients.

From 1984 to 1991 20 multiple trauma patients with pelvic fractures and retroperitoneal bleeding from pelvic vessels underwent angiographic localization and embolization of massively bleeding arterial vessels. Nine patients survived (multiple trauma index grade III, Hanover polytrauma index), three patients with very severe injuries died immediately (multiple trauma index grade IV). After successful control of bleeding by embolization, three other patients died from severe brain injuries and five patients from septic multiorgan failure. The interval to definite localization and treatment of the bleeding source was three times shorter in the group of survivors, and the amount of transfusions needed was less by a factor of three. This underlines the importance of early angiography in multiple trauma patients with pelvic fractures and persisting hemorrhage. Embolization has proven to be effective in the treatment of such injuries.


Epiphyseal chondroblastoma of bone. Long-term effects on skeletal growth and articular function in 15 cases treated surgically.

The authors describe the long-term sequelae of chondroblastoma in 15 patients with open growth plates, whose age at operation ranged from 8 to 15 years. At follow-up, the youngest patient was 21 and the oldest 48 years old. Upper limb length discrepancy ranging from 2 cm to 10 cm was present in the four patients who had a proximal humeral epiphyseal location; in three of them, the range of motion of the shoulder was also limited and X-rays showed marked irregularities of the humeral head. Lower limb length discrepancy ranging from 0.5 cm to 2 cm was found in five of the eight patients in whom the tumor affected lower limb epiphyses. One patient with proximal tibial epiphyseal involvement also had mild genu valgum. Radiographic osteoarthritis was present only in the trapeziometacarpal joint of a patient in whom the first metacarpal bone affected by the tumor was replaced by a free fibular graft. The abnormalities observed did not cause important functional loss in either the everyday or the working activities of any of our patients.


Radiolunate and radioscapholunate arthrodesis.

Eleven patients underwent radiocarpal arthrodesis for a wrist disease other than rheumatoid arthritis. Operations included seven radiolunate fusions and four radioscapholunate fusions. The indication for surgery was posttraumatic changes secondary to radius fracture (five), Kienböck's disease (three), localized arthritis secondary to sepsis (two) and acute comminuted fracture of the distal radius (one). All patients had arthritis or post-traumatic changes limited to the articulation between the radius and carpus. Follow-up ranged from 24 months to 7 years, with an average of 41 months. Postoperatively, average range of motion of the wrist was 30.9 degrees of extension, 22.7 degrees of flexion, 10 degrees of radial deviation, and 19.3 degrees of ulnar deviation, and grip strength averaged 81.8% of that for the uninvolved hand. Pain relief was achieved in all patients, and they were able to return to their previous occupation. Bony union was achieved in all cases. Degenerative changes in the midcarpal joint were not seen.


Immunoreactive neuropeptide nerves in ligamentous tissue in chronic shoulder pain.

Coracoacromial ligament and periligamentous fatty and loose connective tissue obtained during Neer's acromioplasty in patients with chronic painful rotator cuff tendinitis/impingement syndrome was studied for possible signs of inflammatory involvement and for the presence of neuropeptide-containing nerves, using routine histology and immunoperoxidase staining. No accumulations of inflammatory cells were found in the tissues studied. The dense ligamentous tissue proper was practically aneural, as was seen in staining for the generalized neuronal markers protein gene product 9.5 and synaptophysin. In contrast, the periligamentous fatty and loose connective tissue was innervated. Almost all nerves in such tissue contained C-flanking peptide of neuropeptide Y, whereas substance P, calcitonin gene-related peptide, and vasoactive intestinal peptide-containing nerves were not found at all or were extremely rare. This suggests that the coracoacromial ligament is not a target of irritative inflammation. In the periligamentary sheath, nerves containing markers for the C-type nociceptive pain fibers were practically absent and all local nerves were postganglionic sympathetic vaso-regulatory nerves.


Open traumatic posterior dislocation of the hip. A case report.

A case of open traumatic posterior dislocation of the hip is presented. The femoral head and neck were completely out of the skin and there were accompanying fractures of the acetabular floor, the ischial ramus and the greater trochanter. To our knowledge, such a case has not been reported previously and this, together with its interesting mechanism, has led us to report the case. It was followed for 18 months and roentgenographic and 99mtechnetium sulphur colloid scanning studies showed avascular necrosis and osteoarthritis.


Traumatic scapulothoracic dissociation. A case report.

A rare case of scapulothoracic dissociation which was not diagnosed initially is reported. Vascular injuries associated with this injury are potentially life threatening. The key to the diagnosis is accurate interpretation of the radiographs: the lateral dislocation of the acromion and lateral shift of the medial scapular border are evident on chest radiographs. Emergency subclavian arteriography is essential to assess the vascular status. A high index of suspicion has to be maintained so that this dangerous injury is not overlooked.


Leg ulcer clinics: advanced nursing.

The author describes the development of a leg ulcer clinic, based on an electric model of care, which draws on her experience as a clinical nurse specialist. The philosophy of the clinic recognises that a 'legs specific' approach offers only short term solutions, and that a holistic method, which encourages patients to examine their own situation, is more appropriate.


Clinical trials: comparing dressings.

This article describes results from one of the sites involved in a multi-centred comparative study designed to assess the performance of a collagen-alginate dressing used in the treatment of leg ulceration. The research methods used in the trial, as well as the results, will be of interest to practising nurses. Those involved in similar work are invited to submit articles to be considered for publication in future issues of this supplement.


Formation of glycine conjugate and (-)-(R)-enantiomer from (+)-(S)-2-phenylpropionic acid suggesting the formation of the CoA thioester intermediate of (+)-(S)-enantiomer in dogs.

It has been proposed that the chiral inversion of the 2-arylpropionic acids is due to the stereospecific formation of the (-)-R-profenyl-CoA thioesters which are putative intermediates in the inversion. Accordingly, amino acid conjugation, for which the CoA thioesters are obligate intermediates, should be restricted to those optical forms which give rise to the (-)-R-profenyl-CoA, i.e., the racemates and the (-)-(R)-isomers. We have examined this problem in dogs with respect to 2-phenylpropionic acid(2-PPA). Regardless of the optical configuration of 2-phenylpropionic acid administered, the glycine conjugate was the major urinary metabolite and this was shown to be exclusively the (+)-(S)-enantiomer by chiral HPLC. Both (-)-(R)- and (+)-(S)-2-phenylpropionic acid were present in plasma after the administration of either antipode, and further evidence of the chiral inversion of both enantiomers was provided by the presence of some 25% of the opposite enantiomer in the free 2-phenylpropionic acid and its glucuronide excreted in urine after administration of (-)-(R)- and (+)-(S)-2-phenylpropionic acid. The (+)-(S)-enantiomer underwent chiral inversion to the (-)-(R)-antipode when incubated with dog hepatocytes. These data suggests that both enantiomers of 2-phenylpropionic acid are substrates for canine hepatic acyl CoA ligase(s) and thus undergo chiral inversion, but that the CoA thioester of only (+)-(S)-2-phenylpropionic acid is a substrate for the glycine N-acyl transferase. These studies are presently being extended to the structure and species specificity of the reverse inversion and amino acid conjugation of profen NSAIDs.


Pulmonary inversion of 2-arylpropionic acids: influence of protein binding.

The possible contribution of pulmonary metabolism to the putative first-pass metabolism of 2-arylpropionic acid nonsteroidal antiinflammatory drugs has not been documented. Isolated perfused rabbit lungs, perfused with 4.5% bovine serum albumin or 5% dextran, were used to study the pulmonary elimination of (R)- and rac-ibuprofen, fenoprofen, and flurbiprofen. In the absence of protein binding, ibuprofen was metabolized via inversion and other pathways, whereas fenoprofen metabolism was essentially restricted to inversion of the (R)-enantiomer; fraction inverted (+/- SE) was 0.37 +/- 0.05 for (R)-ibuprofen and 0.85 +/- 0.03 for (R)-fenoprofen. In the presence of protein, neither ibuprofen nor fenoprofen was metabolized. Flurbiprofen did not undergo pulmonary elimination under any condition studied. This study illustrates that even though a tissue is capable of metabolism, particularly inversion of 2-arylpropionics, the quantitative importance of such elimination pathways may be minimal in the presence of the high degree of protein binding that is characteristic of these drugs.


An improved synthesis of the enantiomers of BM-5 and their effects on the central in vivo release of acetylcholine.

Racemic N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide (BM-5), a putative postsynaptic agonist and presynaptic antagonist at muscarinic receptors, was resolved into the enantiomers by a new method suitable for large scale preparation. The method involves a chemoselective N-debenzylation as the key step. The enantiomers of BM-5 were obtained after six separate steps in 25% overall yield. The ability of the enantiomers to release acetylcholine was evaluated in vivo by use of brain dialysis. (R)-BM-5 was the more potent enantiomer in this assay.


Absolute configuration and conformation of the pure opioid antagonist (+)-2,9 alpha-dimethyl-5-(m-hydroxyphenyl)morphan.

(+)-2,9 alpha-Dimethyl-5-(m-hydroxyphenyl)morphan is the only phenylmorphan analog whose affinity for opioid kappa-receptors is greater than its affinity for opioid mu-receptors. Pharmacologically, the compound is a pure opioid antagonist devoid of agonist activity in in vivo assays of antinociception. The absolute configuration of the compound has been determined to be (1R,5S,9R) from an X-ray crystallographic study of the chloride salt. Thus, the absolute configuration corresponds to that of the atypical opioid agonist (-)-phenylmorphan while the weak atypical agonist (-)-2,9 alpha-dimethyl-5-(m- hydroxyphenyl)morphan corresponds to the potent morphine-like (+)-phenylmorphan. The preferred orientations of the phenyl ring for the two stereoisomers were determined using the molecular mechanics program MM2-87 and found to vary from that of the two parent compounds. The atypical properties of the two 9 alpha-methyl analogs is consistent with an opioid ligand model which proposes that morphine-like properties require a particular range of phenyl orientations. There was good agreement between the structure obtained from X-ray crystallography and computed with the MM2-87 program.


Application of time-domain fitting in the quantification of in vivo 1H spectroscopic imaging data sets.

Time-domain model function fitting techniques were applied to improve the reconstruction of metabolite maps from the data sets obtained from in vivo 1H spectroscopic imaging (SI) experiments. First, residual water-related signals were removed from the SI data sets by using SVD-based linear time-domain fitting based upon the HSVD (State Space) approach. Second, peak integrals of the metabolites of interest were obtained by quantifying the proton spin-echoes of the voxels by means of non-linear time-domain fitting based upon the maximum likelihood principle. Third, in order to save computational time, interpolation of the metabolite images (from size 32 x 32 to 128 x 128) was performed in the image-domain by applying one-dimensional cubic splines. It was found that the residual water signals can be almost completely removed from the SI data sets by applying the linear HSVD fitting method. Furthermore, it was found that voxel dependency of certain NMR parameters (e.g., variations of the spin-echo offset frequencies and/or phase factors) can be accounted for automatically by applying the nonlinear time-domain fitting technique. For that purpose it appeared to be essential to employ prior knowledge of the NMR spectral parameters.