Isolation and structure of a brain constituent that binds to the cannabinoid receptor.

Arachidonylethanolamide, an arachidonic acid derivative in porcine brain, was identified in a screen for endogenous ligands for the cannabinoid receptor. The structure of this compound, which has been named "anandamide," was determined by mass spectrometry and nuclear magnetic resonance spectroscopy and was confirmed by synthesis. Anandamide inhibited the specific binding of a radiolabeled cannabinoid probe to synaptosomal membranes in a manner typical of competitive ligands and produced a concentration-dependent inhibition of the electrically evoked twitch response to the mouse vas deferens, a characteristic effect of psychotropic cannabinoids. These properties suggest that anandamide may function as a natural ligand for the cannabinoid receptor.

Primary unconstrained shoulder arthroplasty in patients with a fixed anterior glenohumeral dislocation.

BACKGROUND: Reports of shoulder arthroplasty for the treatment of fixed glenohumeral dislocation are rare. The purpose of this study was to analyze the results following shoulder arthroplasty in patients with a fixed anterior shoulder dislocation. METHODS: Eleven patients were evaluated at a minimum of twenty-four months after they underwent an arthroplasty for the treatment of a fixed anterior shoulder dislocation. Four patients underwent a total shoulder arthroplasty, and the remainder were treated with a hemiarthroplasty. Four shoulders had osseous reconstruction of the anterior aspect of the glenoid. The patients were evaluated with use of the Constant score, measurement of active anterior elevation and external rotation, the patient's subjective grading of the result, and a radiographic examination. RESULTS: The mean Constant score improved from 21.1 points preoperatively to 46.0 points following the arthroplasty, and the mean active anterior elevation improved from 48.6 degrees to 90.0 degrees . The pain component of the Constant score was the most reliably improved parameter, increasing from a mean of 4.8 points preoperatively to a mean of 11.0 points postoperatively. Eight patients reported that the result was excellent or good, and the remaining three considered it to be fair. We observed seven complications in five patients, including four cases of anterior instability of the shoulder. Two of the four patients treated with a total shoulder replacement were seen to have definite loosening of the glenoid component on follow-up radiographs. CONCLUSIONS: Shoulder arthroplasty in patients with a fixed anterior shoulder dislocation is fraught with difficulties and complications. Although arthroplasty reliably relieved shoulder pain in this population, limited functional results should be expected.

Repeat exercise renograms in hypertension identify persistent renal dysfunction.

BACKGROUND: Hypertensives may develop bilateral trapping of para-aminohippurate analogues in the tissue of the kidneys during light exercise, as can be demonstrated using radioactively labelled [131I]-hippurate or [99mTc]-mercaptoacetyl-triglycine. Tracer accumulation in the kidneys during exercise results in a typical renographic pattern, the bilateral-abnormal exercise renogram. The disturbance is common during exercise, being found in almost 60% of all hypertensives, regardless of aetiology. OBJECTIVE: To determine whether bilateral-abnormal exercise renograms are spurious phenomena, or whether the results of exercise renography are reproducible. DESIGN: We reviewed the renographic examinations of 27 hypertensive patients, each of whom had undergone at least one resting and two [131I]-hippurate or [99mTc]-mercaptoacetyl-triglycine gamma-camera exercise renograms. The status of the renal artery at the time of scintigraphy was documented, using available arteriograms. The causes of vascular lesions were noted, as were revascularization procedures and the antihypertensive medication being taken at the time of scintigraphy. RESULTS: The average time between exercise renograms was 15.5 months, and 24 of the 27 hypertensive patients had comparable results in the first and the follow-up exercise renogram, divergent results being noted for the other three patients. Re-evaluation of the scintigrams of the three hypertensive patients with divergent results suggested that intermittent pelvic retention might have caused errors of interpretation in two. We found it notable that neither revascularization nor a change in antihypertensive drug therapy influenced the results of exercise renography. Exercise renograms were reproducible over long periods, and potential extraneous influences on blood flow, such as antihypertensive drugs or revascularization, failed to alter the results. CONCLUSION: The results are considered relevant, because a direct relationship appears probable between hypertension and the disturbance investigated. Reproducible results suggest that the exercise-mediated disturbance is fixed to the kidneys, that it can be reactivated repeatedly and that it may play a role in maintaining hypertension.

Renovascular hypertension: a perfusion disturbance that escaped recognition.

A bilateral, exercise-mediated, hippurate transport disturbance was previously described when patients with fixed renovascular hypertension were imaged with o-iodo-hippurate. This study sought to test the hypothesis that patients with an abnormal exercise scintigram have a perfusion abnormality characterized by dysregulation of renal blood flow. We imaged 23 patients with hypertension and angiographically documented renovascular disease in the supine position, as well as during upright exercise. Seven normotensive volunteers served as controls. We measured the resting glomerular filtration rate (GFR) and the effective renal plasma flow (ERPF) with a single compartment radiotracer infusion clearance. The clearance examination also included a measurement period with 25 watt ergometric exercise. Nine hypertensive patients had normal exercise renograms. These patients had age-appropriate clearance values at rest and during exercise, as well as age-appropriate best-organ (generally without stenosis) GFR and ERPF values. The filtration fraction (FF) was 0.21 at rest and 0.22 during exercise. Fourteen hypertensive patients had a bilateral, exercise-induced disturbance of hippurate transport. In these patients, the global resting GFRs and ERPFs were decreased 40% from age-appropriate predicted values. The FF remained at 0.20. Light exercise caused a pronounced contraction of GFR and a less severe reduction in the ERPF. During exercise the mean filtration fraction was only 0.12. The exercise-induced reduction in the clearance values was bilateral, which indicated that the perfusion of nonstenosed organs was compromised as well. We suggest that the described perfusion abnormality occupies a relevant position during the maintenance phase of fixed renovascular hypertension.

Exercise activates renal dysfunction in hypertension.

A bilateral, exercise-mediated renal functional abnormality was first described more than a decade ago. The disturbance is specific for hypertension, is seen in different forms of hypertension, and has been studied most extensively in hypertensives with renovascular disease. The bilateral-abnormal exercise renogram identifies the disturbance. Hypertensives with unilateral renovascular disease were studied in the continuing evaluation of the bilateral function disturbance. We examined 31 hypertensives with documented unilateral renovascular disease, all of whom had renography at rest and during 60 to 80 W ergometric exercise. An additional seven normotensives and 17 essential hypertensives served as controls, and had the same sequence of studies. All patients reported upon continued on to an infusion clearance with 131I-hippurate and 111In-diethylenetriamine pentaacetic acid to determine glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) at rest, and during 25 W ergometric exercise. Eighteen of 31 hypertensives with unilateral renovascular disease were found to have a bilateral-abnormal exercise renogram. Clearance examinations in these identified a prominent reduction of the GFR and a lesser decrease in the ERPF during exercise. Hypertensives with normal exercise renograms did not have the exercise mediated abnormal clearance pattern. Similar results were observed in the control population of essential hypertensives, 65% of whom developed the functional disturbance. The seven normotensives controls did not exhibit the exercise mediated function changes. We conclude that an exercise-mediated bilaterally occurring functional disturbance exists in certain hypertensives, who then have a bilateral-abnormal exercise renogram. Associated with this is a distinctly abnormal clearance during exercise which is characterized by a low filtration fraction.

Intramolecular electrophilic aromatic substitution in gas-phase-protonated difunctional compounds containing one or two arylmethyl groups.

A variety of dibenzyl esters and ethers undergo a rearrangement process upon isobutane chemical ionization and collision-induced dissociation of their MH(+) ions, whereby a new bond is formed between the two benzyl groups, giving rise to abundant [C(14)H(13)](+) (m/z 181) ions. This rearrangement has been explained as an intramolecular electrophilic substitution in the gas phase occurring in an ion-neutral complex formed by the cleavage of one of the benzyl-oxygen bonds. A similar highly efficient intramolecular electrophilic substitution takes place in di-alpha- and beta-naphthylmethyl adipates affording m/z 281 [C(22)H(17)](+) ions, but not in the sterically hindered di-9-anthracylmethyl adipate. An analogous efficient rearrangement occurs in benzyl alpha- and beta-naphthylmethylcyclohexane-1,4-dicarboxylates and in benzyl alpha- and beta-phenylethylcyclohexane-1,4-dimethanol ethers. The analogous rearrangement is much less efficient in benzylallyl, benzylpropargyl and benzyl-9-anthracylmethyl derivatives, even less in benzylisopropyl and benzylacetyl analogs, and it is absent in benzyltetrahydropyranyl derivatives. The distinctive behavior of the protonated difunctional benzyl derivatives is interpreted in terms of the energy requirements of the O-R bond heterolysis of the protonated functionalities, the ability of the neutral R' groups (non-dissociated from the oxygen atom) to play the role of the nucleophile in the intramolecular electrophilic substitution processes and the electrophilicity of the R(+) ions.

Fragmentation of isomeric N-quinolinylphthalimides on electron impact ionization.

The isomeric 2-, 3-, 5-, 6- and 8-quinolinylphthalimides give rise to different electron impact ionization mass spectra, which permit easy distinction. The specific fragmentation process are rationalized in terms of proximity effects and stabilization of cyclic ion structures. Collision-induced dissociation spectra were used to support the proposed ion structures of major fragment ions.

Structural assignment of isomeric 2-(2-quinolinyl)-1H-indene-1,3(2H)-dione mono- and disulfonic acids by liquid chromatography electrospray and atmospheric pressure chemical ionization tandem mass spectrometry.

Positionally isomeric 2-(2-quinolinyl)-1H-indene-1,3(2H)-dione mono- and disulfonic acids give rise to similar electrospray ionization (ESI) and atmosphere pressure chemical ionization (APCI) mass spectra, which show very abundant MH(+) ions and negligible fragmentation. The MH(+) ions of these isomeric acids exhibit notably different behavior under collision-induced dissociation (CID) conditions. The acids with a sulfonic group at position 8' in the quinoline moiety, adjacent to the N-atom, exhibit highly abundant [MH - H(2)SO(3)](+) ions (m/z 272 for the mono- and m/z 352 for the disulfonic acids), which are of lower abundance in the CID spectra of isomers with the SO(3)H group at other positions, remote from the nitrogen atom. The latter isomers undergo efficient eliminations of SO(3) and HSO(3). The isomeric diacids with one SO(3)H group at position 4 of the indene-1,3(2H)-dione moiety, adjacent to one of the carbonyl groups, undergo highly efficient elimination of H(2)O. Mechanistic pathways, involving interactions between adjacent groups, are proposed for the above regiospecific fragmentations. Pronounced different behavior has been also observed in negative ion tandem mass spectrometric measurements of the sulfonic acids. The distinctive behavior of the isomeric acids was strongly pronounced when the measurements were performed with an ion trap mass spectrometer (LCQ), and much less so with a triple-stage quadrupole instrument (TSQ).

Preparative separation of stereoisomeric 1-methyl-4-methoxymethylcyclohexanecarboxylic acids by pH-zone-refining counter-current chromatography.

The application of pH-zone-refining counter-current chromatography (CCC) to the preparative separation of stereoisomeric acids is described. The separation was accomplished on the basis of the difference in acidity of the two stereoisomers. pH-Zone-refining CCC of 400 mg of a crude synthetic mixture of stereoisomeric 1-methyl-4-methoxymethylcyclohexanecarboxylic acids yielded 49.5 and 40 mg of the pure Z- and E-stereoisomers respectively. The two-phase solvent system consisted of hexane-ethyl acetate-methanol-water (1:1:1:1). Trifluoro acetic and octanoic acids were used as retainer acids. The eluent base was aqueous ammonia. The eluted fraction were monitored by gas chromatography-mass spectrometry.

Shoulder arthroplasty in patients with a prior anterior shoulder dislocation. Results of a multicenter study.

BACKGROUND: Prior reports of shoulder arthroplasty performed for dislocation-induced arthropathy have included only patients who had had a prior stabilizing procedure. The purpose of this study was to report the results of shoulder arthroplasty in all patients with a prior anterior shoulder dislocation, including both those previously treated operatively and those previously treated nonoperatively. METHODS: Fifty-five shoulders undergoing arthroplasty for arthritis following a prior anterior shoulder dislocation were evaluated. Twenty-seven of the shoulders had undergone a prior anterior stabilization procedure. The measures used to evaluate the shoulders included the Constant score, adjusted Constant score, active mobility, subjective satisfaction, radiographic result, and complications. RESULTS: The shoulders were evaluated at a mean of 45.0 months. The Constant score improved from a mean of 30.8 points preoperatively to a mean of 65.8 points at the time of follow-up. The adjusted Constant score improved from a mean of 38.2% to a mean of 79.8%. Active forward flexion improved from a mean of 82.1 degrees to a mean of 138.9 degrees. Active external rotation improved from a mean of 4.0 degrees to a mean of 38.6 degrees. Fifty patients rated the result as good or excellent. Negative prognosticators included an older age at the time of the initial dislocation and a rotator cuff tear. No significant differences in demographic factors, pre-arthroplasty function, post-arthroplasty function, pre-arthroplasty radiographic findings, post-arthroplasty radiographic findings, complication rate, or reoperation rate were noted between the patients treated with a prior operation for the anterior instability and those treated nonoperatively. CONCLUSIONS: This investigation documented the good results obtainable with shoulder arthroplasty for the treatment of arthritis following anterior shoulder instability. In addition, our findings suggest that capsulorrhaphy-induced arthropathy may be indistinguishable from arthritis following nonoperatively treated anterior shoulder instability.

[Shoulder arthroplasty for non-operated anterior shoulder instability with secondary osteoarthritis]. / Prothèse d'épaule sur omarthrose secondaire à une instabilité antérieure non opérée: à propos d'une série de 28 cas.

PURPOSE OF THE STUDY: The purpose of this study was to analyze the natural history of osteoarthritis of the shoulder joint secondary to non-operated anterior instability, to evaluate the clinical and radiological outcome after arthroplasty for this indication, and to compare results with data reported in the literature. MATERIAL AND METHODS: Twenty-eight Aequalis shoulder arthroplasties were performed for osteoarthritis secondary to anterior shoulder instability in patients who had not undergone any prior stabilizing surgical procedure. This multicentric series was reviewed retrospectively at a mean follow-up of 44 months (range 24-87 month). Preoperative and last follow-up clinical status was compared using the Constant score. Standard operative technique was used and anatomic position of the implants was achieved in 27 patients. Total shoulder arthroplasty was performed in eighteen patients and simple humeral implantation in ten. Patients were divided into two sub-groups for analysis of outcome (age at first dislocation > or < 40 years). RESULTS: There were four complications including one early loosening that required revision arthroplasty. Outcome was excellent or good in 54% of the cases. Group 1 (age at first dislocation < 40 years) included 17 patients and exhibited male predominance (13/17), young age at first dislocation (mean 28.5 years), high number of dislocations (mean 13), and a long natural history of osteoarthritis (mean 28 years). In this sub-group, imaging disclosed constructive osteoarthritis reflecting a long history. There was one case with a full-thickness tear of the supraspinatus. Outcome was excellent or good in 64% of these 17 patients (14 underwent total shoulder arthroplasty). The sub-group of 11 patients whose first dislocation occurred after the age of 40 years exhibited female predominance (9/11), a small number of dislocations (mean 1.3), and a short natural history of osteoarthritis (mean 6 years). In this sub-group, imaging disclosed six cases of basically chondrolytic osteoarthritis reflecting a short evolution. There were seven cases of full-thickness tears of the supraspinatus. Outcome was excellent or good in 36% of these 11 patients (4 underwent total shoulder arthroplasty). DISCUSSION: The forty-year age cutoff allowed us to distinguish two populations. The first population of patients whose first dislocation had occurred before the age of 40 years was predominantly male, with a long history of constructive osteoarthritis without rotator cuff tears. Most of these patients were treated with total shoulder arthroplasty which gave results similar to those obtained with arthroplasty for primary centered osteoarthritis. The second sub-group of patients aged over 40 years at the time of the first dislocation were predominantly female with a short history of minimally constructive osteoarthritis and frequent rotator cuff tears. Humeral implants were used for most of these patients and gave less favorable results than in the former sub-group, probably due to the high rate of rotator cuff tears.