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Biomedical subjects

J Cayla

Publications and source records attributed to J Cayla.

At least 19 recordsLinked to original sources

In vivo visualization of central muscarinic receptors using [11C]quinuclidinyl benzilate and positron emission tomography in baboons.

The muscarinic antagonist, quinuclidinyl benzilate (QNB), labeled with carbon 11 was used as a radioligand to visualize in vivo by positron emission tomography (PET) the central muscarinic acetylcholine receptors (mAChR) in baboons (Papio papio). The binding characteristics of [11C]QNB showed its specific binding to central mAChR. [11C]QNB brain uptake was high in cerebral cortex and striatum, areas that are rich in mAChR, whereas it decreased rapidly in cerebellum, evidencing non-specific binding in this structure that is almost devoid of mAChR. These results are consistent with the known cerebral distribution of mAChR in primates. [11C]QNB specific cerebral binding was enhanced by pretreatment with methyl-QNB, a peripherally acting muscarinic antagonist. Specifically labeled binding sites alone were blocked by prior administration of dexetimide, a muscarinic antagonist. Specific radioactivity was driven out from mAChR-rich regions by atropine and dexetimide, drugs with high affinity for mAChR. This competition was stereospecific since only dexetimide, the pharmacologically active isomer of benzetimide, was able to compete with the radioligand on its binding sites. A relationship between the occupancy of [11C]QNB-labeled receptors by atropine or dexetimide and the concomitant induction of a pharmacological effect was also detected by simultaneous PET scanning and electroencephalographic recording. Since mAChR form an important part of choline receptors in the central nervous system, [11C]QNB appears to be a suitable radiotracer to monitor cerebral physiological or pathological phenomena linked to the cholinergic system in living subjects.

Animals

Cardiac beta-adrenergic receptor density measured in vivo using PET, CGP 12177, and a new graphical method.

The in vivo quantification of myocardial beta-adrenergic receptor has been obtained in five closed-chest dogs using positron emission tomography (PET). The ligand was racemic (+/-)[11C] CGP 12177, a very potent hydrophilic antagonist of the beta-adrenergic receptor. A kinetic method appeared unsuitable because of the presence of metabolites which made the input function difficult to measure and also inaccurate. Therefore, a graphical method, based on a particular protocol, was proposed. The animals were injected with a trace amount of (+/-)[11C]CGP 12177, which was followed 40 min later by a second injection of radioligand with a low-specific activity. An additional injection of an excess of unlabeled CGP 12177 was administered after 90 min and allowed for the estimation of the dissociation rate constant. The main advantage of this graphical approach is that the results are obtained without having to measure the input function and therefore without estimating the metabolites. The average value of Bmax was 31 +/- 4 pmole/ml of tissue and the dissociation constant was 0.014 +/- 0.002 min-1.

Adrenergic beta-Antagonists

Noninvasive quantification of muscarinic receptors in vivo with positron emission tomography in the dog heart.

The in vivo quantification of myocardial muscarinic receptors has been obtained in six closed-chest dogs by using positron emission tomography. The dogs were injected with a trace amount of 11C-labeled methylquinuclidinyl benzilate (MQNB), a nonmetabolized antagonist of the muscarinic receptor. This was followed 30 minutes later by an injection of an excess of unlabeled MQNB (displacement experiment). Two additional injections of unlabeled MQNB with [11C]MQNB (coinjection experiment) and without [11C]MQNB (second displacement experiment) were administered after 70 and 120 minutes, respectively. This protocol allowed a separate evaluation of the quantity of available receptors (B'max) as well as the association and dissociation rate constants (k+1 and k-1) in each dog. The parameters were calculated by using a nonlinear mathematical model in regions of interest over the left ventricle and the interventricular septum. The average value of B'max was 42 +/- 11 pmol/ml tissue, the rate constants k+1, k-1, and Kd were 0.6 +/- 0.1 ml.pmol-1.min-1, 0.27 +/- 0.03 ml.pmol-1.min-1, and 0.49 +/- 0.14 pmol.ml-1, respectively, taking into account the MQNB reaction volume estimated to 0.15 ml/ml tissue. Although [11C]MQNB binding would appear irreversible, our findings indicate that the association of the antagonist is very rapid and that the dissociation is far from negligible. The dissociated ligand, however, has a high probability of rebinding to a free receptor site instead of escaping into the microcirculation. We deduce that the positron emission tomographic images obtained after injecting a trace amount of [11C]MQNB are more representative of blood flow than of receptor density or affinity. We also suggest a simplified protocol consisting of a tracer injection of [11C]MQNB and a second injection of an excess of cold MQNB, which is sufficient to measure B'max and Kd in humans.

Animals

Erosive arthritis of the costovertebral joint in seronegative spondyloarthropathy.

A 50-year-old male presented with polyarthritis and pain of the right costovertebral angle in the cervicothoracic area. Radiological findings in a sacroiliac joint, the presence of a syndesmophyte, the HLA B-27 phenotype and negative serological studies prompted the diagnosis of HLA-B27 related seronegative spondyloarthropathy. Conventional and computerized tomograms disclosed an erosive arthritis of the 1st right costovertebral joint that was responsible for the pain in the costovertebral angle. We are unaware of previous CT scan documentation of such lesions.

Arthritis

[Bone scintigraphy in metastases].

The three fold interest of bone scintiscanning is discussed in relation to 182 cases of bone metastases of various origins. Firstly, this technic facilitates early diagnosis of invasion of the bone by the detection of metastatic lesions which, in 7.7% of cases are still infraradiologic, or even of reflex algodystrophy of the legs, which can be detected only from a scintiscan, long before X-ray plates can show the lumbar metastasis which is responsible. Secondly, the method is able to pick up more metastatic sites in 54.4% of cases than can be detected by X-ray; this is confirmed by investigation of the S/R ratio (ratio of the number of strongly binding sites to the number of sites showing radiologic damage) which is greater than unity for a considerable period. Thirdly, repeated scintiscanography provides a prognosis, because the survival time appears to be fairly closely correlated with the regression, stability or extension of strongly binding sites, although a "flare phenomenon" may give the erroneous impression that the metastatic process has deteriorated. Repeated scintiscanography also provides a good way of evaluating the efficacy of medical treatment, particularly in the case of bone metastases of mammary or prostatic origin. Sometimes, the decision for or against prophylactic or palliative orthopedic surgery may be based to a considerable extent on data provided by scintiscan.

Bone Neoplasms

[Unusual muscular involvement in ankylosing spondylitis].

Muscle involvement in ankylosing spondylitis has been little studied. The authors report two cases with marked muscular atrophy and functional impotence, which had directed the diagnosis towards a myopathy over a period of several years in the first case, and a suspected primary muscular disease associated with ankylosing spondylitis in the second. Muscle biopsies eliminated the diagnosis of myopathy in both cases, with rapid functional recovery with proper treatment. Following a review of the literature, two hypotheses can be considered to explain the muscular involvement in ankylosing spondylitis: one mechanism which appears well-established is a radiculitis with involvement of the paravertebral muscles: other authors suggest that there is nonspecific, generalized muscular involvement in this disorder.

Adult

[Role of chemotherapy in the treatment of bone metastases of breast cancer].

This study was made on 98 patients with breast cancer, whose first discovered metastasis was to the bone, a mean of 2.8 years following the initial diagnosis. It is most often a lytic lesion, and the majority of patients have more than two areas on bone scintiscan. About half of the patients received palliative radiotherapy; 16 had to undergo surgery for or to prevent pathologic fractures. All patients underwent chemotherapy with vincristine or vinblastine, methotrexate or cyclophosphamide, 5-fluorouracil and, in 37 cases, the addition of adriamycin. Half of the patients also received tamoxifen. Present studies show a mean survival of 31 months with 24% survival at five years. Age, the interval to the discovery of the first metastasis, the use of additional chemotherapy following surgery for the breast lesion, the sedimentation rate, and the number of bony metastases do not play any prognostic role. However, the prognosis is significantly improved by adding tamoxifen, and even more so by adding adriamycin to the chemotherapeutic protocol since mean survival improves from 26 to 52 months. The reduced incidence of bony metastases with chemotherapy following surgery had led some authors to believe that prevention is the best method of treating bony metastases from breast cancer.

Adult

[Studies of the kinetics of bone concentration of mdp-tc 99m in Paget's disease and various treatment methods].

We did 27 bone scintiscans in 20 patients, 15 of whom had Paget's disease. Early variations of isotopic activity were analyzed in the pagetic bone, and in normal bone and muscle tissue using 3 parameters: A1 or the period of maximum activity obtained when the isotope was first injected into the circulation, A2 or the isotopic activity at 30 minutes, and P or slope of the curve in the change of activity between 15 and 30 minutes. These scintigraphic parameters, which seem to reflect the importance of the vascular phase (parameter A1) and of the metabolic activity of the bone (parameter A2/A1 and P) proved to be a good guide in following the course of Paget's disease. In 6 patients with Paget's disease who were treated with calcitonin (5 cases) or by etidronate disodium (1 case), we compared the changes in these isotopic parameters with the clinical and laboratory findings before and after treatment. We were able to note a good correlation between the clinical course of the illness and the scintiscans in most cases.

Adult

[Clinical study of Bi-Profenid in rheumatologic practice].

The effectiveness and tolerance of Bi-Profenid as 150 mg tablets were analyzed in a multicenter study. Each of the 288 patients entered in the study had one of the main conditions found in rheumatologic practice: arthrosis of the hip or knee, rheumatoid arthritis or ankylosing spondylarthritis. Each patient was given one 150 mg Bi-Profenid tablet twice daily for 30 days. Overall effectiveness, as assessed by the pain scale test, produced improvement in 87.3% of cases. In degenerative rheumatic diseases, nocturnal pain, pain upon mobilization and walking distance were very significantly improved. In inflammatory rheumatic diseases, the significantly improved parameters were nocturnal pain, morning stiffness and functional indexes of rheumatoid arthritis. Tolerance was outstanding or very good in 77.1% of cases and the dropout rate was only 7.6%.

Adult

[5 cases of chondrosarcoma. Review of the literature].

Five cases of chondrosarcoma are reported. Some specific characteristics of this tumor are recalled : prevalence is approximately 10% of primary malignant bone lesions, onset usually occurs between 40 and 70 years of age, prevalence is higher in males, elective sites are the proximal long bones and pelvis, pain is often the initial symptomatology, the patient's general condition remains satisfactory over a long period of time, sedimentation rates have no diagnostic or prognostic value, medullary arteriography and computed tomography are helpful for evaluation the topography and the extension of a vertebral localization, and the course is protracted. Prognosis is dependent on both the surgical possibilities and the characteristics of the tumor (site, size, histologic grade). Conversely to metastases which occur electively in grade III tumors, recurrences are not necessarily correlated with the histologic grade; they often occur in tumors whose localization precluded radical surgery and may be the occasion of development into a higher grade of malignancy. Inasmuch as it is feasible, carcinologic surgery is the only effective therapy; it carries hope for 10 year survival times in approximatley 70% of patients.

Adult

[Hemarthrosis of articular chondrocalcinosis. Apropos of 28 cases. Importance of treatment by isotopic synoviorthesis].

32 cases of hemarthrosis observed in 26 patients suffering from articular chondrocalcinosis are used as a basis for a review of the principal clinical anc paraclinical findings. Special mention is made of the fact that hemarthrosis occurs in the shoulder much less rarely than has been classically reported. The diagnostic value of finding microcristals of calcium pyrophosphate in hemorrhagic fluid is also emphasized. In addition to standard treatment, isotopic synoviortheses is shown to be effective for treatment of recurrent hemarthrosis. After an average of 3.3 years of follow-up, this treatment, although lacking certain analgesic effect, frequently leads to lasting cessation of the hemarthrosis, more often it seems, in the shoulder than in the knee.

Aged