ADP plays a key role in thrombogenesis in rats

The relative importance of ADP, arachidonic acid metabolites and serotonin as thrombogenic factors was evaluated in rats by comparing, after oral administration, the effects of two inhibitors of ADP-induced platelet aggregation (ticlopidine and PCR 4099), three cyclo-oxygenase inhibitors (aspirin, triflusal and indobufen) and a selective serotonin 5HT2 receptor antagonist (ketanserin) on platelet aggregation, in four platelet-dependent thrombosis models and on bleeding time. Platelet aggregation induced by ADP and collagen was completely inhibited by ticlopidine and PCR 4099 whereas only the collagen aggregation was reduced by the cyclo-oxygenase inhibitors. Ketanserin or a depletion of platelet serotonin by reserpine did not affect platelet aggregation. Ticlopidine and PCR 4099 greatly prolonged rat tail transection bleeding time. This is probably related to their known ability to inhibit ADP-mediated platelet aggregation. In contrast, the cyclooxygenase inhibitors did not affect bleeding time at all. Reserpine and ketanserin prolonged bleeding time by interfering with the action of serotonin on the vascular wall. Ticlopidine and PCR 4099 were very potent antithrombotics in all the models. Aspirin, only at a high dose, inhibited poorly thrombus formation on a silk thread in an arterio-venous shunt, suggesting that the inhibition of cyclo-oxygenase was not responsible. Triflusal was inactive in all models while indobufen slightly reduced thrombus formation in the silk thread and metallic coil models. Ketanserin and reserpine reduced thrombus only in the metallic coil model. Thrombus formation was greatly reduced in fawn-hooded rats, which lack ADP in their platelet dense granules because of a genetic storage pool deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)     

Biodistribution study of 99mTc-labeled LDL in B16-melanoma-bearing mice. Visualization of a preferential uptake by the tumor

Since there is strong evidence of a preferential LDL accumulation in tumor cells, LDL might be of interest for tumor imaging. We have tested the ability of ^99mTc-LDL in tumor imaging with B16-melanoma-bearing mice as a model for further applications in human studies. The LDL fixation rate was higher with 99^mTc-labeled LDL than with ¹²⁵I labeled LDL. Since technetium-99m remains trapped in the cells, ^99mTc-LDL is a well-adapted radioligand because of information given by this radiotracer on the receptor metabolism. We observed that, at early growth stages, the tumor took up the LDL at a maximal rate, suggesting differences in cholesterol metabolism as a function of tumor growth. Accumulation of label in the tumor area was perfectly observable in tumor-bearing mice on scintigraphic images. Computerized quantification of the regions of interest (as well as biodistribution studies including killing of the animals) showed a 1.81 -fold increase in uptake by the tumor as compared to the liver and a 28-fold increase as compared with corresponding normal tissue (muscle of the left leg) at day 8 of tumor growth. These data give strong support to the value of this non-invasive method in visualizing and quantifying the tissue LDL uptake in vivo, including the precise information provided by nuclear scintigraphy on the distribution of the radiolabeled LDL in the different tissues. ^99mTc-LDL could be an efficient tool for further diagnostic or therapeutic exploration in cancer patients.     

A blinded,controlled evaluation of anxiety and depressive symptoms in patients with fibromyalgia,as measured by standardized psychometric interview scales

The objective of the study was to evaluate the presence of psychopathology in fibromyalgia patients compared with a control group of other rheumatologic patients with pain. Forty-nine fibromyalgia patients and 33 control patients were interviewed blinded, using standardized psychometric scales. Pain was scored on a visual analogue scale. Fibromyalgia patients scored significantly higher than the controls on the Bech-Rafaelsen Melancholia Scale, the Atypical Depression Scale and the Hamilton Anxiety Rating Scale. On the Newcastle Depression Scale there was no difference. In both groups a correlation was found between pain score and psychometric scoring. The fibromyalgia patients scored significantly higher on pain than the controls. After correcting for this difference, the fibromyalgia patients still scored higher on anxiety and depression.     

Examination of the dermal lymphatics in psoriasis⋆

In recent years, research on the aetiology of psoriasis has focused on immune aetiopathogenesis. However, in the last few years, research on the immunoloogical changes in psoriasis has failed to mention the lymphatics. Also, studies emphasizing the importance of the dermal lymphatics have neglected the lymphatic changes seen in psoriasis. Therefore, we decided to put this matter back on the agenda. Skin biopsies from 20 patients with psoriasis vulgaris were examined lymphatically by light microscopy using the orcein stain. We found a considerable increase in both number and dilatation in the lymphatics of psoriatic plaques, compared with both the clinically uninvolved skin of the psoriatic patients and also the skin of the control group.     

Dynamic muscular endurance in primary fibromyalgia compared with chronic myofascial pain syndrome.

The objective of the study was to quantify the voluntary dynamic muscular endurance (DME) in patients with primary fibromyalgia (PF) since easy fatigability of muscles is one of the major symptoms in this syndrome. Consecutive outpatients referred to a rheumatology clinic specializing in PF were investigated. Thirty-six patients with PF were compared with 18 patients with chronic myofascial pain (CMP) syndrome. Subjects were matched according to gender, age, height, weight, peak torque, and contractional work. The DME was defined as the number of repeated knee extensions necessary for the contractional work in two successive knee extensions to be equal to or below 70% of the initial value measured with an isokinetic dynamometer. A significantly lower DME was found in the PF group than in the CMP group: 11 (7-13) and 18 (11-25), respectively (median and quartiles), p less than .005. Patients with PF have a low voluntary muscular endurance compared to CMP patients.     

Pelvic floor muscle training with biofeedback and bladder training in elderly women: a feasibility study.

OBJECTIVE: It is generally assumed that interventions used to treat urinary incontinence (UI) in young women could simply be applied to older competent and motivated women, but these assumptions have not been formally tested. The purpose of this study was to determine the feasibility of using physical therapies to treat UI in older women. DESIGN: Twelve-week time series. SETTINGS AND SUBJECTS: We recruited women older than 75 years with UI from an outpatient urology clinic and a waiting list for incontinence surgery. METHODS: After a baseline evaluation, the women collected data on their incontinence symptoms and bladder habits for 3 weeks using the 72-hour voiding diary and the 24-hour pad test. They then received 6 physical therapy treatments consisting of a combination of bladder training and pelvic floor muscle training assisted with biofeedback for 6 weeks. This was followed by another 3-week period of data collection and a final evaluation. RESULTS: Ten women participated in the study; 7 completed it. They were all comfortable with the treatment. They complied with the study demands in terms of attendance at treatment session (100%), data collection (96%), and completion of exercises at home (82%). The authors observed a decrease in the number of incontinent and urgency episodes. CONCLUSION: This preliminary study demonstrates that some women older than 75 years are good candidates to undertake physical therapies for UI and follow study demands. Random controlled studies that include this population will provide evidence regarding the effectiveness of these therapies.     

Individual chaperones required for Yop secretion by Yersinia.

Pathogenic yersiniae secrete anti-host proteins called Yops, by a recently discovered Sec-independent pathway. The Yops do not have a classical signal peptide at their N terminus and they are not processed during membrane translocation. The secretion domain is nevertheless contained in their N-terminal part but these domains do not resemble each other in the different Yops. We have previously shown that YopE secretion requires SycE, a 15-kDa acidic protein acting as a specific cytosolic chaperone. Here we show that the gene downstream from yopH encodes a 16-kDa acidic protein that binds to hybrid proteins made of the N-terminal part of YopH and either the bacterial alkaline phosphatase or the cholera toxin B subunit. Loss of this protein by mutagenesis led to accumulation of YopH in the cytoplasm and to a severe and selective reduction of YopH secretion. This protein thus behaves like the counterpart of SycE and we called it SycH. We also engineered a mutation in lcrH, the gene upstream from yopB and yopD, known to encode a 19-kDa acidic protein. Although this mutation was nonpolar, the mutant no longer secreted YopB and YopD. The product of lcrH could be immunoprecipitated together with cytoplasmic YopD. lcrH therefore seems to encode a YopD-specific chaperone, which we called SycD. Determination of the dependence of YopB on SycD requires further investigation. SycE, SycH, and SycD appear to be members of a new family of cytosolic chaperones required for Yop secretion.     

Perineal ectopic testis

The case of a 24-year-old patient is presented who was erroneously presumed to have unilateral testicular aplasia following inguinal exploration in early childhood. At the age of 24 years he underwent surgery for a soft perineal mass, which was found to be perineal testicular ectopia associated with a congenital hernia. Histological examination of the excised testicle revealed atrophy of the germinal epithelium. A survey of the literature yielded approximately 175 more cases of perineal testicular ectopia. This is the most frequent from of testicular ectopia with a relative incidence of less than 1% of all cases of undescended testes. Ectopic testes seem only to differ from undescended testes in terms of topography. Little difference can be observed in terms of histology or the incidence of concomitant hernias.     

Characteristics of apathy in Parkinson's disease.

The objective of this study was to use the Lille Apathy Rating Scale to assess apathy in a large population of Parkinson's disease (PD) patients and identify several different apathy profiles. One hundred fifty-nine patients with probable PD and 58 healthy controls participated in the study. Apathy was assessed using the Lille Apathy Rating Scale. Motor, cognitive, and depressive symptoms were rated on standardized scales. Data were analyzed using linear regression and multivariate analyses of variance. Thirty-two percent of the PD patients were classified as apathetic. Apathy was more frequent in patients with dementia. The four apathy dimensions contributed differently to the overall severity of the apathetic condition. Action initiation and intellectual curiosity had a marked influence. Linear regression analysis revealed that the apathy level was mainly determined by cognitive impairment, not associated with the severity of motor symptoms, and only associated with the apathy subcomponent of the Montgomery and Asberg Depression Rating Scale. Apathy is highly prevalent in PD patients. Apathy profiles vary according to the clinical presentation of PD. The high prevalence of apathy in PD suggests the involvement of frontal-subcortical circuits. Although the neurochemical substrate of apathy remains poorly characterized, the strong link between apathy and cognitive impairment observed in several studies suggests the participation of nondopaminergic circuits.