[Residual symptoms after a treated major depressive disorder: in practice ambulatory observatory carried out of city]. / Symptômes résiduels après traitement antidépresseur d'un épisode dépressif majeur: observatoire réalisé en pratique ambulatoire de ville.

INTRODUCTION: The main therapeutic objective for depression is remission (absence of clinical signs of the disorder and low scores on assessment scales), yet partial remission rates remain high (insufficient criteria for diagnosing the disorder while clinically and psychometrically assessable symptoms continue to linger. The presence of residual symptoms is associated with a higher relapse rate of depression, occurring up to 5 times earlier, an increased suicide rate, significant use of healthcare services and a marked social impairment. The most frequently reported symptoms are specific to depression, i.e. anxiety and irritability, depressed mood, feelings of guilt and loss of interest in activities, asthenia and difficulty falling asleep at night. Residual symptoms constitute a valid and reliable clinical marker of prognosis (especially for relapse and chronicity) and must be treated with specific therapeutic strategies. Studies on depression with residual symptoms are few and mainly focus on populations of hospitalized patients or those with a severe form of depression. Since little work has been done with regard to patients monitored on an outpatient basis, we felt it was appropriate to select a population of depressed patients from private psychiatric practice. Our main objective was to analyze the frequency of residual symptoms after 8 to 12 weeks of antidepressant treatment and to study the clinical and socio-demographic characteristics of these subjects. DESIGN: 1 790 patients who had presented with one major depressive episode per DSM IV criteria and who had been receiving antidepressant treatment for 8 to 12 weeks were included and evaluated. 463 private psychiatrists practicing in metropolitan France were randomly selected and stratified by region and sex ratio (30% female and 70% male) to obtain a sample as representative as possible of the French psychiatrist population. The following were measured and assessed: anthropometric and socio-demographic characteristics, the history of depression, a description of the last major depressive episode, a description of its management, current clinical variables, the Hamilton Depression Rating Scale (HDRS) score, the physician's assessment of residual symptoms, and a description of the patient's management on the day of the appointment. RESULTS: Following acute treatment, evaluation of depressive symptoms on the Hamilton scale showed that 549 (32%) of subjects had a score below 8; 792 patients (46.7%) had a score between 8 and 18; and 354 (20%) had a score above 18. Patients in the first group (HDRS<8) who were considered to be in remission started treatment early (chi2=18.28, DOF=4, p<0.01) for a first episode (51.3%) with a low number of initial symptoms (chi2=27.03, DOF=6, p<0.01). The evaluators found persistent depressogenic factors (chi2=15.9, DOF=2, p<0.01) and significant psychiatric co-morbidity (chi2=18.28, DOF=4, p<0.01) in subjects in partial remission (HDRS between 8 and 18). The non-responders (HDRS>18) presented a history of more depressive episodes (chi2=17.04, DOF=4, p<0.01) and a delay of more than 30 days before treatment was initiated (chi2=18.2, DOF=4, p<0.01). With regard to the nature of residual symptoms, at least 50% of subjects in partial remission were very symptomatic for depressive mood (65.4%), psychic anxiety (56.6%), and loss of interest and time away from work (49.4%). Indicators of severe depression (early morning insomnia, psychomotor retardation, agitation, hypochondriasis, weight loss and lack of awareness of the disorder) were reported less frequently, and usually not at all. Conclusion - These results illustrate three important points. First, a significant percentage (46.7%) of patients who responded to treatment subsequent to the acute period presented with residual symptoms. Second, these symptoms are included in the areas of depressed mood - psychic anxiety . Third, a delay in initiating treatment seems to have an effect on response. These results confirm the need to develop strategies to screen for these residual forms for these residual forms of depression, as well as specific methods to treat them.

[Residual symptoms after a treated major depressive disorder: a survey among private psychiatrists]. / Symptômes résiduels après traitement antidépresseur d'un épisode dépressif majeur: enquête d'opinion réalisée auprès de psychiatres à activité libérale.

UNLABELLED: Recent studies suggest that depression with residual symptoms is a frequent progressive form of this disease. It is associated with a poor prognosis that translates into an earlier and higher relapse rate, and has a significant medical and social impact. Several literature reviews emphasize that residual symptoms are under-evaluated and that their treatment should follow an incisive strategy with the goal of complete eradication of symptoms. Specific patterns have not been detected either, and the evaluation of residual symptoms remains subject to numerous biases due to the lack of a validated definition. The purpose of this study was to analyze the opinions and attitudes of psychiatrists about residual symptoms following major depressive episodes treated with antidepressants as part of their daily private practice. DESIGN: 867 psychiatrists were selected from across France to form a representative sample of the medical specialization. They were questioned with a closed-choice questionnaire on the scope of the residual depressive symptoms concept (definition, professional consensus), determining factors in their onset (factors associated with the patient, with the initial episode, with management) and their practical and therapeutic attitude towards these symptoms. RESULTS: The estimated prevalence of residual symptoms in their depressed patients was 25%. Fifty-seven percent of the physicians queried felt the concept was appropriate, but 70.3% thought that it did not have a strong professional consensus. The definitions deemed most appropriate were those involving the persistence of clinical signs (asthenia or minor cognitive impairment), whereas the use of psychometric criteria was mentioned less often. There is a clear absence of consensus concerning the diagnostic delay of residual symptoms, as 30% diagnosed them after 6 months. Responses about factors that may be predictive or affect the onset of residual symptoms (associated with the patient, the nature of the initial episode and the management) did not reflect a unified position, nor did they necessarily correspond to the data in the literature. However, while the therapeutic attitude seemed adequate (verifying treatment compliance, clinical re-evaluation, therapeutic re-adjustment), 64% of the physicians considered residual symptoms to be a therapeutic challenge. CONCLUSION: Through the wide disparity of responses, this observational study demonstrates the absence of consensus with regard to the concept of residual symptoms. While it does appear that practitioners often adopt an approach that is pragmatic yet still close to that recommended by the ANAES [Agence National d'Accréditation et d'Evaluation en Santé, French National Health Accreditation and Evaluation Agency], such an approach does not seem to be optimized for the specific treatment of these symptoms. This clinical concept remains little studied, and lacking a specific definition, appears to be under-evaluated and under-treated by conventional treatment strategies. Further research on residual symptoms is necessary in order to establish true and valid definitions that will.

[Anaphylactic shock after traumatic rupture of a splenic echinococcal cyst].

Anaphylactic shock as a result of trauma is very rare. We describe a 20-year-old Druze soldier who presented with anaphylactic shock due to rupture of a splenic echinococcal cyst induced by blunt trauma to the left chest wall and upper abdomen. The main clinical manifestations, which developed within minutes of the trauma, were high fever, pruritus, edema of the lips and eyelids, dyspnea, stridor and rhinorrhea. Eosinophilia was not present on admission but appeared 4 days later. Surgery revealed an intact echinococcal cyst in the left lobe of the liver and another in the spleen. The splenic cyst was torn, filled with blood and its contents had spread throughout the splenic tissue, but without peritoneal spillage. Recovery was complete after splenectomy and resection of the hepatic hydatid cyst.

Structural changes in fibrin clot associated with the proteolytic activity induced by tissue type plasminogen activator. An NMR study.

The kinetic behavior of fibrin clot lysis as induced by tissue-type plasminogen activator (t-PA) was studied using proton magnetic resonance (PMR) and a release assay of fibrin labeled with technetium-99m isotope (99mTc). The lysis pattern of the preformed clot was examined as a function of gradual changes in the amounts of added t-PA and deactivated t-PA. The behavior of fibrinolysis was found to depend strongly on the amount of t-PA in the assay, which markedly affects the lysis rate of fibrin. The changes induced by the lysis were reflected in pronounced prolongation of the transverse relaxation time. The PMR and the radioisotope release measurements point to the possibility that at least two steps are involved in the mechanism of lysis. The PMR seems to be associated with structural features of the clot and reflects the liberation of compartmentalized water from the clot, while the 99mTc analysis reflects the further fragmentation of fibrin.

Clot uptake of labeled active and inhibited tissue plasminogen activator.

The clot uptake of labeled active and inhibited t-PA was compared. The most efficient inhibition was obtained with diisopropyl fluorophosphate (DFP) after 4 h incubation at room temperature. Enzyme activity was followed by fibrin-plate assay, radioactivity-release technique and proton magnetic resonance (PMR). The novel PMR method developed by us is sensitive to the effect of as low as nanogram amounts of t-PA on the interaction between the fibrin and the compartmentalized water trapped in the clot. Binding of labeled enzyme to fibrin-coated plates showed that the deactivation by DFP did not impair the affinity of t-PA for fibrin. A rapid binding of 125I-labeled t-PA to the clot occurred, which reached a maximum in 30 min and declined with time. This pattern was explained by consecutive clot binding and lysis. The binding of DFP-t-PA to the clot differed markedly from that of the active protein; 2 h post-incubation the uptake of DFP-t-PA was more than double that of the untreated t-PA. Parallel measurements in clots prepared from human blood showed a qualitatively similar trend. The biodistribution of radiolabeled t-PA in mice was similar for the active and inhibited forms. Blood activity reached 10% of the injected dose within 10 min. DFP-t-PA may prove to be a useful reagent for in-vivo localization of thrombi.

Labeling of sarcoma associated monoclonal antibody with 111In, 67Ga and 125I.

Labeling of human sarcoma-associated murine monoclonal antibody (MAb) 23H7 with 67Ga and 111In by the bifunctional ligand method is reported. 67Ga was chelated to the MAb via desferrioxamine B and 111In via the cyclic anhydride of DTPA. Higher specific activity was obtained with 67Ga (4-5 microCi/micrograms) as compared with 111In (2 microCi/micrograms). The binding capacity of the MAb was confirmed by repeated indirect immuno-fluorescence assays performed before and after labeling. A fast blood clearance was observed: 33% recovered dose (R.D.) blood level 3 h post-injection as compared with 56% after injection of control polyclonal IgG. Preliminary results on chemically induced sarcoma bearing mice showed a relatively high tumor uptake of the labeled antibody.

Human sarcoma-associated murine monoclonal antibody labeled with indium-111, gallium-67, and iodine-125.

Monoclonal antibody (MAb) 23H7 is a hybridoma-derived IgG that is generated following fusion of mouse myeloma cell line P3U1 and spleen cells from BALB/c mice hyperimmunized with a human fibrosarcoma. It detects a mesenchymal antigen of 23KD expressed on human sarcoma tissues and other neoplasms, including myeloid leukemias, but it rarely binds to normal tissues. The MAb 23H7 was labeled with 67Ga and 111In using the bifunctional ligand method. The 67Ga was chelated to the MAb via desferrioxamine B, while 111In was chelated via the cyclic anhydride of diethylenetriamine pentaacetic acid. Higher specific activity was obtained with 67Ga than with 111In (4.5 and 2 muCi/microgram, respectively); both gave stable complexes. When 23H7 was labeled with 125I, considerable breakdown was observed. This, together with the physical shortcomings of this isotope, emphasizes the advantages of labeling with 111In and 67Ga. The rapid blood clearance of the labeled sarcoma-associated MAb may be beneficial for early tumor uptake and for imaging shortly after injection.

Factors affecting the labeling of human fibrinogen with 99mTc in vitro.

The preparation of [99mTc]fibrinogen is described. The following factors which could affect the quality of this preparation were studied: pH, SnCl2 and protein concentrations, pre- and post-labeling incubation times and labeling temperature. A 90% labeling yield was achieved by incubating fibrinogen with SnCl2 at pH 9.8 for 22 h before adding the TcO-4 solution. The product obtained was stable and was 85% clottable. The x-ray fluorescence technique was employed to measure the amount of bound tin at different times.

Modified human fibrinogen labeled with 111In.

A method for the labeling of human fibrinogen with 111In is reported. The cyclic anhydride of DTPA, either dissolved in dimethyl sulfoxide or as the solid, is first covalently attached to the protein. The modified fibrinogen is then labeled with [111In]acetate, with an average yield of 90 +/- 3%. The product obtained is highly clottable and stable in vitro and has potential applications in imaging studies.