RNA-binding proteins RBM20 and PTBP1 regulate the alternative splicing of FHOD3.

Regulation of alternative splicing events is an essential step required for the expression of functional cytoskeleton and sarcomere proteins in cardiomyocytes. About 3% of idiopathic dilated cardiomyopathy cases present mutations in the RNA binding protein RBM20, a tissue specific regulator of alternative splicing. Transcripts expressed preferentially in skeletal and cardiac muscle, including TTN, CAMK2D, LDB3, LMO7, PDLIM3, RTN4, and RYR2, are RBM20-dependent splice variants. In the present study, we investigated the RBM20 involvement in post-transcriptional regulation of splicing variants expressed by Formin homology 2 domain containing 3 (FHOD3) gene. FHOD3 is a sarcomeric protein highly expressed in the cardiac tissue and required for the assembly of the contractile apparatus. Recently, FHOD3 mutations have been found associated with heart diseases. We identified novel FHOD3 splicing variants differentially expressed in human tissues and provided evidences that FHOD3 transcripts are specific RBM20 and PTBP1 targets. Furthermore, we demonstrated that the expression of RBM20 and PTBP1 promoted the alternative shift, from inclusion to exclusion, of selected FHOD3 exons. These results indicate that RBM20 and PTBP1 play a role in the actin filament functional organization mediated by FHOD3 isoforms and suggest their possible involvement in heart diseases.

Coordinate phosphorylation of multiple residues on single AKT1 and AKT2 molecules.

Aberrant AKT activation is prevalent across multiple human cancer lineages providing an important new target for therapy. Twenty-two independent phosphorylation sites have been identified on specific AKT isoforms likely contributing to differential isoform regulation. However, the mechanisms regulating phosphorylation of individual AKT isoform molecules have not been elucidated because of the lack of robust approaches able to assess phosphorylation of multiple sites on a single AKT molecule. Using a nanofluidic proteomic immunoassay (NIA), consisting of isoelectric focusing followed by sensitive chemiluminescence detection, we demonstrate that under basal and ligand-induced conditions that the pattern of phosphorylation events is markedly different between AKT1 and AKT2. Indeed, there are at least 12 AKT1 peaks and at least 5 AKT2 peaks consistent with complex combinations of phosphorylation of different sites on individual AKT molecules. Following insulin stimulation, AKT1 was phosphorylated at Thr308 in the T-loop and Ser473 in the hydrophobic domain. In contrast, AKT2 was only phosphorylated at the equivalent sites (Thr309 and Ser474) at low levels. Further, Thr308 and Ser473 phosphorylation occurred predominantly on the same AKT1 molecules, whereas Thr309 and Ser474 were phosphorylated primarily on different AKT2 molecules. Although basal AKT2 phosphorylation was sensitive to inhibition of phosphatidylinositol 3-kinase (PI3K), basal AKT1 phosphorylation was essentially resistant. PI3K inhibition decreased pThr451 on AKT2 but not pThr450 on AKT1. Thus, NIA technology provides an ability to characterize coordinate phosphorylation of individual AKT molecules providing important information about AKT isoform-specific phosphorylation, which is required for optimal development and implementation of drugs targeting aberrant AKT activation.

Melatonin decreases the oxidative stress produced by 2,4-dichlorophenoxyacetic acid in rat cerebellar granule cells.

2,4-Dichlorophenoxyacetic acid (2,4-D) is one of the most widely used herbicides due to its relatively moderate toxicity and to its biodegradability in the soil. In toxic concentrations, 2,4-D displays strong neurotoxicity, partly due to generation of free radicals. Since melatonin has remarkable antioxidant properties, the objective of this study was to assess to what extent it was effective in preventing the 2,4-D effect on redox balance of rat cerebellar granule cells (CGC) in vitro. Cellular viability, generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), reduced glutathione (GSH) levels, and the activities of the antioxidant enzymes Cu/Zn-superoxide dismutase (Cu/Zn-SOD), Mn-SOD, selenium-glutathione peroxidase (Se-GPx) and catalase (CAT) were measured in CGC exposed to 2,4-D and/or melatonin for 48 h. In CGC cultures exposed to 2,4-D, cell viability, GSH levels and CAT activity decreased significantly whereas ROS generation and Se-GPx activities were augmented. Except for Se-GPx activity, all these changes were counteracted by the concomitant addition of 0.1 or 0.5 mM melatonin. In addition, incubation of CGC with melatonin alone resulted in augmentation of cell viability, GSH levels and Se-GPx activity. RNS generation and SOD activity remained unaffected by either treatment. Since melatonin was able to counteract most of redox changes produced by 2,4-D in CGC in culture, the experimental evidence reported further support the efficacy of melatonin to act as a neuroprotector.

Role of patient posture during puncture on successful unilateral spinal anaesthesia in outpatient lower abdominal surgery.

BACKGROUND AND OBJECTIVE: Unilateral spinal anaesthesia is a useful anaesthesia technique in lower abdominal surgery, especially in an outpatient setting. Patient posture is pivotal in the achievement of unilateral anaesthesia. Nevertheless, no studies have elucidated the influence of patient posture during the anaesthetic injection on unilaterality. Thus, the aim was to compare the effect of patient posture, during the induction phase of spinal anaesthesia, on block characteristics. METHODS: Eighty patients, ASA I-II, scheduled for unilateral hernioplasty were randomized into two groups. Anaesthesia was performed in lateral position in Group 1 (G1) with operative side down and in sitting position in Group 2 (G2) whose patients were then immediately turned on their lateral side. All patients were maintained for 20 min in lateral position with their operative side down. Hyperbaric bupivacaine 1% 10 mg were used. RESULTS: Unilateral anaesthesia was seen in 80% (32/40) and 12.5% (5/40) of G1 and G2, respectively. The readiness for surgery was faster in G1 (P < 0.0001). The motor block in the non-operative side was stronger in G2 (P < 0.0001). The offset of sensory block was faster in G1 (P = 0.0001). The offset of motor block was slower in G1 (P = 0.0008). The time for voiding was shorter in G1, although not significant. CONCLUSIONS: Lateral posture during the induction of spinal anaesthesia is pivotal for a higher success of unilateral block, a fast readiness to surgery, and a fast recovery. Therefore, this technique can be considered feasible and time-saving for lower abdominal surgery.

Cytological analysis of the distension fluid used during diagnostic office hysteroscopies in patients with suspected endometrial pathology.

OBJECTIVE: Evaluation of the feasibility and usefulness of cytological analysis of the distension fluid used during diagnostic office hysteroscopy in patients with suspected endometrial pathology. METHODS: In 243 consecutive patients undergoing diagnostic hysteroscopy for suspected endometrial pathology a few milliliters of the distension medium used for uterine visualization were collected and sent for cytological analysis. Findings of these "endometrial washings" were compared to visual hysteroscopic impression, endometrial biopsy and uterine histology--when available. RESULTS: Endometrial washings were considered adequate in 227 patients (93.4%). In 12 cases (5.3%) atypical cells were detected: all of these presented either atypical complex hyperplasia or endometrial cancer at the final histological evaluation of the uterus. Four of the 16 (25%) patients diagnosed with endometrial cancer or atypical complex hyperplasia at the final histopathological analysis of the uterus had inadequate washings. No patient with cancer or atypical hyperplasia had negative cytology. CONCLUSIONS: Collection and analysis of the distension fluid is feasible and, when positive, has a remarkable value in the diagnosis of endometrial cancer and its precursors.

Participación del servicio veterinario de remonta del Ejército Nacional de R.O.U. en la etapa in vivo del proyecto de desarrollo del corazón artificial total ortotópico (CATO) en terneros / No disponible

No disponible

Modification of ultrasonographically measured endometrial thickness after discontinuation of adjuvant therapy with tamoxifen in postmenopausal breast cancer patients.

INTRODUCTION: The aim of this study was to evaluate endometrial changes after five years of tamoxifen treatment by measuring endometrial thickness with transvaginal ultrasonography. MATERIALS AND METHODS: Fifty-five asymptomatic postmenopausal women who had assumed tamoxifen, 20 mg daily, for five years were controlled six months after discontinuation of the therapy. Of these 42 were followed-up at 12 months. Statistical analysis was performed using the analysis of variance for repeated measures and the Anova test; p < 0.05 was considered statistically significant. RESULTS: We found a significant reduction in endometrial thickness at six months (p = 0.0046) and at 12 months (p = 0.0003) but not between six and 12 months (p = 0.06). CONCLUSION: A statistically significant reduction in endometrial thickness after discontinuation of tamoxifen therapy was found. This can probably be attributed to the cessation of the estrogenic side-effects of tamoxifen therapy.

Breast cancer metastatic to the vulva after local recurrence occurring on a rectus abdominis myocutaneous flap: a case report and review of the literature.

INTRODUCTION: Vulvar metastases are the third largest group of malignant tumors of the vulva. We report the tenth case of breast cancer vulvar metastases arising 11 years after the primary diagnosis of breast ductal carcinoma and the first occurring eight years after a local recurrence on a rectus abdominis myocutaneous flap. CASE REPORT: A 49-year-old woman presented with a voluminous lump of the left labium majus and enlargement of the ipsilateral inguinal lymph nodes. The mass was removed together with the ipsilateral inguinal lymph nodes. Microscopic evaluation of the removed lump revealed massive carcinomatous infiltration. No in situ lesions nor normal breast tissue were identified. CONCLUSIONS: Unusual breast cancer metastases sites should not be ruled out. Our case differs from the preceding cases because this patient underwent plastic surgery with reconstruction of the breast with a rectus abdominis myocutaneous flap one year after mastectomy and developed a local recurrence three years thereafter. It can be hypothesized that lymphatic spread through newly formed lymphatics occurred.

Haemostatic molecular markers in patients undergoing radical retropubic prostatectomy for prostate cancer and submitted to prophylaxis with unfractioned or low molecular weight heparin.

BACKGROUND: Deep vein thrombosis and subsequently pulmonary embolism are the most common causes of increased post-operative morbidity and mortality in patients with pelvic or abdominal cancer. Aim of the study was to evaluate variations in coagulative parameters induced by two accepted primary prophylaxis patterns: standardized low doses of unfractioned heparin (UFH) or single doses of low molecular weight heparin (LMWH) in cancer patients submitted to radical retropubic prostatectomy. METHODS: Fifty patients (45-75 yr) were randomly assigned two groups. Group 1 received UFH (5000 units s.c. x 3 daily); group 2 received calcium nadroparin (single daily dose of 0.3 ml s.c.). In both groups prophylaxis began preoperatively and was maintained throughout the entire hospital-stay. Blood cell, platelet count, coagulative system exploring tests, thrombotic molecular markers, and physiological inhibitors of coagulation were determined at baseline conditions and on the first and seventh day after surgery. RESULTS: Preoperative values of fibrinogen, F1+2 fragment, TAT and D-dimer resulted over normal range in both groups. A significant increase of these markers was observed also during the post-operative period. PT, aPTT, ATIII, PC, total and free PS showed the most substantial changes on the 1st post operative day, though their values ranged within normal levels on the three sampling times. The levels of haemostatic markers demonstrated a baseline hypercoagulability, probably related to cancer and thrombin activation caused by prostatectomy. Despite this thrombophylic state, neither of the two groups presented symptomatic bleeding or thromboembolic complications. CONCLUSIONS: These results prove that a single daily dose of nadroparin has been safe and efficient as a thrice-daily dose of UFH, with a better risk/benefit relationship.

[Applied anatomy of the distal "vinculum tendinis" in the fetlock tendon sheath of the hindlimb in cattle]. / Zur angewandten Anatomie des distalen "Vinculum tendinis" in der Fesselbeugesehnenscheide der Beckengliedmasse des Rindes.

A relatively thick (diameter approximately 2 mm), ropelike (length ca. 20 mm) and elastic "Vinculum tendinis" connects--within the fetlock tendon sheath--the dorsal side of the deep digital flexor tendon with the dorsal part of the Manica flexoria (the communicating band of the Musculus interosseous medius to the superficial digital flexor tendon). The extensive fetlock tendon sheath can be involved in diseases such as aseptic and septic inflammations. Spreading of these inflammations makes in some of these cases the partial resection of the tendon of the deep digital flexor muscle and the cutting of these Vincula necessary. The results of this contribution, collected from 60 hindlimbs of adult bovines show variations in number, length, diameter and extent and the inner structure with blood vessels and nerves.

Cloning and functional characterization of the human heterogeneous nuclear ribonucleoprotein type I promoter.

We have cloned and functionally characterized a portion of the human hnRNP I (heterogeneous nuclear ribonucleoprotein type I) gene containing the promoter elements. HnRNP I is an alternative splicing modulator of tissue-specific transcripts that is expressed in three different isoforms. The DNA sequence at the transcription start site, identified by 5'-rapid amplification of cDNA ends, shows a high 'GC' content, lacks canonical TATA sequences and contains multiple putative Sp1 and NF1 transcription factor-binding sites, a GATA box and a CAAT box. By means of a chloramphenicol acetyltransferase reporter construct and deletion analyses, we have identified two regions between -770 bp and -206 bp that had a positive effect on expression activity in HeLa cells.

Life crisis and the body within.

The authors take into account body involvement during the existential critical periods. The concept of body involvement considers both the biological (organic) involvement of the body, i.e. all the 'psychosomatic' (in a wider sense) dimensions, and the involvement of the mental representation of one's body. This involvement refers to some clinical conditions as 'abnormal somatic styles of existence', hypochondriasis and dysmorphophobia (all grouping in the DSM-IV 'somatoform disorders') and the anorexic states. From a structural psychogenetic point of view, this firm involvement of the body (naturally we are referring to the 'experienced body') is stressed in light of its importance in self identity construction and maintenance, especially when, as in some existential critical periods, identity physiologically faces significant modifications and hazardous movements.

Organization of the human gene encoding heterogeneous nuclear ribonucleoprotein type I (hnRNP I) and characterization of hnRNP I related pseudogene.

The human gene hnRNPI encoding the heterogeneous nuclear ribonucleoprotein type I, an alternative splicing modulator of tissue-specific transcripts, also known as PTB (polypyrimidine tract-binding protein), was recently mapped on chromosome 14, as well as on chromosome 19, suggesting that two closely related copies of the same gene might exist in the human genome. We report here that the gene localized on chromosome 14 corresponds to a highly homologous processed pseudogene related to hnRNPI gene (psihnRNPI). Analysis by RT-PCR and by EST database comparison indicates that psihnRNPI is not expressed. In this report we have also analyzed the organization of the actual hnRNPI gene localized on chromosome 19. The DNA sequence at the intron-exon boundaries unveiled the possible mechanism by which three isoforms of the protein (namely hnRNPI, PTB2 and PTB3) are generated by means of alternative splicing of the same hnRNPI gene transcript.

Effects of early antiretroviral treatment on HIV-1 RNA in blood and lymphoid tissue: a randomized trial of double versus triple therapy. Swiss HIV Cohort Study.

To assess the effects of early initiation of antiretroviral therapy on cell-free and cell-associated viral load in blood and lymphoid tissue, we performed a randomized, open-label, multicenter trial comparing a double (zidovudine + lamivudine) and triple (zidovudine + lamivudine + ritonavir) drug combination in treatment-naive, asymptomatic patients with CD4 counts >400 cells/microl. HIV-1 RNA was measured in plasma, peripheral blood mononuclear cells, and sequential tonsil or lymph node biopsies (27 patients); the study follow-up was 2 years. Among 42 randomized patients, the proportion with plasma HIV-1 RNA <50 copies/ml was 16% and 74% at week 24 (p<.001) in those randomized to double and triple therapy, respectively, necessitating frequent treatment intensification in the double arm. After a rapid decline within 4 weeks in both arms, cell-associated HIV-1 RNA decreased further only in those patients with sustained suppression of plasma viral load, but remained almost always detectable at low levels, indicating persisting transcription of viral RNA. CD4 counts increased by 200 to 250 cells/microl at week 96 in both arms without significant differences (intent-to-treat analyses). Thus, even if treatment is initiated early in asymptomatic patients with preserved CD4 counts, three drugs are necessary to achieve sustained decreases of HIV load in blood and lymphoid tissue.

Searching for a general anaesthesia protocol for rapid detoxification from opioids.

The technique for ultra rapid opioid detoxification is designed to shorten the detoxification period by precipitating withdrawal by the administration of opioid antagonists such as naloxone or naltrexone. This procedure is performed under deep sedation or general anaesthesia to ensure that the patient does not consciously experience the acute withdrawal phase. This strategy has aroused controversy regarding the risk of sedation or anaesthesia in this situation. In the present study, ultra rapid opioid detoxification was carried out in 12 opiate-addicted patients by infusion of naloxone 4 mg for a period of 5 h using controlled ventilation during general anaesthesia, induced and maintained with midazolam, propofol and atracurium. Invasive cardiovascular and respiratory monitoring was performed, and withdrawal signs were evaluated using a graduated scale. Anaesthesia was maintained for another hour after the completion of the naloxone infusion. The validity of this anaesthesia protocol was confirmed by the relative lack of change in the patients' haemodynamic values associated with mild signs of withdrawal.

[Anaphylactic reaction to thiopental. A case documented by tryptase values and RAST]. / Reazione anafilattica al tiopentale. Un caso documentato dalla positività della triptasi sierica e del RAST.

During general anesthesia adverse reactions are not uncommon, and the hypothesis of an anaphylactic response cannot be excluded. In these situations, a differential diagnosis from other events which often present identical clinical manifestations is necessary. For this purpose measurement of serum tryptase, as a biochemical marker of the release of mast-cell granules, is considered a valuable and specific method, especially if it is carried out on several hematic samples, obtained in successive times, for pointing out the progressive reduction of the values. If an anapyhlactic pathogenesis is confirmed, the identification of the responsible drug is necessary for a safer approach of the patient in view of a further anesthesia. A severe and protracted reaction has been observed after a standard induction of anesthesia, in which measurement of serum tryptase has shown high values of this protease 2 hours after the reaction which a subsequent decrease in the samples repeated after 5, 8, 11 e 20 hours, suggesting an anaphylactic etiology of the reaction. The specific RAST for the substances employed has excluded a role for muscle relaxant, plasma expander and latex, while it was positive for tiopenthal, suggesting in this case a true anaphylactic reaction caused by the hypnotic drug.

Impact of drug resistance mutations on virologic response to salvage therapy. Swiss HIV Cohort Study.

OBJECTIVE: To assess the prognostic significance of drug-associated mutations in the protease and reverse transcriptase (RT) genes on virological response to salvage therapy. PATIENTS: All patients from four centres of the Swiss HIV Cohort Study who were switched, between February and October 1997, to nelfinavir plus other antiretroviral drugs following failure of highly active antiretroviral therapy (HIV-1 RNA >1000 copies/ml after > 3 months). METHODS: Direct sequencing of RT and protease genes derived from plasma RNA was performed in 62 patients before salvage therapy. Baseline predictors (drug-resistance mutations, drug exposure, clinical and biological parameters) of virological response after 4-12 weeks of therapy were assessed by linear regression analyses. RESULTS: Patients had been treated with RT inhibitors and protease inhibitors for a median duration of 35.6 and 12.2 months, respectively. Baseline median CD4 cell count was 113 x 10(6)/l and HIV-1 RNA 5.16 log10 copies/ml. The median decrease of HIV-1 RNA was 0.38 log10; 32% of the patients showed > 1 log10 decrease. At baseline, 90% of the patients had RT inhibitor-resistance mutations with a median number per patient of four (range, 0-7). Primary and secondary protease inhibitor-resistance mutations were detected in 69% and 89% of the patients, respectively. The median number of total protease inhibitor-resistance mutations per patient was four (range, 0-9). In univariate analysis, virological response to salvage therapy was associated with number of RT inhibitors, primary and secondary protease inhibitor-resistance mutations, history of protease inhibitor use (duration and number), but not with clinical stage, HIV-1 RNA level or CD4 cell count. After adjustment for all variables, the number of RT inhibitor plus protease inhibitor-resistance mutations was the only independent predictor. CONCLUSIONS: In patients with advanced HIV infection, the virological response to salvage therapy containing nelfinavir is best predicted by the number of baseline RT inhibitor plus protease inhibitor-resistance mutations.

Antiretroviral therapies in pregnancy: maternal, fetal and neonatal effects. Swiss HIV Cohort Study, the Swiss Collaborative HIV and Pregnancy Study, and the Swiss Neonatal HIV Study.

BACKGROUND: Therapies containing two reverse transcriptase inhibitors (RTI) with or without protease inhibitors are used with increasing frequency in pregnant HIV-infected women. OBJECTIVE: To assess the safety of antiretroviral therapy in pregnant women and their newborns. METHODS: All clinical events and laboratory abnormalities in pregnant women on RTI with or without protease inhibitors and in their newborns were collected through an observational study. RESULTS: A total of 37 HIV-infected pregnant women have given birth to 30 children (by 30 April 1998). All received RTI, which were combined with protease inhibitors in 16 cases. Twelve women became pregnant while on treatment. Drugs used were as follows: zidovudine (n = 33), lamivudine (n = 33), stavudine (n = 4), indinavir (n = 9), ritonavir (n = 4), nelfinavir (n = 2) and saquinavir (n = 2). Adverse events during pregnancy were anaemia (n = 15), elevation of transaminases (n = 4), nausea/vomiting (n = 4), glucose intolerance (n = 2), nephrolithiasis (n = 2), diarrhoea (n = 2), hypertension (n = 1), insulin-requiring diabetes (n = 1). Adverse events in neonates were prematurity (n = 10), anaemia (n = 8), cutaneous angioma (n = 2), cryptorchidism (n = 2), transient hepatitis (n = 1). Non-life-threatening intracerebral haemorrhage occurred in a premature baby (33 weeks gestation) exposed during fetal life to zidovudine-lamivudine-indinavir, and in a term baby exposed to stavudine-lamivudine-indinavir. Extrahepatic biliary atresia occurred in one newborn exposed to zidovudine-lamivudine-indinavir. Maternal viral load was below 400 copies/ml in 18 out of 30 patients who delivered. One case of mother-to-child HIV transmission was identified. CONCLUSIONS: In HIV-infected pregnant women treated with two RTI with or without protease inhibitors, one or more adverse events occurred in 29 out of 37 women and in 14 out of 30 babies. In newborns, frequent prematurity, one case of biliary malformation and one intracerebral haemorrhage in a term baby are of concern. These observations do not preclude combination therapies during pregnancy but emphasize the necessity to maintain updated registers on their safety.

Toxicity, efficacy, plasma drug concentrations and protease mutations in patients with advanced HIV infection treated with ritonavir plus saquinavir. Swiss HIV Cohort Study.

OBJECTIVE: To assess the safety, efficacy and plasma drug levels of the combination of ritonavir plus saquinavir for the treatment of advanced HIV infection. DESIGN: Multicentre pilot study. PATIENTS: Eighteen protease inhibitor-naive patients, with intolerance or contraindication to reverse transcriptase inhibitors, a median CD4 cell count of 12 x 10(6)/l (range, 1-50 x 10(6)/l), and a median HIV viraemia of 5.25 log10 copies/ml (range, 4.00-6.13 log10 copies/ml). METHODS: Patients received 600 mg twice daily of both ritonavir and saquinavir. Viraemia was measured at baseline and at weeks 5, 9 and 13. Response was defined as a drop of viraemia of more than 1 log10 at week 5. Plasma drug levels were determined after at least 3 weeks of combined treatment: samples were collected before and 1, 2, and 4 h after the morning ingestion of both drugs. The protease gene was sequenced at baseline and under treatment. RESULTS: Among the 16 patients evaluable at week 5, 11 were responders, and among these patients, six remained responders at week 13 (two with undetectable viraemia). Study discontinuations were due to side-effects (n = 4), patient choice (n = 3), protocol violation (n = 1) and death (n = 1). Responders had higher drug levels than non-responders (P < 0.01 for saquinavir, P = 0.04 for ritonavir). In two non-responders, development of multiple new mutations at positions 10, 20, 48, 82, 84 and 90 was observed after 5-13 weeks. CONCLUSION: The response to ritonavir plus saquinavir in advanced HIV infection is unpredictable. A minority of patients respond with disappearance of HIV viraemia. In other patients, rapid cumulative emergence of protease mutations conferring resistance to treatment cannot always be prevented by good compliance and relatively high plasma drug levels.

["Body psychosis": an interpretative hypothesis about some psychiatric disorders]. / Le "psicosi del corpo": una ipotesi di lettura per alcune realtà cliniche.

The authors propose to group some clinical entities as Delusional hypochondria, Dysmorphophobia, Nervous Anorexia, under the term of Body Psychosis. These are considered as psychoses endowed in the body (naturally we are speaking not about the anatomical body, but the phenomenological one, the personal experienced body). The specific clinical frame is justified by the following considerations: 1) in a psychopathological light all the disorders imply an altered relationship with the personal experienced body; 2) in a prognostic light the "experienced body" involvement given specific and common features; 3) clinically a one-other manifestation change is always possible; 4) relationally the human contact (and the medical one too) with this kind of patient got very specific features that often provoke dramatic and perverse changes in the same relation, especially in a sadomasochistic sense. The personal nosological frame is stressed within the actual psychiatric diagnostic classification (ICD 10, DSM IV).