Systemic therapies for Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: a SCORTEN-based systematic review and meta-analysis.

BACKGROUND: The SCORTEN score is a specific predictor of mortality for patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). There is little evidence in support of the common immunomodulating therapies for SJS/TEN. OBJECTIVES: To systematically assess the effectiveness of several therapies for SJS/TEN through the SCORTEN score. METHODS: Databases were searched for original studies on the use of SCORTEN. Six meta-analyses were carried out on patients with SJS/TEN who received supportive care only or in combination with immunomodulating drugs: corticosteroids, cyclosporine, etanercept, immunoglobulins or a combination of corticosteroids with immunoglobulins. A multivariate meta-regression and a network meta-analysis were also performed. RESULTS: Of 3893 studies identified, fifty-two involving 2466 patients with SJS/TEN were preselected. Data from thirty-eight of these studies (1827 patients) were finally pooled, and results [log(SMR)] from meta-analyses were as follows: -0.13 (95% CI, -0.42,0.16) for corticosteroids, -0.39 (95% CI, -0.87,0.09) for immunoglobulins, 0.13 (95% CI, -0.15,0.40) for supportive treatment, -0.88 (95% CI, -1.47, -0.29) for cyclosporine, -0.95 (95% CI, -1.82, -0.07) for etanercept and - 0.56 (95% CI, -0.94, -0.19) for immunoglobulins plus corticosteroids. The meta-regression analysis confirmed that cyclosporine and immunoglobulins plus corticosteroids were associated with less deaths than predicted by SCORTEN. In the network meta-analysis, no treatment achieved a significant reduction in the SMR. LIMITATIONS: Heterogeneity and quality of the included studies. CONCLUSIONS: Some treatments for SJS/TEN show a better performance, but there is not sufficient evidence to recommend its widespread use in all patients.

Accuracy of SCORTEN to predict the prognosis of Stevens-Johnson syndrome/toxic epidermal necrolysis: a systematic review and meta-analysis.

BACKGROUND: The SCORTEN score is a specific predictor of the probability of death for patients diagnosed with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). OBJECTIVES: To evaluate the overall accuracy of SCORTEN and the influence of several moderators such as age, sex, geographical region and age of the study. METHODS: A systematic search was performed on MEDLINE, The Cochrane Library, EMBASE, SCOPUS and Web of Knowledge, with no restriction on language (last update 5 February 2019 for all databases). Original studies on the use of SCORTEN were eligible. The standardized mortality ratio (SMR), defined as the quotient between the number of deaths observed and the number expected following SCORTEN, was taken as the measurement of analysis. RESULTS: Sixty-four papers were part of the main meta-analysis carried out in the study. A pooled log(SMR) of -0.0889 (95% CI: -0.2023 to 0.0245) was obtained, suggesting a reasonable behaviour of SCORTEN as a predictor of mortality. The possible influence of several factors in the accuracy of SCORTEN was studied by means of meta-regression models. Multivariate meta-regression allowed finding that the mean age of the patients and the ending year of the study are the only factors that significantly influence SCORTEN predictions. The mean age of the group of patients was associated with a significant increase in the observed/expected ratio, whereas a progressive reduction in the observed/expected ratio can be appreciated over the years. Finally, an underestimation of mortality was found for SCORTEN values of 3 or less and the opposite for those above 3 (SCORTEN range: 0-7). CONCLUSIONS: The rarity of the disease and the heterogeneity of the studies included are major limitations. Despite the overall remarkable accuracy displayed by SCORTEN, the influence of several factors, as comorbidities (e.g. renal impairment), involved body surface area and patient's age, seem of enough relevance to consider a redefinition of the scale.

Comparative study between thulium laser (Tm: YAG) 150W and greenlight laser (LBO:ND-YAG) 120W for the treatment of benign prostatic hyperpplasia: Short-term efficacy and security. / Estudio comparativo entre láser tulio (Tm: YAG) 150W y láser verde (LBO:ND-YAG) 120W para el tratamiento de la hiperplasia benigna de próstata: eficacia y seguridad a corto plazo.

OBJECTIVE: To compare the results of efficacy and safety of Thulium laser 150W against Greenlight laser 120W in the treatment of short term benign prostatic hyperplasia (12 months after surgery). MATERIAL AND METHODS: This is a retrospective observational study where men who underwent the surgical technique of prostate vaporization over a period of four years in our center are included. The homogeneity of the sample was checked, and postoperative complications (acute urinary retention, reentry, need for transfusion), failures per year of surgery (reoperation, peak flow <15ml/sec, no improvement in comparing the I-PSS), and decreased PSA were compared a year after surgery. A bivariate analysis using Chi-square and t-Student was carried out. RESULTS: 116 patients were treated with thulium and 118 with green laser. The sample was homogeneous for preoperative variables (P>.05). No differences in complications were observed: in urine acute retention, 4.3% with thulium and 6.8% with green laser (P=.41); in readmissions, 2.6% with thulium and 1.7% with green laser (P=.68); in need for transfusion, 2.6% with thulium and 0% with green laser (P=.12). No differences were observed in the percentage of patients reoperation (1.7% in the group of thulium, 5.1% in the green laser, P=.28); or in individuals with Qmáx less than 15ml/sec (6.9% with thulium, 6.77% with green laser, P=.75), or in the absence of improvement in the IPSS (5, 2% with thulium, 3.4% with green laser, P=.65). There was also no difference in the levels of PSA in ng/mL a year after surgery: with thulium 2.78±2.09 and with green laser 1.83±1.48 (P=.75). CONCLUSIONS: Prostate vaporization with thulium laser 150W is comparable to that made with green laser 120W for the treatment of lower urinary tract symptoms caused by BPH, being both effective and safe techniques to 12 months after surgery. Future prospective randomized studies are needed to confirm this conclusion on both techniques.

[Role of chronic prostatic infiltrate from specimens of prostate biopsy in total and free PSA determination]. / Influencia de la inflamación crónica prostática en muestras de biopsia sextante en los niveles séricos de PSA total y PSA libre.

PURPOSE: To analyze the influence in total serum PSA (PSA(t)) and free PSA (PSA(1)) of chronic inflammatory patterns from prostate biopsy specimens of non-symptomatic patients. PATIENTS AND METHODS: 518 non-symptomatic patients underwent ultrasonography and prostatic biopsy for PSA(t) > 4 ng/mL and/or DRE suspicious of malignancy. Those with a negative biopsy were divided into two subgroups: patients with benign prostatic lesions (LBP) and patients with chronic inflammatory signs (SIC). RESULTS: 456 patients (88.03%) were biopsied for elevated PSA(t) or/and DRE suspicious of malignancy in 62 patients (11.97%). Mean volume in patients with LBP was 54cc, while 51cc was the mean volume in patients with histological pattern of chronic inflammatory infiltrate. Mean PSA(t) in patients with LBP was 9.43 (IC 95% +/- 7.8) and 8.8 (IC 95% +/- 5.73) in SIC's group patients. CONCLUSIONS: The presence of SIC has no significant influence in the eventual value of PSA(1) y PSA(t) in a selected population. As a result of that finding data from serum PSA can be reliably evaluated even in the presence of SIC in biopsy specimens.

Trans-rectal ultrasonography (TRUS) with lipiodol injection for localization of the prostatic apex before radiotherapy planning.

PURPOSE: To evaluate reliability of Trans-rectal ultra-sonography (TRUS) guidance with lipiodol injection for prostate localization before radiotherapy planning. MATERIAL AND METHODS: From October 1997 to March 2000, 31 patients with prostatic adenocarcinoma and six patients with anastomotic recurrence after radical prostatectomy had TRUS-guided injection of lipiodol. Two milliliters of lipiodol were injected into each side of the prostate and 1 ml into both seminal vesicles with a 22 Gauge CHIBA needle and US probe guide before radiotherapy planning. We had established a contrast quality index (0 for no prostate enhancement to 5 for efficient pacification without any diffusion). On simulation films, we had performed anatomic measurements for comparison with other anatomic studies. RESULTS: For all 37 patients, TRUS-guided injection was well tolerated. Among 31 patients with the prostate in situ, three had no apex opacification and 15 had no vesicle enhancement or peri-vesicle space diffusion. However, in 19 patients there was good contrast quality with an index score of > or =3. The majority of patients had prostatic apex between 1.5 and 3.5 cm from ischial tuberosities ligne (27 from 28 evaluable for apex). Among 19 evaluable patients, 15 had seminal vesicles 2-4 cm above the top of pubis. For six patients with anastomotic recurrence after radical prostatectomy, lipiodol was precious aid to locate it. We had only one failure because of a precocious bladder absorption relating to a delay which is too long between rectal probe locating and portal films. CONCLUSION: TRUS injection of lipiodol is a simple, inexpensive, relatively safe technique for localization of prostatic apex, but not appropriate for seminal vesicles enhancement. This is also an interesting method to locate anastomotic recurrence.

[Cervical lymph nodes metastasis from an unknown primary: diagnosis, treatment and prognosis. A retrospective study of 127 cases observed from 1959 to 1973 (author's transl)]. / Adénopathies cervicales sans primitif connu. Diagnostic, traitement et pronostic. A propos d'une série de 127 malades suivis au Centre Claudius-Regaud de 1959 à 1973.

Authors present clinical records of 127 patients bearing metastatic cervical lymph nodes of unknown origin and referred to the Cl. Regaud Cancer Center between 1959 and 1973. According the prognosis, it is possible to distinguish patients into three groups. In group I, patients (10%) have a lower neck involvement by an adenocarcinoma. The survival is dramatically bad. Group II includes also 10% of patients who have a fairly better prognosis, they are younger people bearing poorly differenciated squamous metastatic lymphonode(s) in the upper neck. Group III. The remaining eighty per cent of patients are heavy drinkers and smokers. Their upper neck is hurt by lymphatic metastases from a well or moderately differenciated squamous cell carcinoma. They have much about the same prognosis than people bearing a known primary carcinoma of the upper aerodigestive tract. After having excluded the first group of patients who is at high risk of having a widely disseminated illness, we can remark that about one half of relapses occurred in the cervical area. A well planned combination of neck dissection and whole cervical lymphatic areas irradiation may further reduce such recurrences and so may enhance the present results: 23% survival 3 years after completion of treatment.

[Maternal motivation for choice of feeding method]. / Motivations maternelles pour le choix du mode d'allaitement.

We studied the different motivations mothers had for choosing a particular mode of nursing at the University Hospital in Limoges. An anonymous questionnaire was distributed to all mothers who hat delivered between January 1 and April 30, 1992. It was apparent that the medical team did little to promote breast-feeding or to counteract negative attitudes. The results of this study, together with a review of the literature were used to determine conditions for encouraging breast feeding.

[Pyeloureteral fungus ball in patients with urinary lithiasis. Treatment with ureterorenoscopy]. / Fungus ball pieloureteral en pacientes con litiasis urinaria. Tratamiento con ureterorrenoscopia.

INTRODUCTION: C. albicans is the most frequent fungus causing opportunist infections of the urinary tract. Agglutination of necrotic tissue nucleus (papilary necrosis), mucosus debri and chirurgic or lithiasic debri, originates a fungus ball, which can obstruct the urinary tract at any level. CLINICAL DATA: We present 2 patients with obstructive urinary lithiasis developing fungus ball in the dilated upper urinary tract. Patient 1 was bilaterally affected and never had systemic symptoms. Treatment consisted of uretherorrenoscope for removal of fungus ball, bilateral urinary diversion and anphotericine B irrigations and systemic. Patient 2 developed a candidemia and was treated with systemic liposomal anphotericine B, uretherorrenoscopy with removal of ureteric calculus and fungus ball, and placement of a double J catheter and nephrostomy tube for anphotericine B irrigation. DISCUSSION: Urinary lithiasis is a risk factor for fungal infection of the upper urinary tract, provided there is no other predisponent factor for opportunistic fungal infections. Calculi facilitates fungal growth by means of obstruction and subsequent retrograde estasis and creating a nucleus for growth, aggregation and ramification of mycelium. The infection pathway is probably ascendent and may turn into fungemia and septicaemia. Systemic antimicotics, urinary diversion and local irrigations with antimicotics, and endourologic technics, are the three basic items in the treatment. Ureterorrenoscopy plays an important roll as a diagnostic and therapeutic tool as it may solve the obstruction and allows removal of fungus ball.

[Secondary vesical amyloidosis]. / Amiloidosis vesical secundaria.

The bladder involvement is a very unusual fact in systemic amyloidosis. The distinction of primary and systemic amyloidosis disease with bladder involvement (secondary bladder amyloidosis) is important to the urologist. Secondary amyloidosis of the bladder is a rare disease entity (approximately 20 cases published). We document a case of a woman with a large history of rheumatoid arthritis who developed severe macrohematuria. Diagnosis was done by biopsy that revealed amyloidosis, and it was confirmed with an immunohistochemical staining of the specimens that defined the process as amyloid AA (secondary amyloidosis).

An optimized calibration method for surface measurements with MOSFETs in shaped-beam radiosurgery.

Nowadays MOSFET dosimeters are widely used for dose verification in radiotherapy procedures. Although their sensitive area satisfies size requirements for small field dosimetry, their use in radiosurgery has rarely been reported. The aim of this study is to propose and optimize a calibration method to perform surface measurements in 6 MV shaped-beam radiosurgery for field sizes down to 18 × 18 mm(2). The effect of different parameters such as recovery time between 2 readings, batch uniformity and build-up cap attenuation was studied. Batch uniformity was found to be within 2% and isocenter dose attenuation due to the build-up cap over the MOSFET was near 2% irrespective of field size. Two sets of sensitivity coefficients (SC) were determined for TN-502RD MOSFET dosimeters using experimental and calculated calibration; the latter being developed using an inverse square law model. Validation measurements were performed on a realistic head phantom in irregular fields. MOSFET dose values obtained by applying either measured or calculated SC were compared. For calibration, optimal results were obtained for an inter-measurement time lapse of 5 min. We also found that fitting the SC values with the inverse square law reduced the number of measurements required for calibration. The study demonstrated that combining inverse square law and Sterling-Worthley formula resulted in an underestimation of up to 4% of the dose measured by MOSFETs for complex beam geometries. With the inverse square law, it is possible to reduce the number of measurements required for calibration for multiple field-SSD combinations. Our results suggested that MOSFETs are suitable sensors for dosimetry when used at the surface in shaped-beam radiosurgery down to 18 × 18 mm(2).

In-vivo dosimetry for field sizes down to 6 × 6 mm2 in shaped beam radiosurgery with microMOSFET.

The aim of this study is to evaluate microMOSFET as in-vivo dosimeter in 6 MV shaped-beam radiosurgery for field sizes down to 6 × 6 mm2. A homemade build-up cap was developed and its use with microMOSFET was evaluated down to 6 × 6 mm2. The study with the homemade build-up cap was performed considering its influence on field size over-cover occurring at surface, achievement of the overall process of electronic equilibrium, dose deposition along beam axis and dose attenuation. An optimized calibration method has been validated using MOSFET in shaped-beam radiosurgery for field sizes from 98 × 98 down to 18 × 18 mm2. The method was detailed in a previous study and validated in irregular field shapes series measurements performed on a head phantom. The optimized calibration method was applied to microMOSFET equipped with homemade build-up cap down to 6 × 6 mm2. Using the same irregular field shapes, dose measurements were performed on head phantom. MicroMOSFET results were compared to previous MOSFET ones. Additional irregular field shapes down to 8.8 × 8.8 mm2 were studied with microMOSFET. Isocenter dose attenuation due to the homemade build-up cap over the microMOSFET was near 2% irrespective of field size. Our results suggested that microMOSFET equipped with homemade build-up cap is suitable for in-vivo dosimetry in shaped-beam radiosurgery for field sizes down to 6 × 6 mm2 and therefore that the required build-up cap dimensions to perform entrance in-vivo dosimetry in small-fields have to ensure only partial charge particle equilibrium.

[Treatment of trigeminal neuralgia with radiosurgery]. / Traitement de la névralgie essentielle du trijumeau par radiochirurgie stéréotaxique.

Idiopathic trigeminal neuralgia is defined as brief paroxysms of pain limited to the facial distribution of the trigeminal nerve. Drug therapy is considered to be the first-line of treatment for trigeminal neuralgia. Unfortunately, medical treatment does not always provide satisfactory pain relief for 25% of the patients. Moreover, the relief provided by drug therapy generally decreases over time, and increased dosages of these medications are limited because of side effects. In this case, patients can be offered several surgical approaches, such as percutaneous techniques (thermocoagulation, microcompression, glycerol injection) or microvascular decompression in the cerebello-pontine angle (Gardner-Jannetta's technique). In this indication, stereotactic radiosurgery, driven by teams using Gamma Knife(®), has shown promising efficacy and tolerance to allow this treatment being truly part of trigeminal neuralgia treatment. Technological progresses now allow performing radiosurgery with ballistic and dosimetric processes optimized with stereotactic radiosurgery dedicated linear accelerators. This procedure supports frame implantation to guarantee targeting accuracy in accordance of elevated dose distribution. This article on trigeminal neuralgia treatment will review the different medical and surgical therapeutic options and specify the contemporary place of stereotactic radiosurgery in the light of its clinical results and tolerance aspects.

[Medical devices needed for stereotactic radiosurgery and intracranial stereotactic radiotherapy]. / Équipements requis pour la mise en œuvre de la radiochirurgie et de la radiothérapie en conditions stéréotaxiques intracrânienne.

Since the previous special issue of Cancer Radiothérapie dedicated to radiosurgery in 1998, many important technological and computer developments have improved external beam radiotherapy treatment device performances. Whereas the Gamma Knife(®) was the gold standard for intracranial radiosurgery, new linear accelerator developments have led to new possibilities for the clinicians. This article describes quickly the different devices available for cranial radiosurgery or fractionated stereotactic radiotherapy.

[Stereotactic and diagnostic imaging in radiosurgery]. / Imagerie stéréotaxique et diagnostique en radiochirurgie.

Constant progress in medical imaging and particularly magnetic resonance imaging has profound impact in planning for stereotactic radiosurgery and radiotherapy. The purpose of this paper is to discuss the integration of medical imaging modalities in the planning process. Principles of generic algorithms to calculate stereotactic coordinates are treated for tomographic imaging and digital substraction angiography, and their accuracies are analyzed in a review of the literature. The algorithmic foundations and performance of automatic intermodality co-registration methods are developed. Finally, the MRI sequences useful in planning and follow-up are discussed and the role of MR angiographic sequences compared to conventional X-ray angiography in the particular case of the arteriovenous malformation planning.

[Neuromotor assessment of patients with spastic cerebral palsy treated with orthopedic surgery at the National Rehabilitation Institute]. / Evaluación neuromotora de pacientes con parálisis cerebral espástica tratados con cirugía ortopédica en el Instituto Nacional de Rehabilitación.

BACKGROUND: Cerebral palsy (CP) is a static neurologic condition resulting from a brain lesion occurring before the completion of brain development. The goal of management is not cure, but increasing patients' functionality and improving their capabilities and maintaining their locomotion, cognitive development, social interaction and independence. The best results are obtained with an early and intensive management that includes physical and occupational therapy, medical and surgical treatments, mechanical aids and the management of concomitant conditions. OBJECTIVE: To assess the neuromotor improvement in patients with spastic CP after surgical treatment at the National Rehabilitation Institute. PATIENTS AND METHODS: Patients with a diagnosis of spastic CP who presented at the Pediatric Rehabilitation outpatient service were referred to the Joint CP Clinic from January 2007 to January 2008, and underwent surgical treatment of the pelvic limbs. They were assessed 3 times and underwent neuromotor tests with gross motor function measure (GMFM), which was rated with the gross motor function classification system (GMFCS). RESULTS: Most of the patients had improvement in the muscle tone and contracture assessments as well as in the GMFM, and their self-mobility increased one level. CONCLUSIONS: Significant improvements were seen in the muscle tone and contractures after surgery; the GMFM and the self-mobility levels in the GMFCS also improved. Multiple level surgery together with a postoperative physical therapy program results in considerable improvements in the gross motor function measure of patients with spastic CP.

[Dosimetric stereotactic radiosurgical accident: Study of 33 patients treated for brain metastases]. / Traitement des métastases cérébrales par radiochirurgie stéréotaxique : étude de 33 cas liés à un accident de "surexposition".

The consequences of a dosimetric radiosurgery accident are not the same as a conventional radiotherapy accident. The objective of this study was to estimate the clinical and radiological outcome of patients treated by radiosurgery for metastasis during the period of the overexposure accident that occurred in the Toulouse Radiosurgery Unit. Between April 2006 and March 2007, 33 patients with 57 metastases were treated in the Toulouse Radiosurgery Unit (Novalis(®), BrainLab). An initial error in the estimation of the scatter factors led to an overexposure to radiation. The median age was 55 years [range, 35-85]. Twenty-one patients (64%) harbored a single metastasis. The primary tumor location was lung (16 cases), kidney (nine cases), breast (four cases), and others (four cases). The mean tumoral volume was 3.2cm(3) [0.04-14.07]. The mean prescribed dose at the isocenter was 20 Gy [range, 10-23], the mean delivered dose was 31.5 Gy [range, 13-52], and the mean overdose was 61.2% [range, 5.6-226.8]. In order to evaluate the consequences of the overdose, three parameters were analyzed: a risk index using dose and volume, the volume of parenchyma that received more than 12 Gy, and the mean dose in a sphere of 20cm(3) surrounding the target volume. Median actuarial survival was 14.1 months, the survival rate was 79.4 % at six months, 59.1% at 12 months, and 27.2% at 24 months. The rate of tumor control was 80.7%. No morbidity was observed. There was no correlation between death and the parameters studied. The survival rates and times observed in our study of the patients treated for brain metastases by radiosurgery and overexposed were among the good results of the international literature. Deaths were not related to the overdose and no side effect was noted. This dosimetric accident has not had worse consequences in this population.

[On board imaging with cone beam CBCT kV VARIAN: Montauban's radiation therapy department experience]. / Système d'imagerie par tomographie conique de basse énergie (kV)de Varian : expérience de Montauban.

PURPOSE: To describe our practice day to day with a VARIAN linac "Clinac 2100" fully equipped with an On Board Imager (OBI) for patients with prostate cancer. MATERIALS AND METHODS: A volumetric and dosimetric study was performed in 2006 using ARTIVIEW software (AQUILAB) for nine patients and 76 Cone Beam CT kV (CBCT kV). We have contoured targets and organs at risk from CBCT kV slides acquisitions. Second, we achieved a dose-volume histogram (DVH) study for a patient treated in 2007 with IMRT technique in comparison with the 2006 study. RESULTS: 2006 analysis: The study showed a very important variability of organ measurements. Seminal vesicles were strongly influenced by adjacent organs; observed differences for prostate could be explained by contouring uncertainty on the apex. Inter-sessions motions could be observed for bladder, rectum and seminal vesicles (SV). Part of prostate volume not encompassed by PTV is about 2.5%; VS volume outside PTV is about 35%. Tumoral conformation index (TCI) is inferior to 97.5% in 22% of all cases. Anteroposterior displacements of the prostate barycentre is superior to 5mm. From this analysis, we recommended the strict respect of hygienodietetic rules, and we have adapted the system settings for better immobilization, which were applied for the 2007 study. For the 2007 analysis, since April 2007, most of patients are treated with IMRT for prostate cancer, at the second part of the radiation therapy to encompass only the prostate volume. Dose-volume histograms showed a great spreading out for 2006 patients, and not for the 2007 patient. CONCLUSIONS: IMRT and IGRT should permit a margin reduction for PTV. Strict respect of hygienodietetics rules is necessary to avoid rectal distension and local recurrence.

Immunological screening of drugs of abuse and gas chromatographic-mass spectrometric confirmation of opiates and cocaine in hair.

The work presents an analytical strategy to detect drugs of abuse in hair. It involves two sequential steps: a screening by a simple enzyme-linked immunosorbent assay (ELISA) methodology to detect opiates, cocaine and its metabolites, and benzodiacepines, followed by confirmation of opiates and cocaine metabolites in positive samples by gas chromatography coupled to mass spectrometry (GC-MS). In the same GC-MS run other drugs for substitution therapy (e.g. methadone and its main metabolite) can also be detected. After a double washing of hair samples with dichloromethane, hair specimens were cut into small pieces and 10 mg samples were incubated in 2 ml of methanol-trifluoroacetic acid (9:1) mixture, overnight at 37 degrees C. Aliquots of the extract were then evaporated, reconstituted in buffer and analysed according to the ELISA procedure. Confirmation involved solid-phase extraction of another fraction of the extract kept at -20 degrees C, derivatization with heptafluorobutyric anhydride and hexafluoroisopropanol and detection of cocaine, benzoylecgonine, ecgonine methylester, cocaethylene, morphine, codeine, 6-monoacetylmorphine, methadone and 2-ethylidene-1.5-dimethyl-3,3-diphenylpirrolidine (methadone metabolite) by selective ion monitoring after gas chromatographic separation. During the development of the method it was verified that no more than 10% of cocaine, opiates and benzodiacepines were lost when dichloromethane was used to wash real samples. The results also confirmed the increase of extractability power of TFA when it was added to methanol: the recovery for the analytes (cocaine and its metabolites and opiates) added to methanol-TFA alone was of the order of 90% except for benzoylecgonine (75%), and the recovery for the analytes added to methanol-TFA extract of drug-free hair was about 90% for all analytes except for benzoylecgonine and 6-MAM (around 70%). Regarding the stability of labile compounds, only small amounts of ecgonine methylester (2.3%) and morphine (7.2%) were produced, from cocaine and 6-MAM respectively, after the whole extraction procedure and two weeks of storage of methanol-TFA extracts at -20 degrees C. Satisfactory results were obtained when the procedures were applied to the analysis of external proficiency testing hair samples and actual specimens from drug addicts.