Optically guided patient positioning techniques

Optical tracking determines an object's position by measuring light either emitted or reflected from the object. The hallmark of optical tracking systems is their high spatial resolution and measurement in real time; such systems can resolve the position of a point source within a fraction of a millimeter and report at a rate of 10 Hz or faster. Several systems have been developed for radiation therapy, all of which track infrared markers attached to the patient's external surface. The positions of the optical markers relative to the target volume, together with the desired marker positions relative to treatment isocenter, are determined during computed tomography simulation. In the treatment room, the real marker positions are measured relative to isocenter; rigid-body mathematics then determine marker displacements from their desired positions and hence target displacement from isocenter. Real-time feedback allows one to correct the patient's position. The first systems were used for intracranial stereotaxis radiotherapy; rigid arrays of optical markers were attached to the patient via a biteplate linkage. Subsequent systems for extracranial radiotherapy tracked external markers to determine patient position and/or gate the radiation beam based on patient motion. Lastly, optical tracking has been integrated with ultrasound or stereoscopic x-ray imaging to determine the position of internal anatomy targets relative to isocenter.     

History of prolonged-release formulations and the contribution of French pharmacy in this field

The second part of the XXth century have seen the creation of new systems of administration for drugs, including delayed formulation systems or prolonged-release formulations (PRF). It is first within the industry, and mainly in the USA, that such new formulations were developed, with the purpose to increase the duration of action for pharmaceutical active principles. Several approaches were proposed and developed, jointly with more and more sophisticated evaluation techniques. In France, PRF market increased progressively during the 1980's; it then decreased because of more severe restrictions by health authorities for new drug approvals. In French specialty reference book (Vidal) included 518 PRF in the year 2000, from which 121 were tablets and 118 were hard gelatine capsules.     

Simultaneous analysis of the Delta9-THC metabolites 11-nor-9-carboxy-Delta9-THC and 11-hydroxy-Delta9-THC in meconium by GC-MS

Neonates that are exposed to cannabinoids in utero may have characteristic physical and mental developmental problems throughout their lives. The early identification of exposed neonates allows early intervention and anticipation of potential problems. Testing meconium detects maternal marijuana use over the last four months of gestation, providing a better drug exposure marker than urine. However, the distribution of metabolites in meconium is not identical to urine and analytical methods must be adapted. Both the major urine metabolite, 11-nor-9-carboxy-Delta9-tetrahydrocannabinol (9-carboxy-THC), and a minor urine metabolite, 11-hydroxy-Delta9-tetrahydrocannabinol (11-hydroxy-THC), are common in meconium. Currently published methods to extract these two metabolites for instrumental analysis are time-consuming and laborious, often involving the preparation of two fractions. This study describes a simple solid-phase extraction method and an optimized hydrolysis method that allow the preparation and analysis of both metabolites in a single extract. The limit of detection by this extraction method was 5 ng/g for both metabolites with an analytical measurement range from 10 to 500 ng/g. The recovery at 100 ng/g was greater than 62% for both analytes. The analysis of 246 cannabinoid screen positive specimens illustrated the importance of including the 11-hydroxy-THC in a meconium marijuana confirmation: 16 specimens confirmed positive for 11-hydroxy-THC only, resulting in a 6.5% increase in the positivity rate compared to 9-carboxy-THC alone.     

Chemokine receptor-5 (CCR5) is a receptor for the HIV entry inhibitor peptide T (DAPTA)

The chemokine receptor CCR5 plays a crucial role in transmission of HIV isolates, which predominate in the early and middle stages of infection, as well as those, which populate the brain and cause neuro-AIDS. CCR5 is therefore an attractive therapeutic target for design of entry inhibitors. Specific rapid filtration binding assays have been useful for almost 30 years both for drug discovery and understanding molecular mechanisms of drug action. Reported in 1986, prior to discovery of chemokine co-receptors and so thought to act at CD4, peptide T (DAPTA) appears to greatly reduce cellular viral reservoirs in both HAART experienced and treatment na?ve patients, without toxicities. We here report that DAPTA potently inhibits specific CD4-dependent binding of gp120 Bal (IC50=0.06 nM) and CM235 (IC50=0.32 nM) to CCR5. In co-immunoprecipitation studies, DAPTA (1 nM) blocks formation of the gp120/sCD4 complex with CCR5. Confocal microscopic studies of direct FITC-DAPTA binding to CCR5+, but not CCR5-, cells show that CCR5 is a DAPTA receptor. The capability of DAPTA to potently block gp120-CD4 binding to the major co-receptor CCR5 explains its molecular and therapeutic mechanism of action as a selective antiviral entry inhibitor for R5 tropic HIV-1 isolates.     

Interferon alpha therapy for patients with essential thrombocythemia: final results of a phase II study initiated in 1986

BACKGROUND: In 1986, a Phase II trial of recombinant interferon-alpha (IFN-alpha) was initiated as therapy for patients with essential thrombocythemia (ET). METHODS: Patients were treated with subcutaneous IFN-alpha at a dose of 5 x 10(6) units/m(2) daily. In responding patients, the therapy lasted at least 3 years. RESULTS: Twenty-three patients (14 females and 9 males; median age, 41 years; age range, 20-63 years) with a median platelet count of 1350 x 10(9)/L were treated. After a median follow-up of 174 months (14.5 years), 15 of 20 evaluable patients (75%) responded, including 14 patients who achieved a complete hematologic response (CHR) (6 of them with bone marrow remission) and 1 patient who demonstrated a partial response. The median time to response was 6 months (range, 0.5-36 months), and the median response duration was 48 months (range, 5-114 months). Seven patients who achieved a CHR and were taken off therapy after they completed 3 years of maintenance therapy sustained their response for a median of 28 months. No symptoms or signs of thrombosis or hemorrhage were observed in responding patients. Eleven of 14 patients (78%) who achieved a CHR developed a recurrence, and 2 of 5 patients with recurrences who were rechallenged with IFN-alpha achieved a second response. The treatment was tolerated relatively well. CONCLUSIONS: IFN-alpha was safe and effective therapy for patients with ET, and the ability of IFN-alpha to reverse disease pathology and possibly modify the clinical course of patients with ET warrants its investigation in larger, prospective trials.     

Outcome of patients with acute myelogenous leukemia after second salvage therapy

BACKGROUND: Although the prognosis is poor for patients with acute myelogenous leukemia (AML) who have disease recurrence after frontline therapy, this is a general reflection of first salvage therapies. The outcome of patients undergoing second salvage therapy in relation to complete response (CR) rates and survival has not been documented. The authors analyzed the outcome of patients with AML undergoing second salvage therapy, and identified prognostic factors associated with response and survival. METHODS: The records of 594 patients with AML undergoing second salvage therapy from 1980 until 2004 were reviewed. The patient median age was 50 years. Salvage therapy included allogeneic stem cell transplantation (SCT) in 74 patients, standard-dose cytosine arabinoside (ara-C) combinations in 30 patients, high-dose ara-C combinations in 171 patients, non-ara-C combinations in 73 patients, and Phase I-II single agents in 246 patients. RESULTS: Overall, 76 patients (13%) achieved CR. The median CR duration was 7 months. The median survival was 1.5 months, and the 1-year survival rate was 8%. A multivariate analysis of prognostic factors for CR identified the following 6 independent adverse factors: first CR duration < 6 months; second CR duration < 6 months; salvage therapy not including allogeneic SCT; non-inversion 16 AML; platelet counts < 50 x 10(9)/L, and leukocytosis > 50 x 10(9)/L. Patients were divided into low-risk (1-2 adverse factors; 8%), intermediate 1 (3 factors; 20%), intermediate 2 (4 factors; 38%), and high-risk groups (5-6 factors; 33%) with respective CR rates of 54%, 26%, 8%, and 0%. The respective 1-year survival rates were 36%, 21%, 6%, and 1%. A multivariate analysis for survival identified the following 7 independent adverse factors: first CR duration < 12 months; second CR duration < 6 months; bilirubin level > or = 1 mg/dL; albumin level < 3 g/dL; age > 60 years; bone marrow blasts > or = 50%; and year of therapy before 1991. Patients were divided into low-risk (0-2 adverse factors; 39%), intermediate (3 factors; 27%), and high-risk groups (> or = 4 factors; 34%) with estimated 1-year survival rates of 22%, 6%, and 0%, respectively. The respective CR rates were 26%, 8%, and 2%. CONCLUSIONS: The current analysis established the outcome and prognostic factors associated with second salvage therapy in AML. It also proposed risk models and groups that could be used for comparison of results of present and future investigational strategies.     

Experience with laparoscopic adjustable gastric banding (la-band system) up to 8 years

Morbid obesity occurs in 2-5% of the population in Western countries. Laparoscopic adjustable silicone gastric banding is a minimally invasive, adjustable and reversible procedure for the treatment of morbid obesity. The lap-band system was evaluated retrospectively in a series of 222 patients. Postoperative outcome and weight loss patterns at up to 8 years follow-up are presented. The most frequent late complications were a leak between the port and the catheter, which occurred in 21 patients (9.4%) and total and irreversible food intolerance due to pouch dilation and/or slippage, which occurred in 13 patients (5.8%). The postoperative BMI reductions are successful and stable after a follow-up of up to 96 months. The lap-band system seems an effective procedure for achieving appreciable and stable weight loss up to 8 years of follow-up and the complications and re-operation rates are acceptable. In 81% of the cases also, the patient is very satisfied with the results of the operation. From the 47.3% who found their quality of life before the operation bad or even devastating, 93% envoy life after the operation like never before.