HLA-DPB1 gene polymorphism and multiple sclerosis: a large case-control study in the southwest of France

The polymorphism at the HLA-DPB1 locus has been characterized in a large number of patients with multiple sclerosis (n = 112) and in healthy controls (n = 115). Both patients and controls lived in the southwest of France (in the Pyrénées Atlantiques) and had similar ethnic background. The typing procedure involved the selective amplification of the second exon of the DPB1 locus by polymerase chain reaction, followed by hybridization of the amplified DNA with 14 sequence-specific oligonucleotide probes. Individual alleles were identified by the pattern of hybridization of the different probes. The distribution of the DPB1 alleles was not significantly different in multiple sclerosis patients and controls (p = 0.11). This does not corroborate the reported association of multiple sclerosis with the primed lymphocyte typing (PLT)-defined DPw4 specificity and is not in favour of a role played by polymorphic residues of the DP molecule in susceptibility to multiple sclerosis.     

Contribution of genetic factors for melanoma susceptibility in sporadic US melanoma patients

Abstract:  The risks of developing malignant melanoma (MM) include ultraviolet irradiation and genetic factors. To examine the contribution of rare and common variation within known MM genes in sporadic US MM patients, coding regions of known MM susceptibility genes [cyclin-dependent kinase inhibitor 2A ( CDKN2A ), cyclin-dependent kinase 4, melanocortin 1 receptor ( MC1R ) and tyrosinase ( TYR )] were resequenced in 109–135 MM cases. The significance of variants was examined by comparing their frequencies in 390 cancer-free controls. Potential deleterious mutations in CDKN2A were found in two patients and two others had variants of unknown significance. Cases were more likely than controls to harbour the MC1R 'R' variants known or predicted to alter its function ( P  = 0.002), particularly the R160W variant ( P  = 0.0035). The associated TYR R402Q variant (rs1126809*A) was found in 29% of cases, similar to what has been described previously. One MM patient with a family history of MM, who had developed other skin cancers, was homozygous for a novel TYR variant (P406L) of unknown significance. Hence, rare variants in TYR may be important risk factors for skin cancer.     

Phase I and pharmacokinetic study of gefitinib in children with refractory solid tumors: a Children's Oncology Group Study.

PURPOSE: Epidermal growth factor receptor is expressed in pediatric malignant solid tumors. We conducted a phase I trial of gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, in children with refractory solid tumors. PATIENTS AND METHODS: Gefitinib (150, 300, 400, or 500 mg/m2) was administered orally to cohorts of three to six patients once daily continuously until disease progression or significant toxicity. Pharmacokinetic studies were performed during course one (day 1 through 28). RESULTS: Of the 25 enrolled patients, 19 (median age, 15 years) were fully evaluable for toxicity and received 54 courses. Dose-limiting toxicity was rash in two patients treated with 500 mg/m2 and elevated ALT and AST in one patient treated with 400 mg/m2. The maximum-tolerated dose was 400 mg/m2/d. The most frequent non-dose-limiting toxicities were grade 1 or 2 dry skin, anemia, diarrhea, nausea, and vomiting. One patient with Ewing's sarcoma had a partial response. Disease stabilized for 8 to > or = 60 weeks in two patients with Wilms' tumor and two with brainstem glioma (one exophytic). At 400 mg/m2, the median peak gefitinib plasma concentration was 2.2 microg/mL (range, 1.2 to 3.6 microg/mL) and occurred at a median of 2.3 hours (range, 2.0 to 8.3 hours) after drug administration. The median apparent clearance and median half-life were 14.8 L/h/m2 (range, 3.8 to 24.8 L/h/m2) and 11.7 hours (range, 5.6 to 22.8 hours), respectively. Gefitinib systemic exposures were comparable with those associated with antitumor activity in adults. CONCLUSION: Oral gefitinib is well tolerated in children. Development of the drug in combination with cytotoxic chemotherapy will be pursued.     

ImmunoCyt/uCyt+ improves the sensitivity of urine cytology in patients followed for urothelial carcinoma.

ImmunoCyt/uCyt is a fluorescent test combining three monoclonal antibodies. In this study, it has been tested as a complement to cytology in the detection of urothelial carcinoma in urine. It has been performed simultaneously with standard cytology and cystoscopy on 870 urine analyses from one hospital. In 136 cases, one or more bladder tumors were found. Overall sensitivity of cytology, ImmunoCyt/uCyt and combined analyses reached 29, 74 and 84%, respectively, and overall specificity was 98, 62 and 61%. The negative predictive value of cytology, ImmunoCyt/uCyt and both analyses was 88, 93 and 95%, respectively, and the positive predictive value was 70, 26 and 29%. The sensitivity of cytology for low malignant potential neoplasms, low- and high-grade papillary carcinomas was 6, 18 and 53%, while it reached 71, 79 and 93% when combined with ImmunoCyt/uCyt. The sensitivity of cytology for stages Ta, T1, T2 and over and Tis tumors was 12, 67, 47 and 50%, while it reached 78, 83, 79 and 100% when combined with ImmunoCyt/uCyt. In the absence of tumor on cystoscopy but with positive ImmunoCyt/uCyt, 18% of patients developed a tumor, 2-6 months later. Of the 109 cases diagnosed as suspicious for malignancy by cytology, a tumor was present in 30 cases and ImmunoCyt/uCyt was positive in 22 (73%) of them. In conclusion, ImmunoCyt/uCyt may be used to postpone cystoscopies in patients followed for bladder cancer and may help to save cytologist and pathologist screening time.     

Body mass index and age affect Three-Factor Eating Questionnaire scores in male subjects

This cross-sectional analysis evaluated the effect of age and body mass index (BMI) on Three-Factor Eating Questionnaire scores in males. Subjects (n = 60) were recruited according to BMI status. Each completed the 51-item Three-Factor Eating Questionnaire. The group was split at the median age to produce a “younger” and “older” group for statistical analysis. A 2-way between-groups analysis of variance revealed a significant main effect of BMI on disinhibition (P = .003) and hunger (P = .041) with higher levels found in overweight males compared to healthy-weight counterparts. A significant main effect of age on hunger (P = .046) demonstrated older males were less susceptible to hunger than younger males. These insights provide a better understanding of eating behavior across the male life cycle and may assist health professionals to better guide men in weight management in the light of rising overweight/obesity.     

Understanding the minimum clinically important difference: a review of concepts and methods.

BACKGROUND CONTEXT: The effectiveness of spinal surgery as a treatment option is currently evaluated through the assessment of patient-reported outcomes (PROs). The minimum clinically important difference (MCID) represents the smallest improvement considered worthwhile by a patient. The concept of an MCID is offered as the new standard for determining effectiveness of a given treatment and describing patient satisfaction in reference to that treatment. PURPOSE: Our goal is to review the various definitions of MCID and the methods available to determine MCID. STUDY DESIGN: The primary means of determining the MCID for a specific treatment are divided into anchor-based and distribution-based methods. Each method is further subdivided and examined in detail. METHODS: The overall limitations of the MCID concept are first identified. The basic assumptions, statistical biases, and shortcomings of each method are examined in detail. RESULTS: Each method of determining the MCID has specific shortcomings. Three general limitations in the accurate determination of an MCID have been identified: the multiplicity of MCID determinations, the loss of the patient's perspective, and the relationship between pretreatment baseline and posttreatment change scores. CONCLUSIONS: An ideal means of determining the MCID for a given intervention is yet to be determined. It is possible to develop a useful method provided that the assumptions and methodology are initially declared. Our efforts toward the establishment of a MCID will rely on the establishment of specific external criteria based on the symptoms of the patient and treatment intervention being evaluated.     

Dépistage organisé du cancer colorectal

Acta Endoscopica - C’est un test de sélection. C’est un outil important de communication et d’information, c’est dire si elle doit être connue, comprise et bien...     

Review of determinants of patients' preferences for adjuvant therapy in cancer.

PURPOSE: Many studies have determined cancer patients' preferences for adjuvant therapy, for example, by asking patients the extent of benefit they would need in order to accept the therapy. However, little is known about the determinants that influence these preferences. Our research goal was to explore which determinants underlie patients' preferences by means of a literature review. METHODS: PubMed searches were conducted to identify studies in which cancer patients' preferences for adjuvant therapy had been elicited by means of a treatment preference instrument. Twenty-three papers were evaluated with regard to reported relationships between preferences and potential determinants. A total of 40 determinants were recorded and classified into one of seven categories: (1) treatment-related determinants, (2) sociodemographic characteristics and current quality of life, (3) clinical characteristics, (4) measurement instrument-related determinants, (5) time-related determinants, (6) cognitive/affective determinants, and (7) specialist-related determinants. Results: The benefit and toxicity of treatment, experience of the treatment, and having dependents (eg, children) living at home were important determinants of patients' preferences. Furthermore, qualitative data suggested that cognitive/affective and specialist-related determinants might have a large impact on patients' treatment preferences. CONCLUSION: Our results show that patients' preferences cannot fully be explained on the basis of treatment-related determinants and patient and clinical characteristics. More research is needed in the area of cognitive/affective and specialist-related determinants because of the lack of quantitative results. Furthermore, we recommend carrying out larger studies in which the (internal) relationships between determinants and preferences are assessed in the context of a cognitive cost-benefit model.