Severity of demyelination in vivo correlates with serum myelination inhibition activity in guinea pigs having a new form of experimental allergic encephalomyelitis

Guinea pigs received a suboptimal transfer of lymphocytes sensitized to myelin basic protein (BP) and were then immunized with guinea pig BP, BP plus chicken brain or chicken myelin, or chicken brain alone. Sera from these animals were tested for the presence of myelinotoxic antibodies, as detected by the myelination inhibition assay. Myelination inhibition activity correlated with the histologic severity of demyelination.     

Complex open elbow fracture Gustilo-Anderson type IIIB treated with the primary elbow arthroplasty: A case report

Total elbow arthroplasty as a treatment option for open elbow fracture is relatively rare described. We reported a 39 years old polytrauma patient with complex open elbow fracture (Gustilo-Anderson type IIIB). The patient presented with large soft tissues defect on dorsal part of the left elbow, ulnar palsy due to the irreparable loss of the ulnar nerve, distal triceps loss due to the complete loss of the olecranon, loss of both humeral condyles with collateral ligaments and complex elbow instability. Only few similar cases have been published. Reconstructive surgery included repetitive radical debridement, irrigation, vacuum assisted closure system therapy, external fixation, coverage of the soft tissue defect with fascia ecutaneous flap from the forearm. Four months after the injury, total elbow arthroplasty with autologous bone graft (from the proximal radius) inserted in the ulnar component, was performed. At 3 years postoperatively, the patient is able to perform an active flexion from 0 to 110 with full pronosupination. Only passive extension is allowed. The ulnar neuropathy is persistent. Patient has no signs of infection or loosening of the prosthesis.     

Comparison of non-invasive approaches to red marrow dosimetry for radiolabelled monoclonal antibodies

Red marrow is usually the dose-limiting organ during radioimmunotherapy. Several non-invasive approaches to calculate the red marrow dose have been proposed. We compared four approaches to analyse the differences in calculated red marrow doses. The data were obtained from immunoscintigraphy of two antibodies with different red marrow kinetics [iodine-131-16.88 IgM and indium- 111-OV-TL-3 F(ab)₂]. The approaches are based on, respectively, homogeneously distributed activity in the body, a red marrow-blood activity concentration ratio of 0.3, scintigraphic quantification, and a combination of the second and third approaches. This fourth approach may be more adequate because of its independence from the chosen antibody. In addition, the influence of activity accumulation in liver, kidneys or cancellous bone on red marrow dose was studied. The calculated red marrow dose varied between 0.14 and 0.42 mGy/MBq for ¹¹¹ In-OV TL-3 and between 0.13 and 0.68 mGy/MBq for ¹³¹I-16-88. If the radiopharmaceutical shows high affinity for cancellous bone or another organ situated near the red marrow, the activity in these organs must be included in dose calculations. This study shows a large variation in calculated red marrow dose and selection of the definitive non-invasive approach awaits validation. Correspondence to: M.A.B.D. Plaizier     

A Clinical Screening Cooperative Group phase II evaluation of lobaplatin (ASTA D-19466) in advanced head and neck cancer

Summary We evaluated the efficacy and tolerability of lobaplatin, a new platinum compound, given at the dose of 50 mg/m² by i.v. bolus every 4 weeks, in 49 patients with advanced and/or metastatic squamous cell carcinoma of the head and neck (SCCHN). One complete and 2 partial responses were observed in 43 eligible patients for an overall response rate of 7% (95% confidence interval: 1–19%). The duration of responses was 11, 16 and 32 weeks. Toxicities of WHO grade 3 were hematologic: thrombocytopenia in 26%, granulocytopenia in 12% and anemia in 12% of patients. There was no therapy-related death. Nausea/vomiting, diarrhoea and paresthesia were mild and rare. In conclusion, lobaplatin was well tolerated, but its efficacy in advanced SCCHN at the presented dose and schedule, was marginal.     

Mathematical Ability and Lateral Asymmetry

The hypothesis that special ability in mathematics is associated with a reduction in bias to dextral preference and skill was examined in several samples of students and in 97 male and 27 female teachers of mathematics, mainly in Universities and Polytechnics. The maths students and maths teachers differed from controls, both general and academic, in the direction predicted and several comparisons were statistically significant. Differences were in most cases clearer for males than females.An analysis of the findings in relation to the right shift (RS) theory of handedness (Annett, 1972, Annett, 1978) suggests that the incidence of left preference and skill is slightly raised in mathematicians not because of any intrinsic advantage of left preference but rather because extreme bias to the right, as expected in those carrying a hypothesised rs++ genotype, is disadvantageous for mathematical thinking. If the role of mathematics can be regarded as one of developing languages to describe those aspects of human experience which otherwise could be understood only in visuo-spatial images, it can be seen to require a coordination of those aspects of human intelligence which have been distinguished as depending differentially on the left and right cerebral hemispheres. The present findings suggest that this process might be impeded by a double dose of a gene which promotes left hemisphere language specialisation.     

Chronic fluphenazine treatment modifies circadian rhythms of neurotransmitter receptor binding in rat brain

Summary Binding to rat brain- and-adrenergic, muscarinic cholinergic, dopamine and opiate receptors was measured at 4-hour intervals throughout a 24-hour period in animals, chronically treated with fluphenazine, and in controls. Drug treatment significantly changed characteristics of the circadian rhythms in all 5 receptors. In the presence of the drug the 24-hour mean binding to the dopamine receptor was decreased; to the other 4 receptors it was increased. Moreover, there were changes in the timing of the maximal receptor binding (phase-position) and in the amplitude of the rhythms. These results extend previous studies, showing that chronic neuroleptic treatment not only affects the dopamine receptors, but also other neurotransmitter receptors, profoundly modifying their temporal organisation.     

Development of fluridil,a topical suppressor of the androgen receptor in androgenetic alopecia

Nonsteroidal antiandrogens (AA) cannot be topically used for androgenetic alopecia (AGA) because of systemic resorption. A new class of androgen receptor (AR) suppressors designed for safe topical treatment of AGA was synthesized from (3‐amino‐2‐hydroxy‐2‐methyl‐N‐(4‐nitro‐3‐trifluoromethyl)phenyl) propanamide (BP‐34), to contain perfluoroalkyl moieties. The trifluoromethyl derivative (fluridil) at 10 μM decreased expression of the AR in LNCaP human cells by 95%, its serum half‐life was 6 h; it decomposes hydrolytically to BP‐34 and trifluoroacetic acid. Acute intraperitoneal maximum tolerated dose (MTD) of fluridil in mice is 270–300 mg/kg/d and the subacute MTD is 450 mg/kg/d. The oral LD₅₀ in mice was 2,872 mg/kg in males, 2,232 mg/kg in females, and >2,500 mg/kg in rats. Fluridil solution in isopropanol was not cutaneously absorbed in rabbits, did not sensitize or show any phototoxic or photoallergic effects on guinea pig skin, and demonstrated no skin irritation potential in rabbits and humans. Fluridil solid induced only slight and reversible eye irritancy in rabbits and displayed no cytotoxicity to rabbit corneal fibroblasts in vitro. Fluridil demonstrated no significant mutagenicity potential by Ames method. In a double‐blind study, 43 males with AGA, Norwood grade II to Va, used topical 2% fluridil in isopropanol or the vehicle daily for 12 months. Anagens (growing hairs) increased in the fluridil group from 76% to 89%. All hematological and biochemistry values remained within normal range, including testosterone, which varied but seasonally. No fluridil or its decomposition product (BP‐34) was detected in serum. No adverse side effects were reported. Drug Dev. Res. 59:292–306, 2003. © 2003 Wiley‐Liss, Inc.     

Colorectal cancer screening knowledge, attitudes, and beliefs among veterans: does literacy make a difference?

PURPOSE: To evaluate whether lower literacy is associated with poorer knowledge and more negative attitudes and beliefs toward colorectal cancer screening among veterans without recent colorectal cancer screening. PATIENTS AND METHODS: Three hundred seventy-seven male veterans, age 50 years and older, who had not undergone recent colorectal cancer screening, were surveyed about their knowledge, attitudes, and beliefs regarding colorectal cancer screening. Patients' literacy was assessed with the Rapid Estimate of Adult Literacy in Medicine, an individually administered screening test for reading. RESULTS: Thirty-six percent of the 377 men had an eighth grade literacy level or higher. Men with lower literacy were 3.5 times as likely not to have heard about colorectal cancer (8.8% v 2.5%; P =.006), 1.5 times as likely not to know about screening tests (58.4% v 40.9%; P =.0001), and were more likely to have negative attitudes about fecal occult blood testing (FOBT), but not about flexible sigmoidoscopy. Specifically, men with lower literacy skills were two times as likely to be worried that FOBT was messy (26.7% v 13.3%; P =.008), 1.5 times as likely to feel that FOBT was inconvenient (28.7% v 18%; P =.05), and four times as likely to state they would not use an FOBT kit even if their physician recommended it (17.9% v 4.0%; P =.02). CONCLUSION: Limited literacy may be an overlooked barrier in colorectal cancer screening among veterans.