Contributions of occipital and temporal brain regions to visual and acoustic imagery--a spect study

Regional cerebral blood flow (rCBF) was assessed by means of HMPAO-SPECT in two experimental groups. In a control condition both groups listened to abstract words, in the experimental condition they heard five names of objects. One group was advised to form visual images of the objects, the other group was advised to form acoustic images of the sounds made by these objects. Post-experimental questionnaires revealed that most of the subjects in the acoustic imagery condition had had visual images in addition to the acoustic ones. Both imagery conditions lead to approximately equal increases of rCBF in the left inferior occipital region and in the left thalamus. Flow increases in both hippocampal regions and the right inferior and superior temporal regions were larger in the acoustic than in the visual imagery condition. It is concluded that only the activation of left inferior occipital and left thalamic regions can be interpreted as being related to modality-specific visual aspects of imagery.     

Carnitine palmitoyltransferase deficiency in a patient with severe psychomotor retardation

A 13-year-old girl who had severe brain damage due to unknown prenatal cause presented rhabdomyolysis triggered by a mild viral infection. Her muscle biopsy revealed mild variation in fiber size and type 2 fiber atrophy without excess lipid storage. Biochemical analysis of the biopsied material showed decreased carnitine palmitoyltransferase (CPT) activity (15% of the control). Serum and urinary carnitine levels were normal. Skeletal muscle CT scanning showed multiple low density spots. The patient was diagnosed as having CPT deficiency. She recovered from rhabdomyolysis without renal failure after a month with conservative therapy. CPT deficiency is usually found in young healthy persons. This is the first case report of CPT deficiency which presented severe psychomotor retardation since neonatal period.     

Randomized trial of bilateral oophorectomy versus tamoxifen in premenopausal women with metastatic breast cancer

A randomized clinical trial was performed to compare the efficacy of bilateral oophorectomy with that of tamoxifen at a dose of 10 mg twice daily in premenopausal women with metastatic breast cancer, and to examine the efficacy of each as a crossover treatment. Initial treatment responses were seen in ten of 27 patients (37%) treated with oophorectomy and seven of 26 patients (27%) treated with tamoxifen. The difference was not statistically significant. Crossover responses were seen in five of 15 patients (33%) treated with oophorectomy, including three responses in ten prior tamoxifen nonresponders; and two of 18 patients (11%) treated with tamoxifen. Time to progression distributions were not significantly different during initial treatment, and no significant differences in survival were noted. Thus, there was no overall disadvantage to the use of tamoxifen as opposed to oophorectomy as initial hormonal therapy, and a failure to respond to tamoxifen did not preclude a response to subsequent oophorectomy. Exploratory data analysis within subsets indicated consistent differential treatment effects in the visceral dominant patients. Of the 16 such patients treated with oophorectomy, eight (50%) experienced objective responses but there were no responses in the 14 patients treated with tamoxifen. In the nine visceral dominant crossover patients who had not responded to initial tamoxifen, three (33%) subsequently responded to oophorectomy. Time to progression distributions within the visceral dominant subset appeared to be better for the patients treated initially with oophorectomy. However, one must be very cautious in drawing conclusions from exploratory subset analyses, especially with the small sample size. Further studies would be required to test any hypothesis of differential organ site responsiveness.     

Gating modifier toxins of voltage-gated calcium channels.

Some of the most potent and specific inhibitors of voltage-gated calcium channels are peptide toxins that inhibit channel function not by occlusion of the channel pore, but rather by interfering with the voltage dependence and kinetics of channel opening and closing. Many such gating modifier toxins conform to the inhibitor cystine knot structural family and have primary sequence or functional mechanism similar to toxins that target voltage-gated sodium or potassium channels. This review introduces known gating modifiers of calcium channels, discusses the selectivity, binding sites, and mechanism of the toxin-channel interaction, and reviews the usefulness of these toxins as research tools and as the basis for novel calcium channel pharmacology and therapeutics.     

Platelet function in patients with acute coronary syndrome (ACS) predicts recurrent ACS

BACKGROUND: Platelet hyperfunction contributes to acute coronary syndromes (ACS). Thus, we hypothesized that platelet function under high shear stress predicts recurrent ACS during long-term follow-up of ACS patients. PATIENTS AND METHODS: Consecutive ACS patients (n = 208) were prospectively followed-up for an average of 28 months. Platelet function was measured with the platelet function analyzer (PFA-100; Dade Behring, Marburg, Germany) at baseline for collagen/adenosine diphosphate closure times (CADP-CT) and for collagen/epinephrine closure times (CEPI-CT) after infusion of a uniform dose of 250 mg aspirin. RESULTS: Of the conventional risk factors, only the prevalence of diabetes was higher in ACS patients with re-events. However, use of clopidogrel and use of beta blockers were also slightly lower in patients with re-events (P < 0.05). The unadjusted risk hazard ratio (HR) for re-events was 3.3 [95% confidence interval (95% CI): 1.4-7.4; P = 0.005] in those patients with the shortest CADP-CT values (lowest quartile). Similarly, the risk was 2.0-fold higher (95% CI: 1.1-3.6; P = 0.02) in ACS patients with CEPI-CT < 300 s as compared with CEPI-CT >or = 300 s. Inclusion of diabetes, clopidogrel and beta blockers in a multivariate Cox regression model enhanced the predictive value of CEPI-CT (HR: 2.7). Inclusion of von Willebrand factor levels did not alter the HR for recurrent ACS (HR: 2.1; 95% CI: 1.1-5.2; P = 0.03) for CEPI-CT < 300 s, but reduced the HR for CADP-CT (HR: 2.8, 95% CI: 0.8-9.8; P = 0.11). CONCLUSION: Shortened CT values reflect biologically relevant platelet hyperfunction in patients with ACS because they predict recurrent ACS.     

Causes of B chromosome variant substitution in the grasshopper Eyprepocnemis plorans

We have analysed B chromosome frequency for three consecutive years, B transmission rate at population and individual levels, clutch size, egg fertility and embryo–adult viability in a natural population of the grasshopper Eyprepocnemis plorans containing two different B chromosome variants, i.e. B₂ and B₂₄, the second being derived from the first and having replaced it in nearby populations. From 2002 to 2003 the relative frequency of both variants changed, although the differences did not reach significance. A mother–offspring analysis showed no significant effect of any of the two B variants on clutch size, egg fertility or embryo–adult viability, but B₂₄ was more efficiently transmitted than B₂ through males from the 2002 season, which explains the observed frequency change. Controlled crosses, at individual level, showed significant drive through some females for B₂₄ but not for B₂, suggesting that this difference in transmission rate might also be important for the substitution process. The analysis of relative fitness for B₂ and B₂₄ carriers for all fitness components, as a whole, showed a significantly better performance of B₂₄-carrying individuals, suggesting that the cumulative effect of these slight differences might contribute to the replacement of B₂ by B₂₄. Electronic Supplementary Material Supplementary material is available for this article at .     

The advisory process for anticancer drug regulation: a global perspective.

PURPOSE: This paper summarizes the role of external advisors in oncology drug development and regulation from a global perspective. DESIGN: Recently, representatives from the United States Food and Drug Administration, European Medicines Agency, the Japanese Pharmaceuticals and Medical Devices Agency, the Australian Therapeutic Goods Administration and Health Canada held a meeting in conjunction with the American Society of Clinical Oncology meeting. The role of external advisors in oncology drug development and regulation in each of these jurisdictions was presented and discussed. RESULTS: All regulatory bodies described have experience with two forms of outside expertise: advice from individual experts and advice from a group of experts assembled as an advisory group. Regulatory jurisdictions use individual experts variably. In some regions, individual experts provide advice based on knowledge and experience during the drug development phase or in the planning phase for the submission of a drug registration package. In other regions, these individuals serve as external evaluators with the primary responsibility for the review of a clinical trials package submitted for drug registration. Advisory boards have been formalized in all jurisdictions discussed. Advisory boards have a role in discussing specific applications as well as broad policy issues. A common theme is a composition of a core panel of experts with augmentation by additional expertise as needed for consideration of specific scientific questions. In all jurisdictions, advisory board recommendations are not binding on the regulatory body. CONCLUSIONS: Global oncology drug development and registration involves the use of experts by regulatory authorities. The types of experts needed, the expert's role and the transparency of the advisory process reflect the individual needs in different regions.