Reduced regional cerebral blood flow in SPG4-linked hereditary spastic paraplegia

Hereditary spastic paraplegia (HSP) linked to the spastic gait gene 4 (SPG4) is controversial, as the "pure" form traditionally has been considered confined to the long axons of the spinal cord. However, recent immunolabeling experiments have demonstrated extensive Spastin expression in the cortex and striatum. This could indicate a more widespread neuropathology from mutations in the SPG4 gene than previously assumed. The aim of this study was therefore to ascertain the extent of cerebral involvement in SPG4 linked HSP by neuropsychological examination and measurement of the regional cerebral blood flow (rCBF) as an indirect marker of regional neuronal activity. Eighteen SPG4 patients and 18 matched control subjects were studied. Resting state rCBF was measured using Positron Emission Tomography (PET) and the (15)O-labelled water bolus technique and relative group differences were explored using Statistical Parametric Mapping (SPM 99). Neuropsychological assessment was performed using established and nationally validated tests (RH Basic Battery). Compared to healthy controls, the patient group had significantly decreased rCBF in the left fronto-temporal cortex (P<0.05), and more extensive changes were observed in a separate analysis of the most disabled individuals. The neuropsychological assessment revealed only significantly impaired recognition memory for faces. In summary, the findings support cerebral pathology in SPG4-linked HSP, although the decreased rCBF in fronto-temporal cortex was not associated with severe cognitive impairment.     

Reducing atrial tachycardia and atrial fibrillation episodes with a prevention and treatment device and tailored treatment

BACKGROUND: Pacemaker treatment of known trigger mechanisms for atrial tachyarrhythmias (AT) and atrial fibrillation (AF) has shown reduction in the incidence of AF. A new arrhythmia management device, which included storage of AT/AF (for tailoring treatment) and three prevention algorithms and one for treatment, was examined in order to identify the influence on arrhythmia episodes over a 12-month follow-up (FU) period. METHODS: Twenty-three consecutive patients with known tachybradyarrhythmias were examined. Seven patients had to be excluded (two outliers, four developed permanent AF, one had no detection algorithm turned on at implantation). The remaining 16 patients showed 2723 episodes (675 treated episodes) for evaluation of the effect on episodes/month/patient (e/m/p), treatment success, duration of episodes, circadian distribution and quality of life. RESULTS: The AT/AF e/m/p were reduced from 37 +/- 102 e/m/p at 1-month FU to 16 +/- 48 e/m/p at 3-month FU, 15 +/- 48 e/m/p at 6-month FU and 10 +/- 28 e/m/p at 12-month FU (p < 0.05), according to fewer subjective symptoms. Treatment success remained stable during the observation period (29-40%). Only minor changes in the duration of episodes and the distribution of start times were observed. CONCLUSION: Tailoring treatment by the pacemaker examined with several prevention and treatment algorithms reduces e/m/p and might be a promising supplement in the treatment of selected patients with known AT/AF and bradycardia.     

Absence of the genetic variant Val79Met in human chorionic gonadotropin-beta gene 5 in five European populations

Chorionic gonadotropin (CG) is an essential signal in establishment and maintenance of pregnancy in humans and higher primates. A G-to-A transition in exon 3 of human CGbeta gene 5, changing the naturally occurring valine residue to methionine in codon 79 (Val(79)Met) has been reported at carrier frequency 4.2% in a random population from the Midwest of the United States. The biological activity of the variant hCG was similar to that of wild-type (WT) hCG. However, the Val(79)Met beta-subunit displayed impaired ability to assemble with alpha-subunit, and the amount of hCG alpha/beta heterodimers formed and secreted by transfected cells was seriously impaired in the previous study. Because of these functional implications we found it important to study the occurrence of the Val(79)Met hCGbeta variant in other populations. By using a PCR-RFLP method, a search for the Val(79)Met hCGbeta variant was carried out on a total of 580 DNA samples from five European populations (Finland, Denmark, Greece, Germany and the UK). The results demonstrated an absence of the polymorphism in these populations. Hence, the naturally occurring variant (Val(79)Met) of the hCGbeta gene 5, found previously at high frequency in the US, is clearly less common, or absent, in the European populations studied.     

Color Doppler tissue velocity imaging can disclose systolic left ventricular asynchrony independent of the QRS morphology in patients with severe heart failure

A QRS width greater than 120 ms is assumed to be a marker of inter- and intraventricular asynchrony in severe heart failure (HF) patients. Color Doppler tissue velocity imaging (c-TVI) with a time resolution of 10 ms was used to study regional left ventricular (LV) longitudinal systolic contraction pattern in HF patients with left and right bundle branch block (LBBB and RBBB) and in patients with normal QRS width. We studied 12 women and 23 men with severe HF, with a mean age of 66 +/- 11 years in New York Heart Association functional Class 2.9 +/- 0.6. Twenty patients had LBBB and 10 of those were accepted for cardiac resynchronization therapy by biventricular pacing (CRT). Ten patients had normal QRS width, and five had RBBB. In the echocardiographic apical four chamber view, regional peak LV tissue velocities and regional LV time differences of peak tissue velocities were compared at basal and mid-LV segments. There were no significant differences in regional mean peak tissue velocities among the patient groups. In patients with LBBB accepted for CRT, the LV lateral free-wall movement at basal LV was 29 ms delayed during main systole, almost significantly different from LBBB patients not accepted for CRT (P = 0.075). Even in HF patients with normal QRS width or RBBB, significant asynchronous longitudinal LV contraction was observed. Conclusions: For the detection of regional longitudinal LV contraction asynchrony in patients with severe HF, supplementary methods to the surface ECG, such as c-TVI, are strongly recommended.     

Feasibility of color doppler tissue velocity imaging for assessment of regional timing of left ventricular longitudinal movement

OBJECTIVE--The feasibility of color Doppler tissue velocity imaging (c-TVI) with a high time resolution of 10 ms for simultaneous measurement of the temporal characteristics of regional left ventricular (LV) tissue velocities at different LV sites was examined. Methods and results--In 20 subjects with structurally normal hearts, inter- and intraobserver agreement and the beat-to-beat variation were tested in c-TVI profiles from basal and mid-LV segments of the interventricular septum (IS) and of the lateral free wall (LFW). For peak tissue velocities a mean error of less than 1 cm/s was demonstrated. For systolic regional LV velocity time difference, the mean error was +/- 5 ms, with the best agreement when sampling from basal LV sites. For diastolic regional LV velocity time differences, the mean error was +/- 12 ms. The longitudinal LV movement pattern demonstrated a pattern of incremental tissue velocity from basal to mid-LV, and from IS to LFW sites. Conclusion--The c-TVI method has acceptable inter- and intraobserver agreement and is sufficiently accurate to disclose regional time aspects of LV contraction and relaxation.     

The effect of single dose ivermectin alone or in combination with albendazole on Wuchereria bancrofti infection in primary school children in Tanzania

Examination of 1829 children from 6 primary schools in coastal Tanzania revealed overall Wuchereria bancrofti microfilaria (mf) and circulating filarial antigen (CFA) prevalences of 17.3% and 43.7%, respectively. A randomized double-blind field trial with a single dose of ivermectin (150-200 microg/kg body weight) alone or in combination with albendazole (400 mg) was subsequently carried out among these children. Both treatment regimens resulted in a considerable decrease in mean mf intensities, with overall reductions being slightly but statistically significantly higher for the combination than for ivermectin alone. The difference in effect between the two treatment regimens was most pronounced at 6 months, whereas it was minor at 12 months after treatment. The relative effect of treatment on mean CFA units was less pronounced than on mf. For both treatment regimens, reductions in CFA intensity appeared to be higher in children who were both CFA and mf positive before treatment, which may suggest that treatment mainly affected the survival and/or production of mf, rather than the survival of adult worms. New cases of infection appeared after treatment with both regimens among the pre-treatment mf and CFA negative children. Adverse reactions were few and mild in both groups, and mainly reported from pre-treatment mf and CFA positive children. The alarmingly high prevalence of W. bancrofti infection in primary school children highlights the importance of also determining the reversibility of already acquired early lesions, and the development of new measures and strategies to specifically protect children from later developing clinical disease.     

In vitro uptake of a new cholesteryl carborane ester compound by human glioma cell lines

The cellular uptake and retention of a new cholesteryl carborane ester compound, cholesteryl 1,12-dicarba-closo-dodecaboranel-carboxylate (BCH), by two human glioma cell lines, glioblastoma multiforme SF-763 and SF-767, was evaluated. BCH, which is an extremely hydrophobic compound, was formulated into liposomes and incubated with two human glioma tumor cell lines and one human normal neuron cell line. The amount of BCH uptake by the cells was measured by high performance liquid chromatography. The effects of BCH concentration in the culture medium and the incubation time on the cellular uptake of BCH were studied. In addition, BCH uptake by tumor cells was examined in the presence and absence of lipoprotein in the culture medium. It was found that the amount of BCH taken by the glioma cell lines was much more (up to 14 times) than that by the normal neuron cell line. The cellular uptake of BCH was related to the amount of BCH in the medium as well as the incubation time. The cellular uptake of BCH by SF-763 and SF-767 cells after 16 h of incubation was 283.3 +/- 38.9 and 264.0 +/- 36.5 microg boron/g cells, respectively. The majority of BCH taken up in tumor cells was retained after the subsequent incubation. In the presence of lipoprotein, the cellular uptake of BCH by SF-767 tumor cells was about four times as much as that in the absence of lipoprotein. In conclusion, the cellular uptake of BCH by glioma cells was about 14 times higher than by normal neuron cells. The uptake in glioma cells was up to 10 times higher than that required for successful cancer treatment and BCH was well retained in the tumor cells. Lipoprotein seemed to have an important role in the BCH uptake by glioma cells.     

Reducing the duration of untreated first-episode psychosis: effects on clinical presentation

CONTEXT: Most studies on first-episode psychosis show an association between a long duration of untreated psychosis (DUP) and poorer short-term outcome, but the mechanisms of this relationship are poorly understood. OBJECTIVE: To determine whether it is possible to reduce the DUP for first-episode patients in a defined health care area through the introduction of an early detection (ED) program, compared with parallel health care areas without an ED program (No-ED). SETTING AND PATIENTS: We included consecutive patients with a DSM-IV diagnosis of nonorganic, nonaffective psychosis coming to their first treatment in the study health care areas between January 1, 1997, and December 31, 2000. A total of 281 patients (76% of the total) gave informed consent. INTERVENTIONS: The ED and No-ED health care areas offered an equivalent assessment and treatment program for first-episode psychosis. The ED area also carried out an intensive ED program. RESULTS: The DUP was significantly shorter for the group of patients coming from the ED area, compared with patients from the No-ED areas (median, 5 weeks [range, 0-1196 weeks] vs 16 weeks [range, 0-966 weeks]). Clinical status measured by the Positive and Negative Syndrome Scale and the Global Assessment of Functioning Scale was significantly better for patients from the ED area at start of treatment and, with the exception of Positive and Negative Syndrome Scale positive subscale, at 3 months. Multiple linear regression analyses gave no indication that confounders were responsible for these differences. CONCLUSIONS: It is possible to reduce the DUP through an ED program. The reduction in DUP is associated with better clinical status at baseline that is maintained after 3 months.     

Unveiling the foveal blue scotoma through an afterimage

The absence of short-wave-sensitive (S-) cones in the human foveola normally goes unnoticed, but the resulting foveal S-cone, or blue, scotoma can be visualized as the negative afterimage of a short-wavelength adapting field on a larger white background. The afterimage has an annular shape with a lighter inner region that corresponds to Maxwell's spot, and a small bright spot in the center corresponding to the foveal blue scotoma. We have shown that the visibility of the center spot in the afterimage approximately follows the spectral sensitivity curve of the S-cones. We further demonstrate that the central bright spot subtends a retinal area that is coincident with the tritanopic region of the foveola. The macular pigment distribution measured for the same observers also peaks in the central fovea, but has a relatively high density over a broader retinal region than the bright spot in the negative afterimage, and more closely corresponds to the lighter annular region of the afterimage. The results support the hypothesis of an active post-receptoral process for filling-in of chromatic scotomas.