Partial replication of a DRD4 association in ADHD individuals using a statistically derived quantitative trait for ADHD in a family-based association test.

BACKGROUND: Previous research found an association between single nucleotide polymorphisms (SNPs) in the promoter region of DRD4 and statistically derived phenotypes generated from attention-deficit/hyperactivity disorder (ADHD) symptoms. We sought to replicate this finding by using the same methodology in an independent sample of ADHD individuals. METHODS: Four SNPs were genotyped in and around DRD4 in 2631 individuals in 642 families. We developed a quantitative phenotype at each SNP by weighting nine inattentive and nine hyperactive-impulsive symptoms. The weights were selected to maximize the heritability at each SNP. Once a quantitative phenotype was generated at each SNP, the screening procedure implemented in PBAT was used to select and test the five SNPs/genetic model combinations with the greatest power to detect an association for DRD4. RESULTS: One of the four SNPs was associated with the quantitative phenotypes generated from the ADHD symptoms (corrected p-values = .02). A rank ordering of the correlation between each of the ADHD symptoms and the quantitative phenotype suggested that hyperactive-impulsive symptoms were more strongly correlated with the phenotype; however, including inattentive symptoms was necessary to achieve a significant result. CONCLUSIONS: This study partially replicated a previous finding by identifying an association between rs7124601 and a quantitative trait generated from ADHD symptoms. The rs7124601 is in linkage disequilibrium (LD) with the SNPs identified previously. In contrast to the previous study, this finding suggests that both hyperactive-impulsive and inattentive symptoms are important in the association.     

Evaluation of an accelerated protocol for detection of extended-spectrum beta-lactamase-producing gram-negative bacilli from positive blood cultures

We evaluated a protocol for the accelerated detection of extended-spectrum beta-lactamases (ESBLs) in gram-negative bloodstream pathogens. Two hundred eighty-three blood culture bottles were subjected to direct ESBL testing by inoculating samples directly from blood culture bottles onto agar plates containing cefotaxime and ceftazidime disks, with and without clavulanate. Standard ESBL testing in accordance with the NCCLS guidelines after subculturing on agar plates was performed in parallel. Results of the direct ESBL testing were reported 2.3 days sooner and were comparable to those of the standard NCCLS method with sensitivity, specificity, and positive and negative predictive values of 100, 98, 94, and 100%, respectively.     

Molecular and antigenic characterization of a highly evolved derivative of the type 2 oral poliovaccine strain isolated from sewage in Israel

An unusual, highly diverged derivative of the Sabin type 2 oral poliovaccine (OPV) strain was recovered from environmental samples during routine screening for wild polioviruses. Virus was cultivated in L20B cells and then passaged on BGM cells at 40 degrees C (RCT [reproductive capacity at supraoptimal temperature]-positive marker) to select against most OPV strains. All but 1 of 25 RCT-positive OPV-derived environmental isolates were antigenically and genetically (>99.5% VP1 sequence match) similar to the respective Sabin strains. However, isolate PV2/4568-1/ISR98 (referred to below as 4568-1) escaped neutralization with Sabin 2-specific monoclonal antibodies and cross-adsorbed sera, and had multiple nucleotide substitutions (220 of 2,646; 8.3%) in the P1 capsid region. Fourteen of the 44 associated amino acid substitutions in the capsid mapped to neutralizing antigenic sites. Neutralizing titers in the sera of 50 Israeli children 15 years old were significantly lower to 4568-1 (geometric mean titer [GMT], 47) than to Sabin 2 (GMT, 162) or to the prototype wild strain, PV2/MEF-1/EGY42 (GMT, 108). Two key attenuating sites had also reverted in 4568-1 (A(481) to G in the 5' untranslated region and the VP1 amino acid I(143) to T), and the isolate was highly neurovirulent for transgenic mice expressing the poliovirus receptor (PVR-Tg21 mice). The extensive genetic divergence of 4568-1 from the parental Sabin 2 strain suggested that the virus had replicated in one or more people for approximately 6 years. The presence in the environment of a highly evolved, neurovirulent OPV-derived poliovirus in the absence of polio cases has important implications for strategies for the cessation of immunization with OPV following global polio eradication.     

Integration of viral into chromosomal deoxyribonucleic acid in an inducible line of polyoma-transformed cells

RNA-DNA hybridization has shown that in poiyoma-transformed rat cells which can be induced to synthesize infectious virus (LPT cells), polyoma DNA sequences are associated with chromosomal DNARNA complementary to the viral DNA (cRNA) was synthesized in vitro, using purified viral DNA as a template and Escherichia coli RNA polymerase. High-molecular-weight chromosomal DNA was fractionated from linear and supercoiled viral DNA molecules by centrifugation of whole cells through alkaline glycerol gradients. Hybridization carried out between the cRNA and fractionated chromosomal DNA showed that the amount of RNA hybridized to the LPT DNA was two to three times larger than the amount hybridized to DNA from normal rat cells. cRNA was also hybridized, under the same conditions, with mixtures containing a constant amount of normal cell DNA and varying quantities of purified viral DNA. These assays have established that a linear relationship exists between the amount of cRNA specifically hybridized with a given sample of DNA and the quantity of viral DNA in the sample. Using this relationship, it is estimated that LPT chromosomal DNA contains 6–9 genome-equivalents of polyoma DNA per cell. This quantity represents 18–29% of the amount of polyoma DNA found in the cells, as determined by hybridization of cRNA with unfractionated LPT DNA.To exclude the possibility that the chromosomally associated viral DNA is an artifact due to incomplete removal of the extrachromosomal viral DNA, control experiments were performed in which the cells were superinfected with polyoma virus (m.o.i.-500; 3 hr infection). In these experiments, less than 1% of the viral DNA introduced into the cells by the superinfecting virus were found by the same techniques to be associated with chromosomal DNA. Other experiments show that LPT cells do not contain significant amounts of complex viral DNA molecules which sediment in the vicinity of chromosomal DNA. It is therefore suggested that viral and chromosomal DNA are bound to each other by bonds which cannot be disrupted by alkali treatment.     

Percutaneous absorption of physostigmine: optimization of delivery from a binary solvent by thermodynamic control

A series of binary vehicles was used to deliver physostigmine across dermatomed human skin. The vehicles consisted of isopropyl myristate (IPM) and isopropyl alcohol (IPA) mixed in various volume fractions. The kinetics of penetration is conveniently considered as the sum total of two contributing effects: a "push" process resulting from the excess free energy (delta EG) of the penetrant in the donor vehicle, and a "pull" process resulting from the effect of IPA and IPM on the skin barrier. The inverse ratio of the solubility of the drug in a given vehicle to that in pure IPA was used to estimate the relative delta EG, hence the relative "push" effect. The solubility of physostigmine was highest in pure IPA (delta = 11.5), lowest in pure IPM (delta = 8.5), and intermediate in their various mixtures. But the permeability coefficient (Kp) of physostigmine was highest when delivered from a 1:9 (v/v) solution of IPA:IPM and a calculated delta y = 8.8. A further increase in the volume fraction of IPA caused an opposite decrease in the Kp values of physostigmine. The "steady-state" flux (Jss) of IPA from the same vehicle was lowest at a volume fraction of 1:9 and highest at one of 1:1 IPA:IPM. Thus, the maximal physostigmine penetration enhancing effect of IPA occurs at the lowest flux of IPA found in the present series. This indicates that the "pull" process ascribed to the presence of IPA in the barrier membrane is not important enough to outweigh the decrease in delta EG of physostigmine following an increase in the volume fraction of IPA in the donor vehicle, or that an excess of IPA in the barrier is not conducive to further enhancement of physostigmine diffusivity across the barrier. Optimized percutaneous delivery of physostigmine is possible by thermodynamic control of the penetration process.     

Pyogenic liver abscess: Warning indicator of silent colonic cancer

PURPOSE: Carcinoma of the colon, manifested clinically as an enterococcal hepatic abscess, in the absence of liver metastases, is very uncommon. However, having treated a patient with such a condition, we would like to draw the attention of surgeons to this possibility. Most reports describe secondary infections of hepatic metastases only in patients with a known malignancy. However, increased awareness of colonic cancer as an underlying cause of pyogenic liver abscesses will afford earlier diagnosis and treatment. METHODS: The case was analyzed for history, presentation, laboratory data, radiologic studies, and bacteriology. RESULTS: A 66-year-old woman presented with abdominal pain, fever, and chills. Imaging scans revealed a solitary liver abscess, which was successfully treated with percutaneous drainage and broad-spectrum intravenous antibiotics. Pus cultures grew Streptococcus faecalis.A search for the underlying cause led to the discovery of an adenocarcinoma of the sigmoid colon. CONCLUSIONS: An aggressive search for the underlying cause of pyogenic liver abscesses should be an integral part of the definitive treatment of this disease. After prevailing etiologies have been excluded, silent colonic cancer should be considered.     

The intrauterine ponderal index in relation to birth weight discordance in twin gestations

Objective: To establish the relationship between the fetal ponderal index and birth weight discordance in twins. Method: The fetal ponderal index (estimated fetal weight ÷ femur length³) was calculated in 86 pairs of twins delivered within 2 weeks of the last sonography and analyzed in relation to birth weight discordance. Results: A weak but significant correlation between fetal ponderal index and birth weight (r = 0.26, P < 0.0007) but no correlation with gestational age (r = 0.035, P = 0.65) were found. Members of concordant pairs (<15% birth weight difference) had a significantly higher fetal ponderal index compared with members of mildly (15–25%) discordant pairs (P < 0.02), but not as compared with members of severely discordant (>25%) pairs. Conclusion: The characteristics of the fetal ponderal index in twins are similar to those in singletons. Fetal size seems to be diminished in severe but not in mild discordants. However, in its present form, the fetal ponderal index is a poor predictor of discordant growth and therefore should be employed cautiously in twin gestations.     

Apoptosis as an indicator for steroid sensitivity of lymphocytes in B-chronic lymphocytic-leukemia

Apoptosis, programmed cell death, occurs in a variety of cellular systems and in response to many different stimuli. One group of apoptosis inducers are glucocorticosteroids which are also found in the battery of cytotoxic drugs used to treat CLL. In the present study we have examined the potency of the glucocorticosteroid-dexamethasone to induce apoptosis in lymphocytes of patients with B-CLL. Lymphocytes of 15 nontreated patients and 5 controls were isolated and incubated for 24 h in the presence or absence of dexamethasone (2 mu M) Following incubation the cells were harvested and their DNA extracted. The extracted DNA samples were analysed for internucleosomal DNA cleavage by UV illumination after electrophoresis on agarose slab gel containing ethidium bromide. Five patients showed neither spontaneous nor dexamethasone induced apoptosis. Whereas, 10 patients, showed a dexamethasone-non-dependent spontaneous apoptosis which appeared 24 h after the start of incubation. The cells of these patients were the only ones to respond to dexamethasone showing an enhanced apoptosis effect. This study shows that apoptosis monitoring in CLL may provide important information regarding susceptibility of the cells to steroid induced apoptosis.     

Rehabilitation outcomes of terror victims with multiple traumas

OBJECTIVES: To describe the rehabilitation outcomes of terror victims with multiple traumas, and to compare those outcomes with those of patients with nonterror-related multiple traumas treated in the same rehabilitation facility over the same time period. DESIGN: Retrospective chart reviews. SETTING: Rehabilitation department in a university hospital in Jerusalem, Israel. PARTICIPANTS: Between September 2000 and September 2004, we treated 72 victims of terrorist attacks who had multiple traumas. Among them, 47 (65%) had multiple traumas without central nervous system involvement (MT subgroup), 19 (26%) had multiple traumas with traumatic brain injury (TBI subgroup), and 6 (8%) had multiple traumas with spinal cord injury (SCI subgroup). We matched, according to their types of injury and demographic data, each terror victim with a control patient treated in the same period in our rehabilitation department. INTERVENTION: Interdisciplinary inpatient and outpatient rehabilitation. MAIN OUTCOME MEASURES: Hospital length of stay (LOS) in acute care departments, inpatient and outpatient rehabilitation departments, functional outcome (FIM instrument score), occupational outcome (returning to previous occupation), and psychologic outcome (Solomon PTSD [post-traumatic stress disorder] Inventory). RESULTS: The mean LOS of terror victims was 218+/-131 days; for the nonterror group it was 152+/-114 days (P<.01). In comparison with the control subgroups, the MT subgroup of terrorist victims had significantly longer LOS in the acute care and outpatient rehabilitation departments (P=.06) and the terror TBI subgroup had a longer LOS in outpatient department only (P<.05). The LOS of the SCI patients, both terror victims and control patients, was significantly longer than that of the other 2 subgroups. The difference between FIM value at entry and discharge (DeltaFIM) was significantly higher for terror victims than for the controls (41.1+/-21.6 vs 30.8+/-21.8, P=.002). This difference was mainly the result of the significantly higher DeltaFIM achieved by the terror MT subgroup than by the MT controls. The rate of PTSD was higher among terror victims than among controls (40.9% vs 24.2%, P=.04). The rate of return to previous occupations was similar between terror victims and nonterror patients (53% vs 46.9%, respectively). CONCLUSIONS: Victims of terror spent longer periods in rehabilitation than the nonterror group; however, they regained most activity of daily living functions similar to the nonterror group. Despite the higher rate of PTSD, terror victims succeeded in returning to their previous occupations at a similar rate to that of the nonterror group.