Evaluating Differences in Whole Blood,Serum, and Urine Screening Tests for Zika Virus,Puerto Rico,USA, 2016

We evaluated nucleic acid amplification testing (NAAT) for Zika virus on whole-blood specimens compared with NAAT on serum and urine specimens among asymptomatic pregnant women during the 2015–2016 Puerto Rico Zika outbreak. Using NAAT, more infections were detected in serum and urine than in whole blood specimens.     

Culture and in vitro bromodeoxyuridine-labelling of mouse kidney explants

Summary A method is described for extended mouse renal organ culture and is evaluated for the study of cell proliferation in 1 mm³ explants of renal cortex. Explants were maintained for up to 14 days with cellular viability being sustained at 20% of the original tissue block from day 2. Labelling indices in tuft, capsular and tubular cells ranged from 0 to approximately 20% over the culture period, following in vitro bromodeoxyuridine uptake. This technique offers potential for the study of local effects of inhibitors of proliferation.     

The willingness to continue caring in family supporters of older people

Research has revealed the importance of characteristics of the supporter, the care-recipient, and circumstances of caregiving in the success or failure of community-based care of older people. The Dundee Study of Carers and Dementia examined factors associated with the maintenance and care of older people in the community, and with the impact of dementia on family supporters. Two hundred and twenty-eight family supporters of community-resident older people (≥65) (50% with dementia, 50% without, matched for age and sex) were interviewed. Supporters' responses to their relative's condition and circumstances, their ways of coping with stressful caregiving problems, and their willingness to continue their caregiving role, were assessed. Findings indicated that willingness to care and stress were associated in different ways with the supporter's response to his/her relative. Coping was found to be significantly associated with stress, response to relative, and willingness to care in only three out of a total of 45 tests. Willingness to care was positively associated with the coping behaviour internalization. The findings are discussed in the context of developing interventions for improving the well-being of supporters of an older relative in the community.     

The Cerebral Cortex of the Rat and Visual Attentional Function: Dissociable Effects of Mediofrontal, Cingulate, Anterior Dorsolateral, and Parietal Cortex Lesions on a Five-Choice Serial Reaction Time Task

Dissociable effects of bilateral excitotoxic lesions of differentregions of the rat neocortex, including medial prefrontal andanterior cingulate cortices, were investigated in a five-choiceserial reaction time task that provides several indices of theaccuracy and speed of attentional function. Whereas medial prefrontalcortical lesions impaired performance of the task as revealedby a reduction in choice accuracy, an increase in the latencyto respond correctly to the visual target and enhanced perseverativeresponding, lesions of the anterior cingulate cortex specificallyincreased premature responding. By contrast, lateral frontalcortical lesions did not significantly disrupt baseline performanceof the task, but rather increased the latency to respond correctlyto the visual target during various behavioral manipulations,for example, when the length of the intertrial interval wasvaried unpredictably and during interpolation of distractingbursts of white noise. Lesions of the parietal cortex failedto disrupt any aspect of task performance investigated. These behavioral effects in the five-choice task were comparedwith the effect of these same lesions on acquisition and retentionof a one-trial passive avoidance task. The main finding fromthis paradigm was that lesions of the lateral frontal cortexproduced a significant disruption to the retention of passiveavoidance, which stands in marked contrast to the successfulretention observed by animals of the other lesion groups. Inaddition, this pattern of results reveals that the "disinhibitory"effect of cingulate cortex lesions are relatively specific tothe five-choice attentional task. Finally, the results of the present study are compared withthe findings of previous experiments using the five-choice task,which have examined the effect of selective manipulations ofthe ascending noradrenergic, cholinergic, dopaminergic. andserotonergic projections. In particular, the deficits in attentionalfunction observed following cholinergic lesions of the nucleusbasalis magnocellularis appear to be attributable to cholinergicdenervation of the medial frontal cortex. These results arediscussed in terms of the role of parallel distributed neuralsystems within the neocortex that mediate continuous attentionalperformance in the rat.     

Vascular and electromyographic responses evoked in forearm muscle by isometric contraction of the contralateral forearm

There is controversy over whether isometric contraction of the forearm evokes vasoconstriction or vasodilatation in the muscles of the contralateral forearm. In the present study we have investigated in normal man, the effects of isometric contraction of one arm at 75, 50 and 25% maximum voluntary contraction (MVC) on arterial pressure, heart rate, blood flow and vascular resistance of the contralateral forearm and on electromyographic (EMG) activity recorded from that same arm with sensitive, surface electrodes.When EMG activity was not being recorded from the resting arm, isometric contraction of the contralateral arm for 2 min evoked increases in arterial pressure and heart rate whose magnitudes were graded with % MVC and an increase in forearm blood flow and a decrease in forearm vascular resistance at 75, 50 and 25% MVC, indicating vasodilatation. Further experiments in which EMG activity was recorded from the resting arm demonstrated that the decrease in forearm vascular resistance evoked by 75% MVC was associated with a substantial increase in EMG activity of the extensor and flexor muscles of that arm. By contrast, when forearm contraction was performed at 75% MVC whilst subjects viewed the EMG activity in the resting arm on an oscilloscope and kept EMG activity minimal, vascular resistance increased in that arm, indicating vasoconstriction. Further, when subjects performed contraction at 25% MVC whilst showing minimal EMG activity in the contralateral arm, vascular resistance in that same arm increased (from 78 ± 16 to 124 ± 29 mmHg/ml/min/100 ml tissue). These results are discussed in relation to those of previous studies. We propose, that in normal man, isometric contraction of the forearm evokes primary vasoconstriction in the muscles of the contralateral forearm, but that this response may be overcome by muscle vasodilatation occurring secondary to unintended muscle contraction or as part of the alerting response to acute stress.     

Effects of Diethyl Phthalate and Other Plasticizers on Laurate Hydroxylation in Rat Liver Microsomes

Diethyl phthalate (DEP) is used in pharmaceutical coatings, cosmetics, and plastic films to wrap foods. There is a health concern associated with the exposure to certain phthalate esters because they belong to a class of compounds referred to as peroxisome proliferators which have been shown to increase the incidence of liver tumors when administered to rats. In this study, we have compared DEP to four other commonly used plasticizers, 2-diethylhexyl phthalate (DEHP), dibutyl phthalate (DBP), 2-diethylhexyl adipate (DEHA), and acetyltributyl citrate (ATBC), for their ability to induce the cytochrome P450-mediated fatty acid -hydroxylation system, which is one of the initial cellular responses when animals are treated with peroxisome proliferators. The administration of DEHP, DBP, and DEHA to rats increased the specific activity of laurate 12-hydroxylase from 2.8 ± 1.1 in control rats to 30.3 ± 11.6, 14.5 ± 4.1, and 9.7 ± 1.9 nmol 12-hydroxylaurate formed/min/nmol P450, respectively. In contrast, laurate 12-hydroxylase activity in DEP-and ATBC-treated rats were 4.4 ± 1.2 and 4.4 ± 1.0 nmol 12-hydroxylaurate formed/min/nmol P450, respectively. In addition, whereas DEHP increased peroxisomal palmitoyl-CoA oxidation 6-fold, DEP increased this activity only 1.3-fold. Two protein bands, at 51 and 52 kDa, were found to increase 6- to 12-fold in microsomes of DEHP-, DBP-, and DEHA-treated rats, but these bands were increased only 2-fold in DEP- or ATBC-treated rats.     

Safety, pharmacokinetics, and activity of ABX-EGF, a fully human anti-epidermal growth factor receptor monoclonal antibody in patients with metastatic renal cell cancer.

PURPOSE: To determine the antitumor activity of ABX-EGF, a fully human monoclonal antibody to the epidermal growth factor receptor (EGFr), in previously treated patients with metastatic renal cell carcinoma, and to characterize its toxicity, immunogenicity, pharmacokinetics, and pharmacodynamics. PATIENTS AND METHODS: The antitumor activity, as well as the toxicity, pharmacokinetics, pharmacodynamics, and immunogenicity of ABX-EGF, were assessed. RESULTS: Eighty-eight patients were treated with ABX-EGF doses of 1.0, 1.5, 2.0, or 2.5 mg/kg weekly with no loading dose. EGFr immunostaining was performed on 76 tumor biopsy specimens (86%), and 69 (91%) scored positive. Major responses occurred in three patients, and two patients had minor responses. Forty-four patients (50%) also had stable disease at their first 8-week assessment, and the median progression-free survival (PFS) was 100 days (95% CI, 58 to 140 days). Low hemoglobin and high alkaline phosphatase predicted for short PFS. The principal toxicity, an acneiform rash, occurred in 68%, 95%, 87%, and 100% of patients who received at least three doses of ABX-EGF at 1.0, 1.5, 2.0, and 2.5 mg/kg/wk, respectively. A trend indicated that the severity of the rash may relate to PFS. No human antihuman antibodies were detected. ABX-EGF pharmacokinetics fit a model that incorporated both linear and saturable EGFr-mediated clearance mechanisms, and interindividual variability was low. At 2.5 mg/kg/wk, ABX-EGF concentrations throughout treatment exceeded those estimated to saturate nonlinear clearance and inhibit xenograft growth by 90%. CONCLUSION: ABX-EGF was generally well tolerated. The objective response rate was low in previously treated patients with metastatic renal cell carcinoma. Although skin rash may be a pharmacodynamic marker of drug action, its potential as a surrogate marker of clinical benefit requires further evaluation.     

Acknowledgment of Ad Hoc Reviewers for Volume 13

Note

Acknowledgment of Ad Hoc Reviewers for Volume 13