Interobserver Agreement in Scoring Angiographic Results of Basilar Artery Occlusion Stroke Therapy.

BACKGROUND AND PURPOSE: The modified TICI Infarction grading system is a metric currently used to evaluate angiographic results of thrombectomy for large-vessel occlusion in ischemic stroke. Originally designed for evaluating MCA territories, it is currently used for other vessel occlusions, including the posterior circulation. We postulate that the modified TICI use for the posterior circulation is not accurate due to the different vascular territories supplied by vertebrobasilar vasculature, making grading more complex. MATERIALS AND METHODS: We collected angiographic results from 30 patients who presented with acute posterior circulation occlusions between 2015 and 2018 and underwent thrombectomy in our institution. Eight observers were asked to evaluate the TICI scores before and after thrombectomy. The multirater statistics were computed using Fleiss κ analysis. Further data were collected regarding the potential brain territories at risk and the existence of atherosclerotic disease in the basilar artery. RESULTS: The overall agreement κ reached 0.277 (SD, 0.013), which suggests a "fair" agreement among the raters. On average, 45% of observers achieved a high accuracy in predicting brain areas at risk of ischemia. As for the existence of basilar atherosclerotic disease, a high agreement (defined as at least 5 of 6 observers) was seen in 20 of the 30 patients. CONCLUSIONS: Despite TICI being ubiquitous in stroke diagnostics, the high variability of posterior circulation TICI scores calls into question its use in these strokes. Other methods should be developed to assess recanalization in the posterior circulation.

Neural crest stem cells undergo cell-intrinsic developmental changes in sensitivity to instructive differentiation signals.

Rat neural crest stem cells (NCSCs) prospectively isolated from uncultured E14.5 sciatic nerve and transplanted into chick embryos generate fewer neurons than do NCSCs isolated from E10.5 neural tube explants. In addition, they differentiate primarily to cholinergic parasympathetic neurons, although in culture they can also generate noradrenergic sympathetic neurons. This in vivo behavior can be explained, at least in part, by a reduced sensitivity of sciatic nerve-derived NCSCs to the neurogenic signal BMP2 and by the observation that cholinergic neurons differentiate at a lower BMP2 concentration than do noradrenergic neurons in vitro. These results demonstrate that neural stem cells can undergo cell-intrinsic changes in their sensitivity to instructive signals, while maintaining multipotency and self-renewal capacity. They also suggest that the choice between sympathetic and parasympathetic fates may be determined by the local concentration of BMP2.

Hydrogel versus Bare Platinum Coils in Patients with Large or Recurrent Aneurysms Prone to Recurrence after Endovascular Treatment: A Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Some patients are at high risk of aneurysm recurrence after endovascular treatment: patients with large aneurysms (Patients Prone to Recurrence After Endovascular Treatment PRET-1) or with aneurysms that have previously recurred after coiling (PRET-2). We aimed to establish whether the use of hydrogel coils improved efficacy outcomes compared with bare platinum coils. MATERIALS AND METHODS: PRET was an investigator-led, pragmatic, multicenter, parallel, randomized (1:1) trial. Randomized allocation was performed separately for patients in PRET-1 and PRET-2, by using a Web-based platform ensuring concealed allocation. The primary outcome was a composite of a residual/recurrent aneurysm, adjudicated by a blinded core laboratory, or retreatment, intracranial bleeding, or mass effect during the 18-month follow-up. Secondary outcomes included adverse events, mortality, and morbidity (mRS > 2). The hypothesis was that hydrogel would decrease the primary outcome from 50% to 30% at 18 months, necessitating 125 patients per group (500 for PRET-1 and PRET-2). RESULTS: The trial was stopped once 250 patients in PRET-1 and 197 in PRET-2 had been recruited because of slow accrual. A poor primary outcome occurred in 44.4% (95% CI, 35.5%-53.2%) of those in PRET-1 allocated to platinum compared with 52.5% (95% CI, 43.4%-61.6%) of patients allocated to hydrogel (OR, 1.387; 95% CI, 0.838-2.295; P = .20) and in 49.0% (95% CI, 38.8%-59.1%) in PRET-2 allocated to platinum compared with 42.1% (95% CI, 32.0%-52.2%) allocated to hydrogel (OR, 0.959; 95% CI, 0.428-1.342; P = .34). Adverse events and morbidity were similar. There were 3.6% deaths (1.4% platinum, 5.9% hydrogel; P = .011). CONCLUSIONS: Coiling of large and recurrent aneurysms is safe but often poorly effective according to angiographic results. Hydrogel coiling was not shown to be better than platinum.

P3 in schizophrenia is affected by stimulus modality, response requirements, medication status, and negative symptoms.

Eighteen schizophrenics who were not taking medication, 13 schizophrenics who were taking medication, and 37 age-matched controls were tested with event-related potential paradigms designed to elicit P3 response automatically or effortfully (ie, with a choice reaction time task). Electroencephalograms were recorded from the 19 standard 10-20 electrode sites. Compared with controls, both groups of schizophrenics had reduced P3 amplitudes for both effortful and automatic paradigms. P3 latencies were delayed relative to controls for the medication-taking schizophrenics in the effortful paradigms. Negative symptoms derived from the Brief Psychiatric Rating Scale within 1 week of event-related potential testing correlated negatively with both auditory and visual P3 amplitude in the subjects who were not taking medication. There was no evidence that P3 is smaller over left temporal electrode sites in schizophrenics, as has been reported by others. P3 amplitude reduction in schizophrenia is a robust psychobiological phenomenon that is present regardless of medication status or task demands.

HydroCoils reduce recurrence rates in recently ruptured medium-sized intracranial aneurysms: a subgroup analysis of the HELPS trial.

BACKGROUND AND PURPOSE: The HydroCoil Endovascular Aneurysm Occlusion and Packing Study (HELPS) was a randomized, controlled trial comparing HydroCoils with bare-platinum coils. The purpose of this study was to perform a subgroup analysis of angiographic and clinical outcomes of medium-sized aneurysms in the HELPS trial. MATERIALS AND METHODS: Patients with medium-sized aneurysms (5-9.9 mm) were selected from the HELPS trial. Outcomes compared between the HydroCoil and bare-platinum groups included the following: 1) any recurrence, 2) major recurrence, 3) retreatment, and 4) mRS score of ≤2. Subgroup analysis by rupture status was performed. Multivariate logistic regression analysis adjusting for aneurysm neck size, shape, use of adjunctive device, and rupture status was performed. RESULTS: Two hundred eighty-eight patients with medium-sized aneurysms were randomized (144 in each group). At 15-18 months posttreatment, the major recurrence rate was significantly lower in the HydroCoil group than in controls (18.6% versus 30.8%, P = .03, respectively). For patients with recently ruptured aneurysms, the major recurrence rate was significantly lower for the HydroCoil group than for controls (20.3% versus 47.5%, P = .003), while rates were similar between groups for unruptured aneurysms (16.7% versus 14.8%, P = .80). Multivariate analysis of patients with recently ruptured aneurysms demonstrated a lower odds of major recurrence with HydroCoils (OR = 0.27; 95% CI, 0.12-0.58; P = .0007). No difference in retreatment rates or mRS of ≤2 was seen between groups. CONCLUSIONS: HydroCoils were associated with statistically significant and clinically relevant lower rates of major recurrence for recently ruptured, medium-sized aneurysms in the HELPS trial. Because this was not a prespecified subgroup analysis, these results should not alter clinical practice but, rather, provide insight into the design of future clinical trials comparing bare platinum with second-generation coils.

HydroCoils Are Associated with Lower Angiographic Recurrence Rates Than Are Bare Platinum Coils in Treatment of "Difficult-to-Treat" Aneurysms: A Post Hoc Subgroup Analysis of the HELPS Trial.

BACKGROUND AND PURPOSE: The HydroCoil Endovascular Aneurysm Occlusion and Packing Study was a randomized controlled trial that compared HydroCoils to bare platinum coils. Using data from this trial, we performed a subgroup analysis of angiographic and clinical outcomes of patients with "difficult-to-treat" aneurysms, defined as irregularly shaped and/or having a dome-to-neck ratio of <1.5. MATERIALS AND METHODS: Separate subgroup analyses comparing outcomes of treatment with HydroCoils to that of bare platinum coils were performed for the following: 1) irregularly shaped aneurysms, 2) regularly shaped aneurysms, 3) aneurysms with a dome-to-neck ratio of <1.5, and 4) aneurysms with a dome-to-neck ratio of ≥1.5. For each subgroup analysis, the following outcomes were studied at the last follow-up (3-18 months): 1) any recurrence, 2) major recurrence, 3) re-treatment, and 4) an mRS score of ≤2. Multivariate logistic regression analysis was performed to determine if the HydroCoil was independently associated with improved outcomes in these subgroups. RESULTS: Among the patients with an irregularly shaped aneurysm, the HydroCoil was associated with lower major recurrence rates than the bare platinum coils (17 of 66 [26%] vs 30 of 69 [44%], respectively; P = .046). Among the patients with an aneurysm with a small dome-to-neck ratio, the HydroCoil was associated with lower major recurrence rates than the bare platinum coils (18 of 73 [24.7%] vs 32 of 76 [42.1%], respectively; P = .02). No difference in major recurrence was seen between HydroCoils and bare platinum coils for regularly shaped aneurysms (42 of 152 [27.6%] vs 52 of 162 [32.1%], respectively; P = .39) or aneurysms with a large dome-to-neck ratio (41 of 145 [28.3%] vs 50 of 155 [32.3%], respectively; P = .53). CONCLUSIONS: This unplanned post hoc subgroup analysis found that HydroCoils are associated with improved angiographic outcomes in the treatment of irregularly shaped aneurysms and aneurysms with a dome-to-neck ratio of <1.5. Because this was a post hoc analysis, these results are not reliable and absolutely should not alter clinical practice but, rather, may inform the design of future randomized controlled trials.

Assay of therapeutic doses of methotrexate in body fluids of patients with psoriasis.

A microbiologic technique for the assay of methotrexate (MTX) in urine, serum, erythrocytes, feces, and skin is described. The accuracy of the method equals that of routine microbiologic assays of folic acid. Important differences in serum MTX levels in psoriatic patients during the 24 hours after standardized intravenous and intramuscular administration were demonstrated. Repeated intravenous doses tended to be cleared from the blood univormly. After oral doses many patients achieved peak serum levels within 2 hr. with fall of level by 4 hr. Others achieved lower levels and responded less well clinically. Persistence of high serum levels at 24 and 48 hr did not confer obvious clinical benefit or necessarily give rise to by renal function when the creatinine clearance was greater than 50 ml/min. However, impaired renal function was clearly correlated with slow clearance. Routine measurement of MTX blood levels is of value in patients with suspected malabsorption or partial renal failure.

Power transcranial Doppler ultrasound in the detection of intracranial aneurysms.

BACKGROUND AND PURPOSE: We sought to perform a large, prospective, multicenter, blinded study comparing power transcranial color duplex sonography (power TCDS) with intra-arterial digital subtraction angiography (IADSA) in the detection of intracranial aneurysms. METHODS: Contemporaneous TCDS and IADSA examinations were performed in 171 subjects with suspected intracranial aneurysm. Via the temporal bone window, a 2-dimensional hand-held noncontrast transcranial duplex ultrasound imaging system was used operating in power and spectral modes. Sonographers were blinded to clinical history and results of brain CT and IADSA. RESULTS: We found that 157 subjects (92%) had an adequate bone window. Sensitivity per patient was 0.78 (95% CI, 0.66 to 0.87) and 0.46 (95% CI, 0.36 to 0.56) for any anterior circulation aneurysms. Sensitivity was 0.35 (95% CI, 0.24 to 0.46) for aneurysms 5 mm. Accuracy was lower for aneurysms on the cavernous and terminal internal carotid arteries, including posterior communicating artery origin (0.71; 95% CI, 0.63 to 0.79), than for those on the anterior (0.82; 95% CI, 0.74 to 0.89) or the middle cerebral arteries (0.79; 95% CI, 0.71 to 0.86). CONCLUSIONS: Power TCDS is a promising, inexpensive, noninvasive test for anterior circulation intracranial aneurysms but is less sensitive per aneurysm than alternatives such as CT angiography or MR angiography. Sensitivity is poor for aneurysms

ERPs in schizophrenia: effects of antipsychotic medication.

Thirty unmedicated schizophrenics were compared to 29 age-matched controls on auditory and visual event-related brain potential (ERP) paradigms. Twenty-one of these patients were tested again after 1 week on placebo and after 4 weeks on antipsychotic medication. Before treatment, N1, N2, and P3 components of the auditory ERP were smaller in the schizophrenics than in the controls. Although visual N2 was smaller in schizophrenics, visual P3 was not. In spite of significant clinical improvement with antipsychotic treatment, amplitudes of auditory and visual N1, N2, and P3 were not significantly changed. Higher blood levels of antipsychotic medication were related to reductions in auditory P3 latency, however. In addition, higher levels of cerebrospinal fluid (CSF) MHPG (methoxyhydroxyphenylglycol) were associated with larger auditory N1s and larger auditory and visual P3s, suggesting an influence of arousal on these components in schizophrenics. In spite of this influence, reduction of the auditory P3 in schizophrenia is an enduring trait of the disease, which is not affected by antipsychotic medication or clinical improvement.

A novel bacterial vector system for monitoring protein-protein interactions in the cAMP-dependent protein kinase complex.

A bacterial expression vector is described for investigation of protein-protein interactions. Important features of the vector include partition of the cI repressor of bacteriophage lambda into two functional domains separated by a multicloning site, and low level auto-regulated expression of human genes as C-terminal fusions to the DNA-binding domain of cI. Two different reporter systems have been employed; expression of either a suppressor tRNA or the alkaline phosphatase gene is dependent in both cases on the extent of repression of the major leftward promoter of lambda (lambdaP(L)). The cAMP-dependent protein kinase (PKA) has been used as a model protein complex because both homodimer and heterodimer interactions are known to occur and because cAMP acts as a modulator of these interactions. It has been shown that the product of the repressor gene with newly incorporated expressed polylinker restriction sites still functions as a repressor. Substitution of the dimerisation domain of the cI repressor with the regulatory subunit of PKA does not diminish the ability of a cI fusion protein to repress expression of the reporter gene from lambdaP(L), indicating that the regulatory subunit of PKA dimerises the fusion protein in the Escherichia coli cytoplasm. Substitution instead with the catalytic subunit of PKA destroys the repression ability of cI, which is partially restored by separate expression of the regulatory subunit within the same cell. Complete restoration is achieved using a host E. coli strain which has lost its ability to synthesise cAMP and again this can be reversed by the addition of exogenous cAMP to these cells. Human PKA has been reconstituted in the E. coli cytoplasm, where all subunit interactions appear functional and respond as expected to the allosteric modulator cAMP.

Comparison of assays for antibody to HTLVI.

Indirect immunofluorescence, competitive radioimmunoassay, HTLV I-enzyme linked immunosorbent assay and gelatin particle agglutination Serodia-ATLA were compared in terms of their ability to detect antibody to human T cell leukaemia virus I (HTLV I). The sensitivities were 96.9%, 92%, 97.0%, and 100%, respectively, and the specificities 99.3%, 98.9%, 98.6%, and 96.3%. Particle agglutination was very simple to perform and was the most sensitive, though the least specific test. Antibody titres were 10-100 times higher when measured by particle agglutination than by other tests, and antibody titers were considerably higher in patients with neurological disease related to HTLV I than in those with other conditions. Serodia-ATLA is the method of choice for preliminary screening of specimens for antibody to HTLV I, but positive results must be confirmed by another technique.

P50 suppression in recent-onset schizophrenia: clinical correlates and risperidone effects.

Chronic schizophrenic patients often do not suppress the auditory P50 component of the event-related potential to the second of 2 clicks, presented 500 ms apart, suggesting a loss of normal inhibition. This study attempted to replicate the P50 suppression deficit in patients with recent-onset schizophrenia and to examine whether P50 is related to clinical symptoms or is affected by an atypical antipsychotic medication. Data from 22 recent-onset schizophrenia patients and 11 normal controls revealed that disruption in P50 suppression is present during the early stages of illness. In addition, impaired P50 suppression covaried with clinical ratings of anxiety, depression, and anergia; results also suggested that the P50 inhibitory deficit may be related to the degree of patients' attentional impairment. Finally, risperidone, compared with a typical antipsychotic medication, improved inhibition of P50 to the second click. These results support P50 suppression as a measure of disordered neurocognition in schizophrenia.

Elderly men and women are less responsive to startling noises: N1, P3 and blink evidence.

Previously we observed that the P3 component of the event-related brain potential (ERP) elicited by startling noises, and to a lesser extent P3 to target tones, is reduced in the elderly (Ford & Pfefferbaum, 1991). In the current experiment, we tried to eliminate possible effects of age-related hearing deficits on the responses to noises by filtering them to include only frequencies heard best by the elderly (0-1000 Hz) and by setting noise intensity relative to each subject's threshold (sensation level, SL). Twelve younger (mean 22 years) and 12 older (mean 69 years) men and women listened to three sequences of tones (80%, 500 Hz, 70 dB SPL) and noises (20%). One type of noise occurred in each sequence (wide band noise set to 107 dB SPL, narrow band noise set to 107 dB SPL, or narrow band noise set to approximately 65 dB SL). The order of the three sequences was counterbalanced across age and sex. Younger subjects blinked to the noise 4-5 times more often than older subjects and had N1 and P3 amplitudes that were 2-3 times larger, regardless of the noise type. N1 amplitude to the background frequent tones and non-startle blinks did not differ between groups. Thus, even when noises were narrow band and set relative to each subject's threshold, older subjects were less responsive to startling auditory stimuli than were younger.

Food poisoning in a hospital staff canteen.

Eighty-two confirmed cases of salmonella food poisoning arose among hospital staff due to consuming contaminated tartar sauce served in the staff canteen. Many key personnel were affected and the hospital was closed to non-urgent admissions. In order to maintain the accident and trauma services, the normal policy of excluding infected persons from work had to be modified. Staff returned to work 48 h after they had become asymptomatic provided that they did not have contact with patients' mouths, food or drink. There were no secondary cases. During the investigation of the outbreak, lack of national guidelines for the preparation and handling of mayonnaise-based food products became apparent.

Left temporal deficit of P300 in patients with schizophrenia: effects of task.

P300 is often, but not always, observed to be more reduced over left than right temporal lobes in patients with schizophrenia. The possibility that task differences contribute to the inconsistency in the literature was explored in this study. ERPs were collected from 17 right-handed men with schizophrenia (DSM-IIIR) and 11 right-handed healthy male community controls, performing three auditory oddball tasks - respond to a target tone by: (1) counting; (2) pressing a response button with the right index finger; or (3) pressing a response button with the left index finger. Although patients with schizophrenia had smaller and later P300 amplitudes than controls, they did not have smaller P300s over the left temporal scalp (T3) than over the right (T4). P300 recorded over the left (C3) and right (C4) motor cortices indicated sensitivity to responding hand, with greater negativity being associated with contralateral button pressing. Failure to find P300 asymmetry is not related to the presence or absence of a button pressing task, or the hand used for button pressing. Rather, P300 asymmetry may be related to structural neuroanatomical asymmetries.

The bioavailability of a mixed micellar preparation of vitamin K1, and its procoagulant effect in anticoagulated rabbits.

We have investigated the pharmacokinetics and procoagulant activity of a new, mixed-micellar preparation of vitamin K1 (MM-K) in male New Zealand White rabbits. Oral administration of MM-K alone caused a significant (P less than 0.01) increase in the plasma concentrations of vitamin K1 as measured by normal-phase high-performance liquid chromatography (HPLC). Maximum plasma concentrations of vitamin K1 (450 ng mL-1, range 133-824 ng mL-1) were recorded at 3.3 h (range 3-5 h), and were significantly (P less than 0.05) greater than those seen after administration of an existing polyethoxylated castor oil preparation (PE-K; Konakion), which were 260 ng mL-1, range 198-390 ng mL-1 (tmax 0.8 h, range 0.4-1.2 h). AUC after MM-K (4.6 micrograms mL-1 h-1, range 2.1-6.3 micrograms ML-1 h-1) was also significantly (P less than 0.05) greater than after PE-K (1.6 micrograms mL-1 h-1, range 1.0-2.1 micrograms ML-1 h-1). However, the bioavailability of vitamin K1 after administration of MM-K was poor (9.4%), and there was considerable intra-individual variability between the concentrations of vitamin K1 recorded in the plasma samples. Both preparations of vitamin K1 stimulated clotting factor synthesis in rabbits anticoagulated with the potent and long-acting coumarin, brodifacoum. Maximum stimulation of clotting factor synthesis by vitamin K1 after MM-K was 87%, range 44-124% (%PCA). The maximum was seen later (tmax 12 h) than after PE-K (PCA 82%, range 47-125%; tmax 5 h). However, there was considerable intra-individual variability in response to both MM-K and PE-K.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquisition of mature functional responsiveness in T cells: programming for function via signaling.

The results discussed here provide strong evidence that different T-cell effector gene programs are activated by different signals, and that in several cases their responses to the same exogenous stimuli shift during the development and antigen responses of the cells. T-cell responses are thus conditional and plastic at the individual cell level. In the formalism of the introductory section, the results support elements of Models 2 and 3, and suggest a fusion between them as differentiation is explained in terms of alteration in the relative strengths of different intracellular signaling pathways. Returning to an initial question, how are different functional capabilities assigned nonrandomly to cells with different antigen recognition specificities? This question has not been answered, but it can be reformulated. If all virgin T cells can transiently make IL-2, then we must ask what features of cell biology explain the preferential preservation of IL-2 inducibility in CD4+ cells as opposed to CD8+ cells. If the capacity to induce IL-4 expression is not acquired in the thymus, then we may ask whether the initial opening of this locus depends on a CD4-transmitted signal. Similarly, the CD8 molecule itself might participate in inducing the initial differentiation events that render CTL-p inducible for granzyme C and perforin. This would be in accord with a large literature showing that CD8 engagement is much more important in the initial induction of CTL activity than in the exercise of function by pre-primed CTL effectors. The subtext of each of these "questions", however, is that intrathymic events may not directly affect the genes used by terminal effectors for function at all. They may instead bias a cell's complement of triggering receptors, thus rendering it differentially sensitive to particular signals generated during antigen reception. This view is extreme, and will probably turn out to be an overstatement. But it does inspire a unique set of investigations into the basis of T-cell function. It lends urgency to the question of whether CD4+ and CD8+ cells differ in their G proteins, kinases, or inducible proto-oncogenes. If they do, we can then ask whether such differences themselves arise in the periphery, or whether they can be traced back to thymocytes fresh from positive selection--or before.