Strategic control and medial frontal negativity: beyond errors and response conflict

Errors in timed choice tasks typically produce an error-related negativity (ERN) in the event-related potential (ERP). The error specificity of the ERN has been challenged by studies showing a correct response negativity (CRN). Forty-five participants engaged in a flanker task in which both compatibility between flankers and target and the probability of compatible flankers were manipulated. Correct responses elicited a CRN, the amplitude of which increased with the degree of mismatch between the presence of conflict and conflict probability, even on low-conflict (compatible) trials. The fronto-central N2 component was larger on high-conflict (incompatible) correct response trials. However, in contrast to some recent accounts, this N2 was largest for highly probable stimuli. These findings suggest revision to models of the effects of conflict on response-related negativity to account for strategic adjustments made in preparation for the response.     

Vector competence of Mexican and Honduran mosquitoes (Diptera: Culicidae) for enzootic (IE) and epizootic (IC) strains of Venezuelan equine encephalomyelitis virus

Experimental studies evaluated the vector competence of Ochlerotatus taeniorhynchus (Wiedemann), Culex cancer Theobald, Culex pseudes (Dyar and Knab), Culex taeniopus Dyar and Knab, and a Culex (Culex) species, probably Culex quinquefasciatus Say, and Culex nigripalpus Theobald from Chiapas, Mexico, and Tocoa, Honduras, for epizootic (IC) and enzootic (IE) strains of Venezuelan equine encephalomyelitis (VEE) virus. Culex pseudes was highly susceptible to infection with both the IC and IE strains of VEE (infection rates >78%). Patterns of susceptibility to VEE were similar for Oc. taeniorhynchus collected in Mexico and Honduras. Although Oc. taeniorhynchus was highly susceptible to the epizootic IC strains (infection rates > or = 95%, n = 190), this species was less susceptible to the enzootic IE strain (infection rates < or = 35%, n = 233). The Culex (Culex) species were refractory to both subtypes of VEE, and none of 166 contained evidence of a disseminated infection. Virus-exposed Cx. pseudes that refed on susceptible hamsters readily transmitted virus, confirming that this species was an efficient vector of VEE. Although Oc. taeniorhynchus that fed on hamsters infected with the epizootic IC strain transmitted VEE efficiently, only one of six of those with a disseminated infection with the enzootic IE virus that fed on hamsters transmitted virus by bite. These data indicate that Cx. pseudes is an efficient laboratory vector of both epizootic and enzootic strains of VEE and that Oc. taeniorhynchus could be an important vector of epizootic subtypes of VEE.     

Increased matrix metalloproteinase-9 with elastolysis in nocturnal asthma.

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) is capable of degrading elastin, whereas tissue inhibitor of metalloproteinase-1 (TIMP-1) can inhibit MMP-9 activity. We observed reduced airway tissue elastin volume density in six subjects with nocturnal asthma (NA) as compared with seven subjects with nonnocturnal asthma (NNA) and seven normal controls (NL) when endobronchial biopsies were evaluated morphometrically at 4:00 PM and 4:00 AM. OBJECTIVE: We hypothesized that increased metalloproteinases and decreased tissue inhibitors of metalloproteinases in the airways of subjects with NA may be responsible for reduced elastin volume density. METHODS: Ten additional subjects with NA, 10 subjects with NNA, and 7 normal control subjects underwent bronchoscopy with bronchoalveolar lavage at 4:00 PM and 4:00 AM. Levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 were determined in bronchoalveolar lavage by enzyme-linked immunosorbent assay. RESULTS: There was a fourfold circadian increase in bronchoalveolar lavage levels of MMP-9, and there was a twofold increase in MMP-9:TIMP-1 ratio in NA subjects from 4:00 PM to 4:00 AM. There were no circadian changes in the NNA and NL subjects. At 4:00 AM, MMP-9 levels and the MMP-9:TIMP-1 ratio were highest in NA subjects. At 4:00 PM, no significant group differences were observed. The MMP-9 levels positively correlated with the overnight fall in forced expiratory volume in 1 second and the MMP-9/TIMP-1 ratio negatively correlated with the 4:00 AM % predicted forced expiratory volume in 1 second. CONCLUSIONS: Our results from these two pilot studies suggest that increased MMP-9 and decreased TIMP-1 at night in NA may lead to reduced elastin density.     

Site of bone density measurement may affect therapy decision

Summary The purpose of this study was to determine whether bone mineral density (BMD) measurements at the lumbar spine and femoral neck provided comparable information to women planning to use that knowledge to help them make a decision about hormone replacement therapy. Eighty-eight healthy Caucasian women, aged 44–59 and within 0 to 5 years of menopause, participated in the study. BMD measurements were performed at the lumbar spine (L1-L4) and the femoral neck by dual energy X-ray absorptiometry (DXA). Criteria suggested by the National Osteoporosis Foundation were used to categorize women as at risk for osteoporosis, bone density more than one standard deviation (SD) below the young adult mean, or as low risk, bone density at or above this level. The re that 46 women would be classified into the low risk category on the basis of spinal BMD alone. However, 28 of these 46 women would fall into the at risk category when the femoral neck BMD was measured. Sixty-one percent of women informed they were at low risk on the basis of spinal BMD would be considered at risk based on femoral neck BMD. When femoral neck BMD was used as the primary risk indicator, 14% of the women classified as low risk would be at risk if spinal BMD were added. These results suggest that both lumbar spine and proximal femur measurements should be made when women are using bone density measurements as an aid in deciding whether or not to use hormone therapy in their postmenopausal years.     

Cryopreserved,cultured, allogenic,human epidermal grafts for the treatment of chronic ischemic ulcers: A report on two cases

Cultured, allogenic, human epidermal grafts have been successfully used to treat extensive burns, donor sites, leg ulcers, and eroded areas in recessive dystrophic epidermolysis bullosa. The following report describes the use of cryopreserved cultured human epidermal allografts in the treatment of long-standing ischemic ulcers unresponsive to conventional medical therapy in two patients who had previously undergone unsuccessful vascular reconstructive surgery. A marked reduction in ulcer size as well as rapid pain relief was achieved in both patients. In selected cases the use of epidermal grafts as a biologic topical therapy could represent an alternative to other medical treatments. However, thus far, only a few cases have been reported and the uncertain short- and long-term results as well as the excessive costs may limit the widespread application of this treatment modality.     

Tumor proliferative activity and response to first-line chemotherapy in advanced breast carcinoma

Summary The relationship between tumor proliferative activity and response to first-line chemotherapy and survival was investigated in 76 advanced breast cancer patients. Proliferative activity was determined by means of Ki-67 immunohistologic staining on primary tumors (55 patients) or at the relapse site (21 patients), and was classified as low ( 25% of stained cells) or high (> 25% of stained cells). The usual WHO response criteria were used. The median duration of follow-up was 18 months (range 3–58).Forty-seven patients (62%) had tumors with low, and 29 (38%) had tumors with a high rate of proliferative activity. The two groups were well balanced in terms of important variables such as disease-free survival, performance status, age, menopausal status, and the type of first-line chemotherapy (anthracycline-based regimens versus cyclophosphamide-methotrexate-5-fluorouracil). The estrogen receptor (ER) content, measured by means of immunohistochemical assay, was markedly different in the two groups, with 27/47 tumors with low proliferative activity (57%) and 6/29 with high-proliferative activity (21%) being ER positive ( 45% of stained cells) (p = 0.003). Moreover, a significant difference in the metastatic pattern was also evident, with a higher incidence of bone and a lower incidence of soft tissue metastases in the group of patients with tumors with low proliferative activity (p = 0.004). Overall, 10/47 responses (21%: PR = 7, and CR = 3) were observed in the group with a low rate of proliferative activity, versus 14/29 (48%: PR = 9, and CR = 5) in the group with highly proliferative tumors, the difference being statistically significant (p = 0.03). When a multivariate analy-sis was performed, the only factor that retained independent prognostic significance was the predominant site of disease, particularly soft tissues (p = 0.003). Despite the difference in response rate, when survival analysis was performed according to the Kaplan-Meier method, no significant difference was observed in the two groups, but when the analysis was limited to responsive patients, the median survival observed in those with a low and those with a high rate of proliferation was 35 and 19 months respectively (p = 0.02). The same results were obtained when multivariate survival analysis was carried out using Cox's regression model. These data suggest that there is a link between tumor proliferative activity and response to chemotherapy in advanced breast cancer, and may indicate the need to use more intensive treatments in selected patients with highly proliferative tumors.Presented in part at the Annual Meeting of the American Society of Clinical Oncology, May 14–17, 1994, Dallas, TX, USA     

Epirubicin, methotrexate and bleomycin (EMB) in the treatment of recurrent epidermoid cancer of the head and neck.

During the period May 1989 to November 1990, at the "O. Alberti" Radium Institute of Brescia's General Hospital, 35 patients affected by epidermoid head and neck carcinoma were treated every 28 days with the salvage chemotherapy regimen EMB (epirubicin, 50 mg/m2 i.v. day 1; methotrexate, 40 mg/m2. i.v. days 1, 18; bleomycin, 10 mg/m2 i.v. days 4, 11, 18). Sixteen patients had been previously treated with surgery, 15 with radiotherapy and 4 with chemotherapy. Six patients (Group A) received only 1 cycle of chemotherapy because of disease progression and subsequent death. In another 15 patients (Group B) it was possible to administer 2 cycles of EMB, and 9 of them showed local disease progression and died. Among the remaining 6 patients, evaluated as PR, 1 refused further therapy and 5 were amenable to a previously impossible radiotherapy (4 of them are still alive). Fourteen patients received 3 or more cycles of EMB (Group C): 8 subjects showed progression and died; 1 reached CR and is alive without any evidence of tumor; 5 are in PR (3 of them underwent subsequent radiotherapy and 1 chemotherapy with CDDP). Out of 35 patients, 12 (34%) reached a favorable response (CR or PR) and 8 (22%) are still alive. As regards toxicity, the following adverse events were recorded (< or = 2 Miller's scale): leukopenia (8.5%), thrombocytopenia (5.7%), anemia (14.2%), stomatitis (5.7%), vomiting (5.7%), alopecia (8.5%), and fever (11.4%). It can be concluded that the EMB regimen is very well tolerated and shows good effects in the treatment of patients with relapsed head and neck carcinoma.     

Cerebral autoregulation in pediatric traumatic brain injury.

OBJECTIVE: The aims of this study were to document the incidence of impaired cerebral autoregulation in children with traumatic brain injury using transcranial Doppler ultrasonography and to examine the relationship between autoregulatory capacity and outcome in children following traumatic brain injury. DESIGN: Prospective cohort study. SETTING: Harborview Medical Center (level I pediatric trauma center) in Washington state. PATIENTS: Thirty-six children <15 yrs old with traumatic brain injury: Glasgow Coma Scale score <9 (n = 12, group 1), Glasgow Coma Scale score 9-12 (n = 12, group 2), and Glasgow Coma Scale score 13-15 (n = 12, group 3). INTERVENTIONS: Cerebral autoregulation testing was conducted during extracranial surgery. Mean middle cerebral artery flow velocities were measured using transcranial Doppler as mean arterial pressure was increased to whichever variable was greater: 20% above baseline or a set value (80 mm Hg for <9 yrs and 90 mm Hg for 9-14 yrs). Autoregulatory capacity was quantified by the Autoregulatory Index. Autoregulatory Index <0.4 was considered impaired cerebral autoregulation. Discharge outcome using the Glasgow Outcome Scale score was considered good if the Glasgow Outcome Scale score was > or =4. MEASUREMENTS AND MAIN RESULTS: Twenty-four (67%) of 36 children had an Autoregulatory Index > or =0.4. The incidence of impaired cerebral autoregulation was 42% (five of 12) in group 1, 42% (five of 12) in group 2, and 17% (two of 12) in group 3. Ten (42%) of the 24 children with intact cerebral autoregulation had a good outcome compared with only one of 12 (8%) children with impaired cerebral autoregulation (p =.04). Six of 12 (50%) children with impaired cerebral autoregulation had hyperemia compared with one of 24 (4%) children with intact cerebral autoregulation (p <.01). Hyperemia was associated with poor outcome (p =.01). CONCLUSIONS: The incidence of impaired cerebral autoregulation was greatest following moderate to severe traumatic brain injury. Impaired cerebral autoregulation was associated with poor outcome. Hyperemia was associated with impaired cerebral autoregulation and poor outcome.     

Trends in compliance with the national colposcopy guidelines.

This study aims to assess trends in compliance with current colposcopy guidelines in 10 gynaecological units in four English counties since 1996; to identify constraints on compliance and suggest change in practice. All 10 gynaecology units in Oxfordshire, Buckinghamshire, Northamptonshire and Berkshire participated. Data were collected prospectively by colposcopists from 23,500 new referrals across a 55-month period from September 1996 to March 2001. The Oxford Cancer Intelligence Unit performed collation, quality assurance and retrieval of data for incomplete records. Audit results were disseminated annually to colposcopists via the Regional Colposcopy Group. Colposcopy waiting times exceeded the standards, but waiting times for high-grade referrals showed statistically significant improvement. Six standards were achieved; relating to accuracy, appropriateness of management and outcomes. The seven unmet standards relate to waiting times, colposcopist's caseload, follow-up policy and the proportion of cervical epithelial neoplasia (CIN) on histology. Changes in practice are suggested, constraints on compliance are identified and the appropriateness of some guidelines is questioned.