Loss of basal forebrain P75(NTR) immunoreactivity in subjects with mild cognitive impairment and Alzheimer's disease.

The long-held belief that degeneration of the cholinergic basal forebrain was central to Alzheimer's disease (AD) pathogenesis and occurred early in the disease process has been questioned recently. In this regard, changes in some cholinergic basal forebrain (CBF) markers (e.g. the high affinity trkA receptor) but not others (e.g., cortical choline acetyltransferase [ChAT] activity, the number of ChAT and vesicular acetylcholine transporter-immunoreactive neurons) suggest specific phenotypic changes, but not frank neuronal degeneration, early in the disease process. The present study examined the expression of the low affinity p75 neurotrophin receptor (p75(NTR)), an excellent marker of CBF neurons, in postmortem tissue derived from clinically well-characterized individuals who have been classified as having no cognitive impairment (NCI), mild cognitive impairment (MCI), and mild AD. Relative to NCI individuals, a significant and similar reduction in the number of nucleus basalis p75(NTR)-immunoreactive neurons was seen in individuals with MCI (38%) and mild AD (43%). The number of p75(NTR)-immunoreactive nucleus basalis neurons was significantly correlated with performance on the Mini-Mental State Exam, a Global Cognitive Test score, as well as some individual tests of working memory and attention. These data, together with previous reports, support the concept that phenotypic changes, but not frank neuronal degeneration, occur early in cognitive decline. Although there was no difference in p75(NTR) CBF cell reduction between MCI and AD, it remains to be determined whether these findings lend support to the hypothesis that MCI is a prodromal stage of AD.     

Evaluation of a mass dispensing exercise in a Cities Readiness Initiative setting.

PURPOSE: The effectiveness of a point of dispensing (POD) used in a mass dispensing exercise was evaluated. METHODS: Public Health-Seattle & King County (PHSKC), in conjunction with the University of Washington, conducted a functional exercise of mass dispensing plans to test the effectiveness of a POD. Specifically, the organization and maintenance of patient flow, staffing model, signage, and dissemination of public information were evaluated. A data collection application using cellular telephones was used to record time and patient flow data to evaluate patient flow. Questionnaires distributed to staff and volunteer patients at the end of the exercise obtained feedback regarding the setup, organization, and operations of the POD. RESULTS: The POD was operational for approximately 68 minutes. The majority of POD staff reported feeling comfortable with their specific job tasks and duties within 15 minutes of opening the doors to the POD to the public. Staff questionnaires also revealed a high level of self-reported confidence in their ability and in the ability of their colleagues to perform the job-specific responsibilities required of them or respond to this hypothetical event. The majority of volunteer patients found the signs helpful and easy to follow and the check-in form easy to complete. Despite efforts to provide patients with oral and written information about the medications being dispensed, only 80% indicated that they knew how to take the medication, and only 73% reported understanding the medication instructions for all the individuals for whom they picked up medication. CONCLUSION: The majority of volunteer patients and staff who participated in a functional exercise of mass dispensing plans found the POD to be effective. Time-flow analysis provided preliminary estimates of the total amount of time needed to complete the dispensing process for each head of household.     

Early responses to chemotherapy of normal and malignant hematologic cells are prognostic in children with acute lymphoblastic leukemia.

PURPOSE: Improved cure rates for children with acute lymphoblastic leukemia (ALL) have resulted from better relapse prediction, using clinical and laboratory features at diagnosis, and more intensive therapy in high-risk patients. More recently, measurements of the variation in the response of malignant lymphoblasts to chemotherapy in vivo have further improved relapse prediction. It is unknown whether the variation in the response of nonmalignant hematologic cells after chemotherapy correlates with the response of lymphoblasts or risk of relapse. PATIENTS AND METHODS: We retrospectively evaluated myelosuppression during induction and consolidation chemotherapy in 227 children uniformly treated for ALL on consecutive Australian and New Zealand Children's Cancer Study Group protocols. The early response to treatment was assessed in a representative subset (n = 62) by determining minimal residual disease (MRD) level by molecular techniques on the end-of-induction bone marrow sample. RESULTS: We found that a slow rate of myeloid recovery at the end of induction chemotherapy, reflected in a low absolute neutrophil count (ANC), was highly predictive of relapse (P < .0001). Additionally, patients with a high end-of-induction MRD level had a high risk of relapse (P = .001). Multivariate analysis confirmed the independent prognostic significance of MRD and ANC at the end of induction chemotherapy (P < .05). There was no significant association between other measures of myelotoxicity and MRD or relapse. CONCLUSION: We conclude that the responses of normal myeloid cells and malignant lymphoblasts to chemotherapy predict outcome by distinct mechanisms. While these results are promising, their use in the clinical setting needs to be examined in a future randomized controlled trial.     

Motor and non-motor sequence learning in children and adolescents with cerebellar damage.

Cerebellar involvement in motor and non-motor sequence learning was examined with serial reaction time tasks (SRT). Our sample consisted of 8 children and adolescents who had undergone surgical removal of a benign posterior fossa tumor (PFT) during childhood. None of them had undergone chemotherapy or cranial radiation therapy (CRT). Ages ranged from 1-11 years at surgery and 9-17 years at testing. The children were tested not earlier than 2.5 years after surgery (M = 5.9 years), enabling brain plasticity and recovery of functions. Their performance was compared with a matched control sample. The PFT group was not impaired in the implicit learning of sequences, as reflected in their performance in blocks with a repeated sequence, both before and after a random block. However, in the perceptual task, their performance deteriorated more than that of the control group when a random block was introduced, suggesting that it was more difficult for the patients to respond flexibly or change their response set when encountering changing task demands. These results are in line with another study by our group on task switching with the same patients.     

Echogenic Appearance of Colorectal Liver Metastases on Intraoperative Ultrasonography is Associated with Survival After Hepatic Resection

Survival after resection of colorectal liver metastases has traditionally been associated with clinicopathologic factors. We sought to investigate whether echogenicity of colorectal liver metastasis as assessed by intraoperative ultrasound (IOUS) was a prognostic factor after hepatic resection. Prospective data on tumor IOUS appearance were collected in 84 patients who underwent hepatic resection for colorectal liver metastasis. Images were digitally recorded, blindly reviewed, and scored for echogenicity (hypo-, iso-, or hyperechoic). The median tumor number was 1 and the median tumor size was 5.0 cm. At the time of surgery, the IOUS appearance of the colorectal liver metastases were hypoechoic in 35 (41.7%) patients, isoechoic in 37 (44.0%) patients, and hyperechoic in 12 (14.3%) patients. Traditional clinicopathologic prognostic factors were similarly distributed among the three echogenicity groups (all p > 0.05). Patients with a hypoechoic lesion had a significantly shorter median survival (30.2 months) compared with patients who had either an isoechoic (53.2 months) or hyperechoic (42.3 months) lesion (p = 0.005). The 5-year survival after hepatic resection of colorectal liver metastasis was also associated with the echogenic appearance of the lesion (hypoechoic 14.4 vs isoechoic 37.4 vs hyperechoic 46.2%) (p < 0.05). Intraoperative ultrasound echogenicity should be considered a prognostic factor after hepatic resection of metastatic colorectal cancer. This study was presented at the 47th annual meeting of The Society for Surgery of the Alimentary Tract, Los Angeles, CA, USA, 22 May 2006.     

It's all about sex: gender, lung development and lung disease.

Accumulating evidence suggests that gender affects the incidence, susceptibility and severity of several lung diseases. Gender also influences lung development and physiology. Data from both human and animal studies indicate that sex hormones might contribute to disease pathogenesis or serve as protective factors, depending on the disease involved. In this review, the influence of gender and sex hormones on lung development and pathology will be discussed, with specific emphasis on pulmonary fibrosis, asthma and cancer.     

Travel distance, age, and sex as factors in follow-up visit compliance in the post-gastric bypass population

BACKGROUND: There is no consensus regarding the optimal rate of follow-up in the post-bariatric surgery patient population. METHODS: The records of all patients who underwent laparoscopic Roux-en-Y gastric bypass from 2001 to 2003 were reviewed. Using patient zip codes, travel distances were calculated between the patients' places of residence and our clinic. Patients were then assigned to 1 of 3 cohorts according to the following distances: (1) < 50 miles, (2) 50 to 100 miles, and (3) > 100 miles. Patient compliance with follow-up appointments at 3 weeks, 3 months, 6 months, 9 months, and 12 months was analyzed. Linear trends were identified using the Mantel-Haenszel test. Age and sex were analyzed as possible predictors of compliance using the chi(2) test. P values < .05 were considered statistically significant. RESULTS: The study group comprised 150 patients (127 females and 23 males). The 3 cohorts contained 115, 21, and 14 patients, respectively. All patients in each cohort were compliant with the 3-week follow-up appointment. Although there were differences in compliance between cohorts at each of the remaining appointments, only the 9-month (70.3% vs 61.9% vs 35.7%) visit showed statistical significance (P = .035). The 6-month visit trended toward significance (85.2% vs 76.2% vs 64.3%; P = .088). Males were more likely to be compliant with the 12-month follow-up (P = .040). When controlling for sex, travel distance was also a predictor of compliance at this follow-up visit (P = .024). Age was not predictive of compliance (P = .827). CONCLUSION: Based on our findings, we conclude that travel distance from the clinic does not significantly affect compliance at the initial follow-up, 3-month, and 12-month appointments. However, distance does tend to affect compliance at the 6-month appointment and significantly affects compliance at the 9-month appointment. Males are more likely to be compliant at the 12 month follow-up visit. We must continue to strive for 100% follow-up in our post-bariatric surgery patients.