This study employs a multiple respondent research technique to assess the efficacy of a framework intended to improve the quality of health care provided to patients. We use survey data from 78 matched respondents to answer the question to what extent does IT capability intentions affect a hospital's ability to detect and reduce clinical errors. We investigate empirically the impact of IT capability intentions and IT infrastructure integration on elements of IT-enabled quality of care. Our findings position IT capability intentions as an antecedent to IT infrastructure integration and suggest IT infrastructure integration is the key component in overcoming a highly fragmented delivery system. The degree of IT infrastructure integration has significant effects on quality of care, in terms of both patient-centric responsiveness and error detection and reduction.

HD (Huntington's disease) is characterized by dysfunction and death of striatal MSNs (medium-sized spiny neurons). Excitotoxicity, transcriptional dysregulation and mitochondrial abnormalities are among the mechanisms that are proposed to play roles in HD pathogenesis. To determine the extent of cell-autonomous effects of mhtt (mutant huntingtin) protein on vulnerability to excitotoxic insult in MSNs in vivo, we measured the number of degenerating neurons in response to intrastriatal injection of QA (quinolinic acid) in presymptomatic and symptomatic transgenic (D9-N171-98Q, also known as DE5) mice that express mhtt in MSNs but not in cortex. After QA, the number of degenerating neurons in presymptomatic DE5 mice was not significantly different from the number in WT (wild-type) controls, suggesting the early, increased vulnerability to excitotoxicity demonstrated in other HD mouse models has a largely non-cell-autonomous component. Conversely, symptomatic DE5 mice showed significantly fewer degenerating neurons relative to WT, implying the resistance to excitotoxicity observed at later ages has a primarily cell-autonomous origin. Interestingly, mitochondrial complex II respiration was enhanced in striatum of symptomatic mice, whereas it was reduced in presymptomatic mice, both relative to their age-matched controls. Consistent with the QA data, MSNs from symptomatic mice showed decreased NMDA (N-methyl-D-aspartate) currents compared with age-matched controls, suggesting that in addition to aging, cell-autonomous mechanisms mitigate susceptibility to excitotoxicity in the symptomatic stage. Also, symptomatic DE5 mice did not display some of the electrophysiological alterations present in other HD models, suggesting that blocking the expression of mhtt in cortical neurons may restore corticostriatal function in HD.

Objective: Alzheimer's disease (AD) is a progressive neurodegenerative disease of the central nervous system (CNS). Recently, an increased interest in the role diet plays in the pathology of AD has resulted in a focus on the detrimental effects of diets high in cholesterol and fat and the beneficial effects of caloric restriction. The current study examines how dietary composition modulates cerebral amyloidosis and neuronal integrity in the TgCRND8 mouse model of AD.Methods: From 4 wks until 18 wks of age, male and female TgCRND8 mice were maintained on one of four diets: (1) reference (regular) commercial chow; (2) high fat/low carbohydrate custom chow (60 kcal% fat/30 kcal% protein/10 kcal% carbohydrate); (3) high protein/low carbohydrate custom chow (60 kcal% protein/30 kcal% fat/10 kcal% carbohydrate); or (4) high carbohydrate/low fat custom chow (60 kcal% carbohydrate/30 kcal% protein/10 kcal% fat). At age 18 wks, mice were sacrificed, and brains studied for (a) wet weight; (b) solubilizable A beta content by ELISA; (c) amyloid plaque burden; (d) stereologic analysis of selected hippocampal subregions.Results: Animals receiving a high fat diet showed increased brain levels of solubilizable A beta, although we detected no effect on plaque burden. Unexpectedly, brains of mice fed a high protein/low carbohydrate diet were 5% lower in weight than brains from all other mice. In an effort to identify regions that might link loss of brain mass to cognitive function, we studied neuronal density and volume in hippocampal subregions. Neuronal density and volume in the hippocampal CA3 region of TgCRND8 mice tended to be lower in TgCRND8 mice receiving the high protein/low carbohydrate diet than in those receiving the regular chow. Neuronal density and volume were preserved in CA1 and in the dentate gyrus.Interpretation: Dissociation of A beta changes from brain mass changes raises the possibility that diet plays a role not only in modulating amyloidosis but also in modulating neuronal vulnerability. However, in the absence of a study of the effects of a high protein/low carbohydrate diet on nontransgenic mice, one cannot be certain how much, if any, of the loss of brain mass exhibited by high protein/low carbohydrate diet-fed TgCRND8 mice was due to an interaction between cerebral amyloidosis and diet. Given the recent evidence that certain factors favor the maintenance of cognitive function in the face of substantial structural neuropathology, we propose that there might also exist factors that sensitize brain neurons to some forms of neurotoxicity, including, perhaps, amyloid neurotoxicity. Identification of these factors could help reconcile the poor clinicopathological correlation between cognitive status and structural neuropathology, including amyloid pathology.

The manner in which today’s government functions is changing both to make use of available technologies and to leverage the power of consolidated operations. In 2002, the State of Louisiana released its IT Master Plan, which provided a framework for modifying and extending the way in which information technology was utilized within the state government. This plan outlined the state’s intent to form consolidated data storage facilities, to eliminate redundant IT functions, and to develop more continuity with respect to the hardware and software platforms utilized within the state. This investigation will use a case study approach to examine the status of Louisiana’s endeavor and to identify how activities such as data integration, service consolidation, and contract negotiations have transformed because of this initiative. The authors will also explore the presence of resistance to the state’s IT Master Plan by project leadership and agency stakeholders.

A 22-month-old white girl with a 5-month history of watery, nonbloody diarrhea of large volume (2-4 episodes per day) was admitted to Jackson Memorial Hospital after 2 days of increased diarrhea and new onset of vomiting. She had no history of fever, irritability, or upper respiratory tract infection, and she was receiving no medications. She had lost 5 lb over the last 2 months despite good intake and normal diet. She had no other significant medical history or history of foreign travel, food allergy, unusual ingestion, or day-care attendance. Immunizations were up to date. The child had been born at term after a normal pregnancy; birth weight was 7 ½ lb.

Listeria monocytogenes 4b surface protein extract was used in an immunoblot assay to analyze the antibody profile in sera from 40 healthy urban workers (U group), 40 healthy slaughterhouse workers (W group) and four healthy carriers with positive L. monocytogenes 4b feces culture (positive controls). In addition, pooled rabbit sera, before and after immunization with L. monocytogenes 4b whole-cell suspension, were analyzed against L. monocytogenes 4b surface protein extract in order to determine the specific L. monocytogenes 4b antibody pattern. The degree of similarity (S) between such a pattern and each of those obtained with serum samples from the three subject groups was assessed. For U and W group sera, mean S values were 24.3 +/- 13.5 and 32.8 +/- 14.3, respectively. An 3 value greater than 65, corresponding to mean S(U) value +/- 3 standard deviation, was considered as an indicator of a healthy carrier. Thus, the estimated healthy carrier percentages found in U and W groups were 2.5 and 5%, respectively. The proposed immunoblot assay may prove a useful tool for epidemiological surveys to determine whether a healthy person is a L. monocytogenes 4b carrier.

This study summarizes our experiences with the silver staining of nucleolus organizer regions (AgNORs) in a total of 580 tumours from ten different tissues. In contrast to other investigators, we made use of automatic image analysis for the evaluation of AgNORs. This provided good reproducibility as determined by the standard cumulative means technique and intra-observer (r1) and inter-observer (r2) agreement in 30 benign (r1 = 0.83-0.95, r2 = 0.76-0.92) and 50 malignant tissue samples (r1 = 0.72-0.85, r2 = 0.51-0.78). By using a series of staining times on sections from 30 tissue blocks taken from the ten types of tissue investigated, considerable variation in the argyrophilic staining of NORs in different tissues and in different blocks from one tumour was shown. The mean AgNOR area of resting lymphocytes or connective tissue cells within tissue blocks of the same organ system varied up to four-fold, even though identical staining times had been used. The most suitable silver reaction time which rendered a good diagnostic difference in the AgNOR content of benign and malignant tissue ranged, for example, in the breast cancer specimens, from 23 to 35 min. We therefore conclude that the staining time has to be adjusted to the individual silver-binding characteristics of each tissue block or even each section. The use of internal staining standards like lymphocytes or connective tissue cells in the same tissue section is mandatory. This, in turn, is most precisely controlled by morphometry.

The value of automatic image analysis in the investigation of nucleolus regions (AgNOR) has been examined in tissue sections of 52 malignant and 30 benign breast lesions. Determination of the AgNOR number per cell alone revealed a considerable overlap between benign (range 1.2–3.8) and malignant specimens (range 1.5–16.2). They differed however, highly significantly (P<0.001) in their AgNOR sizes. In benign breast disorders the mean AgNOR area per tumour ranged from 0.22 μm2 to 1.07 μm2 (mean 0.39 μm2), whereas in carcinomas AgNOR sites ranged from 0.05 μm2 to 0.22 μm2 (mean 0.09 μm2). AgNOR counts showed a good correlation with histopathological grade (P<0.05), aneuploidy (P<0.01), proliferation rate as determined by Ki67 immunostaining (P<0.01), as well as oestrogen and progesterone receptor content (P<0.01). Image analysis proved to be advantageous over AgNOR counting alone as it facilitated the standardization of the AgNOR technique itself and thus, significantly improved its diagnostic specifity.

The silver staining of nucleolar organizer regions (AgNORs) was evaluated in a total of 697 tumours from ten different tissues. By means of qualitative light microscopy, type, duration and delay of fixation proved to be influential in determining the AgNOR result. For standardization of the AgNOR technique, staining time series in 30 tissue blocks of the ten types of tissue were evaluated using digital image analysis. The silver incubation time which rendered the most distinct diagnostic difference in the AgNOR content of benign and malignant tissue varied considerably. Accordingly, staining time has to be adjusted to the individual argyrophilia of each tissue block or tissue section, for which the use of internal staining standards such as lymphocytes or connective tissue was found to be mandatory. For routine purposes, the appropriate silver incubation time is achieved if AgNORs are visible as black dots mainly within the nucleoli of proliferating cells.

The purpose of this investigation is to give an introduction to a novel method in tumor pathology, namely the Ag-NOR technique. The basis of this method is the argyrophilic staining of intranucleolar, non-histon proteins which are specifically associated with transcriptionally active sites of ribosomal DNA. They can therefore be considered as a marker for the protein synthesis and thus the proliferation rate of a given cell. The morphologic basis ofthe argyrophilic reaction is presented by metaphasic and interphasic tissue culture cells. The applicability of Ag-NOR technique to tumor pathology is exemplified by main results of three studies dealing with tissue sections of 65 meningiomas, whole organ sections of 50 renal carcinomas, and cytospin preparations of 30 urinary washout specimens. These studies document the considerable value of the Ag-NOR content for both, malignancy diagnosis and tumor grading. With the help of image analysis it can be shown that besides the mean number of Ag-NORs the mean area per Ag-NOR dot is of diagnostic significance. In conclusion the Ag-NOR technique is a simple inexpensive and accurate method which can be applied both to formalin fixed, paraffin-embedded tissue and cytologic specimens. As a marker of malignancy it is an invaluable new tool for the diagnostic pathologist.

A total of 306 patients with small cell lung cancer (SCLC) were randomized to receive chemotherapy in a sequential or alternating mode. Sequential chemotherapy consisted of eight cycles of cyclophosphamide, Adriamycin (doxorubicin), and vincristine (CAV) and alternating chemotherapy consisted of three cycles (1, 3, 5) of etoposide, vindesine, and ifosfamide (EVI); three cycles (2, 4, 6) of cisplatin, Adriamycin, and vincristine (PAV); and two cycles (7, 8) of cyclophosphamide, methotrexate, and CCNU (CMC). Responsive patients received prophylactic cranial irradiation after three cycles and chest irradiation after eight cycles of chemotherapy. No maintenance therapy was applied to patients achieving complete remission. Minimum follow-up was 2 years. Of the 302 patients evaluable, overall response rate was 59% in the sequential arm and 70% in the alternating arm. Patients treated with CAV had a complete response rate of 21% in contrast to 36% for those receiving alternating therapy. The median survival for all patients was 9.8 versus 11.3 months, for limited disease 11.1 versus 13.4 months, and for extensive disease 8.9 versus 9.9 months, all in favor of the alternating treatment. Two-year survival rate for all patients was 6% versus 9%, for limited disease 11% versus 14%, and for extensive disease 3% versus 6%, all preferring the alternating treatment mode. Progression-free survival demonstrated a strong correlation to the extent of response irrespective of the treatment regimen applied. Toxicity included 11 lethal and 8 life-threatening complications with a higher frequency in the alternating treatment arm. These results suggest that alternating treatment of SCLC with different drug combinations is more effective than sequential application of CAV.

Introduccióneste trabajo utilizamos una estrategia para el análisis de la actividad científica antropológica-social referida a la Subárea Circumpuneña. Esta estrategia consiste en la elaboración de un paradigma descriptivo constituido por cinco categorías u orientaciones de investigación, las cuales consideramos relevantes para abordar situaciones socioantropológicas significativas de acuerdo a la naturaleza holística de la disciplina.