Care of children with diabetes as inpatients: frequency of admissions, clinical care and patient experience.

AIM: Hospital inpatient care for children with diabetes is frequently mentioned by parents as unsatisfactory. The aim of this study was to examine the reasons for inpatient admission of children with diabetes and to understand patient and carer experience in order to improve services. METHODS: Questionnaires were given to medical teams, parents and children during admissions of children with diabetes under 16 years of age in three regions of England. RESULTS: There were 401 admissions over 6 months from 3247 patients: 334 (83%) emergency admissions and 59 (15%) elective; the reason is unknown in eight (2%). One hundred and forty-three (36%) were emergency admissions with diabetic ketoacidosis/hyperglycaemia. Clinical teams reported adverse events around insulin administration in 25, hypoglycaemia (sometimes recurrent) in 120 and food provision in 14 admissions. Others included seven incidents around elective surgery. Diabetes clinical teams were not always informed about admissions and only 33% were informed within 2 h. Parents and children reported fewer problems: 62% were involved in care most of the time and 87% were able to give insulin. Most negative comments were about poor staff management of out-of-range blood glucose levels, knowledge of insulin pumps and care of children waiting in the emergency department. CONCLUSIONS: There were a large number of admissions and the majority were emergencies. Parents generally felt that they receive good care, although with some lack of knowledge amongst the ward staff. There were an unacceptable number of adverse incidents reported. We recommend that education of ward staff in diabetes is carried out regularly with reference to the standards of care.

Functional characterization of human NTRK2 mutations identified in patients with severe early-onset obesity.

OBJECTIVE: The neurotrophin receptor TrkB has been implicated in the regulation of energy homeostasis in rodents. We have previously identified four rare missense mutations in the gene encoding TrkB, NTRK2, in 198 severely obese children with developmental delay. We have now undertaken a more detailed analysis of the in vitro functional consequences of the mutations identified: I98V, P660L, T821A and Y722C. DESIGN: Wild-type and mutant TrkB receptor constructs were stably transfected into PC12 cells and the signaling responses to the endogenous ligand, brain-derived neurotrophic factor (BDNF), were examined by Western blotting of cell lysates. In the case of Y722C, PC12 cells stably expressing this mutant were studied for their ability to respond to BDNF by promoting neurite outgrowth and cell survival. RESULTS: Further functional characterization of the previously reported Y722C TrkB mutation reveals impaired activation of mitogen-activated protein kinase, phospholipase C-gamma and Akt, as well as reduced BDNF-induced neurite outgrowth and cell survival in stably transfected PC12 cell lines. However, the signaling properties of I98V, P660L and T821A were all indistinguishable from wild type. CONCLUSION: We provide further evidence for the impairment in signaling by Y722C and show that as well as a loss of signaling, this mutation affects the ability of TrkB to promote neurite outgrowth in response to BDNF. Thus, impaired hypothalamic neurogenesis may contribute to the severe hyperphagia and obesity seen in the individual harboring the Y722C variant. The other three rare TrkB variants do not show reduced autophosphorylation or impaired downstream signaling in vitro and, as yet, it is unclear whether these variants contribute to obesity in these patients.

Joint transform optical correlator designed and analyzed by use of two- and one-dimensional hilbert transforms.

Novel real-time joint transform, Hilbert transform optical correlators are proposed in which only a half or a quarter of the Fourier plane is written onto an optically addressable spatial light modulator. A point source is used to recover the result for the whole plane. As a result, images with a two- or four-times larger space-bandwidth product can be matched in amplitude and phase. The effect of truncating the transform plane is explained with two- and one-dimensional Hilbert transform analysis. Results of computer simulation are shown.

Hilbert transform and mirror-image optical correlators.

An optical correlator, believed to be novel, adds an x-y mirror image to the input and filter images to perform convolution involving amplitude and phase. The resulting real Fourier transform filters can be loaded into a liquid-crystal device (LCD). In contrast, a complex filter would require high-resolution film. A Hilbert transform and a point source are applied at the filter plane to reduce filter storage and LCD loading time by a factor of 2. An optional spatial filter removes an offset intensity and squares the result. Filters have only twice the number of pixels of the images. Analysis is verified by computer simulation, and performance is discussed.

Regular albuterol, nedocromil sodium, and bronchial inflammation in asthma.

Adult, nonsmoking patients with mild to moderate asthma were randomized to receive 4 mg nedocromil sodium (n = 13), 200 micrograms albuterol (n = 13), or placebo (n = 12) four times daily for 16 wk in a double-blind, double-dummy protocol. Before and after treatment, patients underwent histamine bronchial provocation, followed by fiberoptic bronchoscopy. Bronchial mucosal biopsy tissue and bronchoalveolar lavage fluid were examined in detail. Daily diary cards were kept by each patient. Compared with baseline, the numbers of total (EG1) and activated (EG2) eosinophils, expressed as cells per square millimeter of bronchial biopsy tissue, decreased after treatment with nedocromil sodium (pretreatment: EG1 = 152.2 +/- 42.5 and EG2 = 143.8 +/- 36.8; post-treatment: EG1 = 115.4 +/- 35.1 and EG2 = 104.9 +/- 31.6) and increased after treatment with albuterol (pretreatment: EG1 = 129.3 +/- 28.0 and EG2 = 127.5 +/- 30.2; post-treatment: EG1 = 238.0 +/- 55.0 and EG2 = 211.4 +/- 50.4). Although the changes between the active treatment groups were significantly different (p < 0.05), no such significant differences were found in eosinophil numbers before and after treatment when comparisons were made between either of the active treatment groups and the placebo group. Although not significant, the changes in concentration of eosinophil cationic protein in bronchoalveolar lavage reflected the changes seen in numbers of activated eosinophils. No treatment differences were detected for mast cell or lymphocyte numbers. There were no statistical differences between treatment groups for clinical findings, with the exception of evening peak flow, which was significantly increased (p < 0.05) in the albuterol group.(ABSTRACT TRUNCATED AT 250 WORDS)

The expression of intercellular adhesion molecule-1 and the beta 1-integrins in asthma.

Expression of intercellular adhesion molecule-1 (ICAM-1) appears to be important to the development of bronchial hyperresponsiveness and eosinophilia in Ascaris sensitized monkeys. Beta 1-integrins are expressed on epithelial cells, and may contribute to adherence of epithelial cells to the basement membrane. The aim of this study was to determine whether adhesion receptor expression was altered in human asthmatic bronchial epithelium. Using monoclonal antibody staining, we have examined the expression of ICAM-1 and the alpha 1-alpha 6-subunits of the beta 1-integrin family in bronchial mucosal biopsies from 33 asthmatic and 13 nonasthmatic subjects. The epithelium was positive for ICAM-1 in 26 out of 33 asthmatics, although negative in all 13 nonasthmatics. ICAM-1 expression was not associated with bronchial responsiveness or with medication requirements. Beta 1-integrin staining showed that alpha 2-, alpha 3- and alpha 6-subunits stained the epithelium in all cases. Alpha 4 staining was weakly positive in the epithelium in five asthmatics. Alpha 5 staining was weak in asthmatics and normals. Alpha 4 and alpha 6-subunits also stained inflammatory cells. Epithelial upregulation of ICAM-1 is present in asthma. Beta 1-integrins with alpha 2-, alpha 3- and alpha 6-subunits appear to be constitutively expressed in bronchial epithelium.

Placebo-controlled immunopathologic study of four months of inhaled corticosteroids in asthma.

The effect of prolonged inhaled corticosteroid treatment on bronchial immunopathology was assessed in 25 nonsmoking mildly asthmatic subjects previously receiving intermittent inhaled beta 2-agonist alone. Inhaled beclomethasone dipropionate (BDP), 500 micrograms twice per day or placebo was administered for 4 mo in a double-blind parallel group study. Histamine bronchial provocation, fiberoptic bronchoscopic biopsy, and bronchoalveolar lavage (BAL) were performed before and after treatment. There was no difference in bronchial responsiveness or lung function between groups. In patients treated with BDP compared with placebo, there was a significant reduction in toluidine blue-staining mast cells (p = 0.028) and total (p = 0.005) and activated eosinophils (p = 0.05) in biopsies but no difference in eosinophils or eosinophil cationic protein in BAL. Granulocyte-macrophage colony-stimulating factor expression was significantly reduced in the bronchial epithelium, and the thickness of Type III collagen deposition in the bronchial lamina reticularis reduced from 29.7 +/- 4.4 to 19.8 +/- 3.4 microns (mean +/- 95% confidence interval) (p = 0.04). No change in helper or activated helper T cells occurred. Prolonged BDP treatment reduces inflammatory infiltration, proinflammatory cytokine expression, and subepithelial collagen deposition, a recognized abnormality in asthma.

Optical perceptron learning for binary classification with spatial light rebroadcasters.

Binary classification of an object in a two-dimensional image is considered. A spatial light rebroadcaster is shown to be advantageous for learning in this case because it can store the weights and permit upward and downward adjustments. Two learning algorithms, based on the perceptron, are considered. A modification of the perceptron algorithm is developed so that only positive weights are needed. This is convenient because light intensity is positive only. The modified algorithm is shown to converge in a finite number of steps for positive linear separable classes. Optical experiments show the classification of four characters in two groups, in which alternative groupings are used to show robustness. In the second group of experiments the complements of the two-dimensional characters are used, and the convergence is equally fast. Adding the results from the original and complementary patterns provides a discrimination superior to that obtained using either on its own.

Optical adder that uses spatial light rebroadcasters.

We show novel experimental results for an all-optical cascadable module that consists of a spatial light rebroadcasters, an image intensifier, and a liquid-crystal light valve. The module may be used for all-optical logic, memory, or arithmetic. Previous experimental systems involving spatial light rebroadcasters use a video camera and computer to overcome their lack of cascadability. The results of laboratory experiments show correct operation for a half-adder constructed from the cascadable module. Optical setups are proposed for constructing all-optical parallel ripple-carry and bit-slice full adders by using a single optical half-adder.

Co-ordinate expression of the alpha-6 integrin laminin receptor sub-unit and laminin in breast cancer.

Interactions between cells and extracellular matrices are mediated in part by a family of heterodimeric molecules known as integrins. We have investigated, using immunohistology, the distribution of six integrin alpha sub-units in normal breast tissue and 26 breast carcinomas. Alpha-1 integrin (collagen/laminin receptor sub-unit) was detected in myoepithelium, but not in luminal epithelium nor in most (20/26) carcinomas. Its expression on fibroblasts was enhanced in desmoplastic stroma. Both benign and malignant epithelium showed uniform positive staining for alpha-2 (collagen receptor sub-unit) and for alpha-3 (collagen/fibronectin/laminin receptor sub-unit). All epithelium was negative for alpha-4 (sub-unit of a fibronectin receptor). Epithelial staining for alpha-5 (fibronectin receptor sub-unit) was weak in all samples. Alpha-6 (sub-unit of two integrin laminin receptors) showed conspicuous changes in all invasive carcinomas. In normal tissues, there was weak staining of epithelial cytoplasm with alpha-6 antibody and moderate cell membrane staining. Strongest staining was present in a basement membrane distribution. In carcinomas, loss of cytoplasmic and cell membrane staining was variable, but basal membrane staining was diminished or absent in all tumours. Loss of basal membrane staining for alpha-6 integrin corresponded closely to loss of immunoreactivity for its ligand laminin in invasive breast cancer.

Spatial light rebroadcaster bit-slice word-addressable holographic memory.

A heteroassociative memory is proposed that allows a key word in a dictionary of key words to be used to recall an associated holographic image in a database of images. A novel bit-slice search approach finds the word sought in a dictionary of key words and generates a beam that selects the corresponding holographic image from a directory of images. Spatial light rebroadcasters are proposed for the key-word database. Optical experimental results demonstrate that spatial light rebroadcasters may be used in loops with image intensifiers and optically addressable liquid-crystal light valves and that the approach can be used to select holograms based on key-word matching. In the case considered, a holographic image having more than 40,000 bits is selected from 8 by using a key word from a dictionary of 8 words.

Optical heteroassociative memory using spatial light rebroadcasters.

A new device, a spatial light rebroadcaster, is described that can have optical disk resolution and high speed. Experimental results demonstrate resolution, speed, linearity, logic operation, and arithmetic computation. The device is suitable for optical computing, in particular for memory systems. Optical masking for controlling memory recall and 100 x 100 matrix-vector multiplication are demonstrated. A one pass optical heteroassociative memory system was assembled that uses an optical outer product formulation to store associated 32-bit vectors. Recall is achieved by optical matrix-vector multiplication. The results show the suitability of these devices for memory systems in optical computers.

Real-time optical expert systems.

Optics has advantages for overcoming limitations arising when applying existing electronic technologies to real-time parallel computation. In particular, spatial light modulators (SLMs) permit simultaneous storage, multiplication, and/or complex interconnection. A simple expert uses an SLM crossbar switch to provide a flexible and fast implementation of combinatorial logic. A second expert system, illustrated using medical diagnosis, uses the Bayes theorem to update recursively the probabilities of various illnesses given additional symptom information. The a priori probability matrices are stored in SLMs which provide matrix-vector multiplication and interconnection. Computation of the best next symptom question is possible because of the high speed.

Changes in Metabolite Levels in Kalanchoë daigremontiana and the Regulation of Malic Acid Accumulation in Crassulacean Acid Metabolism.

Changes in glucose-6-P, fructose-6-P, fructose-1,6-diP, 6-phospho-gluconate, phosphoenolpyruvate, 3-phosphoglycerate, and pyruvate levels in the leaves of the Crassulacean plant Kalanchoë daigremontiana Hammet et Perrier were measured enzymically during transitions from CO(2)-free air to air, air to CO(2)-free air, and throughout the course of acid accumulation in darkness. The data are discussed in terms of the involvement of phosphoenolpyruvate carboxylase in malic acid synthesis and in terms of the regulation of the commencement of malic acid synthesis and accumulation through the effects of CO(2) on storage carbohydrate mobilization and its termination through the effects of malic acid on phosphoenolpyruvate carboxylase activity.

The pathway of carbon dioxide fixation in crassulacean plants.

Combined gas chromatography-mass spectrometry of malic acid derivatives has been used to show unequivocally that malic acid, synthesized during active acid accumulation in the dark by Kalanchoë daigremontiana Hammet et Perrier in the presence of (13)CO(2) is produced by a pathway involving a single carboxylation. The significance of the finding that crassulacean malate synthesized in the dark and in the presence of (14)CO(2) often contains 66% of the total carboxyl label in carbon atom 4, which has previously been taken to indicate the operation of a double carboxylation pathway or has been dismissed as an artefact, is discussed.