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PubMed2006

Fluorophotometry as a diagnostic tool for the evaluation of dry eye disease.

BACKGROUND: Dry eye disease is a common debilitating ocular disease. Current diagnostic tests used in dry eye disease are often neither sensitive nor reproducible, making it difficult to accurately diagnose and determine end points for clinical trials, or evaluate the usefulness of different medications in the treatment of dry eye disease. The recently developed fluorophotometer can objectively detect changes in the corneal epithelium by quantitatively measuring its barrier function or permeability. The purpose of the study is to investigate the use of corneal fluorescein penetration measured by the fluorophotometer as a diagnostic tool in the evaluation of dry eye patients. METHODS: Dry eye patients (16 eyes), who presented with a chief complaint of ocular irritation corresponding with dry eye, low Schirmer's one test (<10 mm after 5 minutes) and corneal fluorescein staining score of more than two, were included in the study. Normal subjects (16 eyes), who came for refraction error evaluation, served as controls. Institutional Review Board (IRB) approved consent was obtained before enrolling the subjects in the study and all questions were answered while explaining the risks, benefits and alternatives. All Fluorophotometry of the central corneal epithelium was done utilizing the Fluorotron Master. Each eye had a baseline fluorescein scan performed, after which 50 l of 1% sodium fluorescein dye was instilled. Three minutes later, the fluorescein was washed with 50 ml of normal saline. Fluorescein scans were then started immediately after washing and were recorded at 10, 20, 40, and 60 minutes thereafter. The corneal peak values of fluorescein concentration were recorded within the central cornea in both dry eyes and in controls. RESULTS: Ten minutes after fluorescein installation, patients with dry eye disease averaged a five-fold increase in corneal tissue fluorescein concentration (mean = 375.26 +/- 202.67 ng/ml) compared with that of normal subjects (mean = 128.19 +/- 85.84 ng/ml). Sixty minutes after dye installation, patients with dry eye disease still revealed higher corneal tissue fluorescein concentration (mean = 112.87 +/- 52.83 ng/ml) compared with that of controls (mean = 40.64 +/- 7.96 ng/ml), averaging a three-fold increase. CONCLUSION: Patients with dry eye disease demonstrated an increased corneal permeability and a slower rate of elimination to topically administered fluorescein when measured by the fluorophotometer. This suggests that fluorophotometry may serve as a valuable quantitative and objective tool for the diagnosis of dry eye disease, and in following patients' response to new treatment modalities. Fluorophotometry may serve as an objective non-invasive tool for end-point analysis in clinical trials of new treatments for dry eye disease.

Adult↗
PubMed2000

Immunocytochemical evidence that collision sensing neurons in the locust visual system contain acetylcholine.

The lobula giant movement detector (LGMD1 and -2) neurons in the locust visual system are parts of motion-sensitive pathways that detect objects approaching on a collision course. The dendritic processes of the LGMD1 and -2 in the lobula are localised to discrete regions, allowing the dendrites of each neuron to be distinguished uniquely. As was described previously for the LGMD1, the afferent processes onto the LGMD2 synapse directly with each other, and these synapses are immediately adjacent to their outputs onto the LGMD2. Here we present immunocytochemical evidence, using antibodies against choline-protein conjugates and a polyclonal antiserum against choline acetyltransferase (ChAT; Chemicon Ab 143), that the LGMD1 and -2 and the retinotopic units presynaptic to them contain acetylcholine (ACh). It is proposed that these retinotopic units excite the LGMD1 or -2 but inhibit each other. It is well established that ACh has both excitatory and inhibitory effects and may provide the substrate for a critical race in the LGMD1 or -2, between excitation caused by edges moving out over successive photoreceptors, and inhibition spreading laterally resulting in the selective response to objects approaching on a collision course. In the optic lobe, ACh was also found to be localised in discrete layers of the medulla and in the outer chiasm between the lamina and medulla. In the brain, the antennal lobes contained neurons that reacted positively for ACh. Silver- or haematoxylin and eosin-stained sections through the optic lobe confirmed the identities of the positively immunostained neurons.

Acetylcholine↗
PubMed2002

Interventions targeted at women to encourage the uptake of cervical screening.

BACKGROUND: Cervical cancer is the third most common cancer world-wide. Increasing the uptake of screening, alongside increasing informed choice is of great importance in controlling this disease through prevention and early detection. OBJECTIVES: To assess the effectiveness of interventions aimed at increasing uptake, and informed uptake of cervical cancer screening. SEARCH STRATEGY: Twenty-three electronic databases (to March 2000) were searched with no language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs), or quasi-RCTs of interventions to increase uptake/informed uptake of cervical cancer screening. DATA COLLECTION AND ANALYSIS: Data on study characteristics and quality were extracted independently by two reviewers. Where data were available, relative risks and 95% CI were calculated and a chi-squared test for heterogeneity was performed. MAIN RESULTS: Thirty-five studies were included (27 RCTs and eight quasi-RCTs). Heterogeneity between studies limited statistical pooling of data. Overall, however, invitations appear to be effective methods of increasing uptake. In addition, there is limited evidence to support the use of educational materials. The number and quality of included studies limited evidence regarding effectiveness of other interventions. Informed uptake of cervical screening was not considered by any studies. REVIEWER'S CONCLUSIONS: There was some evidence to support the use of invitation letters to increase the uptake of cervical screening. There was limited evidence to support educational interventions but it was unclear what format was most effective. The majority of the studies were from developed countries and so the relevance to developing countries is unclear.

Female↗
PubMed1991

Relationship between head circumference and height in normal adults and in the nevoid basal cell carcinoma syndrome and neurofibromatosis type I.

Occipitofrontal circumference (OFC) was strongly correlated with height in 72 normal Caucasian men (r = 0.28, P = 0.018) and 78 women (r = 0.53, P less than 0.0001). OFC:height ratios were approximately normally distributed in each sex with a mean of 0.326 (standard deviation [sd] = 0.0139) in males and 0.335 (sd = 0.0177) in females. Relative macrocephaly (an OFC greater than the 95th centile for height) was seen in seven of nine probands with the nevoid basal cell carcinoma syndrome (NBCC), eight of 32 non-probands with NBCC, three of four neurofibromatosis type 1 (NF1) probands, and six of nine non-probands with NF1. Thirty-one percent of the non-proband NBCC cases had OFC less than the 50th centile for height, while none of the NF1 cases had this finding. Head size appears to be related to proband status in NBCC, while the evidence suggests that NF1 is a true macrocephaly syndrome. Objective detection of relative abnormalities in head size may aid in syndrome delineation and diagnosis.

Adult↗
PubMed1986

Paucity of subtle myocardial injury after angioplasty delineated with MB CK.

To determine the extent to which PTCA elicits subtle myocardial ischemic injury, 28 patients were studied prospectively. The presence of myocardial injury was assessed by analysis of frequent (q4 hours) serial samples of MB CK, a sensitive and specific marker of myocardial injury. Immediately prior to angioplasty, baseline 12-lead ECGs and blood samples for evaluation of total CK and MB CK were obtained. Additional ECGs were obtained immediately after the procedure and on the following morning, and serial samples for total and MB CK were obtained at 4-hour intervals for 24 hours. Patients requiring cardiac surgery within 24 hours after PTCA were excluded. Samples (n = 203) were assayed by the glass bead method. Total CK rose by more than 20 IU/L in only five patients, four of whom had received intramuscular premedication. Mean MB CK was 3.4 +/- 6.1 IU/L at 12 hours and 4.1 +/- 4.7 IU/L at 24 hours compared to 3.1 +/- 1.7 IU/L prior to angioplasty. Only one patient with obvious infarction had a value for MB CK above the normal range. Thus, uncomplicated PTCA is not accompanied by objectively detectable subtle myocardial injury.

Angioplasty, Balloon↗
PubMed1987

Subcortical connections of the superior colliculus in the mustache bat, Pteronotus parnellii.

The mustache bat, Pteronotus parnellii, depends on echolocation to navigate and capture prey. This adaptation is reflected in the large size and elaboration of brainstem auditory structures and in the minimal development of visual structures. The superior colliculus, usually associated with orienting the eyes, is nevertheless large and well developed in Pteronotus. This observation raises the question of whether the superior colliculus in the echolocating bat has evolved to play a major role in auditory rather than visual orientation. The connections of the superior colliculus in Pteronotus were studied with the aid of anterograde and retrograde transport of wheat germ agglutinin conjugated to HRP. These results indicate that the superior colliculus of Pteronotus is composed almost entirely of the layers beneath stratum opticum. The retinal projection is restricted to a very thin zone just beneath the pial surface. Prominent afferent pathways originate in motor structures, particularly the substantia nigra and the deep nuclei of the cerebellum. Sensory input from the auditory system originates in three brainstem nuclei: the inferior colliculus, the anterolateral periolivary nucleus, and the dorsal nuclei of the lateral lemniscus. The projections from these auditory structures terminate mainly in the central tier of the deep layer. The most prominent efferent pathways are those to medial motor structures of the contralateral brainstem via the predorsal bundle and to the ipsilateral midbrain and pontine tegmentum via the lateral efferent bundle. Ascending projections to the diencephalon are mainly to the medial dorsal nucleus and zona incerta. Thus, the superior colliculus in Pteronotus possesses well-developed anatomical connections that could mediate reflexes for orienting its ears, head, or body toward objects detected by echolocation.

Afferent Pathways↗
PubMed1988

Imaging system for morphometric assessment of absorption or fluorescence in stained cells.

An image acquisition and processing system has been developed for quantitative microscopy of absorption or fluorescence in stained cells. Three different light transducers are used in the system to exploit the best characteristics of these sensors for different biological measurements. A digital scanner, in the form of a linear array charge-coupled device (CCD), acquires data with high spatial and photometric resolution. A color (RGB) camera is employed when spectral information is required for the segmentation of cellular subcomponents. An image-intensified charged-injection device (CID) camera provides for very low light intensity measurements, primarily for fluorescence-labeled cells. Properties of these transducers, such as contrast transfer function, linearity, and photo-response nonuniformity, have been measured. Two dedicated image processing units were incorporated into the system. The front-end processor, based on a digital signal processor, provides functions such as object detection, raw image calibration, compression, artifact removal, and filtering. The second image processor is associated with the frame memory and includes a histogram processor, a dedicated arithmetic logic unit for image processing functions, and a graphics module for one-bit overlay functions. An interactive program was developed to acquire cell images and to experiment with a range of segmentation algorithms, feature extractions, and other image processing functions. The results of any image operation are displayed on the video monitor. Once a desired processing sequence is determined, the sequence may be stored to become part of a command library and can be executed thereafter as a single instruction.

Algorithms↗
PubMed1989

Reciprocal relationship between mouse germ-cell mutagenesis and basic genetics: from early beginnings to future opportunities.

The scientific foundations for several mammalian germ-line mutagenesis tests in common use today were laid in the 1930s, 1940s, and early 1950s. Subsequent developments in the field have had multiple objectives: detection of mutagenicity of environmental agents (which has led to the development of numerous methodologies), identification of biological and physical factors that affect mutation yield, analysis of the structural nature of the genetic alterations, and assessment of the organismic effects of various types of mutations. Mutagenesis studies have made numerous contributions to basic genetics by generating mutant types that led to elucidation of sex-determining mechanisms in mammals; formulation of the single-active-, or inactive-, X-chromosome hypothesis; correlation of genetic and cytological maps; discovery of genetic "imprinting" phenomena; study of developmental pathways and cell lineages, etc. Particularly useful are sets of complexly overlapping deletions that have been recovered in radiation mutagenesis studies, propagated in breeding stocks, and genetically analyzed; these have constituted prerequisites for molecular genetic studies aimed at development of the DNA structure-function relationships for important genomic regions. Mutagenesis experiments have also served to identify mutagens that are particularly effective in inducing specific types of genetic lesions desired for basic studies. Reciprocally, basic genetics has contributed to the development of mutagenesis tests and has enhanced the value of the specific-locus test by adding to its quantitative capabilities the capability for qualitatively characterizing the actions of mutagens.

Animals↗
PubMed1995

Patterns of thermoregulation associated with cold intolerance after digital replantation.

Twelve patients with complete thumb amputations were analyzed to determine the interrelations between thermoregulation for pain and cold intolerance and sensory nerve recovery. Patients were examined at 3 months, 6 months, 1 year, and after 2 years following replantation. Medical thermography was introduced to assess postoperative circulation following digital replantation, while vasomotor tone was assessed by cold-stress plethysmography testing. Postoperative circulation was divided into two different patterns based upon skin temperature, the transition of which over time correlated well with sensory nerve recovery. Patients with cold intolerance showed a persistent vasoconstriction pattern, the cold change of which was objectively detected by thermography.

Adult↗
PubMed2001

Dynamic contrast-enhanced MRI of experimental spinal cord injury: in vivo serial studies.

The progression of experimental spinal cord injury (SCI) was followed with in vivo dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and neurobehavioral studies on postinjury days 0, 2, 4, 7, 10, 14, 17, 21, 28, 35, and 42. Gadopentate dimeglumine (Gd) was administered IV and postcontrast, T(1)-weighted, axial images were acquired repetitively for up to 60 min. Images were analyzed to determine the spatial and temporal evolution of the intensity enhancement. A statistical decision mechanism was developed to objectively detect the enhancement. Strong and rapid enhancement was observed at the epicenter of injury, indicating a significant compromise in blood spinal cord barrier. The enhanced regions in each slice were combined to estimate the area and volume of the lesion. On the day of injury, around 85% of the total cord area at the epicenter showed enhancement within the first 15 min of Gd administration. At the same time, the enhanced volumes attained nearly 40% of the total cord volume and extended axially over 8 mm along the cord. These quantities decreased steadily with time, with a concomitant improvement in the motor functions. The volume of enhancement correlated highly with the neurobehavioral tests (r = -0.87). DCE-MRIs revealed small hyperintense regions distributed inside white matter about two weeks postinjury. Based on histology, these enhancements appear to represent new vessels with "leaky endothelium." Magn Reson Med 45:614-622, 2001.

Animals↗
PubMed2004

PGD analysis for aneuploidy in a patient heterozygous for a polymorphism of chromosome 16 (16qh-).

OBJECTIVES: Detection and study of a polymorphism of chromosome 16qh in preimplantational embryos as well as in peripheral blood from the carrier. METHODS: A polymorphism of chromosome 16 (16qh-) was detected in PGD analysis for aneuploidy using a probe for the centromeric region of chromosome 16. The lack of pericentromeric heterochromatin in one of the chromosomes 16 could lead to misdiagnosis in PGD. PGD analysis using telomeric probes for this chromosome was performed to confirm the polymorphism as well as to avoid misdiagnosis in embryo blastomeres. FISH in lymphocyte metaphases was used to detect the carrier. RESULTS: Telomeric probes allowed detection of a polymorphism for the centromeric region of chromosome 16. FISH with centromeric and telomeric probes in lymphocyte metaphases of the parents showed that the patient was the carrier of the polymorphism. CONCLUSION: It is highly recommended that telomeric probes for chromosome 16 be used in preimplantation genetic diagnosis when a high frequency of monosomy for chromosome 16 is observed after regular aneuploidy analysis.

Adult↗
PubMed1979

Cytostatic treatment of meningeal blastoses.

Intrathecal treatment with MTX was attempted in patients with diffuse meningeal blastoses. As a rule, symptoms and clinical findings improved rapidly. As objective parameters, the differential cell pictures of the CSF showed dissimilar results during therapy (25 mg MTX weekly i.t.). In leukoses (n = 10) and malignant lymphomas (n = 12), the CSF could be cleared with three exceptions which concerned differentiated tumors. The success was similarly good with meningeal dissemination of a seminoma. Meningeal carcinoses with mammary carcinoma (n = 7) and melanoma (n = 2) showed dissimilar results. No alteration of the cytograms of four bronchial carcinomas and one colon carcinoma was demonstrable. Besides the growth form, the degree of differentiation appears to be decisive for the success of therapy. The labeling index appears to be a useful indicator. Since symptoms and clinical findings often markedly improve even when a success cannot be objectively detected cytologically, an attempt at therapy is always to be recommended.

Breast Neoplasms↗
PubMed2002

Coherence between one random and one periodic signal for measuring the strength of responses in the electro-encephalogram during sensory stimulation.

Coherence between a pulse train representing periodic stimuli and the EEG has been used in the objective detection of steady-state evoked potentials. This work aimed to quantify the strength of the stimulus responses based on the statistics of coherence estimate between one random and one periodic signal, focusing on the confidence limits and power of significance tests in detecting responses. To detect the responses in 95% of cases, a signal-to-noise ratio of about -7.9 dB was required when using 48 windows (M) in the coherence estimation. The ratio, however, increased to -1.2 dB when M was 12. The results were tested in Monte Carlo simulations and applied to EEGs obtained from 14 subjects during visual stimulation. The method showed differences in the strength of responses at the stimulus frequency and its harmonics, as well as variations between individuals and over cortical regions. In contrast to those from the parietal and temporal regions, results for the occipital region gave confidence limits (with M = 12) that were above zero for all subjects, indicating statistically significant responses. The proposed technique extends the usefulness of coherence as a measure of stimulus responses and allows statistical analysis that could also be applied usefully in a range of other biological signals.

Adolescent↗
PubMed2007

[On the relation between binaural difference potentials and directional hearing].

BACKGROUND: Central auditory processing disorders (CAPD) are associated with reduced discriminatory abilities of the auditory system. One of these abilities is directional hearing, which is based on the evaluation of interaural signal differences. Since these differences affect also the binaural difference potentials (BDP), these derived evoked potentials could be suitable for the objective detection of disabilities in acoustic localization. METHOD: Auditory brainstem responses (ABR) evoked by monaural and binaural stimulation were recorded in 32 adult normal-hearing volunteers at stimulus levels between 10 and 80 dB nHL and the BDP were derived. Additionally, a test of directional hearing was performed and evaluated. RESULTS: BDP are detectable at all stimulus levels without difficulties, with acceptable examination times and with satisfactory reliability in a routine clinical environment. The electrodes can be positioned at the mastoid (A1 and A2) and vertex (Cz) as for conventional ABR recording. Normal ranges are given for latency and amplitude as well as for their lateral differences. CONCLUSION: The spectrum in directional hearing ability as covered by normal-hearing subjects is not mirrored in the parameters of their BDP. Nevertheless, it cannot be ruled out that a real impairment of directional hearing goes along with significantly altered BDP.

Adult↗
PubMed2005

Postcentral neurons with covert receptive fields in conscious macaque monkeys: their selective responsiveness to simultaneous two-point stimuli applied to discrete oral portions.

The representation of the oral structures in the postcentral somatosensory cortex was studied in conscious macaque monkeys by recording the activity of single neurons. A total of 2,807 neurons were isolated in the oral regions of three hemispheres in two animals. Of these, 375 neurons (area 3a, 3; area 3b, 123; area 1, 99; area 2, 150) lacked an apparent receptive field (RF), and their relative frequency was significantly higher in area 2 (19%) than in more rostral areas (area 3a, 8%; area 3b, 10%; area 1, 12%). We tested the responsiveness of these neurons to stimuli applied simultaneously to two discrete, but functionally related, oral structures (interstructural two-point stimuli: iTPS). Neurons in areas 3a, 3b, and 1 that lacked an apparent RF were not responsive to iTPS. However, 35 neurons in area 2 responded stably to iTPS applied to either of the following sets of oral structures: the tongue and incisors (n=18), incisors and lip (n=9), lip and tongue (n=12), or upper and lower lips (n=8). Of them, 19 neurons were activated during self-movements such as tongue protrusion, lip licking, and food manipulation. The neurons selectively responsive to iTPS might detect converging inputs from different oral structures and play a pivotal role in detecting objects straddling different oral structures and the mutual contact of oral structures.

Action Potentials↗
PubMed2006

The role of the follow-up chest radiograph in suspected non-accidental injury.

BACKGROUND: Rib fractures in children under the age of 2 years have a strong correlation with non-accidental injury (NAI). Follow-up radiographs can improve detection. OBJECTIVE: To evaluate the value of the follow-up chest radiograph in suspected non-accidental injury. MATERIALS AND METHODS: The study included all children less than 2 years of age who were investigated for suspected NAI in our institution between January 1998 and October 2003. Prior to January 2000, only selected patients were asked to attend for a follow-up chest radiograph. From January 2000 onwards all children were asked to reattend. RESULTS: Of 200 children included in the study, 59 (29.5%) reattended for a follow-up chest radiograph. The follow-up film provided useful additional information in 7 (12%) of the 59 children. In two children rib fractures were noted only on the follow-up chest radiograph. In a further two patients additional rib fractures were noted. Additional dating information was obtained for two patients. For one child both additional fractures and dating information were noted. CONCLUSIONS: The follow-up chest radiograph provides useful information in children with suspected NAI and it is recommended that it should be included routinely in the imaging investigations of these children.

Child Abuse↗
PubMedDate not supplied

Preoperative identification of psychiatric illness in aesthetic facial surgery patients.

The purpose of this study was to evaluate the preoperative use of a two-part standardized assessment program (Prime-MD, Biometrics Research Department, New York State Psychiatric Institute) to objectively detect psychiatric disorders in facial plastic surgery patients, and to compare its use to findings identified by the facial plastic surgeon. Seventy-five new patients requesting aesthetic facial surgery at two academic centers and two private practice locations were evaluated.

Face↗
PubMedDate not supplied

Distance discrimination during active electrolocation in the weakly electric fish Gnathonemus petersii.

Weakly electric fish use active electrolocation for orientation at night. They emit electric signals (electric organ discharges) which generate an electrical field around their body. By sensing field distortions, fish can detect objects and analyze their properties. It is unclear, however, how accurately they can determine the distance of unknown objects. Four Gnathonemus petersii were trained in two-alternative forced-choice procedures to discriminate between two objects differing in their distances to a gate. The fish learned to pass through the gate behind which the corresponding object was farther away. Distance discrimination thresholds for different types of objects were determined. Locomotor and electromotor activity during distance measurement were monitored. Our results revealed that all individuals quickly learned to measure object distance irrespective of size, shape or electrical conductivity of the object material. However, the distances of hollow, water-filled cubes and spheres were consistently misjudged in comparison with solid or more angular objects, being perceived as farther away than they really were. As training continued, fish learned to compensate for these 'electrosensory illusions' and erroneous choices disappeared with time. Distance discrimination thresholds depended on object size and overall object distance. During distance measurement, the fish produced a fast regular rhythm of EOD discharges. A mechanisms for distance determination during active electrolocation is proposed.

Animals↗