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2.  Reconstructing foveal pit morphology from optical coherence tomography imaging 
The British Journal of Ophthalmology  2009;93(9):1223-1227.
The aim of this study was to describe an automated method for extracting quantitative measures of foveal morphology from optical coherence tomography (OCT) images of the human retina.
We performed a methodological study and retrospective investigation of selected cases. Sixty-five human subjects were included: 61 healthy subjects and four female carriers of blue-cone monochromacy (BCM). Thickness data from B-scans traversing the foveal pit were fitted to a mathematical model designed to capture the contour of the foveal surface. From this model, various metrics of foveal morphology were extracted (pit depth, diameter and slope).
Mathematical descriptions of foveal morphology enabled quantitative and objective evaluation of foveal dimensions from archived OCT data sets. We found a large variation in all aspects of the foveal pit (depth, diameter and slope). In myopes and BCM carriers, foveal pits were slightly less deep and had a more shallow slope, although these differences were not significant.
Offline analysis of OCT data sets enables quantitative assessment of foveal morphology. The algorithm works on the Stratus™ and Cirrus™ macular thickness protocols, as well as the Spectralis® and Bioptigen© radial-line scan protocols, and can be objectively applied to existing data sets. These metrics will be useful in following changes associated with diseases such as retinopathy of prematurity and high myopia, as well as in studying normal postnatal development of the human fovea.
PMCID: PMC3327485  PMID: 19474001
3.  Principles of antidote pharmacology: an update on prophylaxis, post-exposure treatment recommendations and research initiatives for biological agents 
British Journal of Pharmacology  2010;161(4):721-748.
The use of biological agents has generally been confined to military-led conflicts. However, there has been an increase in non-state-based terrorism, including the use of asymmetric warfare, such as biological agents in the past few decades. Thus, it is becoming increasingly important to consider strategies for preventing and preparing for attacks by insurgents, such as the development of pre- and post-exposure medical countermeasures. There are a wide range of prophylactics and treatments being investigated to combat the effects of biological agents. These include antibiotics (for both conventional and unconventional use), antibodies, anti-virals, immunomodulators, nucleic acids (analogues, antisense, ribozymes and DNAzymes), bacteriophage therapy and micro-encapsulation. While vaccines are commercially available for the prevention of anthrax, cholera, plague, Q fever and smallpox, there are no licensed vaccines available for use in the case of botulinum toxins, viral encephalitis, melioidosis or ricin. Antibiotics are still recommended as the mainstay treatment following exposure to anthrax, plague, Q fever and melioidosis. Anti-toxin therapy and anti-virals may be used in the case of botulinum toxins or smallpox respectively. However, supportive care is the only, or mainstay, post-exposure treatment for cholera, viral encephalitis and ricin – a recommendation that has not changed in decades. Indeed, with the difficulty that antibiotic resistance poses, the development and further evaluation of techniques and atypical pharmaceuticals are fundamental to the development of prophylaxis and post-exposure treatment options. The aim of this review is to present an update on prophylaxis and post-exposure treatment recommendations and research initiatives for biological agents in the open literature from 2007 to 2009.
PMCID: PMC2992890  PMID: 20860656
biological; anthrax; botulism; cholera; encephalitis; melioidosis; plague; Q fever; ricin; smallpox
4.  Elevated CSF outflow resistance associated with impaired lymphatic CSF absorption in a rat model of kaolin-induced communicating hydrocephalus 
We recently reported a lymphatic cerebrospinal fluid (CSF) absorption deficit in a kaolin model of communicating hydrocephalus in rats with ventricular expansion correlating negatively with the magnitude of the impediment to lymphatic function. However, it is possible that CSF drainage was not significantly altered if absorption at other sites compensated for the lymphatic defect. The purpose of this study was to investigate the impact of the lymphatic absorption deficit on global CSF absorption (CSF outflow resistance).
Kaolin was injected into the basal cisterns of Sprague Dawley rats. The development of hydrocephalus was assessed using magnetic resonance imaging (MRI). In one group of animals at about 3 weeks after injection, the movement of intraventricularly injected iodinated human serum albumin (125I-HSA) into the olfactory turbinates provided an estimate of CSF transport through the cribriform plate into nasal lymphatics (n = 18). Control animals received saline in place of kaolin (n = 10). In a second group at about 3.5 weeks after kaolin injection, intraventricular pressure was measured continuously during infusion of saline into the spinal subarachnoid space at various flow rates (n = 9). CSF outflow resistance was calculated as the slope of the steady-state pressure versus flow rate. Control animals for this group either received no injections (intact: n = 11) or received saline in place of kaolin (n = 8).
Compared to saline injected controls, lateral ventricular volume in the kaolin group was significantly greater (0.087 ± 0.013 ml, n = 27 versus 0.015 ± 0.001 ml, n = 17) and lymphatic function was significantly less (2.14 ± 0.72% injected/g, n = 18 versus 6.38 ± 0.60% injected/g, n = 10). Additionally, the CSF outflow resistance was significantly greater in the kaolin group (0.46 ± 0.04 cm H2O.μL-1.min, n = 9) than in saline injected (0.28 ± 0.03 cm H2O.μL-1.min, n = 8) or intact animals (0.18 ± 0.03 cm H2O.μL-1.min, n = 11). There was a significant positive correlation between CSF outflow resistance and ventricular volume.
The data suggest that the impediment to lymphatic CSF absorption in a kaolin-induced model of communicating hydrocephalus has a significant impact on global CSF absorption. A lymphatic CSF absorption deficit would appear to play some role (either direct or indirect) in the pathogenesis of ventriculomegaly.
PMCID: PMC2831828  PMID: 20181144
5.  Is screening for sexually transmitted infections in men who have sex with men who receive non‐occupational HIV post‐exposure prophylaxis worthwhile? 
Non‐occupational HIV post‐exposure prophylaxis (NPEP) is routinely prescribed after high risk sexual exposure. This provides an opportunity to screen and treat individuals at risk of concurrent sexually transmitted infections (STI). The aim of this study was to assess the efficacy of an STI screening programme in individuals receiving NPEP.
STI screens were offered to all individuals receiving NPEP from March 2001 to May 2004. Screen results were compared to type of sexual exposure and baseline patient characteristics.
A total of 253 subjects were screened, representing 85% of the target population. All were men who have sex with men (MSM). Common exposure risks were receptive anal intercourse (RAI) in 61% and insertive anal intercourse (IAI) in 33%. 32 (13%) individuals had one or more STI. The most common STIs were rectal infections with Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) in 11 (4.5%) and six (2.5%) individuals, respectively. Subjects with rectal CT were significantly more likely to be co‐infected with rectal NG (p<0.001). There was no association between the presence of a rectal STI and age or exposure risk. Only six (19%) individuals with an STI were symptomatic at screening.
In this cohort of MSM receiving NPEP, high rates of concomitant STIs are observed highlighting the importance of STI screening in this setting.
PMCID: PMC2563841  PMID: 16461596
HIV post‐exposure prophylaxis; sexually transmitted infections; screening
6.  Correlation of histological findings with gadolinium enhanced MRI scans during healing of a PHEMA orbital implant in rabbits 
BACKGROUND/AIMS—To investigate a poly(2-hydroxyethyl methacrylate) (PHEMA) orbital implant with a spongy anterior hemisphere and a smooth gel posterior hemisphere, by histology correlated with magnetic resonance images.
METHODS—Following enucleation, eight rabbits received PHEMA implants to which the muscles were directly sutured, and underwent gadolinium enhanced magnetic resonance imaging (MRI) from 3 to 52 weeks. After the rabbits were killed, the implants were removed, cut in a plane corresponding to the scan, and processed for light and electron microscopy.
RESULTS—All eight rabbits retained their implant to the end of the study period without complications. The scans demonstrated muscle attachment to the anterior half of the implant, and enhancement was seen on injection of gadolinium chelate. Histology confirmed muscle attachment, and cellular and vascular ingrowth. Over time, a transformation from reactive inflammatory to relatively non-vascular scar tissue was seen within the implant. Calcium deposits in one implant were detected by imaging and histology.
CONCLUSION—The implants are readily visualised on MRI. Muscle attachment and fibrovascular ingrowth into the anterior hemisphere are seen, while encapsulation of the posterior hemisphere is minimal. Histological findings confirm the progress of the healing response, with initial inflammation and marked vascularisation, developing later into quiescent scar tissue predominantly of fibroblasts.

PMCID: PMC1723032  PMID: 10216066
7.  Estimation of the retinal nerve fibre layer thickness in the papillomacular area of long standing stage IV macular holes 
AIM—To compare the thickness of the retinal nerve fibre layer (RNFL) in the papillomacular area of patients with long standing stage IV macular holes with age matched controls, using a scanning laser polarimeter.
METHODS—The nerve fibre analyser (NFA) was used to measure the mean thickness of the RNFL around the optic nerve head, the thickness values of temporal and nasal 45 degrees sectors and the integral values in 10 patients with macular holes and in 10 age matched controls.
RESULTS—The mean RNFL thickness around the optic nerve head was 79.71 (SD 15.06) µm in the macular hole group and 75.1 (10.8) µm in the control group (p = 0.44). The mean thickness in the temporal sector was 63.69 (12.08) µm in the macular hole group and 58.65 (8.9) µm in the control group (p = 0.3). The mean ratio between the temporal and nasal sector thickness values was 0.8441 in the macular hole group and 0.7819 in the controls (p = 0.42).
CONCLUSIONS—There was no significant difference in the thickness of the RNFL in the papillomacular area in the two groups. This suggests that there may be no changes in the thickness of the RNFL in patients with long standing macular holes.

PMCID: PMC1723025  PMID: 10216057
9.  Insecticide resistance and vector control. 
Emerging Infectious Diseases  1998;4(4):605-613.
Insecticide resistance has been a problem in all insect groups that serve as vectors of emerging diseases. Although mechanisms by which insecticides become less effective are similar across all vector taxa, each resistance problem is potentially unique and may involve a complex pattern of resistance foci. The main defense against resistance is close surveillance of the susceptibility of vector populations. We describe the mechanisms of insecticide resistance, as well as specific instances of resistance emergence worldwide, and discuss prospects for resistance management and priorities for detection and surveillance.
PMCID: PMC2640263  PMID: 9866736
10.  Reduction in mydriatic drop size in premature infants. 
In a prospective study of 26 premature infants, 5 microliters microdrops were compared with standard 26 microliters eye drops of cyclopentolate 0.5% and phenylephrine 2.5%. There was no statistical difference in pupil dilatation. The 5 microliters microdrops have potentially fewer adverse effects in premature infants.
PMCID: PMC504531  PMID: 8318484
11.  Human intraovarian interleukin-1 (IL-1) system: highly compartmentalized and hormonally dependent regulation of the genes encoding IL-1, its receptor, and its receptor antagonist. 
Journal of Clinical Investigation  1992;89(6):1746-1754.
To delineate the scope of the human intraovarian IL-1 system we used a solution hybridization/RNase protection assay to test for expression of the genes encoding IL-1, its type I receptor (IL-1R), and its receptor antagonist (IL-1RA). IL-1 transcripts were not detected in whole ovarian material from days 4 or 12 of an unstimulated menstrual cycle but transcripts (IL-1 beta much greater than IL-11 alpha) were detected in preovulatory follicular aspirates from gonadotropin-stimulated cycles. Concurrently obtained peripheral monocytes did not contain IL-1 beta transcripts but macrophage-depleted follicular aspirates did, thus implicating the granulosa cells as the site of IL-1 expression. IL-1R transcripts were detected in RNA from whole ovaries and follicular aspirates but not in RNA from peripheral monocytes. IL-1RA transcripts were detected in whole ovarian material as well as in macrophage-free follicular aspirates. Cultured human granulosa and theca cells did not contain mRNA for IL-1 beta or IL-1RA but did contain mRNA for IL-1R. Treatment of cell cultures with forskolin (25 microM) induced IL-1 beta transcripts in granulosa but not theca cells. Forskolin also increased the basal levels of IL-1R transcripts in both granulosa and theca cells but did not induce IL-RA transcripts in either cell type. Taken together, these findings reveal the existence of a complete, highly compartmentalized, hormonally dependent intraovarian IL-1 system replete with ligands, receptor, and receptor antagonist.
PMCID: PMC295864  PMID: 1534816
12.  Neurone specific enolase (NSE) in small cell lung cancer: a tumour marker of prognostic significance? 
British Journal of Cancer  1990;61(4):605-607.
Pretreatment serum levels of neurone specific enolase (NSE) were measured in patients with small cell lung cancer (SCLC). Median values were significantly higher in patients with extensive compared with limited stage disease (48 ng ml-1 v. 17 ng ml-1: P less than 0.001). Serial NSE levels paralleled the clinical response to treatment. In 37 patients with limited SCLC, receiving identical chemotherapy, the pretreatment NSE level was of prognostic significance: with an approximate reduction in median survival of 10% for each 5 ng ml-1 incremental rise in NSE (P = 0.004).
PMCID: PMC1971357  PMID: 2158809
13.  Nutritional survey of patients in a general surgical ward: is there an effective predictor of malnutrition? 
Journal of Clinical Pathology  1987;40(7):803-807.
A survey of patients in a general surgical ward was undertaken to establish biochemical and anthropometric standards which could be used to detect malnourished patients in hospital. Results of biochemical and anthropometric tests of nutritional status were compared with assessment by a clinician and the quick nutritional index of Seltzer. Triceps skinfold thickness and serum albumin concentrations indicated that 29% and 35% of patients, respectively, were undernourished compared with 16% by clinical assessment and 17% by the quick nutritional index. Significant correlations (p less than 0.001) between serum albumin and transferrin concentrations and arm muscle area were found for men but not for women. Poor nutritional specificity and sensitivity of some anthropometric and biochemical tests may account for the difference in the level of undernutrition found by these tests and clinical assessment. This shows the importance of the choice of test in influencing the level of undernutrition detected.
PMCID: PMC1141102  PMID: 3624502
14.  Oral vitamin E supplements can prevent the retinopathy of abetalipoproteinaemia. 
Six patients with abetalipoproteinaemia are described who received large doses of oral vitamin E for between 12 and 18 years in addition to a low fat diet and supplements of the other fat soluble vitamins. The progressive retinopathy observed in untreated abetalipoproteinaemia was substantially modified and most probably prevented by this therapy. Angioid streaks were noted in one patient. Treatment with vitamin A alone did not prevent or arrest the progression of the retinal lesion.
PMCID: PMC1040960  PMID: 3954973
15.  Microbial Colonization of the Intestinal Epithelium in Suckling Mice 
Infection and Immunity  1973;7(4):666-672.
Colonization by indigenous microorganisms of the mucosal epithelia of the large bowels of suckling mice was followed by microbial culture techniques and by light, fluorescence, and electron microscopy. Certain microbes colonize in distinctive patterns the cecal and colonic epithelia in these mice. Coliforms and enterococci colonize the large bowel 7 to 9 days after birth and reach high population levels during the second week. During that period, these facultative anaerobes can be detected by immunofluorescence techniques in microcolonies in the mucin on the epithelium. During the third week, however, after their populations decline to the low levels characteristic of adult mice, coliforms and enteroccoci can be observed only infrequently in the mucous layer. Anaerobic fusiform-shaped bacteria appear in the mucous layers along with the microcolonies of enterococci and coliforms during the second week after birth. These anaerobes increase in numbers in the mucin until they form thick layers on the mucosal epithelium by the end of the third week. They remain in the mucous layer throughout the life of the normal mouse. Anaerobic spiral-shaped microbes also colonize the mucous layer on the cecal and colonic epithelium. But these organisms can be detected by immunofluorescence in 1-week-old mice, well in advance of the time the fusiform-shaped bacteria can be found. In the second week, the latter microbes co-inhabit the mucous layer with the spiral-shaped organisms. The fusiform- and spiral-shaped microbes remain associated in the mucin on the cecal and colonic mucosal epithelia into the adult life of mice.
PMCID: PMC422740  PMID: 4586864
17.  The preprotachykinin A promoter interacts with a sequence specific single stranded DNA binding protein. 
Nucleic Acids Research  1993;21(7):1637-1641.
An element within the Preprotachykinin A (PPT) promoter is highly homologous to an element from the rat type II Na channel promoter. This Na Channel element has been previously proposed to be common to a number of neuronal genes. We demonstrate that the PPT element binds a sequence specific DNA binding protein. The protein binds to only one strand of the PPT element and has little or no specificity for the double stranded DNA species. Gel retardation analysis indicates that the protein is found in both rat neuronal tissue and adult dorsal root ganglia neurons in culture but not in established tissue culture cell lines. Using the PPT element linked to magnetic beads we have been able to demonstrate the enrichment of a protein with a molecular weight of 40k with that of the binding activity. A mechanism for protein binding to the DNA is proposed based on the fact that the region binding the protein is the loop of a larger stem-loop structure in the DNA.
PMCID: PMC309374  PMID: 8479915

Results 1-17 (17)