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Biomedical subjects

H Lewis

Publications and source records attributed to H Lewis.

At least 19 recordsLinked to original sources

Maturation of cerebral electrical activity and development of cortical folding in young very preterm infants.

OBJECTIVE: The aim of this study was to examine the relationship between cortical development and cerebral electrical activity at early gestational ages. METHODS: We obtained EEGs (7.2+/-3.8 days) and MR brain images (3.2+/-2.9 days) after birth in 17<30 week gestation infants without evidence of focal brain injury The EEGs were assessed for discontinuity and characteristic maturational features (delta brush, occipital and temporal sawtooth); cortical development was quantified from MR scans using a specially designed computer programme to measure cortical folding. RESULTS: The inter-burst interval shortened and cortical folding increased with increasing post-menstrual age (PMA). In contrast, the minimum duration of bursts was independent of PMA and cortical folding. Delta brush (8-20 Hz activities) was seen at all PMAs; temporal and occipital sawtooth activities were always more prominent than delta brush but were seen less frequently with increasing PMA and complexity of cortical folding. CONCLUSION: There was a positive correlation between some but not all maturational features of the preterm neonatal EEG and the complexity of whole brain cortical folding and PMA. These relationships were strong for the inter-burst interval, a global measure of maturation, but not strongly seen for regional features such as occipital and temporal sawtooth within this gestational age range. SIGNIFICANCE: Combining neurophysiological examination with detailed neuroimaging gives insights into developmental changes occurring in the very preterm brains and suggests further comparative studies focusing on measures of focal brain development at different gestational ages.

Cerebral Cortex↗

An unusual complication of ice skating and the emergence of a previously undiagnosed bleeding disorder.

We report the case of an 8-year-old boy with no prior abnormal bleeding history who presented with severe central abdominal pain following a freak accident at a local ice rink. Clinical examination confirmed a tender periumbilical mass. An ultrasound scan confirmed a large haemorrhagic fluid collection adjacent to the second part of his duodenum that was causing a subacute small-bowel obstruction. He was found to have a persistently prolonged prothrombin time between 17.3 and 18.1 s but normal liver function tests. There was no suggestion of dietary vitamin K deficiency. Further investigations confirmed factor VII deficiency with levels between 30.4 and 33.6 IU dL-1. His prothrombin time did not normalize with intravenous vitamin K. He was subsequently treated with three 30 microg kg-1 body weight doses of novoseven at 4-h interval and made an excellent recovery. The haematoma virtually resolved completely confirmed by a follow-up ultrasound scan 3 months after the initial event.

Accidental Falls↗

Normalization of factor VIII levels in a patient with mild haemophilia A during a 35-year period.

We report the case of a 45-year-old man who was diagnosed in June 1969 9 years old as having mild haemophilia A following a traumatic left shoulder bleed when his factor VIII (FVIII) activity was 11 IU dL(-1) based on a two-stage assay. The bleed resolved following treatment with intravenous cryoprecipitate. There was no family history of haemophilia. Cryoprecipitate infusions were required to treat further traumatic bleeds between 1971 and 1981. During this time, his FVIII activity was confirmed at 14 IU dL(-1). He defaulted many hospital appointments until 1991 when his FVIII activity had risen to 42 IU dL(-1). There was no evidence of infection, inflammatory or liver disease to account for this change. By 2005 he had a normal FVIII activity of 62 IU dL(-1) based on a one-stage assay. FVIII gene analysis confirmed a codon 531 mutation. It appeared that the discrepant FVIII results related to whether a two-stage or one-stage assay was used that has been previously reported for other patients with these mutations. We felt it important to raise awareness that this phenomenon may lead to apparent correction of haemophilia A.

Blood Coagulation Tests↗

Quantification of Alzheimer pathology in ageing and dementia: age-related accumulation of amyloid-beta(42) peptide in vascular dementia.

Clinicopathological observations suggest there is considerable overlap between vascular dementia (VaD) and Alzheimer's disease (AD). We used immunochemical methods to compare quantities of amyloid-beta (Abeta) peptides in post mortem brain samples from VaD, AD subjects and nondemented ageing controls. Total Abeta peptides extracted from temporal and frontal cortices were quantified using a previously characterized sensitive homogenous time-resolved fluorescence (HTRF) assay. The HTRF assays and immunocapture mass spectrometric analyses revealed that the Abeta(42) species were by far the predominant form of extractable peptide compared with Abeta(40) peptide in VaD brains. The strong signal intensity for the peak representing Abeta(4-42) peptide confirmed that these N-terminally truncated species are relatively abundant. Absolute quantification by HTRF assay showed that the mean amount of total Abeta(42) recovered from VaD samples was approximately 50% of that in AD, and twice that in the age-matched controls. Linear correlation analysis further revealed an increased accumulation with age of both Abeta peptides in brains of VaD subjects and controls. Interestingly, VaD patients surviving beyond 80 years of age exhibited comparable Abeta(42) concentrations with those in AD in the temporal cortex. Our findings suggest that brain Abeta accumulates increasingly with age in VaD subjects more so than in elderly without cerebrovascular disease and support the notion that they acquire Alzheimer-like pathology in older age.

Aged↗

Bounding the risk of crew loss following orbital debris penetration of the International Space Station at assembly stages 1J and 1E.

Orbital debris impacts on the International Space Station occur frequently. To date, none of the impacting particles has been large enough to penetrate manned pressurized volumes. We used the Manned Spacecraft Crew Survivability code to evaluate the risk to crew of penetrations of pressurized modules at two assembly stages: after Flight 1J, when the pressurized elements of Kibo, the Japanese Experiment Module, are present, and after Flight 1E, when the European Columbus Module is present. Our code is a Monte-Carlo simulation of impacts on the Station that considers several potential event types that could lead to crew loss. Among the statistics tabulated by the program is the probability of death of one or more crew members in the event of a penetration, expressed as the risk factor, R. This risk factor is dependent on details of crew operations during both ordinary circumstances and decompression emergencies, as well as on details of internal module configurations. We conducted trade studies considering these procedure and configuration details to determine the bounds on R at the 1J and 1E stages in the assembly sequence. Here we compare the R-factor bounds, and procedures could that reduce R at these stages.

Accident Prevention↗

Age-related impairment of synaptic transmission but normal long-term potentiation in transgenic mice that overexpress the human APP695SWE mutant form of amyloid precursor protein.

We have studied synaptic function in a transgenic mouse strain relevant to Alzheimer's disease (AD), overexpressing the 695 amino acid isoform of human amyloid precursor protein with K670N and M671L mutations (APP(695)SWE mice), which is associated with early-onset familial AD. Aged-transgenic mice had substantially elevated levels of Abeta (up to 22 micromol/gm) and displayed characteristic Abeta plaques. Hippocampal slices from 12-month-old APP(695)SWE transgenic animals displayed reduced levels of synaptic transmission in the CA1 region when compared with wild-type littermate controls. Inclusion of the ionotropic glutamate receptor antagonist kynurenate during preparation of brain slices abolished this deficit. At 18 months of age, a selective deficit in basal synaptic transmission was observed in the CA1 region despite treatment with kynurenate. Paired-pulse facilitation and long-term potentiation (LTP) were normal in APP(695)SWE transgenic mice at both 12 and 18 months of age. Thus, although aged APP(695)SWE transgenic mice have greatly elevated levels of Abeta protein, increased numbers of plaques, and reduced basal synaptic transmission, LTP can still be induced and expressed normally. We conclude that increased susceptibility to excitotoxicity rather than a specific effect on LTP is the primary cause of cognitive deficits in APP(695)SWE mice.

Aging↗

Macular translocation: unifying concepts, terminology, and classification.

PURPOSE: To describe some unifying concepts, terminology, and classification of macular translocation so as to facilitate communication within the scientific community. METHODS: A panel of ophthalmologists with expertise in macular translocation reviewed available data and developed some unifying concepts, terminology, and classification of macular translocation. RESULTS: Macular translocation may be defined as any surgery that has a primary goal of relocating the central neurosensory retina or fovea intraoperatively or postoperatively specifically for the management of macular disease. It may be classified according to the size of the retinotomy and, where applicable, the technique of chorioscleral shortening used. The direction of macular translocation is denoted by the movement of the neurosensory macula relative to the underlying tissues. Effective macular translocation may be defined as successful intraoperative or postoperative relocation of the fovea overlying a subfoveal lesion to an area outside the border of the lesion. The concepts of minimum desired translocation and median postoperative foveal displacement can give some useful idea of the likelihood of effective macular translocation before surgery. CONCLUSIONS: Use of a common standardized terminology for macular translocation will facilitate communication within the scientific community and enhance further research in this area. However, the definitions, terms, classification, and concepts concerning macular translocation are likely to continue to evolve as macular translocation undergoes further modifications and refinements.

Humans↗

Macular translocation for subfoveal choroidal neovascularization in angioid streaks.

PURPOSE: To report a case of visual improvement after macular translocation performed for a subfoveal choroidal neovascular membrane in a patient with pseudoxanthoma elasticum and angioid streaks. METHODS: The fovea was translocated inferiorly by scleral imbrication, intentional retinal detachment with a small posterior retinotomy, and partial fluid-air exchange. The choroidal neovascular membrane was photocoagulated 1 week later. RESULTS: The visual acuity of the patient improved from 20/125 to 20/40. The center of the foveal avascular zone was moved inferiorly 844 microm. The choroidal neovascular membrane was extrafoveal after translocation and was treated with laser photocoagulation. CONCLUSION: Macular translocation may be considered in the management of subfoveal choroidal neovascular membrane in patients with pseudoxanthoma elasticum and angioid streaks.

Adult↗

Macular traction detachment and diabetic macular edema associated with posterior hyaloidal traction.

PURPOSE: To review the clinical, photographic, fluorescein angiographic, and optical coherence tomographic findings in patients with the diabetic macular traction and edema (DMTE) associated with posterior hyaloidal traction (PHT). METHODS: We performed a prospective review of nine eyes of nine patients with diabetic macular edema (DME) and PHT on clinical examination. The patients had a comprehensive ophthalmic history and examination, color photographs, fluorescein angiography, and optical coherence tomography (OCT). RESULTS: All patients had diabetic retinopathy and DME. Of the nine eyes, eight patients had previous focal or grid photocoagulation. All nine eyes had a thickened, taut, glistening posterior hyaloid on clinical biomicroscopic examination with no posterior vitreous separation. Fluorescein angiography was performed on seven eyes, and all had early hyperfluorescence with deep, diffuse, late leakage in the macular area consistent with DMTE associated with PHT. Optical coherence tomography scans of the macular region revealed retinal thickening in all eyes with a mean retinal thickness of 556.9 +/- 114.7 microns. In addition, eight of the nine eyes had a shallow macular traction detachment associated with PHT. CONCLUSION: Eyes with DME associated with PHT may have a shallow, subclinical, macular detachment. Optical coherence tomography may be useful in evaluating patients with DME to see if a macular detachment is present.

Aged↗

Macular translocation with chorioscleral outfolding: an experimental study.

PURPOSE: Macular translocation by chorioscleral infolding has been proposed as a surgical intervention for exudative age-related macular degeneration, but the surgery is unpredictable and can be associated with severe complications. We tested a new surgical technique, macular translocation with chorioscleral outfolding secured by neurosurgical clips. METHODS: This was a prospective interventional study in two parts; the first in human cadaver eyes and the second in pigs. Chorioscleral infolding was performed on six human donor eyes, and chorioscleral outfolding was performed on an additional six. The inner surface of the eye wall was measured, and then the fold was unfolded and the distance was measured again. In the second half of the study, macular translocation surgery was performed on 33 pig eyes with one of three sclera shortening methods: 1) a circumferential chorioscleral infolding using 5-0 nylon sutures, 2) a circumferential chorioscleral outfolding using scleral clips, or 3) a radial chorioscleral outfolding using scleral clips. Foveal translocation was measured. RESULTS: The inner wall of the human cadaver eye was shortened in the chorioscleral infolding group by a mean of 1.6 mm, and in the chorioscleral outfolding group by 3.0 mm. In the pig eyes, the fovea was translocated a mean 2377 microm by circumferential suturing, 2582 microm by circumferential clipping, and 3386 microm by radial clipping. Irregular deformation of the globe was more apparent in the circumferential suture group. Undesirable retinal folds often formed after circumferential infolding but not after radial clipping. CONCLUSION: Radial chorioscleral outfolding with clips is more predictable and effective than infolding. It produces more translocation and prevents folds across the fovea, one of the most undesirable complications in macular translocation surgery.

Animals↗

Macular translocation with chorioscleral outfolding: a pilot clinical study.

PURPOSE: A new surgical technique to translocate the macula was used to treat patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD). DESIGN: Prospective, interventional case series. METHODS: Twenty-five eyes of 25 patients underwent macular translocation with either circumferential or radial chorioscleral outfolding using three clip sizes: 2-mm, 3-mm, and 4-mm. Postoperative photocoagulation was performed on only those eyes that had an extrafoveal choroidal neovascular membrane following surgery. RESULTS: The surgery successfully displaced the fovea in 22 (88%) of the eyes. The median postoperative foveal displacement was 1142 microm (range 0 to 3200 microm). Patients who had radial outfolding with 4-mm clips had the greatest displacement of the fovea (range 1644 to 3200 microm median 1977 microm). The fovea was successfully displaced to a location outside the choroidal neovascular membrane in 17 (68%) of the 25 eyes. The best-corrected visual acuity improved in 11 eyes (median, 17 letters), remained unchanged in 4 eyes, and decreased in 10 eyes (median, 12 letters). Visual acuity increased by a median of 2 letters. The final best-corrected visual acuity was 20/64 in 3 eyes; 20/80 in 3 eyes; 20/100 in 4 eyes; 20/126 in 4 eyes; 20/200 in 4 eyes; 20/250 in 4 eyes; and 20/400 in 3 eyes. CONCLUSIONS: Macular translocation with radial chorioscleral outfolding using 4-mm clips resulted in the best foveal displacement and improvement in visual function, and was associated with the least amount of vision loss and complications. Further refinements are needed to make this surgical procedure more predictable, and more research (randomized clinical trials) is needed to determine the role of macular translocation in the treatment of subfoveal choroidal neovascularization in patients with AMD.

Aged↗

Ischemic maculopathy in patients with acquired immunodeficiency syndrome.

PURPOSE: To describe the characteristics of ischemic maculopathy in patients with human immunodeficiency virus (HIV) infection, as a means of understanding this uncommon disorder more fully. METHODS: This is a multicenter, retrospective review of clinical data available for five HIV-infected patients who were given the diagnosis of ischemic maculopathy. RESULTS: All cases had been diagnosed on the basis of fluorescein angiograms obtained after patients complained of vision loss. Four of the five patients had bilateral macular disease. Visual acuity at presentation in the nine affected eyes ranged from 20/20 to count fingers. Vision loss was gradual in both eyes of one patient and was abrupt in onset in seven eyes. Each of the seven eyes with abrupt vision loss had opacification of the superficial retina and/or intraretinal hemorrhages near the fovea. Fluorescein angiography revealed enlargement of the foveal avascular zone and mild staining of the juxtafoveal vessels in affected eyes. Six eyes had active or clinically inactive cytomegalovirus retinitis at presentation, and a seventh eye developed cytomegalovirus retinitis 2 weeks later. All patients were receiving anticytomegalovirus drugs when they developed visual symptoms. Visual acuity remained stable in five eyes, became worse in two eyes, and improved in two eyes; final visual acuity ranged from 20/25 to count fingers. CONCLUSIONS: Ischemic maculopathy may cause profound and permanent vision loss in HIV-infected individuals. Fluorescein angiography should be considered in all HIV-infected patients with unexplained loss of vision. The pathogenesis of ischemic maculopathy remains unknown.

Acquired Immunodeficiency Syndrome↗

Traumatic macular hole: observations, pathogenesis, and results of vitrectomy surgery.

PURPOSE: To review our experience with vitrectomy surgery techniques for the treatment of traumatic macular holes and the biomicroscopic and surgical findings. DESIGN: Retrospective noncomparative, multicenter, case series. PARTICIPANTS AND INTERVENTION: Twenty-five patients with traumatic macular hole underwent surgical repair. INTERVENTION: Vitrectomy with membrane peeling and gas injection followed by prone positioning for 7 to 14 days. MAIN OUTCOME MEASURES: Postoperative evaluation included visual acuity testing, closure of the macular hole, and ocular complications. RESULTS: The macular hole was successfully closed in 24 of 25 cases (96%). The visual acuity improved two or more lines in 21 (84%) cases, and 16 (64%) achieved 20/50 or better vision. CONCLUSIONS: Vitrectomy surgery can successfully close macular holes associated with trauma and improve vision.

Adolescent↗