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Biomedical subjects

C J Hammond

Publications and source records attributed to C J Hammond.

At least 19 recordsLinked to original sources

Parvovirus B19 infection of brain: possible role of gender in determining mental illness and autoimmune thyroid disorders.

Major theories about the etiologies of chronic mental illnesses such as bipolar disorder and schizophrenia include genetic and environmental factors such as famine and infection. It is likely that multiple genes play a role in the pathogenesis of these disorders, but no single gene has been identified as causative. Several viruses have been investigated as potential candidates, but conflicting reports exist. Although a relationship between bipolar disorder and schizophrenia with autoimmune disorders has also been documented for many years, reports are often conflicting. We hypothesize that parvovirus B19 (B19), a common human pathogen, due to its ability to infect the brain and induce autoimmunity, is a strong candidate that may unite prevailing theories. In particular, our preliminary data suggest that B19 may be most likely involved in co-morbid bipolar and autoimmune thyroid disorders in females. In schizophrenics, the gender trend may be reversed. We propose that there is a complex interaction between immuno-genetics, autoimmunity, gender, and B19 infection that leads to at least some forms of bipolar disorder and schizophrenia. Future studies that investigate this hypothesis are warranted and outlined.

Adult↗

Factors affecting the test-retest variability of Heidelberg retina tomograph and Heidelberg retina tomograph II measurements.

AIMS: To evaluate the test-retest variability of stereometric parameter measurements made with the Heidelberg retina tomograph (HRT) and Heidelberg retina tomograph-II (HRT-II), and to establish which parameter(s) provided the most repeatable and reliable measurements with both devices. An investigation into the factors affecting the repeatability of the measurements of this parameter(s) was conducted. METHODS: 43 ocular hypertensive and 31 glaucoma subjects were recruited to a test-retest study. One eye from each subject underwent HRT and HRT-II imaging by two observers on each of two occasions within 6 weeks of each other. Lens grading was carried out by LOCS III grading and Scheimpflug camera generated densitogram analysis. RESULTS: Rim area (RA) and mean cup depth measurements were found to be least variable. Both inter-test reference height difference and image quality had a strong relation (R(2)>0.5, p<0.0001) with inter-test RA difference and, together, are responsible for 70% of RA measurement variability. Image quality was influenced by lens opacity, cylindrical error, and age. Inter-test RA measurement differences were unrelated to the observer or visit interval. CONCLUSIONS: RA represents an appropriate measure for monitoring glaucomatous progression. Reference height difference and image quality were the factors that most influenced RA measurement variability. Image analysis strategies that address these factors may reduce test-retest variability.

Adult↗

Functional characterization of Na(+)/H(+) exchangers in primary cultures of prairie dog gallbladder.

Gallbladder Na(+) absorption is linked to gallstone formation in prairie dogs. We previously reported Na(+)/H(+) exchanger (NHE1-3) expression in native gallbladder tissues. Here we report the functional characterization of NHE1, NHE2 and NHE3 in primary cultures of prairie dog gallbladder epithelial cells (GBECs). Immunohistochemical studies showed that GBECs grown to confluency are homogeneous epithelial cells of gastrointestinal origin. Electron microscopic analysis of GBECs demonstrated that the cells form polarized monolayers characterized by tight junctions and apical microvilli. GBECs grown on Snapwells exhibited polarity and developed transepithelial short-circuit current, I(sc), (11.6 +/- 0.5 microA. cm(-2)), potential differences, V(t) (2.1 +/- 0.2 mV), and resistance, R(t) (169 +/- 12 omega. cm(2)). NHE activity in GBECs assessed by measuring dimethylamiloride-inhibitable (22)Na(+) uptake under a H(+) gradient was the same whether grown on permeable Snapwells or plastic wells. The basal rate of (22)Na(+) uptake was 21.4 +/- 1.3 nmol x mg prot(-1) x min(-1), of which 9.5 +/- 0.7 (approximately 45%) was mediated through apically-restricted NHE. Selective inhibition with HOE-694 revealed that NHE1, NHE2 and NHE3 accounted for approximately 6%, approximately 66% and approximately 28% of GBECs' total NHE activity, respectively. GBECs exhibited saturable NHE kinetics ( V(max) 9.2 +/- 0.3 nmol x mg prot(-1) x min(-1); K(m) 11.4 +/- 1.4 m M Na(+)). Expression of NHE1, NHE2 and NHE3 mRNAs was confirmed by RT-PCR analysis. These results demonstrate that the primary cultures of GBECs exhibit Na(+) transport characteristics similar to native gallbladder tissues, suggesting that these cells can be used as a tool for studying the mechanisms of gallbladder ion transport both under physiologic conditions and during gallstone formation.

Animals↗

Chlamydia pneumoniae infection promotes the transmigration of monocytes through human brain endothelial cells.

We have investigated the effects of Chlamydia pneumoniae on human brain endothelial cells (HBMECs) and human monocytes as a mechanism for breaching the blood-brain barrier (BBB) in Alzheimer's disease (AD). HBMECs and peripheral blood monocytes may be key components in controlling the entry of C. pneumoniae into the human brain. Our results indicate that C. pneumoniae infects blood vessels and monocytes in AD brain tissues compared with normal brain tissue. C. pneumoniae infection stimulates transendothelial entry of monocytes through HBMECs. This entry is facilitated by the up-regulation of VCAM-1 and ICAM-1 on HBMECs and a corresponding increase of LFA-1, VLA-4, and MAC-1 on monocytes. C. pneumoniae infection in HBMECs and THP-1 monocytes up-regulates monocyte transmigration threefold in an in vitro brain endothelial monolayer. In this way, C. pneumoniae infection in these cell types may contribute to increased monocyte migration and promote inflammation within the CNS resulting from infection at the level of the vasculature. Thus, infection at the level of the vasculature may be a key initiating factor in the pathogenesis of neurodegenerative diseases such as sporadic AD.

Alzheimer Disease↗

Investigation of prevalence of MRSA in referrals to neurosurgery: implications for antibiotic prophylaxis.

In order to establish the appropriateness of our current prophylactic antibiotic regimen we analysed the prevalence of MRSA in emergency referrals to our unit. MRSA screening records for all emergency admissions for a 3-month period were analysed. One-hundred-and-seventy-five patients were admitted as transfers from another hospital. Evidence of screening was found in 61% (107 patients). Of the screened patients, 15% (16) were MRSA positive. Source of referral or length of inpatient stay after referral to the time of transfer were not predictive for MRSA status. Gentamicin is active against more than 95% of MRSA strains cultured in our hospital and against 87% of MRSA strains cultured in the neurosurgery unit. A number-needed-to-treat (NNT) analysis showed that, with MRSA prevalence at 15%, cefuroxime plus gentamicin at induction could prevent one MRSA infection per 421 treated patients compared with cefuroxime alone. Vancomycin had minimal additional benefit over cefuroxime plus gentamicin (NNT: 1684). We conclude that MRSA carriage is common in patients referred as emergencies from other hospitals. Cefuroxime plus gentamicin can be used as antibiotic prophylaxis in this group. Vancomycin can be reserved for patients known to be colonized with MRSA (NNT: 51).

Adult↗

Racehorse injuries, clinical problems and fatalities recorded on British racecourses from flat racing and National Hunt racing during 1996, 1997 and 1998.

For improvements to the safety and welfare of racehorses to be possible, it is essential to have access to basic descriptive information about the veterinary incidents encountered during horseracing. A 3 year surveillance study (1996-1998) was conducted by The Jockey Club into racing injuries, other postrace clinical problems and fatalities from all 59 British racecourses (mainland Britain only) to identify risk factors. During the survey there were 222,993 racing starts: 106,897 starts in flat races on turf (47.9%), 26,519 starts in flat races on all-weather surfaces (11.9%), 30,932 starts in chases on turf (13.9%), 51,786 starts in hurdle races on turf (23.2%) and 6,859 starts in National Hunt flat races (3.1%). Information was recorded about age of horses, racing surfaces and clinical events observed or attended by a veterinary team of 2 clinicians and one veterinary surgeon employed by the racing authority. Of the 2358 clinical events reported (1.05% of all starts), 1937 involved the musculoskeletal system and 421 involved other body systems. Six hundred and fifty-seven incidents (0.29% of starts) resulted in death or euthanasia. Eighty-one percent of limb injury reports involved forelimbs and 46% involved flexor tendons/suspensory ligaments. Nonlimb problems included epistaxis (0.83/1000 starts), 'exhausted horse syndrome' (0.47/1000 starts) and paroxysmal atrial fibrillation (0.20/1000 starts). Incidents including fatalities per 1000 starts were 24.7 from chases, 19.45 from hurdle races, 8.46 from National Hunt flat races and 3.97 from flat races. The overall tendon injury was higher in chases than in hurdle races, even though age-specific rates of tendon injury were higher in hurdle races than in chases. The risk of injuries per start increased significantly with age, while softer racing surfaces were associated with fewer fatalities and injuries than firmer surfaces. The survey described in this paper has provided an up-to-date description of the fatal and non-fatal horseracing incidents under conditions on mainland Britain, enabling progress to be made towards improving the safety and welfare of racehorses.

Age Factors↗

Spinal meningioma after treatment for Hodgkin disease. Case report.

Long-term survivors of Hodgkin disease may develop second primary tumors caused by the mutagenic effects of radio- and chemotherapy. The authors describe the case of a 35-year-old woman who presented with an unusual meningioma of the cervical spine 9 years after undergoing combined-modality treatment for Hodgkin disease. To the authors' knowledge, this is the first report of spinal meningioma as a complication of such therapy. Whereas radiation-induced intracranial meningiomas are well described in the literature, treatment-induced meningiomas of the spine have not been widely recognized.

Adult↗

The heritability of age-related cortical cataract: the twin eye study.

PURPOSE: A classical twin study was performed to establish the relative importance of genes and environment in cortical cataract. METHODS: Five hundred six pairs of unselected female twin volunteers (226 monozygotic and 280 dizygotic) with a mean age of 62 years (range, 49-79 years) were examined. Cortical cataract was assessed using the slit-lamp-based Oxford Clinical Cataract Classification and Grading System (clinical grading) and the Wilmer Automated Grading System, which analyzed digital retroillumination images of subjects' lenses (digital grading). The worse eye categorized score for each individual was used in maximum likelihood path modeling of the correlations within twin pairs. These correlations were used to determine the underlying liability to cortical cataract. RESULTS: Prevalence of significant cortical cataract (>/=5% of lens area) was similar in monozygotic and dizygotic twins, occurring in 19.4% and 20.6% with the clinical grading system and 24% and 23% using the digital grading system, respectively. Modeling suggested liability to cortical cataract is explained by additive and dominant genes, individual environment, and age. Estimates of the broad sense heritability of cortical cataract were 58% (95% confidence interval [CI], 51%-64%) for the clinical grading system and 53% (95% CI, 45%-60%) for the digital system. Dominant genes were estimated to contribute to 38% (95% CI, 1%-64%) of the genetic effect with the clinical grading and 53% (95% CI, 28%-60%) with the digital grading. Individual environment explained 26% and 37% and age 16% and 11% of cortical cataract variance in clinical and digital gradings, respectively. CONCLUSIONS: Genetic effects are important in the development of cortical cataract and involve the action of dominant genes.

Aged↗

Genes and environment in refractive error: the twin eye study.

PURPOSE: A classical twin study was performed to examine the relative importance of genes and environment in refractive error. METHODS: Refractive error was examined in 226 monozygotic (MZ) and 280 dizygotic (DZ) twin pairs aged 49 to 79 years (mean age, 62.4 years). Using a Humphrey-670 automatic refractor, continuous measures of spherical equivalent, total astigmatism, and corneal astigmatism were recorded. Univariate and bivariate maximum likelihood model fitting was used to estimate genetic and environmental variance components using information from both eyes. RESULTS: For the continuous spectrum of myopia/hyperopia, a model specifying additive genetic and unique environmental factors showed the best fit to the data, yielding a heritability of 84% to 86% (95% confidence interval [CI], 81%-89%). If myopia and hyperopia (< or = -0.5 D and > or = 0.5 D, respectively) were treated as binary traits, the heritability was 90% (95% CI, 81%-95%) for myopia and 89% (95% CI, 81%-94%) for hyperopia. For total and corneal astigmatism, modeling showed dominant genetic effects are important; dominant genetic effects accounted for 47% to 49% of the variance of total astigmatism (95% CI, 37%-55%) and 42% to 61% of corneal astigmatism variance (95% CI, 8%-71%), with additive genetic factors accounting for 1% to 4% and 4% to 18%, respectively (95% CIs, 0%-13% and 0%-60%, respectively). CONCLUSIONS: Genetic effects are of major importance in myopia/hyperopia; astigmatism appears to be dominantly inherited.

Aged↗

Genetic and environmental factors in age-related nuclear cataracts in monozygotic and dizygotic twins.

BACKGROUND: Age-related cataracts are a major public health problem. The relative importance of genes and environment in the causation of nuclear cataracts, the most common form of age-related cataracts, is not known. METHODS: We studied 506 pairs of female twins (226 monozygotic and 280 dizygotic) who were 50 to 79 years old (mean, 62). The amount of nuclear cataract in the right and left eyes was determined objectively by analysis of Scheimpflug lens photographs (yielding three measures) and subjectively with use of the Oxford Clinical Cataract Classification and Grading System (yielding one measure). All eight measures (four in each eye) were subsequently combined in one summary measure of nuclear cataract for each woman. A univariate maximum-likelihood model was used to estimate the variance of the genetic and environmental contributions to each of the measures. RESULTS: The different measures of cataract formation were highly correlated (correlation coefficients, 0.71 to 0.94). The mean scores were similar for the right and left eyes and for monozygotic and dizygotic twins. Quantitative genetic modeling of each of the nuclear-cataract scores invariably resulted in a best-fitting model that involved additive genetic effects, unique environmental effects, and age. The common environmental and dominant genetic effects could be removed from the models without significant loss of fit. The overall heritability in the combined nuclear-cataract score (the proportion of the variance explained by genetic factors) was 48 percent (95 percent confidence interval, 42 to 54 percent); age accounted for 38 percent of the variance (95 percent confidence interval, 31 to 44 percent) and unique environmental effects for 14 percent (95 percent confidence interval, 12 to 18 percent). CONCLUSIONS: Genetic effects are important even in such a clearly age-related disease as nuclear cataract, explaining almost 50 percent of the variation in the severity of this disease.

Age Factors↗

Factors affecting pupil size after dilatation: the Twin Eye Study.

BACKGROUND/AIMS: Well dilated pupils make eye surgery easier. A classic twin study was established to examine the relative importance of genes and environment in the variance of pupil size after mydriasis, and to examine the effects of other factors such as age, iris colour, and refractive error. METHODS: 506 twin pairs, 226 monozygotic (MZ) and 280 dizygotic (DZ), aged 49-79 (mean age 62.2 years, SD 5.7) were examined. Dilated pupil size was measured using a standardised grid superimposed over digital retroillumination images taken 50-70 minutes after mydriasis using tropicamide 1% and phenylephrine 10%. Univariate maximum likelihood model fitting was used to estimate genetic and environmental variance components. RESULTS: Dilated pupil size was more highly correlated in MZ compared with DZ twins (intraclass correlation coefficients 0.82 and 0.39 respectively). A model specifying additive genetic and unique environmental factors showed the best fit to the data, yielding a heritability of 78-80%. Individual environmental factors explained 18-19% of the variance in this population. Age only accounted for 2-3% of the variance and refractive error and iris colour did not significantly contribute to the variance. CONCLUSIONS: Pupil size after mydriasis is largely genetically determined, with a heritability of up to 80%.

Aged↗

The spectrum of eye disease in children with AIDS due to vertically transmitted HIV disease: clinical findings, virology and recommendations for surveillance.

BACKGROUND: Eye disease in children infected with HIV is uncommon, but there is little information on which children require screening or surveillance and the management of those with retinitis. METHODS: We examined 12 children with symptomatic HIV disease (of a cohort of 98 HIV-positive children) using indirect ophthalmoscopy. When retinitis was found it was documented photographically at the time of diagnosis and on follow-up. RESULTS: Four cases of infective retinitis were diagnosed: three with probable cytomegalovirus retinitis and one with progressive outer retinal necrosis. CONCLUSION: Detection of reactivation is difficult and we recommend fundus photography under general anaesthesia wherever possible. Children with other end-organ disease, symptomatic eye disease and advanced HIV disease with severe immunosuppression require ophthalmological surveillance.

Acquired Immunodeficiency Syndrome↗

Comparison between an ophthalmic optician and an ophthalmologist in screening for diabetic retinopathy.

The best method of screening for diabetic retinopathy is still debated: fundus photography, general practitioners, hospital physicians and ophthalmic opticians have been advocated. This study compared the performance of an ophthalmic optician with an ophthalmologist, both using mydriatic and slit lamp biomicroscopy and direct ophthalmoscopy. A total of 474 eyes of diabetics in a single group practice were examined by both practitioners at their annual check. There was total agreement about presence or absence of retinopathy in 366 eyes (77%). Although the optician diagnosed less background diabetic retinopathy (83 versus 123 eyes) and diabetic maculopathy (47 eyes versus 63 eyes), he would have referred 20 of 26 eyes with moderate or severe maculopathy and 33 of 36 eyes with moderate or severe background retinopathy: sensitivities of 0.77 and 0.92 respectively. This compares favourably with previous studies and we suggest that ophthalmic opticians with suitable training would be an effective body to screen for diabetic retinopathy.

Clinical Competence↗