Biomedical subjects
Publications and source records attributed to C Harper.
The dentitions of 23 skulls, mostly excavated from a 'plague pit' dating from 1348, were investigated using a Reflex Metrograph. The measurements obtained were compared with those from a modern control sample. It was found that in the medieval dentitions the arch widths were significantly wider, arch lengths and tooth lengths smaller, and the degree of irregularity of the teeth was greater than a modern group.
A study of open, randomized, parallel-group design was performed to investigate the impact of a second freeze-thaw cycle on the cure rate, at 3 months, from cryotherapy of common warts on the hands and feet. Cryotherapy was performed at 3-week intervals, and subjects were randomized to receive either one or two freeze-thaw cycles. In addition, all subjects used keratolytic wart paints throughout the study, and plantar warts were pared prior to freezing. Three hundred subjects were recruited. At 3 months, 124 were cured, 83 were not cured, and 93 had defaulted. Among those who did not default the cure rate was 57% from the single freeze technique, and 62% from the double freeze technique, a difference of 5% (P = 0.53, 95% CI-8.1-18.6). Separate analyses for subjects with warts on the hands and on the feet demonstrated no effect of double freezing on hand warts. In contrast, for plantar warts, the cure rate was 41% from single freezing and 65% for double freezing, a difference of 24% (P = 0.04, 95% CI 2.9-44.4). The use of a double freeze-thaw cycle confers little or no advantage over a single freeze in the treatment of hand warts, but may be considerably more effective for plantar warts.
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The aim of the symposium on alcohol-induced brain damage is to review current opinion and recent advances concerning factors which are thought to play a significant role in this disorder. The three principal factors are: alcohol specific neurotoxicity, associated vitamin B1 (thiamine) deficiency (the Wernicke-Korsakoff syndrome) and liver failure secondary to alcoholic cirrhosis. There is a complex interaction of these and other factors and it is difficult to dissect out the relative importance of each in the pathogenesis of alcohol-related brain damage. Moreover recent molecular and biochemical studies suggest that several of these factors may have pathogenetic mechanisms in common-for example, excitotoxicity, mitric oxide and free radicals. The application of new technologies in neuropathological studies of carefully selected groups of alcoholic cases is beginning to reveal a far more complex pattern of damage than current view holds. Quantitative morphometry and immunohistochemistry can be combined to create three dimensional images of various anatomical regions of the brain together with detailed analyses of neuronal counts, sizes and neurochemical type. In the Wernicke-Korsakoff syndrome (WKS) there is good evidence (in support of neuropsychological and neuroradiological data) to suggest that specific populations of neurons are damaged in cortical and subcortical regions. In those cases with the WKS there is also evidence of pathological damage in cortical and subcortical regions other than the well described periventricular distributions. These more detailed studies provide us with a more comprehensive understanding of alcohol-related brain damage.
Three independent autopsy samples of brains without apparent neuropathology were studied to ascertain whether there was sexual dimorphism in the human corpus callosum (CC). Using planimetric measurements on midsagittal brain sections, several morphometric features of the CC were studied: total callosal area, maximum dorsoventral splenial width, the posterior one fifth of the total area of the CC (mostly splenium), and brain weight. Ratio data correcting for brain size were also studied. In all samples, absolute brain size was larger in males, and significantly so. Measurements of splenial dorsoventral width were higher in females than males, but not significantly, except in the Australian sample. Total callosal area was absolutely higher in the Australian female sample than in males, and almost equal in the two American samples, without statistically significant differences. The posterior one-fifth area (splenium) was larger for females in each of the samples. The variables which were corrected for brain size were usually significantly larger in females, although this pattern varied in each sample. The statistical pattern of sexual dimorphism for the human CC differs from that found in most other neural structures, such as the amygdaloid nucleus, cerebellum, hippocampus, and thalamus. The absolute sizes of these structures are always significantly larger in males. When corrected for brain size, the relative sizes are not significantly larger. The CC is the only structure to show a larger set of relative measures in females.
Two patients with acute Wernicke's encephalopathy, with the diagnosis confirmed pathologically at autopsy, showed substantial vacuolation and neuronal degeneration in discrete nuclei of the thalamus. Thalamic vacuolation has not been described previously in acute Wernicke's encephalopathy. The use of frozen sections to minimize processing artifact was fundamental in demonstrating this pathology. The pathogenic mechanism underlying this change appears to be different to that seen in the more typical periventricular, mamillary body and brainstem lesions. We hypothesize that a specific neural pathway may be involved and suggest that this pathway could be the ascending nitric oxide-containing cholinergic pathway from the brainstem.
One thousand patients, referred to the Oxford Colposcopy Clinic, were treated with either large loop excision of the transformation zone (LLETZ, 891 cases) or LLETZ cone (109 cases). Forty-five LLETZ cones were performed empirically, 64 under microcolposcopic guidance. Over 98% of patients were managed as outpatients under local anaesthesia, and 87% of new patients treated with LLETZ had treatment at their first visit. Ninety percent of patients had at least cervical intraepithelial neoplasia grade one (CIN I) and 73% had CIN II or worse. Seventeen cases of invasive or possibly invasive disease were detected, 6 of them unsuspected. The overall rate of complete excision of CIN or worse was 72%. Follow-up was cytologic with or without colposcopy depending on lesion severity. Ninety-one percent of 967 treated patients were free of dyskaryosis at a mean follow-up of 23 months, with complete excision of CIN or worse at LLETZ a significant predictive factor. No cases of invasive carcinoma have developed following treatment. Major morbidity was uncommon, with 3.8% severe hemorrhage. Stenosis was noted in 3.8% cases, mostly after LLETZ cone. One patient (0.1%) has reduced fertility possibly attributable to LLETZ. Questionnaire assessment revealed a very high degree of acceptability of the treatment to patients. LLETZ and LLETZ cone have proved highly acceptable and effective outpatient diagnostic and treatment alternatives to both local ablation and cone biopsy in the Oxford Colposcopy Clinic.
There are several lines of evidence to suggest that serotonergic neurons in the brain are detrimentally affected by chronic alcohol consumption. The present study aims to quantify pathological changes in brainstem regions containing serotonergic neurons in chronic alcoholics compared to age-matched non-alcoholic controls. An antibody specific for tryptophan hydroxylase was used to immunohistochemically demonstrate serotonergic neurons in serial sections of postmortem brainstem. The cases analyzed were divided into four groups on the basis of their clinical and pathological presentation; chronic alcoholics with Wernicke's encephalopathy, chronic alcoholics with additional Korsakoff's psychosis, non-alcoholic controls, and a single chronic alcoholic without neurological complications. There was an overall reduction in the number of serotonergic neurons in all alcoholic cases when compared with controls. All brainstem regions were affected, but the largest neuronal loss was found in areas of the medullary and caudal pontine reticular formation (reduced by 80-90%). Alcoholics with Korsakoff's psychosis did not differ in the amount or extent of pathology from the other alcoholic cases analyzed. The data indicate that significant numbers of serotonergic neurons degenerate in chronic alcoholics. Such a loss is likely to have significant clinical consequences.
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The loss of noradrenergic locus coeruleus neurons has been identified as the possible critical lesion inducing amnesia in alcoholic patients with the Wernicke-Korsakoff syndrome. The present study aims to test this hypothesis by quantifying the number of pigmented locus coeruleus neurons in 4 alcoholics with the Wernicke-Korsakoff syndrome, 5 alcoholics with Wernicke's encephalopathy alone but no amnesia, and 1 alcoholic and 5 age-matched controls with no neurological disorders. Apart from an increased vascularity in the locus coeruleus of alcoholics, no significant differences in the number, morphology or distribution of pigmented locus coeruleus neurons was noted between any of the groups analysed. There was a significant correlation between the number of locus coeruleus neurons and brain weight. These data demonstrate that neither alcohol neurotoxicity nor thiamine deficiency result in a reduction in the number of pigmented cells in the locus coeruleus and refute the hypothesis that locus coeruleus cell loss is critical for the amnesia in the Wernicke-Korsakoff syndrome.
OBJECTIVE: To evaluate the effects of intraarticular injection of recombinant human interleukin-1 beta (IL-1 beta) on levels of proteoglycans, stromelysin, and leukocytes in rabbit synovial fluid (SF), and to determine the effects of leukocyte depletion on SF proteoglycan and stromelysin levels. METHODS: Levels of leukocytes and of proteoglycans, stromelysin, and collagenase were evaluated 12 hours after the intraarticular injection of various doses of IL-1, and over a 24-hour period after injection at a single dose level. We used a monoclonal antibody (MAb) against leukocyte integrins, which markedly depressed leukocyte accumulation in SF, to evaluate the role of synovial leukocytes on IL-1-induced increases in SF proteoglycan and stromelysin levels. RESULTS: Levels of both proteoglycans and stromelysin increased in the IL-1-injected joints between 4 hours and 24 hours after the injection of a single 200-ng dose of IL-1. The highest levels of stromelysin and proteoglycans were achieved with IL-1 doses greater than or equal to 100 ng. Infiltration of polymorphonuclear cells (PMN) into the joint fluid of the IL-1-injected rabbits also increased, in a dose-dependent manner. Treatment of rabbits with MAb 1B4 markedly reduced infiltration of PMN into the joint, without affecting either stromelysin or proteoglycan levels. CONCLUSION: Taken together, the data suggest that there is a coordinate increase in SF stromelysin and proteoglycan levels in rabbits injected with IL-1, and that leukocytes play a minimal role in the accumulation of proteoglycans and stromelysin in the SF.
OBJECTIVE: To examine the in vivo expression of the matrix metalloproteinase stromelysin in the synovium and articular cartilage of rabbits injected intraarticularly with recombinant human interleukin-1 beta (IL-1). METHODS: The direct isolation of messenger RNA (mRNA) from articular cartilage without the prior isolation of chondrocytes is described. The in vivo expression of stromelysin was examined at the mRNA level by Northern blot analysis, and at the protein level by in situ immunolocalization and by enzyme-linked immunosorbent assay. RESULTS: In the synovium of IL-1-injected joints, stromelysin mRNA levels were highest at 4 hours and declined to background levels within 24 hours. In the cartilage of IL-1-injected joints, stromelysin mRNA was elevated at 4 hours and continued to increase until 8 hours, before declining. Stromelysin mRNA expression preceded a similar increase in stromelysin protein levels in both synovium and cartilage. CONCLUSION: Intraarticular injection of IL-1 induced the endogenous expression of stromelysin mRNA and protein in both synovium and cartilage. The kinetics of stromelysin expression correlated well with the accumulation of stromelysin and proteoglycan in synovial fluids. Therefore, the de novo synthesis of stromelysin in cartilage may have contributed to the loss of proteoglycan from that tissue.
Little neuropathology has been documented in sudden infant death syndrome (SIDS) infants. Two hypotheses predict abnormalities in the hypoglossal nucleus and dorsal motor nucleus of the vagus: first, that upper airways are obstructed as a result of abnormal innervation (principally the hypoglossal nerve), and second, that they are obstructed as a result of abnormal cardiorespiratory control (the vagus nerve). A quantitative morphometric analysis was carried out to test these hypotheses in SIDS infants and controls (who died in accidents). The following nuclei dimensions were analyzed; length, volume, density, and estimated total cell number. In addition, cell size was analyzed. There were no differences in the anatomical distribution, site, or number of neurons between the groups. The most significant difference between the SIDS and control infants was the neuronal size: control infants had significantly larger neurons. In many other variables, there were trends suggesting a difference between the groups: the volume occupied by the neuronal populations was smaller in the SIDS infants, and therefore the neuronal density was increased. These values suggest differences in the development of these nuclei between SIDS and control infants.
In an autopsy study on Australian Aborigines (29 males, 27 females) and Caucasians (57 males, 37 females) the postnatal growth of the hippocampus was studied and described by mathematical growth functions. For male adults no significant difference in hippocampal volume was found. In contrast, hippocampal volume was significantly smaller for Aboriginal females compared to Caucasian females. Growth analysis showed slower growth rates and later half-value times for Aborigines compared to Caucasians. These results are discussed in relation to secular changes of growth parameters of the human brain during the last century, the socioeconomic and health status of Aborigines, and sexual differences in development and plasticity of the hippocampus.
Postnatal development of the human visual cortex is characterized by an overshooting growth pattern of its volume with a maximum at 8 postnatal months and by loss of a substantial proportion of its neurons. The highest rate of reduction in neuronal numbers is observed in layers II-IVa, with other layers showing a more gradual postnatal decrease.
Recent quantitative neuropathological analyses of the effects of alcohol on the central nervous system have revealed some interesting findings. CT scan studies have suggested shrinkage of the brain in alcoholics and this has been confirmed pathologically. Brain shrinkage relates to a loss of the white matter rather than the grey. However the cortical grey matter is not spared. There is a selective loss of neurones from the frontal region and in this and other cortical regions (motor and cingulate) there is shrinkage of the neuronal soma. This is reflected in a retraction of neuronal dendritic arbor which could account for a loss of white matter but does not explain the reversible brain shrinkage that sometimes follows prolonged abstinence. These studies were extended to specific population groups including moderate drinkers, female alcoholics and alcoholics with cirrhosis of the liver and the Wernicke-Korsakoff syndrome.