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1.  Scrotal cancer in the north-west of England, 1962-68 
Lee, W. R., Alderson, M. R., and Downes, J. E. (1972).Brit. J. industr. Med.,29, 188-195. Scrotal cancer in the north-west of England, 1962-68. During the seven years 1962 to 1968 there were 103 cases of scrotal cancer reported to the Manchester Regional Cancer Registry. It was possible to obtain reasonably full occupational histories concerning 89 of these cases either from the men themselves or from close relatives. Fifty-one had been mule spinners, 40 of whom had worked in no other industry with a hazard of scrotal cancer, but the other 11 had. Another 19 men had never been mule spinners but had worked in occupations with a recognized hazard of this condition. Of the remainder, 14 had worked in occupations with a possible risk, although perhaps not generally recognized as such, and in five no clear cause was apparent. Because of the small numbers, it was possible to compare the observed and expected incidences only in broad occupational groups and these showed a statistically significant excess (P<0·001) only in textile workers and unskilled workers. However, our findings, taken with those of earlier workers, suggest that further attention might be given to four other groups, namely, automatic lathe operators, road workers, dye workers, and chain makers.
Cancer of the scrotum tends to be a disease of the elderly. In 42% of men (other than mule spinners) scrotal cancer developed after the men had passed the age of retirement and therefore too late for routine medical examination at the workplace to be of any value. Fifty of the men had died, but scrotal cancer was registered as the underlying cause in only 19 and appeared on the death certificate in a further four.
PMCID: PMC1009398  PMID: 5063206
2.  Occurence of oral and pharyngeal cancers in textile workers 
Moss, E. and Lee, W. R. (1974).British Journal of Industrial Medicine,31, 224-232. Occurrence of oral and pharyngeal cancers in textile workers. The occupations of male textile workers who died of oral and pharyngeal cancers in the five years 1959-63 have been examined to discover whether the high incidence of oral cancer in these workers noted by the Office of Population Censuses and Surveys (1972) is associated with particular textile occupations or fibres.
There was a 77% excess of deaths from these cancers in male textile workers as a whole compared with the male population of England and Wales, the excess being significant at the 0·1% level. An excess occurred in each of the three sites tongue (ICD 141), mouth (ICD 143, 144), and pharynx (ICD 145-148) and is significant at the 5% level in the first two sites but not in the third.
Fibre preparers had an excess of 330% which is significant at the 0·01% level. Weavers and knitters had a deficit of 32% and the remaining three groups had moderate excesses of from 32 to 85%, none of the four being statistically significant.
In the 1951 census there were 8 414 male cotton workers and 14 723 male wool workers engaged in fibre preparing. There was one death from oral cancer in cotton fibre preparers and 18 deaths in wool fibre preparers. The difference is significant at the 1% level. The difference is also significant for the individual sites pharynx and tongue but not mouth.
PMCID: PMC1009588  PMID: 4479250
3.  Ventricular fibrillation threshold for AC shocks of long duration, in dogs with normal acid-base state 
Scott, Janet R., Lee, W. R., and Zoledziowski, S. (1973).British Journal of Industrial Medicine,30, 155-161. Ventricular fibrillation threshold for AC shocks of long duration, in dogs with normal acid-base state. Earlier experimental studies of threshold ventricular fibrillating currents passing along the common accident pathway of forelimb to leg have shown a wide range of results for any one shock duration. In the present investigation the acid-base state of the experimental animals (dogs) was held within normal limits. It was found that whereas the mean minimum fibrillating current, 82·2μA for 3-second shocks, was within the values found by other workers, the range of results was reduced considerably to 67-101μA. Further, when the shock duration was increased, in stages, up to 60 seconds, again keeping the acid-base state within normal limits, the mean minimum fibrillating current did not alter markedly (being 80μA at 60 seconds) but the range of results progressively fell and was 73-88μA at 60 seconds. In the light of these findings the mechanism of ventricular fibrillation is discussed.
PMCID: PMC1009498  PMID: 4703086
4.  Emergence of occupational medicine in Victorian times1 
Lee, W. R. (1973).British Journal of Industrial Medicine,30, 118-124. Emergence of occupational medicine in Victorian times. The events surrounding the establishment and development of legislation to protect the health of people at work in Victorian times are already well documented. This paper deals with some other aspects of the development of occupational medicine.
Medical opinions at the time did not always see the misuse of child labour as due simply to avaricious mill owners, but in part due to the parents and in part to the workmen subcontractors. The establishment of the certifying surgeons is briefly reviewed and their coming together to form an association in 1868 may be related to questions about the need for medical certificates of age which were being requested by the many factory owners brought under factory legislation for the first time in 1864 and 1867.
The plight of injured workmen and their dependents was early recognized, although it was late in the Victorian era before any statutory provision was made for them. The idea of linking compensation with preventive measures came to the fore in 1845 when some Manchester doctors, later supported by Edwin Chadwick, examined the workings at the Woodhead railway tunnel across the Pennines. When compensation legislation was passed some half a century later the idea was lost, and to this day compensation for and prevention of industrial injury and disease remain separated.
The change of industrial diseases from a medical curiosity to a problem requiring State intervention is traced over the latter part of the Victorian era.
The whole piecemeal pattern illustrating the precept that `social problems come first, social philosophy after' has persisted until the far-reaching changes in health and safety legislation of the present day.
PMCID: PMC1009492  PMID: 4267346
5.  An anatomy of occupational medicine1 
Lee, W. R. (1973).British Journal of Industrial Medicine,30, 111-117. An anatomy of occupational medicine. Previous writers have attempted to describe occupational medicine by considering the functions of a doctor working in industry. In different communities, and even in the same community at different times, a doctor working in industry may have different functions. `Occupational medicine', so described, would therefore not be a discipline but would merely be medicine practised in a certain area. Furthermore, such an approach leaves out other aspects of occupational medicine such as recompense for injury at work and statutory supervision of workplaces, and any interaction between these two.
Men think in terms of conceptual models which predetermine to a greater or less extent their approach to future problems. The present essay attempts to formulate a coherent intellectual framework of occupational medicine.
The conceptual model proposed here is based on the globe proposed by Himsworth (1970) as a model representing the structure of scientific knowledge. Using this, a place for occupational medicine can be determined related to medicine, industry, and the `basic' sciences. Occupational medicine is thus seen as a coherent entity.
The argument is supported by a comparison of some of the provisions for occupational medicine in this country and in France. In this comparison the underlying components are distinguished from the mechanisms set up to deal with them. It is these components which go to make up the structure of occupational medicine and it is the coherence and close relationship of them which must be studied to find and describe an entity to be called occupational medicine.
PMCID: PMC1009491  PMID: 4270047
6.  Detection and quantification of S-100 protein in ocular tissues and fluids from patients with intraocular melanoma. 
S-100 protein is a 21,000 dalton acidic calcium-binding protein present in ocular melanomas and some normal ocular tissues. Ocular fluids and extracts of ocular tumours were examined by a sensitive radioimmunoassay that could detect less than 5 ng of S-100 protein in minute volumes of fluid. Three ocular melanoma biopsy specimens had S-100 protein at levels between 25 and 1300 ng/ml, comparable to that found in a cutaneous melanoma biopsy specimen (1000 ng/ml). (SI conversion: ng/ml = microgram/l.) Six melanoma culture lines had 1000 to 125,000 ng/ml. Four lymphoblastoid cultures had less than 2 ng/ml, and three colon carcinoma cultures had 180 ng/ml. Subretinal fluid from 23 melanoma-containing eyes had 10 to 76,800 ng/ml. Lesser amounts were found in eyes with small, anteriorly located, lightly pigmented tumours. Vitreous from 3 melanoma-containing eyes had 10,000 to 11,000 ng/ml. Vitreous obtained from three eyes during tractional retinal detachment repair had 500 to 1600 ng/ml, and vitreous obtained at necropsy from six normal eyes had 2 to 120 ng/ml. Aqueous from six melanoma-containing eyes had 10 to 30 ng/ml, levels not significantly different from those observed in three normal eyes (80-120 ng/ml). This approach provides new insight into the interaction of ocular tumours and adjacent ocular fluids and may, with more specific tumour markers, have diagnostic applications.
PMCID: PMC1041610  PMID: 3207666
7.  Corneal endothelial cell abnormalities in an early stage of the iridocorneal endothelial syndrome. 
A corneal disc, obtained from a 52-year-old woman suffering from an early stage of the iridocorneal endothelial syndrome (ICE), was investigated by various morphological techniques to analyse the structural variations in the endothelial cells and to identify the collagen types within the abnormal layer of Descemet's membrane. Scanning electron microscopy of the posterior corneal surface revealed a mosaic of (a) flat hexagonal cells resembling irregular but normal endothelial cells, and (b) rounded hexagonal (ICE) cells with numerous surface microvilli. Degenerative changes were present in each cell type, but were more common in the flat hexagonal cells which contained intracytoplasmic spaces. By transmission electron microscopy the flat hexagonal cells exhibited many of the features of normal endothelial cells in terms of organelles and intercellular attachments, but lateral invaginations were absent. The ICE cells differed in that the apical surface was covered by microvilli and the cytoplasm contained tonofilaments, which were also observed by light microscopic immunocytochemical staining. Most commonly, intercellular attachments were rudimentary in both types of cell and intercellular spaces were dilated, but desmosomes were sometimes prominent in the ICE cells where interdigitations were pronounced. In some sectors, the basal surface of the ICE cells was indented by deposition of clumps of fibrillar collagenous material. An immunocytochemical study of the abnormal posterior deposits localised type IV collagen to the amorphous matrix and collagen types III and V, but not type I, to the collagen fibril bundles. Mononuclear inflammatory cells were identified between the ICE cells in the monolayer. The evidence suggests that some of the flat hexagonal cells were undergoing a degenerative change while others were transforming into ICE cells.
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PMCID: PMC504888  PMID: 7918291
9.  Isolation of the Fungus Geosmithia argillacea in Sputum of People with Cystic Fibrosis▿  
Journal of Clinical Microbiology  2010;48(7):2615-2617.
We report the repeated isolation of the fungus Geosmithia argillacea from sputum samples of people with cystic fibrosis. Identification was based on morphology and DNA sequence analysis. Isolation of G. argillacea did not appear to be associated with clinical deterioration. The pathogenic potential of G. argillacea is discussed.
doi:10.1128/JCM.00184-10
PMCID: PMC2897513  PMID: 20421435
10.  Immunogold study of non-collagenous matrix components in normal and exfoliative iris. 
The present investigation was undertaken to determine if some of the components of exfoliation material in iris tissue were unique to exfoliation or were part of normal iris architecture. Eleven normal iris specimens and 10 exfoliative iris specimens were processed for cryoultramicrotomy and London resin white embedding. Immunogold electron microscopy was used to investigate the fine structural distribution of amyloid P component, elastin, entactin, fibronectin, gp115, and vitronectin in normal iris and their association with exfoliation material. Exfoliation material was positive for amyloid P component and possibly gp115, neither of which were present in normal iris tissue. Elastin and fibronectin were present in the normal iris stroma but were not associated with exfoliation material. The distribution of amyloid P component in the vessel lumen and wall led to the conclusion that amyloid P is a serum contaminant. The presence of gp115 in exfoliation material represents the synthesis of a component novel to the iris vascular cell synthetic repertoire.
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PMCID: PMC504972  PMID: 7531491
11.  Post-traumatic hyperlipofuscinosis in the human retinal pigment epithelium. 
Light microscopy (including fluorescence microscopy) and electron microscopy were applied to a study of the photoreceptor-retinal pigment epithelium (RPE) complex in a human eye which had been severely traumatised nine months prior to enucleation. The main feature of interest was a massive accumulation of lipofuscin in the retinal pigment epithelium at the posterior pole, and quantitative fluorescence microscopy provided values three times those obtained in appropriate control tissue. The photoreceptor layer was normal at the posterior pole but became progressively atrophic towards the periphery. The concentration of lipopofuscin was proportional to the degree of preservation of the retinal photoreceptors. By electron microscopy the cells in the RPE were seen to be packed with a mixture of lipofuscin granules and melanolysosomal complexes, but occasional photoreceptor phagosomes were found. Bruch's membrane and the choriocapillaris were normal. We attribute this hitherto unreported abnormality of the RPE after trauma to a dysfunction consequent on an overload of the monolayer by photoreceptor debris at the time of trauma.
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PMCID: PMC504109  PMID: 1991090
12.  Ultrastructural distribution of collagen types I-VI in aging human retinal vessels. 
Retinal vessels from freshly enucleated human eyes were classified into three stages of the hyalinisation process. The distribution of collagen types I-VI within the vessel walls was studied ultrastructurally by immunogold labelling combined with the tissue preparation techniques of cryoultramicrotomy and London resin white embedding. Collagen types I, III, IV, V, and VI were found in large vessels, types I, IV, and V plus small amounts of III and VI in small vessels, and types I, IV, and V in capillaries. Hyalinised vessel walls consisted mainly of types I, IV, and VI collagen.
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PMCID: PMC1042067  PMID: 2337548
13.  Morphological changes in the human conjunctival epithelium. II. In keratoconjunctivitis sicca. 
A clinicopathological correlation was performed on 24 patients suffering from keratoconjunctivitis sicca (KCS). Examination of conjunctival biopsies by light and transmission electron microscopy revealed stratification of the conjunctival epithelium with separation of the superficial cell layers, and this was directly proportional to the clinical severity of the disease. Counts of goblet cells were found to be inversely proportional to the degree of stratification. The goblet cells were morphologically identical to, but significantly fewer in number than, those found in normal conjunctival tissue. A reduction in epithelial cell stratification and separation and an increase in goblet cell density were closely related to nasolacrimal duct occlusion--an operation performed only in the severe examples of KCS in this series. The possible causes of 'mucous' plaques and 'filaments' are discussed in relation to these phenomena. Moreover, there is a dramatic reduction and deformation in the microplicae on the surface of the conjunctival epithelium. The significance of this was considered in relation to tear film stability.
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PMCID: PMC1043356  PMID: 718821
14.  Morphological changes in the human conjunctival epithelium. I. In the normal elderly population. 
Forty-nine biopsies of bulbar conjunctiva from patients with no apparent conjunctival disease were studied by light and transmission electron microscopy. No significant morphological changes were recorded in those specimens from patients less than 79 years old. However, in the older age group the epithelium showed irregularities in thickness, a reduction in the goblet cell population, and in 25% the presence of 'hyaline bodies'. The epithelial irregularities consisted of mild superficial stratification, which was observed also in a few of the specimens from the younger age groups. The goblet cells appeared morphologically normal in all age groups. The significance of the hyaline bodies and their possible relationship to goblet cells is discussed.
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PMCID: PMC1043355  PMID: 82444
15.  The trabecular wall of Schlemm's canal: a study of the effects of pilocarpine by scanning electron microscopy. 
The scanning electron microscope was used to study the endothelium lining the trabecular wall of Schelemm's canal in 10 human eyes enucleated in treatment of choroidal melanomas. The eyes of 5 patients had been treated before enucleated with pilocarpine drops, and the remaining 5 were untreated and served as controls. In the pilocarpine-treated tissue there was an increased prominence of cellular bulges in the endothelial monolayer, and the endothelial pores were both larger and more frequent than in the untreated eyes. By the use of Poiseuille's formula it was calculated that the resistance offered by the pore system to the drainage of aqueous in the pilocarpine-treated group was approximately one-ninth of that in the control series.
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PMCID: PMC1043378  PMID: 760777
16.  Prediction values for the ventilatory capacity in male West Pakistani workers in the United Kingdom 
Thorax  1972;27(5):611-619.
The ventilatory functions (forced vital capacity, forced expiratory volume in one second, and peak expiratory flow rate) of West Pakistani immigrants working near Manchester were measured. There were 198 `normal' healthy adult workers aged 25 to 60 years and 129 workers aged 16 to 24 years. The subjects were considered `normal' if they did not admit to persistent cough and phlegm. The regression equations on age and height for the two groups are presented together with the corresponding nomograms for the adult group.
Ventilatory function reached its maximum between the ages of 25 and 30 years; smokers and dust-exposed subjects did not differ significantly from non-smokers and non-dust-exposed subjects (P>0·1). This was probably due to their relatively light smoking habits and the short duration of dust exposure. The effects of age, in workers over the age of 25 years, and the predominant effects of height on the FVC, FEV1·0, and PEFR are similar to those found in other studies.
The ventilatory capacity of the subjects was found to be somewhat lower than that of Caucasians, about equal to that of Negroes living in America, and higher than that of Indians of Asian origin living in Guyana or of Bantu Negroes in South Africa.
The predicted FEV1·0/FVC% in the West Pakistani subjects is a little higher than any calculated from the results of other authors, but its regression on age is consistent with the findings of other studies and, therefore, can be used in clinical practice to assess the pulmonary conductance.
PMCID: PMC470567  PMID: 5083729
18.  Morquio syndrome: electron microscopic findings 
doi:10.1136/bjo.2004.055400
PMCID: PMC1772727  PMID: 15965185
Morquio syndrome
19.  Multidrug resistance in ocular melanoma. 
The British Journal of Ophthalmology  1996;80(11):1009-1012.
AIMS/BACKGROUND: Metastatic disease in patients with ocular melanoma is resistant to chemotherapy. One of the main mechanisms of modulating multidrug resistance is the expression of the multidrug resistance gene 1 (MDR1) product (p-glycoprotein) by tumour cells. The purpose of this study was to evaluate the frequency of expression of the MDR1 gene in ocular melanoma whose primary treatment was surgical excision or enucleation. METHODS: Twelve recent ocular melanomas were received fresh, snap frozen and cryostat sections of tumour were analysed for expression of MDR1 by immunohistochemistry using a well characterised monoclonal antibody to MDR1. Tumour explants were established in short term tissue culture from four tumours and cell blocks were examined by immunohistochemistry. RESULTS: MDR1 expression was present in five of 12 ocular melanomas. Upregulation of protein expression was found in four cell lines established in short term culture from tumour explants. A recurrent tumour, initially treated by local excision and radioactive plaque, showed overexpression of MDR1 mRNA. CONCLUSIONS: These results suggest that significant level of MDR1 may be intrinsically present in ocular melanomas before exposure to drugs involved in multidrug resistance, and indicate the possible importance of MDR1 in modulating chemoresistance in ocular melanoma. Chemosensitisation may be of potential value in planning adjuvant chemotherapy for patients with metastatic disease.
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PMCID: PMC505681  PMID: 8976731
20.  Bilateral Kimura's disease of the eyelids. 
A case of Kimura's disease affecting the eyelids bilaterally is reported in a 5-year-old boy of Afro-Caribbean extraction who has been followed for 12 years with repeat biopsies. He initially presented at 5 years of age with swelling of the left upper eyelid, left cervical lymphadenopathy, and eosinophilia. One year later he developed swelling of the right upper eyelid. There has been no change in the clinical appearance over the next 12 years. Repeated biopsies of the eyelids showed a diffuse inflammatory infiltrate with many eosinophils and lymphocytes. A lymph node biopsy showed reactive lymphoid hyperplasia. Immunohistochemistry using lymphoid markers showed a polyclonal pattern. Kimura's disease is a rare cause of eyelid swelling, particularly at such a young age and with bilateral involvement. This case demonstrates that bilateral orbital lymphoid lesions with cervical node involvement do not always imply lymphoma, but may have a benign pathogenesis. The unusually long follow up in this case confirms an excellent prognosis for Kimura's disease with conservative management. Accurate diagnosis in small orbital biopsies may spare the patient unnecessary radical surgery.
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PMCID: PMC504400  PMID: 1486082
21.  Type IV collagen and laminin in Bruch's membrane and basal linear deposit in the human macula. 
Tissue obtained from the macula in 10 human eyes (53-77 years) was used for an investigation into the extracellular matrices of the retinal pigment epithelium (RPE), Bruch's membrane, and the choriocapillaris. The ultrastructural distribution of type IV collagen and laminin was documented using immunogold labelling. Labelling for type IV collagen was strongly positive in all the specimens in the basement membranes of the choriocapillaris but not that of the RPE where labelling was either weak or absent. Laminin was localised to deposits of granular material in Bruch's membrane but was absent from the basement membrane of the RPE and the choriocapillaris. Basal linear deposit, observed in three cases, demonstrated labelling for laminin but not for type IV collagen. The series was too small for correlation of these morphological changes with age.
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PMCID: PMC505233  PMID: 1420043
22.  Plasmacellular differentiation in extranodal marginal zone B cell lymphomas of the ocular adnexa: an analysis of the neoplastic plasma cell phenotype and its prognostic significance in 136 cases 
Aim: To determine (a) the expression of plasma cell related antigens in extranodal marginal zone B cell lymphomas (EMZL) of the ocular adnexa; and (b) the prognostic value of plasmacellular differentiation in these tumours.
Methods: A consecutive case series of 136 ocular adnexal EMZL obtained from three ocular pathology centres over 20 years was analysed retrospectively. An extensive immunohistochemical panel, including the plasma cell related antigens VS38c, CD38, CD138, multiple myeloma oncogene-1-protein (MUM1/IRF4), and CREB binding protein (CBP) was performed. EMZL were defined as “plasmacellular differentiated” on the basis of morphological features, evidence of cytoplasmic immunoglobulin, negativity for BSAP/PAX5, and expression of at least one of the investigated plasma cell related antigens. Controls included normal or hyperplastic lymphatic tissues. Detailed clinical data were collected for most patients, and compared with the results of immunohistochemistry. The end points considered for statistical analysis were development of local tumour recurrence, development of systemic disease, and lymphoma related death.
Results: 57 (42%) of the 136 ocular adnexal EMZL showed a plasmacellular differentiation; 45 of these plasmacytoid cases were primary tumours. In contrast with most admixed normal plasma cells, which displayed co-expression of MUM1/IRF4, Vs38c, CD38, CD138, and CBP, the plasmacellular differentiated EMZL tumour cells demonstrated co-expression of all five plasma cell related antigens in only six of 57 (11%) plasmacellular differentiated ocular adnexal EMZL. The most commonly expressed plasma cell related antigen was MUM1/IRF4, immunoreactivity being seen in 56/57 (98%) plasmacellular differentiated EMZL examined. Although the association of plasmacellular differentiation in primary ocular adnexal EMZL and disseminated disease was statistically significant on univariate analysis (p = 0.042), this was weaker on multivariate analysis.
Conclusion: Plasmacellular differentiated tumour cells in EMZL demonstrate an aberrant immune profile for plasma cell related antigens when compared with normal plasma cells. On multivariate analysis, plasmacellular differentiation in ocular adnexal EMZL was not significantly associated with local recurrence, the development of systemic disease, or with lymphoma related death.
doi:10.1136/bjo.2004.047092
PMCID: PMC1772544  PMID: 15722318
ocular adnexal lymphoma; extranodal marginal zone B cell lymphoma; lymphoma classification; plasmacellular differentiation
24.  Immunogold localisation of laminin in normal and exfoliative iris. 
Immunoelectron microscopic studies of exfoliative iris tissue (seven specimens) revealed the presence of laminin in the fibrillar component of exfoliation material. The immunogold label was uniformly distributed on the exfoliation fibres. Deposition of laminin labelled exfoliation material in the dilator muscle was a noteworthy feature, as was an apparent depletion of laminin in the basement membranes of ostensibly unaffected vessels. In control iris tissue (five enucleated eyes) laminin was identified in the basement membrane round vascular contractile cells, but not beneath the endothelium.
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PMCID: PMC1042171  PMID: 2390517

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