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Biomedical subjects

D J Davies

Publications and source records attributed to D J Davies.

At least 19 recordsLinked to original sources
PubMed1992

Intractable leg ulceration caused by cutaneous cholesterol embolism.

OBJECTIVE: To present a case of chronic intractable leg ulceration caused by cholesterol crystal embolism. CLINICAL FEATURES: A 76-year-old Caucasian male with a history of ischaemic heart disease had repeated hospital admissions for diagnosis and treatment of recurrent leg ulceration of more than three years' duration. INTERVENTION AND OUTCOME: Definitive diagnosis was made after the third biopsy when the specimen obtained included subcutaneous arteries. Complete healing occurred within three weeks of excision and a skin graft, and subsequent treatment which included systemic steroids. CONCLUSION: Cholesterol crystal embolism is probably an underdiagnosed cause of intractable leg ulceration and can be identified by a biopsy specimen which includes vessels in subcutaneous fat. Systemic steroids may be helpful in its treatment.

Aged↗
PubMed1990

Lead intake and blood lead in two-year-old U.K. urban children.

A comprehensive study of a group of 2-year-old urban children (n = 97), designed to provide quantitative information simultaneously for lead intakes via all identified pathways, has been carried out in Birmingham (U.K.). Results showed that for children whose blood levels and exposure to environmental lead were within the normal range for the U.K., blood lead concentration was significantly related to a combination of house dust lead loading and an overall rate of touching objects, to water lead concentration and to the parents' smoking habits. On the basis of assumptions used by the Royal Commission on Environmental Pollution (RCEP), the estimated average total uptake of lead was 36 micrograms day-1; of this, 97% was from ingestion from dust, food and water and only 3% from inhalation.

Air Pollutants↗
PubMed1990

Diverse target antigens recognized by circulating antibodies in anti-neutrophil cytoplasm antibody-associated renal vasculitides.

Antibodies that are directed against cytoplasmic constituents of neutrophils and monocytes (anti-neutrophil cytoplasm antibodies, ANCA) have been described in Wegener's granulomatosis, microscopic polyarteritis (MPA) and some cases of segmental necrotizing glomerulonephritis (SNGN). Other antibodies occasionally described in Wegener's granulomatosis and MPA include anti-nuclear antibodies (ANA) and anti-glomerular basement membrane (GBM) antibodies. We have studied the diversity of the corresponding antigens in ANCA-associated renal diseases. Sera from 46 patients with active histologically proven Wegener's granulomatosis, MPA and SNGN were tested for ANCA by indirect immunofluorescent examination of normal peripheral blood neutrophils. Thirty-four sera (74%) were positive; 16 were associated with diffuse cytoplasmic staining (cANCA) and 18 with perinuclear staining (pANCA). In addition, five demonstrated antineutrophil-specific nuclear staining (ANNA). On Western blotting of the neutrophil extract, five sera recognized a 29-kD molecule recently identified as neutrophil proteinase 3. Two sera with typical cANCA bound to molecules of 36, 38 and 116 kD and another to a molecule of 22 kD. The final serum associated with pANCA bound to a molecule of about 12 kD. Thirteen sera out of 46 (28%) tested in an ELISA contained anti-myeloperoxidase antibodies; 10 of these were associated with pANCA and two others with ANNA. Three sera of 17 (18%) tested contained anti-elastase antibodies; these also contained anti-myeloperoxidase antibodies and were associated with pANCA. However, eight sera with pANCA were negative for anti-myeloperoxidase antibodies and three of these were also negative for anti-elastase antibodies, suggesting further unidentified target antigen or antigens associated with the pANCA. Fifteen of the 34 sera positive for ANCA also demonstrated anti-nuclear staining on Hep-2 cells (53%) in a speckled, homogeneous, or nucleolar pattern. ANA were significantly associated with the presence of pANCA (P less than 0.01), and levels of ANA and ANCA fell in parallel after treatment. One serum with a pANCA was also positive for anti-GBM antibodies. Inhibition studies using ELISAs for anti-GBM antibodies indicated that there was no cross-reactivity between target molecules recognized by these antibodies. The diversity of target molecules recognized by ANCA suggests that cross-reactivity with bacterial structures is less likely as the primary aetiological event in the development of these antibodies than tissue destruction; and that cross-reactivity with vascular endothelium is also unlikely as the pathogenetic basis of vessel disease.

Antibodies, Antinuclear↗
PubMed1990

Anti-neutrophil cytoplasm antibodies (ANCA).

Circulating antibodies directed against cytoplasmic constituents of granulocytes and monocytes (anti-neutrophil cytoplasm antibodies, ANCA) are found in about 80% of active cases of Wegener's granulomatosis and microscopic polyarteritis. Antibodies are detected by indirect immunofluorescence on normal peripheral blood leucocytes, or by ELISA or radio-immunoassay using a neutrophil cytoplasm extract. There are 2 patterns of staining seen on indirect immunofluorescent examination of leucocytes and a number of different molecules recognised on Western blots. In Wegener's granulomatosis diffusely granular cytoplasmic staining (cANCA) is associated with a 29KD molecule that has recently been identified as neutrophil proteinase 3. A finely granular pattern may also be seen in microscopic polyarteritis. A perinuclear pattern (pANCA) is present in some other cases of segmental necrotising glomerulonephritis and occasionally in rheumatoid arthritis but almost never in Wegener's granulomatosis. This pattern is often associated with the presence of anti-myeloperoxidase and anti-elastase antibodies. Levels of anti-neutrophil cytoplasm antibodies usually reflect disease activity but a pathogenetic role for these antibodies in the development of small vessel vasculitides is, as yet, unproven.

Autoantibodies↗
PubMed1990

Thin basement membranes in minimally abnormal glomeruli.

The light microscopic, immunofluorescence, and electron microscopic appearances of renal biopsy specimens were reviewed and correlated with the clinical and laboratory findings in 61 patients in whom the findings were initially considered to be either normal or to show only minor non-specific abnormalities. In all cases this reassessment included quantitative measurement of glomerular basement membrane thickness by an orthogonal intercept technique. On the basis of the indication for biopsy, patients were classified into three groups: those with haematuria (group I, n = 41); those with a minor degree of proteinuria (group II, n = 16); and those without any urinary abnormality but in whom possible renal disease as a result of systemic disease was suspected (group III, n = 6). About half of the patients with haematuria had significantly thinner glomerular basement membranes than those in the other two groups, irrespective of the variable selected for assessment, and in three this was confirmed in follow up biopsy specimens. Follow up for up to eight years showed that in patients either with or without thin basement membranes haematuria commonly persisted, but the long term outlook in all three groups was otherwise good and no patient developed impaired renal function.

Anthropometry↗
PubMed1990

Lead exposure in young children from dust and soil in the United Kingdom.

A survey of metals in United Kingdom dusts and soils has confirmed widespread lead contamination with a geometric mean value for lead in surface (0-5 cm) garden soils of 266 micrograms/g and in housedusts of 561 micrograms/g (excluding old mining areas). A subsequent detailed survey of 97 householders in Birmingham with 2-year-old children showed dust lead loading in the home environment to be an important predictor of blood lead concentrations in young children, when both variables fell within the normal range for the U.K. The total estimated lead uptake by the young child was 36 micrograms/day of which 1 microgram was by inhalation and 35 micrograms by ingestion.

Child, Preschool↗
PubMed1990

Antineutrophil cytoplasm antibody (ANCA) associated vasculitis.

In 1982 we first reported the presence of antineutrophil cytoplasm antibodies (ANCA) in 8 patients with systemic vasculitis and segmental necrotizing glomerulonephritis. The results of long-term follow-up are described. Screening of 7,500 serum samples revealed positive ANCA in 9 additional patients with vasculitis. Eighty-eight other patients with vasculitis were ANCA negative, including 7 with microscopic polyarteritis nodosa (MPAN) and 8 with Wegener's granulomatosis (WG). Conversely, ANCA were never detected in the absence of vasculitis. Fourteen patients presenting with glomerulonephritis and ANCA were followed for a median of 6.3 years. Eleven patients had MPAN and 3 WG. Remissions were obtained with immunosuppressive therapy in all patients. Clinical relapse was associated with the reappearance of ANCA. Five-year survival was 89% and 5-year dialysis free survival was 77%. ANCA are specific markers for a sub-group of patients with vasculitis and are sensitive markers of disease activity. Glomerulonephritis associated with ANCA positive vasculitis has a favorable outcome with immunosuppressive therapy.

Antibodies, Antinuclear↗
PubMed1989

Protamine sulphate-induced proteinuria: the roles of glomerular injury and depletion of polyanion.

It has been claimed that intrarenal injection of polycations results in proteinuria due to neutralization of glomerular basement membrane polyanionic charge without any glomerular morphological changes. To study the effects of polycation infusion on the renal glomerulus, the left kidney of rats was directly injected with protamine sulphate through the renal artery. Urine was collected from each kidney before and after injection, and protein excretion rates were determined. Ninety minutes after completion of the injection both kidneys were perfusion-fixed and the morphology and colloidal iron staining of the kidneys were studied by light and electron microscopy. Intrarenal injection of 0.5, 1, and 2 mg of protamine sulphate produced minimal or mild proteinuria in the majority of animals. Higher doses (5 mg) commonly resulted in decreased protein excretion associated with oliguria. Colloidal iron staining of glomerular polyanionic sites was undiminished when compared with control kidneys. Injection of protamine sulphate resulted in capillary thrombosis and severe damage to both glomerular and tubular epithelium in 6 of 16 kidneys. In the remaining kidneys, milder focal changes were apparent. Although its mechanism of action is unclear, it is apparent that protamine sulphate, even in small doses, is toxic to the cellular components of the glomerulus and tubules, thus accounting for the range of changes observed in renal function.

Animals↗
PubMed1989

The effect of long-term feeding of Aroclor 1254 to female rhesus monkeys on their polychlorinated biphenyl tissue levels.

The result of feeding Aroclor 1254 to female Rhesus monkeys at doses of 0, 5, 20, 40 and 80 micrograms/kg body weight/day for a period of 37 months was measured in terms of polychlorinated biphenyl (PCB) levels in blood, adipose tissue, and feces. PCB concentrations in whole blood increased more rapidly during the first 10 months of the study than in the remaining 27 months for all dose groups. On a blood-lipid basis, however, another rapid increase in PCB levels was observed after 27 months of dosing, which could not be explained on the basis of an overall decrease in blood-lipid levels. Concentrations in adipose tissue and adipose fat increased continuously during the 37 months of dosing. These observations were reflected in the ratio profiles of PCB levels in blood/PCB levels in adipose tissue, which remained relatively static between the 2nd and 27th month of continuous feeding. Expressing the data in terms of relative concentrations (concentration/dose) suggests that bio-accumulation or retention of PCBs may be dose-dependent, particularly for adipose tissue, with the higher relative concentrations of the lowest dose group significantly (p less than 0.001) different from all other dose groups. Similarly, the limited feces data available suggests a dose-dependent PCB absorption. The distribution of PCB peaks in the gas chromatographic elution pattern of all analyzed substrates showed considerable deviation from that of administered Aroclor 1254. Only minor changes in the percent distribution pattern were observed between dose groups.

Adipose Tissue↗
PubMed1989

Ultrastructural changes in renal tubules associated with glomerular bleeding.

Renal biopsies from ten patients presenting with macroscopic or heavy microscopic hematuria, shown to be glomerular in origin, were examined by light and electron microscopy. All biopsies showed erythrocytes within tubules by light microscopy and, in five cases, there were morphologic features of acute tubular necrosis. In four biopsies there was clear evidence by electron microscopy of uptake of erythrocytes by renal tubular epithelial cells, associated with some blunting of epithelial microvilli, vacuolar change and increased lysosomal content. Associated with erythrophagocytosis, the subsequent pathway of erythrocyte destruction within renal tubular epithelial cells closely resembled the hemolytic pathway described in macrophages of the reticuloendothelial system.

Adult↗
PubMed1989

Localization of terminal complement components S-protein and SP-40,40 in renal biopsies.

The terminal complement complex has been implicated in the development of glomerular injury in both experimental and, indirectly, in human glomerulonephritis. Recent data suggests that the terminal complement complex in human glomerulonephritis may be in the cytolytically inactive SC5b-9 form which also contains S-protein and a recently identified protein, SP-40,40. In this study renal biopsies were examined by immunofluorescence to determine the incidence and inter-relation of deposition of the SC5b-9 components C6, C9, S-protein and SP-40,40. All components of SC5b-9 were found in arteries and arterioles, along the tubular basement membrane and in areas of glomerulosclerosis in all biopsies. This deposition was sometimes associated with C3 but never immunoglobulin deposition and correlated with the degree of renal injury. In addition, in biopsies with glomerular deposition of immunoglobulin and C3, the SC5b-9, components co-localized with the immune deposits. Glomeruli without immune deposits or glomerulosclerosis contained none of the SC5b-9 components. The incidence and pattern of distribution of SP-40,40 was similar to that of S-protein, C6 and C9 in all of cases. These data confirm that the terminal complement complex in the kidney is, at least partly, in the SC5b-9 form both in the specific immune glomerular deposition and in the "non-specific" deposition in areas of renal injury. SP-40,40 is also found in the SC5b-9 complex in all forms of renal disease.

Biopsy↗
PubMed1989

Two ELISAs to detect anti-neutrophil cytoplasm antibodies (ANCA) in various vasculitides.

Anti-neutrophil cytoplasm antibodies (ANCA) are present in the serum of patients with Wegener's granulomatosis, microscopic polyarteritis, and some other small vessel vasculitides. There are at least 2 different anti-neutrophil cytoplasm antibodies identified by their distinctive cytoplasmic staining patterns on indirect immunofluorescence examination. The only antigen identified to date is myeloperoxidase which has a perinuclear distribution on alcohol-fixed neutrophils and monocytes. We have established an ELISA that detects all anti-neutrophil cytoplasm antibodies and one specific for anti-myeloperoxidase antibodies. In the ELISA for anti-neutrophil cytoplasm antibodies, all sera with diffuse cytoplasmic or perinuclear neutrophil staining on indirect immunofluorescence examination bound at levels greater than the normal range (34%, m + 4SD). Three convalescent sera that were negative by indirect immunofluorescence examination were also negative in the assay. Positive sera could be detected at a dilution of 2 and inhibition studies showed that the binding was specific for the neutrophil extract. However, the presence of anti-neutrophil antibodies (ANA), anti-mitochondrial antibodies or immune complexes resulted occasionally in binding in the positive range. Where positive binding was noted in non-vasculitic segmental necrotizing glomerulonephritis, the binding could not be inhibited by pre-incubation with the neutrophil extract. The ELISA for ANCA is a sensitive, objective screening technique that can be performed in parallel with the assay for anti-glomerular basement antibodies to exclude the presence of anti-neutrophil cytoplasm antibodies in patients presenting with rapidly progressive glomerulonephritis. The ELISA for anti-myeloperoxidase antibodies may identify a subset of patients with distinct clinical or prognostic features.

Cytoplasm↗
PubMed1988

Pemphigus vulgaris of the esophagus.

We describe a case of pemphigus vulgaris involving the lower esophagus, in a patient with gastroesophageal reflux. As near as we can tell, this is the first reported case of esophageal involvement by pemphigus in the absence of oropharyngeal disease. Gastroesophageal reflux may have precipitated the development of esophageal pemphigus.

Aged↗
PubMed1987

Lead levels in Birmingham dusts and soils.

Lead concentrations were measured in housedust, pavement dust, road dust and garden soil in and around 97 inner-city houses in Birmingham, England. The highest mean dust lead concentration within the home, 615 micrograms g-1, was noted in samples from under the doormat. Generally, the housedust lead levels were lower than the national mean (507 micrograms g-1), although soil lead concentrations were slightly higher. The age of the property was found to influence the lead levels in both housedust and garden soil, with older houses (greater than 35 years) having significantly higher concentrations than newer properties (less than 35 years). Houses being decorated at the time of sampling were found to have significantly higher lead concentrations than those that were not. Elevated lead levels were also noted in housedust and garden soil from houses located within a 500 m radius of commercial garages. Increased lead concentrations were found in soil samples from gardens in close proximity to waste land (demolition sites and tips), metal-using industries and from those within 10 m of a road. Road dust samples from industrial areas had significantly higher lead concentrations than those from residential areas.

Dust↗