Biomedical subjects

A Milford-Ward

Publications and source records attributed to A Milford-Ward.

At least 19 recordsLinked to original sources

PubMed2002

Changing face of adult coeliac disease: experience of a single university hospital in South Yorkshire.

OBJECTIVE: To determine the incidence and presenting features of adult coeliac disease in a single university hospital in South Yorkshire. DESIGN: A retrospective case finding study. Data were obtained from pathology and immunology databases, clinical notes, dietetic records, and patient questionnaires. SETTING: Royal Hallamshire Hospital in South Yorkshire, England. PARTICIPANTS: All recorded cases of coeliac disease. MAIN OUTCOME MEASURES: Crude annual incidence rates for coeliac disease was obtained. The numbers of coeliac antibody profiles requested per year from the Royal Hallamshire Hospital were ascertained. Age at diagnosis, sex, year of diagnosis, presenting symptoms, associated conditions, and delay in diagnosis was documented. In addition the specialty of the clinician who made the diagnosis was noted. RESULTS: There were 264 cases in total (male n=86, ratio 1:2). Mean age at diagnosis was 44.9 years (range 1-82, median 44.5). A trend was observed from 1990 to 2000 inclusive, of an annual increase in the incidence of coeliac disease. There has been a coincidental increase in the measurement of associated antibodies. Although 28.4% of patients presented with gastrointestinal symptoms, 20.1% had iron deficiency anaemia. The ratio of typical to atypical symptoms was 1:2.5. (single sample test of proportions p<0.001). The diagnosis was made by a gastroenterologist in only 52.7% of cases. The median duration of symptoms before the diagnosis of coeliac disease was 4.9 years (range 0.25-16 years). CONCLUSION: Coeliac disease is now presenting more commonly without gastrointestinal symptoms and often to specialties other than gastroenterology. Although more cases are diagnosed, this may be a reflection of increasing recognition rather than a true increase in incidence.

Adolescent↗

PubMed2000

External quality assessment of bone metabolism marker assays. initial experiences in a UK NEQAS programme.

This paper reports on a pilot external quality assessment scheme for bone markers including serum bone alkaline phosphatase and procollagen 1-carboxy terminal propeptide together with urine deoxypyridinoline, N- and C-telopeptides. The data shows poor numerical agreement between commercial assays, between-laboratory imprecision that could be improved, and the need for international standardisation of assays.

Alkaline Phosphatase↗

PubMed1997

Identification of ovarian antibodies by immunofluorescence, enzyme-linked immunosorbent assay or immunoblotting in premature ovarian failure.

The development of new techniques for the detection of ovarian antibodies has challenged early concepts about the rarity of ovarian antibodies in idiopathic premature ovarian failure (POF), but few attempts have been made to compare results between assays. We have sought to define the prevalence of ovarian autoimmunity in a group of 30 idiopathic POF patients compared to a group of 12 patients with POF plus an associated autoimmune disease and a group of 38 controls, using an enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence (IFL). Ovarian antibodies were detected in 27% of idiopathic POF patients by ELISA (not significantly different compared to POF patients with associated autoimmune disease; P < 0.0003 compared to controls) but only 7% of these patients were positive by IFL. In a further, pre-selected group of individuals, all positive for ovarian antibodies by IFL, 53% had measurable antibodies by ELISA. Some overlap was therefore demonstrated between the two techniques but many POF patients had ovarian antibodies detectable by only one method. Immunoblotting studies revealed that no consistent pattern of binding could be demonstrated for these patients. These results call into question the specificity of ovarian antibodies as a marker for autoimmune POF.

Adult↗

PubMed1997

Urinary and serum type III collagen: markers of renal fibrosis.

BACKGROUND: The progression of chronic renal failure is characterized by the progressive fibrosis of the kidneys. Such fibrosis reflects the increased deposition of collagens (I, III, and IV) as well as fibronectin within scarred kidneys. In this study, we determined whether changes in renal extracellular matrix (ECM) components are reflected by parallel changes in their circulating or urinary levels. PATIENTS AND METHODS: We studied 40 patients with a range of subacute and chronic nephropathies who underwent a renal biopsy. At the time of the biopsy, their serum and urinary levels of collagens III (amino terminal peptide of procollagen III; PIIINP) and IV, as well as fibronectin were measured. Clinical, biochemical and histological parameters were correlated. Multiple regression analysis was applied to determine the predictive value of circulating and urinary ECM components for the severity of renal fibrosis. RESULTS: We noted an increase in circulating and urinary levels of collagens III and IV but not fibronectin in patients with nephropathies compared to healthy volunteers. Increased immunoreactivity for these ECM components was also detected in kidney biopsies when compared to normal kidneys. A strong positive correlation was detected between circulating and urinary procollagen III (PIIINP) and the severity of renal interstitial fibrosis (serum PIIINP: r = 0.49, P < 0.01; urine PIIINP: r = 0.51, P < 0.01). CONCLUSION: We conclude that the measurements of urinary collagen III (PIIINP), and to a lesser extent serum collagen III (PIIINP), are useful indicators of the extent of renal fibrosis. This may have diagnostic implications and may prove useful for the monitoring of disease progression.

Adolescent↗

PubMed1997

Cytokines and the malnutrition of chronic renal failure.

Malnutrition in uremic patients remains one of the major causes of morbidity and mortality. Its mediators remain largely unknown. Uremia is characterized by changes in circulating levels of catabolic cytokines and anabolic growth factors. The aim of this study was to investigate whether these changes are associated with the malnutrition of patients with chronic renal failure (CRF). We have studied the prevalence of malnutrition in a small group of patients (n = 20) with CRF (serum creatinine = 551 +/- 105 mumol/l, mean +/- SD) and 25 age-matched controls. Nutritional status was assessed by dietary diaries, subjective global assessment (SGA), and by measurement of anthropometric parameters. Regression analysis was applied to examine the relationship between biochemical and anthropometric parameters. Simultaneously, we have investigated changes in the circulating levels of catabolic cytokines [tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta and IL-6] and an anabolic growth factor [insulin-like growth factor-I (IGF-I)]. We observed a high prevalence of malnutrition as judged initially by SGA: 50% moderately malnourished and 15% severely malnourished. This was confirmed by anthropometric measurements. We noted a significant reduction in both triceps skinfold thickness (TST; 35% of patients < 25th centile) and midarm muscle circumference (MAMC, 65% of patients < 25th centile). We also noted a reduction in serum IGF-I in malnourished patients (IGF-I in well-nourished patients = 207 +/- 48 micrograms/l, in malnourished patients = 133 +/- 33 micrograms/l, p < 0.01). IGF-I correlated with TST (r = 0.71, p < 0.001) and MAMC (r = 0.47, p < 0.05). IGF-I had a high predictive value for TST (R2 = 51%, p < 0.001). In contrast, TNF-alpha levels were higher in malnourished patients: 19.5 +/- 30 pg/ml compared to 3.9 +/- 8 pg/ml in healthy patients (p < 0.001) and TNF-alpha showed a negative correlation with MAMC (r = -0.69, p < 0.01; R2 = 47%, p < 0.01). IL-1 beta levels were higher in CRF than in controls but did not correlate with nutritional parameters. No significant changes could be detected in serum IL-6. A significant percentage of predialysis patients with CRF suffer from some degree of malnutrition. This may be attributed in part to a fall in circulating anabolic growth factors and an increase in catabolic cytokines.

Adult↗

PubMed1996

Does cryptic gluten sensitivity play a part in neurological illness?

BACKGROUND: Antigliadin antibodies are a marker of untreated coeliac disease but can also be found in individuals with normal small-bowel mucosa. Because neurological dysfunction is a known complication of coeliac disease we have investigated the frequency of antigliadin antibodies, as a measure of cryptic gluten sensitivity, and coeliac disease in neurological patients. METHODS: Using ELISA, we estimated serum IgG and IgA antigliadin antibodies in 147 neurological patients who were divided into two groups. There were 53 patients with neurological dysfunction of unknown cause despite full investigation (25 ataxia, 20 peripheral neuropathy, 5 mononeuritis multiplex, 4 myopathy, 3 motor neuropathy, 2 myelopathy). The remaining 94 patients were found to have a specific neurological diagnosis (16 stroke, 12 multiple sclerosis, 10 Parkinson's disease, 56 other diagnoses) and formed the neurological control group. 50 healthy blood donors formed a third group. FINDINGS: The proportions of individuals with positive titres for antigliadin antibodies in the three groups were 30/53, 5/94, and 6/50 respectively (57, 5, and 12%). The difference in proportion between group 1 and the combined control groups was 0.49 (95% CI 0.35-0.63). Distal duodenal biopsies in 26 out of 30 antigliadin-positive patients from group 1 revealed histological evidence of coeliac disease in nine (35%), non-specific duodenitis in ten (38%), and no lesion in seven (26%) individuals. INTERPRETATION: Our data suggest that gluten sensitivity is common in patients with neurological disease of unknown cause and may have aetiological significance.

Biopsy↗

PubMed1996

Further characterization of anti-endothelial cell antibodies in systemic lupus erythematosus by controlled immunoblotting.

Anti-endothelial cell antibodies in systemic lupus erythematosus were further characterized by controlled immunoblotting studies with EN4 defined membrane and cytosol preparations of human umbilical vein endothelial cells. Antibodies to endothelial cell membranes, some of which reacted with the membranes of both dermal fibroblasts and T-cell lymphoma HUT78, were detected in 26/33 patients (78%), but in only 4/34 normal controls (P < 0.001) and 3/11 patients with a recent myocardial infarction. Although the antibody response was very heterogeneous against epitopes ranging from 17 to 205 kDa, there was a tendency to detect particular membrane epitopes at 31-33 kDa (15 cases), 72-78 kDa (eight cases), 66-68 kDa (seven cases) and 17-19 kDa (five cases). No correlations between antibodies to particular epitopes and disease manifestations were observed nor was a relationship to disease activity detected in a retrospective analysis. However, the possibility that anti-endothelial cell antibodies may be pathogenically important was supported by prospective serial studies in two cases with nephritis who showed diminution and disappearance of anti-endothelial cell antibodies as their active disease was treated into remission.

Adult↗

PubMed1996

Asian women are at increased risk of gestational thyrotoxicosis.

Gestational thyrotoxicosis is now widely believed to result from excessive thyroidal stimulation by hCG. Our clinical impression has been that this condition is more frequent in Asian women than in those of European origin. To assess this possibility further, we analyzed thyroid hormone levels in the sera of 294 Asian women, obtained as part of a screening program at 15-16 weeks of pregnancy, and compared these with 292 sera from age- and parity-matched European women at a similar time of gestation. TSH levels were significantly lower in the Asian group (P < 0.001). Suppressed TSH levels (< 0.35 mIU/L) were found in 15.7% of Asian women and 4.8% of European women (P < 0.001). In both groups of women with suppressed TSH values, hCG and hCG beta levels were higher than in the women with normal TSH levels. Free T4 levels in the Asian women were significantly higher in those with suppressed TSH (P < 0.001), but this was not found in the European women. There was also a significant increase in the free T3 index in the Asian women with suppressed TSH compared to that in an age-matched group of Asian women with normal TSH levels (P < 0.02), but this was not observed in European women with suppressed TSH. None of the women with suppressed TSH had thyroid-stimulating antibodies. These results show that Asian women more frequently develop biochemical evidence of thyrotoxicosis at the beginning of the second trimester of pregnancy than those of European origin and are, therefore, likely to be at greater risk of clinically apparent gestational thyrotoxicosis and hyperemesis gravidarum. Genetically determined differences in the production or metabolism of hCG isoforms may account for this increased risk.

Asian People↗

PubMed1996

Consensus of a group of professional societies and diagnostic companies on guidelines for interim reference ranges for 14 proteins in serum based on the standardization against the IFCC/BCR/CAP Reference Material (CRM 470). International Federation of Clinical Chemistry. Community Bureau of Reference of the Commission of the European Communities. College of American Pathologists.

The release in 1993 of a new reference material for serum proteins, CRM 470/RPPHS 5 has given rise to a great improvement in the between-laboratory variability of serum protein measurements worldwide. Conversion to the new reference material results in significant changes in reference values for some proteins. The establishment of new reference ranges will take a considerable time, and in the interim several professional societies and diagnostic companies have agreed to use consensus reference ranges based on studies already undertaken.

Blood Proteins↗

PubMed1994

Symptomatic IgG3 deficiency successfully treated with intravenous immunoglobulin therapy.

We report the case of a 35 year old female who presented with an 8 year history of repeated upper respiratory tract infection, lymphadenopathy and sinusitis associated with IgG3 deficiency. Courses of monthly intravenous immunoglobulin therapy (0.4 g/kg) resulted in a dramatic clinical improvement on three different occasions. We suggest that investigation of adults with features of immunosuppression, despite normal levels of total IgG, should include IgG3 subclass analysis and that symptomatic patients should be given a trial of immunoglobulin replacement therapy.

Adult↗

PubMed1994

A comparison of carbohydrate deficient transferrin with other markers of alcohol misuse in male soldiers under the age of thirty.

The paper describes a study of 58 consecutive male soldiers under 30 years old admitted to an alcohol treatment unit in London, and 51 age- and gender-matched controls to compare the efficacy of isoelectric focusing, a non-quantitative measure of carbohydrate deficient transferrin (CDT), with other markers of alcohol misuse. The Severity of Alcohol Dependence Questionnaire, the Michigan Alcohol Screening Test and the CAGE questions were all more sensitive in detecting alcohol misusers than the laboratory markers measured. At standard cut-off levels, the laboratory markers yielded low sensitivities even in those subjects who admitted to drinking over 80 g alcohol daily for at least 3 weeks immediately prior to the study. CDT was the most sensitive (31%), followed by mean cell volume (14%) and gamma glutamyl transferase (11%). The questionnaires and laboratory markers had good specificities.

Adult↗

PubMed1993

Familial cold urticaria. Investigation of a family and response to stanozolol.

BACKGROUND: Familial cold urticaria is a rare cutaneous and systemic reaction to cold with autosomal dominant inheritance, distinctive clinical features, and unknown pathogenesis. Release of a chymotrypsinlike substance has been postulated. To date, no effective treatment has been reported. OBSERVATIONS: Eight cases from a large family pedigree are described. Three members showed a very favorable response in their cold urticaria, when treated with stanozolol; the response was reproducible. Histologic examination of an early lesion in one case revealed evidence of mast cell degranulation. CONCLUSIONS: The biochemical observations are probably secondary epiphenomena. Correction of a deficiency of an inhibitory protein is a possible mechanism of action of stanozolol as in hereditary angioedema.

Adult↗

PubMed1993

Recurrent lymphocytic meningitis associated with hereditary isolated IgG subclass 3 deficiency.

We report the case of an otherwise healthy young adult woman who has suffered three episodes of lymphocytic meningitis of possible enteroviral aetiology during a 5 year period. Analysis of immunoglobulin subclasses has revealed a sustained reduction of IgG3 to below the fifth percentile. In addition, the patient's father and brother have a similar degree of IgG3 deficiency. Isolated IgG3 deficiency has previously been described in association with recurrent upper respiratory tract infections, asthma, obstructive lung disease and enteral infections. However, our patient did not have any of these and there was no other identifiable immune defect to account for the recurrent meningitis. Although a mere chance association is possible, the case is interesting as antibody responses involving IgG3 tend to be triggered by protein antigens such as viral envelopes, while humoral immunity is known to be important in the clearance of enteroviral infection.

Adolescent↗

PubMed1993

The acquisition of anti-pneumococcal capsular polysaccharide Haemophilus influenzae type b and tetanus toxoid antibodies, with age, in the UK.

Antibody levels specific for capsular polysaccharides of Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) and to tetanus toxoid (TT), were measured in serum samples of 750 age-stratified subjects from the UK. The study subjects comprised healthy adult volunteers and hospitalized children undergoing elective surgery, excluding those with a history of infection or under investigation for immunological or haematological disorders. These antibody levels were calibrated by comparison with serum pool obtained from healthy adult volunteers, who were immunized with Hib polyribose-phosphate vaccine (Merieux). The data are intended to provide reference ranges to assist in the interpretation of specific antibody measurements in the clinical setting. Maternal IgG pneumococcal capsular polysaccharide (PCP) specific antibody levels, geometric-mean titre (GMT) 1/22, were lost by 6 months of age (GMT of 1/9). They remained low until 3-5 years (GMT of 1/20), and consisted principally of IgG1. Thereafter, IgG anti-PCP antibody titres increased steadily to adult levels (GMT of 1/275), of which 80% was IgG2. Anti-PCP antibody titres of the IgM isotype rose steadily from a GMT 1/21 (0-6 months) to 1/420 (3-5 years), a level which was maintained until adulthood. Anti-Hib antibody concentrations, determined by RABA, again demonstrated the decline in maternal antibody, from 0.18 micrograms/ml in the 0-6 month age cohort, to 0.09 microgram/ml between 6 and 12 months. Geometric-mean antibody concentrations remained below 0.2 micrograms/ml until 3-5 years, then increased with age, attaining the mean adult level of 1.02 micrograms/ml. Anti-TT antibody concentrations were measured in the same sera, by ELISA. Two peaks in anti-TT antibody levels were seen in children of 0.059 IU/ml and 0.166 IU/ml corresponding to the schedule of routine childhood immunization in the first year and at 5 years of age.

Adolescent↗

PubMed1992

Plasma levels of the anaphylatoxins C3a and C4a in patients with IgA nephropathy/Henoch-Schönlein nephritis.

Measurements of plasma anaphylatoxins C3a and C4a were carried out as an indicator of in vivo complement activation in 46 patients suffering from IgA nephropathy/Henoch-Schönlein nephritis. There was a significant correlation between plasma levels of C4a and plasma creatinine and urea. We also found a significant correlation of plasma levels of C3a with plasma creatinine. We propose that the measurement of anaphylatoxin levels provides a sensitive indicator of in vivo complement activation and may serve as an additional method for monitoring the progress of disease in these patients.

Adult↗

PubMed1992

The value of acute phase protein measurements in clinical practice.

There is clearly a role for the measurement of acute phase proteins and other indices of the acute phase reaction but it is equally clear that no one laboratory test is suitable for use in all clinical situations. The choice of acute phase protein measurement depends on the diagnostic sensitivity and specificity of the measurement in the particular clinical situation. The choice of measurement must also include a decision on time of sampling and whether single or serial sampling would be more appropriate. In most situations where acute phase measurement is useful CRP is the assay of choice with alpha 1-antichymotrypsin also being useful in inflammatory bowel disease and other situations where a wider time window is required. The ESR or plasma viscosity can be useful to screen for disease. Cytokine and enzyme-inhibitor complex measurements may be important assays in the future.

Acute-Phase Proteins↗

PubMed1991

Plasma levels and mode of excretion of the anaphylatoxins C3a and C4a in renal disease.

Plasma levels of the anaphylatoxins C3a and C4a were examined in patients suffering with various renal diseases. Raised levels were observed in a considerable number of patients; although such elevation could be ascribed to in vivo complement activation in cases of immune complex glomerulonephritis, we found that raised plasma C4a levels appeared to be related to impaired renal function, suggesting that C4a anaphylatoxin is cleared by the kidneys. No such relationship was found in the case of the anaphylatoxin C3a suggesting the possible existence of another mechanism of elimination of C3a.

Adult↗

PubMed1989

Carbohydrate deficient transferrin: a marker for alcohol abuse.

OBJECTIVE: To assess the value of serum carbohydrate deficient transferrin as detected by isoelectric focusing on agarose as an indicator of alcohol abuse. DESIGN: Coded analysis of serum samples taken from patients with carefully defined alcohol intake both with and without liver disease. Comparison of carbohydrate deficient transferrin with standard laboratory tests for alcohol abuse. SETTING: A teaching hospital unit with an interest in general medicine and liver disease. PATIENTS: 22 "Self confessed" alcoholics admitting to a daily alcohol intake of at least 80 g for a minimum of three weeks; 15 of the 22 self confessed alcoholics admitted to hospital for alcohol withdrawal; 68 patients with alcoholic liver disease confirmed by biopsy attending outpatient clinics and claiming to be drinking less than 50 g alcohol daily; 47 patients with non-alcoholic liver disorders confirmed by biopsy; and 38 patients with disorders other than of the liver and no evidence of excessive alcohol consumption. INTERVENTION: Serial studies performed on the 15 patients undergoing alcohol withdrawal in hospital. MAIN OUTCOME measure--Determination of relative value of techniques for detecting alcohol abuse. RESULTS: Carbohydrate deficient transferrin was detected in 19 of the 22 (86%) self confessed alcohol abusers, none of the 47 patients with non-alcoholic liver disease, and one of the 38 (3%) controls. Withdrawal of alcohol led to the disappearance of carbohydrate deficient transferrin at a variable rate, though in some subjects it remained detectable for up to 15 days. Carbohydrate deficient transferrin was considerably superior to the currently available conventional markers for alcohol abuse. CONCLUSION: As the technique is fairly simple, sensitive, and inexpensive we suggest that it may be valuable in detecting alcohol abuse.

Alcoholism↗