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.

Alpha-1-antitrypsin Pi S phenotype and liver cell inclusion bodies in alcoholic hepatitis.

Typical liver cell inclusions of alpha-1-antitrypsin deficiency were found in a patient with the Pi S phenotype and acute alcoholic hepatitis. It is suggested that the inclusions resulted from the combined effects of the S phenotype and alcohol and, on the basis of the known chemistry of the variant antitrypsins, that the lowered serum concentration of antitrypsin associated with the S allele may be due to hepatic holdup.

Hereditary angioedema and thyroid autoimmunity.

Sera from 91 patients with hereditary angioedema were screened for thyroid antibodies. The results for the 77 patients more than 17 years old were compared with previously published data for the prevalence of thyroid disease in a large community (Whickham). Of the female patients with hereditary angioedema, the prevalence of thyroglobulin antibodies (TGA) was 14.0%, higher than the expected 3% (p less than 0.001). The prevalence of thyroid microsomal antibodies (TMA) was 20%, also higher than the expected 7.6% (p less than 0.01). The age distributions of the females in both groups differed: in the group with hereditary angioedema there was a greater proportion of younger patients which should have resulted in a lower prevalence of thyroid antibodies. Adjusting for related patients with hereditary angioedema, there was still an increased prevalence of TGA (p less than 0.01) and TMA (p less than 0.01).

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.

Amniotic fluid alkaline ribonuclease activity: an indicator of foetal growth retardation and anencephaly.

Amniotic fluid alkaline ribonuclease (RNase) activity was measured in 55 normal and 29 neural tube defect pregnancies. The pregnancies which resulted in neural tube defects gave a mean value of 2,500 U/l with a SD of 600 compared with a mean activity of 1,600 U/l (SD 350) from the control normal pregnancies. The mean amniotic fluid RNase activity of 15 anencephalic pregnancies was 2,600 U/l (SD 600), compared with 1,600 U/l (SD 350), for 28 gestational age-matched controls. Highest RNase activities appear to be related to anencephaly.

Immunochemical assays of serum proteins: a European external quality assessment survey and the effects of calibration procedures on interlaboratory agreement.

An external quality assessment survey of immunochemical assays of 9 proteins (immunoglobulins G, A and M, complement components C3 and C4, alpha1-antitrypsin, orosomucoid, haptoglobin and transferrin) in 5 European countries (Austria, France, Hungary, Italy and UK) showed inter-country differences in the mean values obtained. Reprocessing of the results using one of the two specimens distributed as a 'calibrant' effectively eliminated or reduced substantially these differences. Consideration of the methods used by participants confirmed previous indications from national surveys that the differences were due to lack of agreement among commercial calibrants. Such interlaboratory variations were also minimised by the 'calibration' in this survey. The role of European working calibration materials in ensuring interlaboratory agreement on an international basis is discussed.

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.

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.

Overestimation of immunoglobulins in the presence of rheumatoid factor by kinetic immunonephelometry and rapid immunoturbidimetry.

The United Kingdom External Quality Assessment Scheme for Specific Proteins has demonstrated that one method group, comprised of kinetic immunonephelometric assays, gives significantly higher results for immunoglobulins in certain pathological sera containing rheumatoid factor. Using IgM as a model, we have compared kinetic immunonephelometry and a rapid (5 min incubation) immunoturbidimetric assay with radial immunodiffusion (RID) on seven sera. Compared with RID significantly higher results were obtained by kinetic nephelometry on all five sera positive for rheumatoid factor, and by turbidimetry on three of the four of these studied. In a serum with IgM increased due to primary biliary cirrhosis lower results (P0.005) were obtained by nephelometry than by RID. The remaining serum was normal, and no significant intermethod differences were found. The possible causes for these discrepancies are discussed.

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.

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.

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.

Human T-cell mediated response to homologous lens antigen.

T-Cell response to a suspension of homologous whole lens antigen was investigated in three groups: (1) adults with normal eyes; (2) patients with mature and hypermature cataract with an intact lens capsule; and (3) patients, who had had extracapsular cataract surgery or lens injury, some of whom had clinical evidence of severe lens-induced inflammation. The results show that sensitized T-cells occur only in some patients in the third group. To our knowledge, this is the first direct evidence of a difference in the response to T-cells to lens antigen released from mature and hypermature lenses, and to lens antigen exposed by lens injury or extracapsular cataract surgery. The test may be useful to confirm clinical suspicion of delayed hypersensitivity to lens antigen in patients with severe sterile purulent inflammation or milder delayed sterile non-purulent inflammation following lens injury or extracapsular surgery, in the absence of histological proof.

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.

Combined cold urticaria and cholinergic urticaria--clinical characterization and laboratory findings.

Thirteen patients with both cold and cholinergic urticaria are reported. There was considerable variability, particularly in the cold urticaria which was of the common cold contact type in seven patients, of the generalized cold induced cholinergic type in two and in four patients the lesions induced by direct contact with ice were morphologically like cholinergic urticaria, but appeared despite prior application of an acetyl choline antagonist. The natural history, laboratory findings and the effects of therapy are discussed.

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.

Serum copper concentration significantly less in abnormal pregnancies.

We estimated copper concentration in maternal serum during 244 normal and 15 abnormal pregnancies. Values were lower in the abnormal pregnancies than in the normal ones, and did not vary with gestational age between 15 to 18 weeks in normal pregnancies.

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.

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.